17

var title_f6_17_6416="First degree AV block III";
var content_f6_17_6416=[" <div id=\"graphicsToolbar\">",

" <div id=\"graphicsCopy\">",
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=CARD
%2F54122&source=image_view&view=print&elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=CARD
%2F54122&source=image_view&view=print&elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" First degree AV block with a prolonged PR interval and wide QRS",
" </div>",
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nN3GSZGydg5+RulWWW5EEpF2g+c4Owcc9KSN5PSOv5935H/2Q==);\">",
" </div>",
" <div class=\"lgnd\">",
" The PR interval is 0.43 sec and the QRS duration is 0.11 sec. The markedly
prolonged PR interval suggests slow conduction through the AV node, but the
somewhat widened QRS also suggests infranodal conduction delay.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Morton F Arnsdorf, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_17_6416=[""].join("\n");
var outline_f6_17_6416=null;
var title_f6_17_6417="Hidradenitis suppurativa nodule and sinus tracts unroofed";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=SURG
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=SURG
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Hidradenitis suppurativa nodule and sinus tracts unroofed",
" </div>",
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dPpRYQ3sTTSxJOO9PbkcU0e+MigaP/2Q==);\">",
" </div>",
" This picture shows the completely unroofed inflamed hidradenitis suppurativa
nodule and multiple sinus tracts. Note the skin edges are beveled and the base is
scraped clean of debris by rough gauze grattage. Hemostasis is controlled using
ferric chloride and the wound is cleansed with hydrogen peroxide and covered with
petrolatum dressing.",
" </div>",
" Reproduced with permission from: F William Danby, MD, FRCPC, FAAD. Copyright
© 2011.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6418="Atopic dermatitis papular";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=DERM
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=DERM
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Atopic dermatitis",
" </div>",
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lk9GXczBG7EsqK+7k8UVO065PCk55zniir5UB//9k=);\">",
" </div>",
" Numerous erythematous papules are present on the hands of this patient with
atopic dermatitis.",
" </div>",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6419="Vitiligo focal leg";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=PC
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PC
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Focal vitiligo",
" </div>",
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" </div>",
" Area depigmented by vitiligo.",
" </div>",
" Reproduced with permission from: Goodheart, HP. Goodheart's Photoguide of
Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins, Philadelphia
2003. Copyright ©2003 Lippincott Williams & Wilkins.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6420="Alteplase: Patient drug information";
var content_f6_17_6420=[" <noscript>",
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"for medical advice, diagnosis, or treatment. Always seek the advice of your own
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"other qualified health care professional regarding any medical questions or
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" ©2013 UpToDate, Inc.",
" </div>",
" <div id=\"drugTitle\">",
" Alteplase: Patient drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" <p>",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/41/11929?source=see_link\">",
" see \"Alteplase: Drug information\"",
" </a>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?12/2/12328?
source=see_link\">",
" see \"Alteplase: Pediatric drug information\"",
" </a>",
" )",
" </p>",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F132252\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Activase®;",
" </li>",
" <li>",
" Cathflo® Activase®",
" </li>",
" </ul>",
" </div>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F132253\"
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" Activase® rt-PA;",
" </li>",
" <li>",
" Cathflo® Activase®",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yya-os drugH1Div\" id=\"F10012275\"
" What is this drug used for?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" •",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2691474",
" </span>",
" </span>",
" <span class=\"content\">",
" It is used to stop heart muscle problems during a heart attack.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2691322",
" </span>",
" </span>",
" It is used to clear blood clots out of catheters.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2691756",
" </span>",
" </span>",
" It is used to treat blood clots.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt coi-os drugH1Div\" id=\"F10012274\"
" What do I need to tell my doctor before I take this drug?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2701474",
" </span>",
" </span>",
" If you have an allergy to alteplase or any other part of this drug.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2705171",
" </span>",
" </span>",
" If you are allergic to any drugs, foods, or other substances. Tell your
doctor about the allergy and what signs you had, like rash; hives; itching;
shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or
any other signs.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2703237",
" </span>",
" </span>",
" If you have any of these health problems: Aneurysm, arteriovenous
malformations, bleeding problems, brain tumor, injury to the brain or spine in the
last 2 months, stroke, surgery on the brain or spine in the last 2 months, or very
high blood pressure.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yye-os drugH1Div\" id=\"F10012279\"
" What are some things I need to know or do while I take this drug?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2699677",
" </span>",
" </span>",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2697238",
" </span>",
" </span>",
" If you have had any recent surgery or dental care, talk with your doctor.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2696717",
" </span>",
" </span>",
" Check all drugs you are taking with your doctor. This drug may not mix well
with some other drugs.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2697760",
" </span>",
" </span>",
" Use care to stop injury and avoid falls or crashes.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2697641",
" </span>",
" </span>",
" Tell your doctor if you are pregnant or plan on getting pregnant. You will
need to talk about the benefits and risks of using this drug while you are
pregnant.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2697636",
" </span>",
" </span>",
" Tell your doctor if you are breast-feeding. You will need to talk about any
risks to your baby.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyf-os drugH1Div\" id=\"F10012280\"
" What are some side effects of this drug?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2698324",
" </span>",
" </span>",
" Very bad bleeding may rarely happen.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyh-os drugH1Div\" id=\"F10012282\"
" What are some side effects that I need to call my doctor about right away?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2698721",
" </span>",
" </span>",
" If you think there has been an overdose, call 1-800-222-1222 (the American
Association of Poison Control Centers), your local poison control center
(file://www.aapcc.org), or emergency room (ER) right away.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2699066",
" </span>",
" </span>",
" Signs of an allergic reaction, like rash; hives; itching; red, swollen,
blistered, or peeling skin with or without fever; wheezing; tightness in the chest
or throat; trouble breathing or talking; unusual hoarseness; or swelling of the
mouth, face, lips, tongue, or throat.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2698626",
" </span>",
" </span>",
" Chest pain or pressure.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2699105",
" </span>",
" </span>",
" Any bruising or bleeding.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2699058",
" </span>",
" </span>",
" Change in thinking clearly and with logic.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2699031",
" </span>",
" </span>",
" Very bad headache.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2699004",
" </span>",
" </span>",
" Very bad back pain.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2699008",
" </span>",
" </span>",
" Very bad belly pain.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2698658",
" </span>",
" </span>",
" Feeling very tired or weak.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2698603",
" </span>",
" </span>",
" Any rash.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2698977",
" </span>",
" </span>",
" Side effect or health problem is not better or you are feeling worse.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyc-os drugH1Div\" id=\"F10012277\"
" How is this drug best taken?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2695991",
" </span>",
" </span>",
" It is given as a shot into a vein.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b498:s2695992",
" </span>",
" </span>",
" It is given as a shot into the catheter.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyd-os drugH1Div\" id=\"F10012278\"
" What do I do if I miss a dose?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2696446",
" </span>",
" </span>",
" Call your doctor to find out what to do.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyi-os drugH1Div\" id=\"F10012283\"
" How do I store and/or throw out this drug?",
" </span>",
" •",
" </span>",
" urn:lims:b498:s2699596",
" </span>",
" </span>",
" This drug will be given to you in a hospital or doctor's office. You will
not store it at home.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyj-os drugH1Div\" id=\"F10012284\"
" General drug facts",
" </span>",
" •",
" </span>",
" urn:lims:b259:s2699675",
" </span>",
" </span>",
" If your symptoms or health problems do not get better or if they become
worse, call your doctor.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s2699673",
" </span>",
" </span>",
" Do not share your drugs with others and do not take anyone else's drugs.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s2699678",
" </span>",
" </span>",
" Keep all drugs out of the reach of children and pets.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s2699709",
" </span>",
" </span>",
" If you have any questions about this drug, please talk with your doctor,
pharmacist, or other health care provider.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s3302581",
" </span>",
" </span>",
" In Canada, take any unused drugs to the pharmacy. Also, visit
file://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/disposal-defaire-eng.php#th to learn about
the right way to get rid of unused drugs.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s2699677",
" </span>",
" </span>",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s2699671",
" </span>",
" </span>",
" These are not all of the side effects that may occur. If you have questions
about side effects, call your doctor. Call your doctor for medical advice about
side effects.",
" </span>",
" </li>",
" •",
" </span>",
" urn:lims:b259:s2699683",
" </span>",
" </span>",
" Talk with the doctor before starting any new drug, including prescription
or OTC, natural products, or vitamins.",
" </span>",
" </li>",
" </ul>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
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" Release: 21.6- C21.56",
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" <br/>",
" Licensed to:",
" <span class=\"emphasis\">",
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" </span>",
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"</div>"].join("\n");
var outline_f6_17_6420=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
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" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F132252\">",
" </a>",
" </li>",
" Brand Names: Canada",
" </a>",
" </li>",
" What is this drug used for?",
" </a>",
" </li>",
" What do I need to tell my doctor before I take this drug?",
" </a>",
" </li>",
" What are some things I need to know or do while I take this drug?",
" </a>",
" </li>",
" What are some side effects of this drug?",
" </a>",
" </li>",
" What are some side effects that I need to call my doctor about right away?",
" </a>",
" </li>",
" How is this drug best taken?",
" </a>",
" </li>",
" What do I do if I miss a dose?",
" </a>",
" </li>",
" How do I store and/or throw out this drug?",
" </a>",
" </li>",
" General drug facts",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/41/11929?
source=related_link\">",
" Alteplase: Drug information",
" </a>",
" </li>",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?12/2/12328?
" Alteplase: Pediatric drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_17_6421="Ethotoin: Drug information";
" </div>",
" </noscript>",
" <br>",
" <sup>",
" ®",
" </sup>",
" <br>",
" </a>",
" ©2013 UpToDate",
" <sup>",
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here to print\">",
" Print",
" </a>",
" |",
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" Back",
" </a>",
" </div>",
" </div>",
" <div id=\"drugTitle\">",
" Ethotoin: Drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?9/20/9541?source=see_link\">",
" see \"Ethotoin: Patient drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F168814\"
" </span>",
" <ul>",
" <li>",
" Peganone®",
" </li>",
" </ul>",
" </div>",
" <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F168825\"
" Pharmacologic Category",
" </span>",
" <ul>",
" <li>",
" Anticonvulsant, Hydantoin",
" </li>",
" </ul>",
" </div>",
" <div class=\"block doa drugH1Div\" id=\"F168816\"
" Dosing: Adult",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Generalized tonic-clonic or complex-partial seizures: Oral: Initial dose:
≤1 g/day; usual maintenance dose: 2-3 g/day",
" </p>",
" </div>",
" <div class=\"block dop drugH1Div\" id=\"F168821\"
" Dosing: Pediatric",
" </span>",
" Anticonvulsant: Children ≥1 year: Oral: Maximum initial dose: 750 mg/day;
usual maintenance dose: 0.5-1 g/day; maximum dose: 3 g/day",
" </p>",
" </div>",
" <div class=\"block doe drugH1Div\" id=\"F168817\"
" Dosing: Geriatric",
" </span>",
" Refer to adult dosing.",
" </p>",
" </div>",
" <div class=\"block dor drugH1Div\" id=\"F15881396\"
" Dosing: Renal Impairment",
" </span>",
" No dosage adjustment provided in manufacturer’s labeling.",
" </p>",
" </div>",
" <div class=\"block doh drugH1Div\" id=\"F15881397\"
" Dosing: Hepatic Impairment",
" </span>",
" Use is contraindicated in patients with hepatic abnormalities.",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F168802\"
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Tablet, oral:",
" </p>",
" Peganone®: 250 mg [scored]",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F168791\"
" Generic Equivalent Available: U.S.",
" </span>",
" No",
" </p>",
" </div>",
" <div class=\"block meg drugH1Div\" id=\"F10380944\"
" Medication Guide",
" </span>",
" An FDA-approved patient medication guide, which is available with the product
information and at",
" <a href=\"file://www.fda.gov/downloads/Drugs/DrugSafety/UCM217560.pdf\"
" file://www.fda.gov/downloads/Drugs/DrugSafety/UCM217560.pdf",
" </a>",
" , must be dispensed with this medication.",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F4303477\"
" Administration",
" </span>",
" Administer after food to decrease GI distress. Administer in 4-6 divided
doses daily, spaced as evenly as practical.",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F168803\"
" Use",
" </span>",
" Generalized tonic-clonic or complex-partial seizures",
" </p>",
" </div>",
" <div class=\"block ars drugH1Div\" id=\"F168823\"
" Adverse Reactions Significant",
" </span>",
" Frequency not defined.",
" </p>",
" Cardiovascular: Chest pain",
" </p>",
" Central nervous system: Ataxia, dizziness, fatigue, fever, headache,
insomnia",
" </p>",
" Dermatologic: Skin rash, Stevens-Johnson syndrome",
" </p>",
" Gastrointestinal: Diarrhea, gingival hyperplasia, nausea, vomiting",
" </p>",
" Hematologic: Blood dyscrasias",
" </p>",
" Neuromuscular & skeletal: Numbness",
" </p>",
" Ocular: Diplopia, nystagmus",
" </p>",
" Miscellaneous: Lymphadenopathy, systemic lupus erythematosus (SLE)-like
syndrome",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F168805\"
" Contraindications",
" </span>",
" Hepatic abnormalities; hematologic disorders",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F168794\"
" Warnings/Precautions",
" </span>",
" <b>",
" <i>",
" Concerns related to adverse effects:",
" </i>",
" </b>",
" </p>",
" • Blood dyscrasias: Have been reported with use; patients with a
previous history of adverse hematologic reaction to any drug may be at increased
risk. Early detection of hematologic change is important; advise patients of early
signs and symptoms including fever, sore throat, mouth ulcers, infections, easy
bruising, petechial or purpuric hemorrhage. Discontinue therapy in patients with
decreased blood counts. Hydantoin-like compounds may interfere with folic acid
metabolism precipitating megaloblastic anemia.",
" </p>",
" • Suicidal ideation: Pooled analysis of trials involving various
antiepileptics (regardless of indication) showed an increased risk of suicidal
thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of
patients receiving placebo); risk observed as early as 1 week after initiation and
continued through duration of trials (most trials ≤24 weeks). Monitor all
patients for notable changes in behavior that might indicate suicidal thoughts or
depression; notify healthcare provider immediately if symptoms occur.",
" </p>",
" <b>",
" <i>",
" Concurrent drug therapy issues:",
" </i>",
" </b>",
" </p>",
" • Sedatives: Effects with other sedative drugs or ethanol may be
potentiated.",
" </p>",
" <b>",
" <i>",
" Other warnings/precautions:",
" </i>",
" </b>",
" </p>",
" • Withdrawal: Anticonvulsants should not be discontinued abruptly
because of the possibility of increasing seizure frequency; therapy should be
withdrawn gradually to minimize the potential of increased seizure frequency,
unless safety concerns require a more rapid withdrawal.",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F168822\"
" Metabolism/Transport Effects",
" </span>",
" <b>",
" Inhibits",
" </b>",
" CYP2C19 (weak)",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F168798\"
" Drug Interactions",
" </span>",
" <br/>",
" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
" <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
" Launch Lexi-Interact™ Drug Interactions Program",
" </a>",
" )",
" </div>",
" <div class=\"lexi\" id=\"lexiInteractImgB\">",
" <img border=\"0\" height=\"17\"
src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
" </div>",
" </div>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Acetaminophen: Anticonvulsants (Hydantoin) may increase the metabolism of
Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase
the risk of liver damage.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of
Alcohol (Ethyl).",
" <i>",
" </i>",
" </p>",
" Allopurinol: May increase the serum concentration of Anticonvulsants
(Hydantoin).",
" <i>",
" </i>",
" </p>",
" Antacids: May decrease the serum concentration of Anticonvulsants
(Hydantoin).",
" <i>",
" </i>",
" </p>",
" Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of
Azelastine (Nasal).",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" Buprenorphine: CNS Depressants may enhance the CNS depressant effect of
Buprenorphine. Management: Consider reduced doses of CNS depressants used in
combination with buprenorphine. Consider avoiding other CNS depressants in
patients thought to be at high risk of buprenorphine overuse or self-injection.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of
Anticonvulsants (Hydantoin). Specifically, osteomalacia and rickets.",
" <b>",
" Exceptions:",
" </b>",
" Brinzolamide; Dorzolamide.",
" <i>",
" </i>",
" </p>",
" Chloramphenicol: May decrease the metabolism of Anticonvulsants (Hydantoin).
Anticonvulsants (Hydantoin) may decrease the serum concentration of
Chloramphenicol. Increased chloramphenicol concentrations have also been seen.",
" <i>",
" </i>",
" </p>",
" CNS Depressants: May enhance the adverse/toxic effect of other CNS
Depressants.",
" <b>",
" Exceptions:",
" </b>",
" Levocabastine (Nasal).",
" <i>",
" </i>",
" </p>",
" Droperidol: May enhance the CNS depressant effect of CNS Depressants.
Management: Consider dose reductions of droperidol or of other CNS agents (e.g.,
opioids, barbiturates) with concomitant use.",
" <i>",
" </i>",
" </p>",
" HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants.",
" <i>",
" </i>",
" </p>",
" Ketorolac (Nasal): May diminish the therapeutic effect of Anticonvulsants.",
" <i>",
" </i>",
" </p>",
" Ketorolac (Systemic): May diminish the therapeutic effect of
Anticonvulsants.",
" <i>",
" </i>",
" </p>",
" Magnesium Sulfate: May enhance the CNS depressant effect of CNS
Depressants.",
" <i>",
" </i>",
" </p>",
" Mefloquine: May diminish the therapeutic effect of Anticonvulsants.
Mefloquine may decrease the serum concentration of Anticonvulsants. Management:
Mefloquine is contraindicated for malaria prophylaxis in persons with a history of
convulsions. Monitor anticonvulsant concentrations and treatment response closely
with concurrent use.",
" <i>",
" </i>",
" </p>",
" Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of
Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS
Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with
initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage
adjustments should be initiated only after clinically effective methotrimeprazine
dose is established.",
" <i>",
" </i>",
" </p>",
" Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine.",
" <i>",
" </i>",
" </p>",
" Mirtazapine: CNS Depressants may enhance the CNS depressant effect of
Mirtazapine.",
" <i>",
" </i>",
" </p>",
" Paraldehyde: CNS Depressants may enhance the CNS depressant effect of
Paraldehyde.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" Perampanel: May enhance the CNS depressant effect of CNS Depressants.
Management: Patients taking perampanel with any other drug that has CNS depressant
activities should avoid complex and high-risk activities, particularly those such
as driving that require alertness and coordination, until they have experience
using the combination.",
" <i>",
" </i>",
" </p>",
" Pramipexole: CNS Depressants may enhance the sedative effect of
Pramipexole.",
" <i>",
" </i>",
" </p>",
" ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole.",
" <i>",
" </i>",
" </p>",
" Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine.",
" <i>",
" </i>",
" </p>",
" Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the
adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the
risk of psychomotor impairment may be enhanced.",
" <i>",
" </i>",
" </p>",
" Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants.
Management: Consider alternatives to combined use. When combined use is needed,
consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol
or sedative hypnotics is contraindicated.",
" <i>",
" </i>",
" </p>",
" Vitamin K Antagonists (eg, warfarin): Ethotoin may enhance the anticoagulant
effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum
concentration of Ethotoin. Management: Anticoagulant dose adjustment will likely
be necessary when ethotoin is initiated or discontinued. Monitor patients extra
closely (INR and signs/symptoms of bleeding) when using this combination.",
" <i>",
" </i>",
" </p>",
" Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem.
Management: Reduce the Intermezzo brand sublingual zolpidem dose to 1.75 mg for men
who are also receiving other CNS depressants. No such dose change is recommended
for women. Avoid use with other CNS depressants at bedtime; avoid use with
alcohol.",
" <i>",
" </i>",
" </p>",
" </div>",
" <div class=\"block foi drugH1Div\" id=\"F168812\"
" Ethanol/Nutrition/Herb Interactions",
" </span>",
" Ethanol: May increase CNS depression; monitor for increased effects with
coadministration. Caution patients about effects.",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F168799\"
" Pregnancy Risk Factor",
" </span>",
" D (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F168807\"
" Pregnancy Implications",
" </span>",
" Maternal ingestion of antiepileptic agents has been associated with neonatal
coagulation defects/bleeding usually within 24 hours of birth. Congenital
malformations (including a pattern of malformations termed the “fetal
hydantoin syndrome” or “fetal anticonvulsant syndrome”) have been
reported with the use of other hydantoin derivatives, however, case reports using
ethotoin during pregnancy are few. Epilepsy itself, the number of medications,
genetic factors, or a combination of these probably influence the teratogenicity of
anticonvulsant therapy.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Patients exposed to ethotoin during pregnancy are encouraged to enroll
themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional
information is available at www.aedpregnancyregistry.org.",
" </p>",
" </div>",
" <div class=\"block lac drugH1Div\" id=\"F168818\"
" Lactation",
" </span>",
" Enters breast milk/not recommended",
" </p>",
" </div>",
" <div class=\"block brc drugH1Div\" id=\"F168808\"
" Breast-Feeding Considerations",
" </span>",
" The manufacturer recommends discontinuing breast-feeding during ethotoin
therapy.",
" </p>",
" </div>",
" <div class=\"block dic drugH1Div\" id=\"F168809\"
" Dietary Considerations",
" </span>",
" Should be taken after meals.",
" </p>",
" </div>",
" <div class=\"block fee drugH1Div\" id=\"F168806\"
" Pricing: U.S. (Medi-Span®)",
" </span>",
" <b>",
" Tablets",
" </b>",
" (Peganone Oral)",
" </p>",
" 250 mg (100): $157.22",
" </p>",
" </div>",
" <div class=\"block mop drugH1Div\" id=\"F4303479\"
" Monitoring Parameters",
" </span>",
" CBC and urinalysis (initiation of therapy and monthly for several months);
liver function tests if signs of dysfunction; suicidality (eg, suicidal thoughts,
depression, behavioral changes)",
" </p>",
" </div>",
" <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F168810\"
" International Brand Names",
" </span>",
" <ul>",
" <li>",
" Peganone (CA)",
" </li>",
" </ul>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F4303470\"
" Mechanism of Action",
" </span>",
" Stabilizes the seizure threshold and prevents the spread of seizure
activity",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F4303472\"
" Pharmacodynamics/Kinetics",
" </span>",
" Absorption: Rapid",
" </p>",
" Metabolism: Hepatic; forms metabolites",
" </p>",
" Half-life elimination: 3-9 hours",
" </p>",
" Excretion: Urine, feces, saliva (minimal)",
" </p>",
" </div>",
" </div>",
" </a>",
" .",
" </div>",
" </div>",
" </div>",
" </span>",
" |",
" </span>",
" </a>",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" Licensed to:",
" </span>",
" </span>",
" |",
" </span>",
" Support Tag: [0604-118.195.65.243-8D13A6BE0D-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
" </a>",
" </div>",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <ul>",
" </a>",
" </li>",
" Pharmacologic Category",
" </a>",
" </li>",
" Dosing: Adult",
" </a>",
" </li>",
" Dosing: Pediatric",
" </a>",
" </li>",
" Dosing: Geriatric",
" </a>",
" </li>",
" Dosing: Renal Impairment",
" </a>",
" </li>",
" Dosing: Hepatic Impairment",
" </a>",
" </li>",
" Dosage Forms: U.S.",
" </a>",
" </li>",
" Generic Equivalent Available: U.S.",
" </a>",
" </li>",
" Medication Guide",
" </a>",
" </li>",
" Administration",
" </a>",
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" Use",
" </a>",
" </li>",
" Adverse Reactions Significant",
" </a>",
" </li>",
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" </a>",
" </li>",
" Warnings/Precautions",
" </a>",
" </li>",
" Metabolism/Transport Effects",
" </a>",
" </li>",
" Drug Interactions",
" </a>",
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" Ethanol/Nutrition/Herb Interactions",
" </a>",
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" Pregnancy Risk Factor",
" </a>",
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" Pregnancy Implications",
" </a>",
" </li>",
" Lactation",
" </a>",
" </li>",
" Breast-Feeding Considerations",
" </a>",
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" Dietary Considerations",
" </a>",
" </li>",
" Pricing: U.S. (Medi-Span®)",
" </a>",
" </li>",
" Monitoring Parameters",
" </a>",
" </li>",
" International Brand Names",
" </a>",
" </li>",
" Mechanism of Action",
" </a>",
" </li>",
" Pharmacodynamics/Kinetics",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/8929\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/8929|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
title=\"Lexicomp clinical abbreviations\">",
" Lexicomp clinical abbreviations",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <ul>",
" <a class=\"drug drug_patient\" href=\"UTD.htm?9/20/9541?
" Ethotoin: Patient drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_17_6422="Malignant mesothelioma III MRI";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=PULM%2F59885%7EPULM
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PULM%2F59885%7EPULM
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Malignant mesothelioma",
" </div>",
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" </div>",
" MRI scan, coronal, T1 weighted sequence, shows circumferential encasement of
the left lung with loss of volume and ipsilateral shift of the mediastinum to the
left. The aortic arch and the descending aorta are encased by tumor.",
" </div>",
" Courtesy of Paul Stark, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
" Malignant mesothelioma",
" </div>",
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7j/PpVDVCFtjyEwvQVuaq8W/cMMOuBXM6xeKYWDABj0FAHOOMHOQRTTSn602gAooooA//2Q==);\">",
" </div>",
" MRI scan, sagittal T2 weighted sequence, shows large right sided pleural
effusion layering dorsally in this recumbent patient. The diaphragm is intact.
Above the lung apex, the right subclavian vein is seen in cross- section and forms
a bright round signal. Behind it is the right subclavian artery forming a smaller
circle. Above the vascular structures, the brachial plexus is seen in cross-section
forming several less bright rounded structures.",
" </div>",
" Courtesy of Paul Stark, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6423="Pleomorphic calcifications";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" </a>",
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Pleomorphic calcifications (suspicious)",
" </div>",
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m/hT/sE2n/olKAOkooooAKKKKACiiigAooooAKKKKACiiigD//Z);\">",
" </div>",
" Three different cases of pleomorphic calcifications seen in a segmental
distribution in Panel A; faint, with some linear branching calcifications in Panels
B and C.",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6424="Treatment and prevention of giardiasis";
" </div>",
" </noscript>",
" <br>",
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" ®",
" </sup>",
" <br>",
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" ©2013 UpToDate",
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here to print\">",
" Print",
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" Back",
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" </div>",
" <div id=\"topicTitle\">",
" Treatment and prevention of giardiasis",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/17/6424/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/17/6424/contributors\">",
" Flor M Munoz, MD, MSc",
" </a>",
" <br/>",
" </div>",
" <div>",
" Section Editors",
" </a>",
" <br/>",
" Peter F Weller, MD, FACP",
" </a>",
" <br/>",
" Sheldon L Kaplan, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" Deputy Editor",
" </a>",
" <br/>",
" Elinor L Baron, MD, DTMH",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/17/6424/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" |",
" </span>",
" This topic last updated:",
" </span>",
" Jan 18, 2013.",
" </div>",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" — Giardia lamblia (also known as G. duodenalis or G.
intestinalis) is a flagellated protozoan parasite [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/1-3\">",
" 1-3",
" </a>",
" ]. G. lamblia causes both epidemic and sporadic disease and is an important
etiology of waterborne and foodborne diarrhea, day-care center outbreaks, and
diarrhea in international travelers and adoptees [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/1\">",
" 1",
" </a>",
" ]. The treatment and prevention of giardiasis will be reviewed here. The life
cycle, epidemiology, clinical manifestations, and diagnosis of giardiasis are
discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?32/28/33224?
" \"Epidemiology, clinical manifestations, and diagnosis of giardiasis\"",
" </a>",
" .)",
" </p>",
" SUPPORTIVE CARE",
" </span>",
" — Supportive measures for the treatment of individuals with
symptomatic giardiasis are largely related to correction of fluid and electrolyte
abnormalities that result from the diarrhea. (See",
" \"Clinical assessment and diagnosis of hypovolemia (dehydration) in
children\"",
" </a>",
" and",
" \"Treatment of hypovolemia (dehydration) in children\"",
" </a>",
" and",
" \"Oral rehydration therapy\"",
" </a>",
" .)",
" </p>",
" ANTIMICROBIAL THERAPY",
" </span>",
" </p>",
" Indications",
" </span>",
" — Symptomatic patients with giardiasis should be treated with
antimicrobial therapy. Symptoms include diarrhea, malaise, steatorrhea, abdominal
cramps, bloating, flatulence, nausea, and, especially in young children, weight
loss and failure to thrive. (See",
source=see_link&anchor=H7#H7\">",
" \"Epidemiology, clinical manifestations, and diagnosis of giardiasis\",
section on 'Clinical manifestations'",
" </a>",
" .)",
" </p>",
" <p>",
" Patients with giardiasis should be counseled to avoid lactose-containing foods
for at least one month after therapy [",
" 4",
" </a>",
" ]. Acquired lactose intolerance occurs in up to 20 to 40 percent of cases and
can take weeks or many months to resolve even after parasite clearance [",
" 5",
" </a>",
" ]. (See",
" </a>",
" .)",
" </p>",
" <p>",
" Treatment is not usually recommended for asymptomatic individuals [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/6,7\">",
" 6,7",
" </a>",
" ]. However, treatment may be warranted to prevent the spread of infection if a
patient is a household contact of a pregnant woman, an immunocompromised individual
(especially in the setting of hypogammaglobulinemia), or a child in a day-care or
other setting who might transmit infection to others [",
" 6,8",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H17\">",
" 'Prevention'",
" </a>",
" below.)",
" </p>",
" Treatment regimens",
" </span>",
" — A number of drugs are available for the treatment of
giardiasis (",
" <a class=\"graphic graphic_table graphicRef61810 \" href=\"UTD.htm?
34/16/35084\">",
" table 1",
" </a>",
" ). In randomized trials",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" systematic reviews, these drugs have been shown to relieve symptoms and
eradicate Giardia with minimal side effects [",
" 9",
" </a>",
" ]. The data are discussed in the following sections.",
" </p>",
" <p>",
" We favor",
" tinidazole",
" </a>",
" ,",
" metronidazole",
" </a>",
" , or",
" nitazoxanide",
" </a>",
" as the drugs of choice for the treatment of giardiasis [",
" 6,10",
" </a>",
" ]. Alternatives include",
" albendazole",
" </a>",
" ,",
" paromomycin",
" </a>",
" , furazolidone (no longer available in the United States), and quinacrine (not
commercially available but compounded at some pharmacies).",
" </p>",
" Nitroimidazoles",
" </span>",
" — Nitroimidazoles include",
" tinidazole",
" </a>",
" and",
" metronidazole",
" </a>",
" .",
" </p>",
" Tinidazole",
" </span>",
" — ",
" Tinidazole",
" </a>",
" is highly effective for the treatment of giardiasis and is approved by the FDA
for the treatment of giardiasis in patients older than three years [",
" 11,12",
" </a>",
" ]. Tinidazole has a longer half-life than",
" metronidazole",
" </a>",
" and offers the advantage of a single-dose treatment. A single dose of
tinidazole has efficacy >90 percent with few associated side effects [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/9,13-16\">",
" 9,13-16",
" </a>",
" ]. Tinidazole is available only in tablet form. For children unable to swallow
tablets, a pharmacist may crush the tablets and mix them with flavored syrup; the
syrup suspension should be shaken before use and is good for seven days at room
temperature [",
" 17",
" </a>",
" ]. Side effects include metallic taste in the mouth, nausea, vomiting,
headache, and disulfiram-like effects [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/8,10,18\">",
" 8,10,18",
" </a>",
" ]. To minimize gastrointestinal side effects, tinidazole should be taken with
food [",
" 19",
" </a>",
" ].",
" </p>",
" Metronidazole",
" </span>",
" — ",
" Metronidazole",
" </a>",
" can be used in children and adults (although giardiasis is not a US Food and
Drug Administration-approved indication for metronidazole). A five day course has
efficacy of 75 to 100 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/6,13,18,20\">",
" 6,13,18,20",
" </a>",
" ]. Some compounding pharmacies can prepare a stable oral suspension for
children who are not able to swallow tablets. Side effects include nausea,
gastrointestinal discomfort, headache, and a metallic taste in the mouth; less
commonly, dark urine, paresthesias, and dizziness occur [",
" 8",
" </a>",
" ]. These side effects may occur in up to 27 percent of patients [",
" 13",
" </a>",
" ]. Metronidazole may have a disulfiram-like effect, and alcohol consumption
should be avoided. Isolates of Giardia with decreased susceptibility to
metronidazole have been described.",
" </p>",
" Nitazoxanide",
" </span>",
" — ",
" Nitazoxanide",
" </a>",
" , a nitrothiazolyl-salicylamide derivative, has been approved by the FDA for
the treatment of giardiasis in children older than one year [",
" 21",
" </a>",
" ]. A number of head-to-head trials have shown nitazoxanide to be at least as
effective as",
" metronidazole",
" </a>",
" in relieving symptoms in individuals with giardiasis, with efficacy ranging
from 81 to 85 percent [",
" 18,22-24",
" </a>",
" ]. In addition, nitazoxanide is effective in treating multiple other
intestinal parasites (eg, cryptosporidium and amebiasis) [",
" 6,25-27",
" </a>",
" ]. Nitazoxanide is available in liquid and tablet form [",
" 19",
" </a>",
" ]. Side effects include nausea, anorexia, flatulence, increased appetite,
enlarged salivary glands, yellow eyes, dysuria, and discolored (bright yellow)
urine [",
" 18",
" </a>",
" ].",
" </p>",
" Albendazole or mebendazole",
" </span>",
" — Comparative clinical trials have demonstrated that",
" albendazole",
" </a>",
" is at least as effective as",
" metronidazole",
" </a>",
" in the treatment of giardiasis when given for five days or more [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6424/abstract/13,18,28-30\">",
" 13,18,28-30",
" </a>",
" ]. Albendazole is also active against helminths and has fewer side effects
than metronidazole and",
" tinidazole",
" </a>",
" . Albendazole comes only in tablets, and should be taken with food to increase
bioavailability [",
" 8",
" </a>",
" ].",
" </p>",
" <p>",
" Mebendazole",
" </a>",
" has a cure rate of approximately 80 percent for giardiasis; some studies have
reported efficacy as high as 100 percent [",
" 13,31,32",
" </a>",
" ]. It is also active against other parasites and is associated with fewer side
effects than",
" metronidazole",
" </a>",
" or",
" tinidazole",
" </a>",
" [",
" 10,31-33",
" </a>",
" ]. Mebendazole is not approved for the treatment of giardiasis in the United
States. It comes in tablets and suspension, and should be taken with food to
increase bioavailability.",
" </p>",
" Paromomycin",
" </span>",
" — ",
" Paromomycin",
" </a>",
" is an aminoglycoside with activity against G. lamblia and Entamoeba. It is not
approved in the United States for the treatment of giardiasis. In clinical studies,
the reported range of efficacy for Giardia is 55 to 90 percent [",
" 8",
" </a>",
" ]. It has poor intestinal absorption and is a reasonable alternative for
patients in whom other agents are contraindicated.",
" </p>",
" Furazolidone",
" </span>",
" — Furazolidone, a nitrofuran compound, is an alternative
therapy for the treatment of giardiasis that is no longer available in the United
States. Furazolidone is effective and well tolerated, although its efficacy is
generally reported to be slightly lower than",
" metronidazole",
" </a>",
" (approximately 80 percent), and it must be administered four times per day [",
" 8,18,19,34",
" </a>",
" ]. Side effects of furazolidone include gastrointestinal upset, headache,
hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, and
neuropathy [",
" 8,18",
" </a>",
" ].",
" </p>",
" Quinacrine",
" </span>",
" — Quinacrine, the first effective drug for giardiasis, is no
longer distributed in the United States (although it is available from specific
formulating pharmacies). Quinacrine may cause nausea, vomiting, dizziness,
headache, yellow-orange discoloration of the skin and mucous membranes, and
hemolysis in children with glucose-6-phosphate dehydrogenase deficiency [",
" 8,18",
" </a>",
" ].",
" </p>",
" Pregnancy",
" </span>",
" — There is no consistently recommended therapy for giardiasis
in pregnancy because of the potential for adverse drug effects to the fetus. When
the disease is mild and hydration and nutrition can be maintained, therapy can be
delayed at least until after the first trimester [",
" 8",
" </a>",
" ]. If treatment is necessary,",
" paromomycin",
" </a>",
" can be used as systemic absorption is poor [",
" 8",
" </a>",
" ].",
" Metronidazole",
" </a>",
" or",
" tinidazole",
" </a>",
" are alternative agents but should not be used during the first trimester.",
" </p>",
" Response to therapy",
" </span>",
" — Among patients with acute giardiasis who are appropriately
treated, symptoms typically resolve within five to seven days, and parasites are
cleared from the stool in three to five days [",
" 8",
" </a>",
" ]. There is no need to repeat the stool examination to check for parasite
clearance in individuals whose symptoms resolve.",
" </p>",
" <p>",
" In patients with chronic or longer standing giardiasis, symptoms usually do
not abate quickly. Reevaluation of stool specimens should be undertaken in patients
who develop recurrent diarrhea after treatment.",
" </p>",
" RECURRENCE OF SYMPTOMS",
" </span>",
" — Recurrent diarrhea following treatment may be due to
residual lactose intolerance or other associated small bowel absorptive
deficiencies, rather than recurrent infection or antimicrobial resistance. As a
result, reevaluation of stool specimens should be undertaken before empiric
retreatment is administered [",
" 8",
" </a>",
" ]. Patients should be counseled to avoid lactose-containing foods for one or
more months after therapy [",
" 4",
" </a>",
" ]. (See",
" 'Indications'",
" </a>",
" above.)",
" </p>",
" <p>",
" In some patients, poor weight gain and symptoms of bloating, diarrhea, and
nausea may persist after treatment and documentation of negative stool samples.
Residual duodenal inflammation has been identified in some of these patients,
although the etiology is unclear [",
" 35,36",
" </a>",
" ].",
" </p>",
" <p>",
" Recurrent diarrhea and documented Giardia infection after initial therapy may
be caused by reinfection or drug resistance. Potential sources of reinfection
should be sought by reviewing the exposure history, risk factors, and hygiene
practices. (See",
" </a>",
" .)",
" </p>",
" <p>",
" Either a second course of the original agent or a different treatment can be
administered [",
" 6",
" </a>",
" ]. Patients who have been reinfected should have a clinical response to the
original antigiardial drug. Treatment failures, clinical resistance, and in vitro
drug resistance have been reported with commonly used antigiardial agents [",
" 13,37,38",
" </a>",
" ]. This has resulted in active research for new drugs for the treatment of
giardiasis [",
" 38,39",
" </a>",
" ].",
" </p>",
" <p>",
" Options for treatment of refractory cases include:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Use of a drug from a different class (eg, a trial of",
" nitazoxanide",
" </a>",
" if the initial treatment was with",
" metronidazole",
" </a>",
" or",
" tinidazole",
" </a>",
" ) [",
" 34,40,41",
" </a>",
" ]. This approach is the most likely to be successful and is the safest in
children. More than one switch to a different class of antigiardial agent may be
necessary in some cases.",
" </li>",
" <li>",
" Longer courses of the original agent (eg,",
" metronidazole",
" </a>",
" for 10 days instead of 5) [",
" 9,42",
" </a>",
" ]. However, reevaluation of symptoms during and after the prolonged course
is necessary since the organism may be resistant to the original treatment.",
" </li>",
" <li>",
" Higher doses of the original agent [",
" 40",
" </a>",
" ]. The dose of",
" metronidazole",
" </a>",
" , for example, can be increased to 35",
" mg/kg",
" </span>",
" per day. Although this option has been used in adults, it is not well
studied in children in whom safety is a concern.",
" </li>",
" <li>",
" Combination regimens may be necessary in patients with infection refractory
to other alternative approaches and patients with underlying immunodeficiencies.
Reported effective combinations include:",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Albendazole",
" </a>",
" (15",
" mg/kg",
" </span>",
" per day PO, maximum dose 400 mg) plus",
" metronidazole",
" </a>",
" (15",
" mg/kg",
" </span>",
" PO per day divided in three doses, with a maximum dose of 250 mg per dose)
for five days; this combination has been reported to be highly efficacious in
patients who have failed standard metronidazole therapy [",
" 8,30,43,44",
" </a>",
" ]. In a study of 38 adults with metronidazole refractory giardiasis treated
during an outbreak,",
" albendazole/metronidazole",
" </span>",
" for one week was effective in 79 percent of patients [",
" 45",
" </a>",
" ].",
" </li>",
" <li>",
" Metronidazole",
" </a>",
" (15",
" mg/kg",
" </span>",
" PO per day divided in three doses, with a maximum dose of 250 mg per dose)
or",
" tinidazole",
" </a>",
" (50",
" mg/kg",
" </span>",
" PO single dose, with a maximum dose of 2 g) plus quinacrine (6",
" mg/kg",
" </span>",
" per day PO divided in three doses; maximum dose 100 mg per day) for 14 to 21
days [",
" 46",
" </a>",
" ]. In an adult study, three patients who had failed sequential",
" albendazole",
" </a>",
" /metronidazole",
" </span>",
" combination and",
" paromomycin",
" </a>",
" therapy responded to a combination of metronidazole plus quinacrine
administered for three weeks [",
" 45",
" </a>",
" ].",
" <br/>",
" <br/>",
" Combination therapy may be warranted in immunocompromised patients who have
been unresponsive to other treatment strategies for refractory disease [",
" 6",
" </a>",
" ]. In such patients, several different combinations or sequential approaches
may be necessary for success. Consultation with a specialist in infectious diseases
is suggested when combination therapy is being considered.",
" </li>",
" </ul>",
" </p>",
" <p>",
" The possibility of underlying immunodeficiency (eg, hypogammaglobulinemia, IgA
deficiency, HIV infection) should be considered in patients with either treatment
refractory or repeated recurrences of giardiasis. (See",
" \"Approach to the child with recurrent infections\"",
" </a>",
" .)",
" </p>",
" PREVENTION",
" </span>",
" — Preventive measures include hygienic measures for infection
control, outbreak investigation, and water treatment. No vaccine against Giardia
lamblia is available.",
" </p>",
" Infection control",
" </span>",
" — To prevent transmission of Giardia to other patients and
hospital staff, patients with Giardia infection who are in diapers or are
incontinent should be placed on contact precautions for the duration of illness (in
addition to standard precautions) [",
" 6",
" </a>",
" ]. (See",
" \"General principles of infection control\", section on 'Isolation
precautions'",
" </a>",
" .)",
" </p>",
" <p>",
" Attention to hygiene is necessary to prevent person-to-person transmission of
giardiasis. Strict hand-washing, care with diaper disposal, and treatment of
symptomatic children can prevent the spread of giardiasis in day care centers. Hand
sanitizer is effective against trophozoites passed in the stool but not against the
cyst form that survives in the environment.",
" </p>",
" Outbreaks",
" </span>",
" — The local health department should be contacted when an
outbreak of Giardia is suspected [",
" 6",
" </a>",
" ]. Involvement of the health department will facilitate identification and
treatment of all symptomatic individuals, child care workers, and family members
who are infected. Individuals with diarrhea should be excluded from child care
centers until they are asymptomatic [",
" 6",
" </a>",
" ]. However, exclusion of asymptomatic carriers from child care is not
necessary.",
" </p>",
" <p>",
" Treatment of asymptomatic carriers is not effective for outbreak control, with
the exception of asymptomatic carriers who are also food handlers [",
" 6,47",
" </a>",
" ]. (See",
" 'Indications'",
" </a>",
" above.)",
" </p>",
" Waterborne infection",
" </span>",
" — Boiling or heating water to at least 70ºC for 10
minutes eliminates Giardia cysts [",
" 48",
" </a>",
" ]. For hikers and campers, iodine-based water treatments are more effective
than chlorine-based treatments [",
" 48",
" </a>",
" ]. High-quality water filtration units are also effective for Giardia cyst
removal [",
" 48",
" </a>",
" ]. Information about water purification and a traveler's guide for buying
water filters is available from the United States Centers for Disease Control and
Prevention (",
" <a class=\"external\" href=\"file://www.cdc.gov/travel/\">",
" www.cdc.gov/travel/",
" </a>",
" ) [",
" 6",
" </a>",
" ]. (See",
" \"Travel advice\"",
" </a>",
" .)",
" </p>",
" <p>",
" Individuals with Giardia diarrhea should refrain from using recreational water
venues (eg, swimming pools, lakes, rivers, etc.) until they have been asymptomatic
for two weeks [",
" 6",
" </a>",
" ].",
" </p>",
" Breast-feeding",
" </span>",
" — Breast milk contains detectable titers of secretory IgA,
which is protective for nursing infants; this protective mechanism is particularly
important in developing countries [",
" 49",
" </a>",
" ]. This was illustrated in a study from Egypt in which breast-fed infants had
a lower incidence of symptomatic and asymptomatic infection with Giardia [",
" 50",
" </a>",
" ]. In addition, infected infants who were exclusively breast-fed had fewer
clinical manifestations (anorexia, abdominal pain, and mucous in stool) than
infants who were not exclusively breast-fed.",
" </p>",
" <p>",
" Although breast-feeding may prevent Giardia in infants, if the mother is
undergoing treatment for Giardia infection, the safety of continued breast-feeding
depends upon the antibiotic therapy that is used to treat the mother.",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </span>",
" — UpToDate offers two types of patient education materials,
“The Basics” and “Beyond the Basics.” The Basics patient
education pieces are written in plain language, at the 5",
" <sup>",
" th",
" </sup>",
" to 6",
" <sup>",
" th",
" </sup>",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" <sup>",
" th",
" </sup>",
" to 12",
" <sup>",
" th",
" </sup>",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
“patient info” and the keyword(s) of interest.)",
" </p>",
" <p>",
" <li>",
" Basics topics (see",
" <a class=\"medical medical_basics\" href=\"UTD.htm?21/1/21522?
" \"Patient information: Giardia (The Basics)\"",
" </a>",
" )",
" </li>",
" <li>",
" Beyond the Basics topics (see",
" <a class=\"medical medical_patient\" href=\"UTD.htm?28/0/28673?
" \"Patient information: Giardia (Beyond the Basics)\"",
" </a>",
" ).",
" </li>",
" </ul>",
" </p>",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <li>",
" Supportive measures for the treatment of children with symptomatic
giardiasis include correction of fluid and electrolyte abnormalities. (See",
" \"Clinical assessment and diagnosis of hypovolemia (dehydration) in
children\"",
" </a>",
" and",
" \"Treatment of hypovolemia (dehydration) in children\"",
" </a>",
" and",
" \"Oral rehydration therapy\"",
" </a>",
" .)",
" </li>",
" <li>",
" We recommend antimicrobial therapy for symptomatic patients with giardiasis
(",
" <a class=\"grade\" href=\"._grade_1?title=Grade 1A\">",
" Grade 1A",
" </a>",
" ). Treatment is not indicated for most patients with Giardia who are
asymptomatic. To prevent the spread of infection, however, we suggest treatment of
asymptomatic carriers who are food handlers, household contacts of pregnant women
or immunocompromised individuals, or children in a day care or other setting who
might transmit infection to others (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). (See",
" 'Indications'",
" </a>",
" above.)",
" </li>",
" <li>",
" We suggest",
" metronidazole",
" </a>",
" ,",
" tinidazole",
" </a>",
" , or",
" nitazoxanide",
" </a>",
" as the drugs of choice for initial therapy (",
" <a class=\"grade\" href=\"._grade_4?title=Grade 2A\">",
" Grade 2A",
" </a>",
" ). Alternatives include",
" albendazole",
" </a>",
" ,",
" mebendazole",
" </a>",
" ,",
" paromomycin",
" </a>",
" , furazolidone, and quinacrine. Patients should be counseled to avoid
lactose-containing foods for one month after therapy. (See",
" 'Indications'",
" </a>",
" above and",
" 'Treatment regimens'",
" </a>",
" above.)",
" </li>",
" <li>",
" There is no need to repeat the stool examination for parasite clearance in
patients whose symptoms resolve. Patients with recurrent diarrhea should undergo
reevaluation of the stool for parasites before empiric retreatment since the
diarrhea may be related to lactose intolerance rather than recurrent Giardia.
(See",
" 'Recurrence of symptoms'",
" </a>",
" above and",
" 'Response to therapy'",
" </a>",
" above.)",
" </li>",
" <li>",
" The optimal approach to relapse after treatment is uncertain. We suggest
treatment with a drug from a different class (",
" Grade 2C",
" </a>",
" ). Alternative approaches include treatment with a second course of the
original agent, treatment with a longer course or higher dose of the original
agent, or treatment with a combination of drugs. (See",
" 'Recurrence of symptoms'",
" </a>",
" above.)",
" </li>",
" <li>",
" Person-to-person spread of giardiasis can be prevented through strict
handwashing, care with diaper disposal, and treatment of symptomatic patients. The
local health department should be contacted when an outbreak of giardiasis is
suspected. (See",
" 'Outbreaks'",
" </a>",
" above and",
" 'Infection control'",
" </a>",
" above.)",
" </li>",
" <li>",
" Waterborne Giardia infection can be prevented through effective treatment of
drinking water. Individuals with giardiasis should refrain from using recreational
water venues until they have been asymptomatic for two weeks. (See",
" 'Waterborne infection'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
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" Escobedo AA, Núñez FA, Moreira I, et al. Comparison of
chloroquine, albendazole and tinidazole in the treatment of children with
giardiasis. Ann Trop Med Parasitol 2003; 97:367.",
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" Pengsaa K, Limkittikul K, Pojjaroen-anant C, et al. Single-dose therapy for
giardiasis in school-age children. Southeast Asian J Trop Med Public Health 2002;
33:711.",
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" Fung HB, Doan TL. Tinidazole: a nitroimidazole antiprotozoal agent. Clin
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" Tan, TQ. Giardiasis. In: Textbook of Pediatric Infectious Diseases, 6th ed,
Feigin, RD, Cherry, JD, Demmler-Harrison, GJ, Kaplan, SL (Eds), Saunders,
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" </li>",
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" American Academy of Pediatrics. Drugs for parasitic infections. In: Red Book:
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American Academy of Pediatrics, Elk Grove Village, IL 2012.",
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" Drugs for Parasitic Infections. Medical Lett Drugs Ther; August 2004
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" Romark Alinia adult dose 'approvable'; anti-parasitic approved for children.
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" Ortiz JJ, Ayoub A, Gargala G, et al. Randomized clinical study of
nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis
in children from Northern Peru. Aliment Pharmacol Ther 2001; 15:1409.",
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" Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Giardia
intestinalis and Entamoeba histolytica or E. dispar: a randomized, double-blind,
placebo-controlled study of nitazoxanide. J Infect Dis 2001; 184:381.",
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" Davila-Gutierrez CE, Vasquez C, Trujillo-Hernandez B, Huerta M. Nitazoxanide
compared with quinfamide and mebendazole in the treatment of helminthic infections
and intestinal protozoa in children. Am J Trop Med Hyg 2002; 66:251.",
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" Diaz E, Mondragon J, Ramirez E, Bernal R. Epidemiology and control of
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2003; 68:384.",
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diarrhea: a pediatric perspective. Curr Med Res Opin 2005; 21:999.",
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comparing mebendazole and secnidazole for the treatment of giardiasis. Ann Trop Med
Parasitol 2003; 97:499.",
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study of therapy for giardiasis in children. Am J Dis Child 1981; 135:164.",
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G. Variability and variation in drug susceptibility among Giardia duodenalis
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" Dunn LA, Andrews KT, McCarthy JS, et al. The activity of protease inhibitors
against Giardia duodenalis and metronidazole-resistant Trichomonas vaginalis. Int J
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" Abboud P, Lemée V, Gargala G, et al. Successful treatment of
metronidazole- and albendazole-resistant giardiasis with nitazoxanide in a patient
with acquired immunodeficiency syndrome. Clin Infect Dis 2001; 32:1792.",
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metronidazole in giardial infections. Trans R Soc Trop Med Hyg 1990; 84:694.",
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" Goldin AJ, Hall A, Sarker RN, et al. Diagnosis of Giardia duodenalis
infection in Bangladeshi infants: faecal antigen capture ELISA. Trans R Soc Trop
Med Hyg 1993; 87:428.",
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" Cacopardo B, Patamia I, Bonaccorso V, et al. [Synergic effect of albendazole
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giardiasis]. Clin Ter 1995; 146:761.",
" </a>",
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" Mørch K, Hanevik K, Robertson LJ, et al. Treatment-ladder and genetic
characterisation of parasites in refractory giardiasis after an outbreak in Norway.
J Infect 2008; 56:268.",
" </a>",
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" Nash TE, Ohl CA, Thomas E, et al. Treatment of patients with refractory
giardiasis. Clin Infect Dis 2001; 33:22.",
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" Bartlett AV, Englender SJ, Jarvis BA, et al. Controlled trial of Giardia
lamblia: control strategies in day care centers. Am J Public Health 1991;
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" Ongerth JE, Johnson RL, Macdonald SC, et al. Back-country water treatment to
prevent giardiasis. Am J Public Health 1989; 79:1633.",
" </a>",
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" Nayak N, Ganguly NK, Walia BN, et al. Specific secretory IgA in the milk of
Giardia lamblia-infected and uninfected women. J Infect Dis 1987; 155:724.",
" </a>",
" </li>",
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" Mahmud MA, Chappell CL, Hossain MM, et al. Impact of breast-feeding on
Giardia lamblia infections in Bilbeis, Egypt. Am J Trop Med Hyg 2001; 65:257.",
" </a>",
" </li>",
" </ol>",
" </div>",
" </div>",
" </div>",
" </span>",
" |",
" </span>",
" </a>",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" Licensed to:",
" </span>",
" </span>",
" |",
" </span>",
" Support Tag: [0504-201.211.0.116-EC95FD50DF-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
" </a>",
" </div>",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H25\" id=\"summRecButton\">",
" <span>",
" SUMMARY & RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" SUPPORTIVE CARE",
" </a>",
" </li>",
" ANTIMICROBIAL THERAPY",
" </a>",
" </li>",
" Indications",
" </a>",
" </li>",
" Treatment regimens",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" - Nitroimidazoles",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" Tinidazole",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" Metronidazole",
" </a>",
" </li>",
" - Nitazoxanide",
" </a>",
" </li>",
" - Albendazole or mebendazole",
" </a>",
" </li>",
" - Paromomycin",
" </a>",
" </li>",
" - Furazolidone",
" </a>",
" </li>",
" - Quinacrine",
" </a>",
" </li>",
" Pregnancy",
" </a>",
" </li>",
" Response to therapy",
" </a>",
" </li>",
" RECURRENCE OF SYMPTOMS",
" </a>",
" </li>",
" PREVENTION",
" </a>",
" </li>",
" Infection control",
" </a>",
" </li>",
" Outbreaks",
" </a>",
" </li>",
" Waterborne infection",
" </a>",
" </li>",
" Breast-feeding",
" </a>",
" </li>",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" </a>",
" </li>",
" </a>",
" </li>",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"ID/6024\" rel=\"outline_link\">",
" GRAPHICS",
" View All",
" </a>",
" </div>",
" </h1>",
" <ul>",
" <div class=\"openRelatedGraphics\" id=\"ID/6024|TAB\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?34/16/35084\" title=\"table
1\">",
" Treatment of giardiasis",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <ul>",
" Approach to the child with recurrent infections",
" </a>",
" </li>",
" Clinical assessment and diagnosis of hypovolemia (dehydration) in children",
" </a>",
" </li>",
" Epidemiology, clinical manifestations, and diagnosis of giardiasis",
" </a>",
" </li>",
" General principles of infection control",
" </a>",
" </li>",
" Oral rehydration therapy",
" </a>",
" </li>",
" Patient information: Giardia (Beyond the Basics)",
" </a>",
" </li>",
" Patient information: Giardia (The Basics)",
" </a>",
" </li>",
" Travel advice",
" </a>",
" </li>",
" Treatment of hypovolemia (dehydration) in children",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_17_6425="Phencyclidine (PCP) intoxication in adults";
" </div>",
" </noscript>",
" <img alt=\"UpToDate\" src=\"./../images/wk_utd-rgb.myextg\" width=\"220px\">",
" </img>",
" </div>",
" <sup>",
" ®",
" </sup>",
" </a>",
" <br>",
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </br>",
" </div>",
here to print\">",
" Print",
" </a>",
" |",
" </span>",
" Back",
" </a>",
" </div>",
" </div>",
" Phencyclidine (PCP) intoxication in adults",
" </div>",
" <div>",
" </a>",
" Authors",
" </a>",
" <br/>",
" Kennon Heard, MD",
" </a>",
" <br/>",
" Jason Hoppe, DO",
" </a>",
" <br/>",
" </div>",
" <div>",
" Section Editor",
" </a>",
" <br/>",
" Stephen J Traub, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" Deputy Editor",
" </a>",
" <br/>",
" Jonathan Grayzel, MD, FAAEM",
" </a>",
" <br/>",
" </div>",
" </div>",
" Disclosures",
" </a>",
" </div>",
" <span>",
" </span>",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" </span>",
" Oct 2013.",
" |",
" </span>",
" </span>",
" Sep 19, 2012.",
" </div>",
" INTRODUCTION",
" </span>",
" — Despite a fall in popularity since the 1970s, phencyclidine
(PCP) remains a commonly abused drug that accounts for a significant number of
poison center calls and hospitalizations. Early identification and prompt
symptomatic treatment are vital to avoid possible sequelae, including
rhabdomyolysis and seizures.",
" </p>",
" <p>",
" Phencyclidine is a synthetic arylcycloalkylamine discovered in 1926, and
subsequently developed as Sernyl in the 1950s for use as a nonnarcotic anesthetic
[",
" 1,2",
" </a>",
" ]. Sernyl exerted a calming effect at low anesthetic doses and induced
cataplexy at higher doses, but it did not markedly suppress blood pressure or
respiration. The use of Sernyl as a dissociative anesthetic was discontinued due to
postoperative dysphoria and hallucinations, and by 1967 was limited to veterinary
use [",
" 3",
" </a>",
" ]. In April of 1979, all legal manufacturing of PCP in the United States was
terminated [",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" In the early 1970s a laboratory investigation of PCP derivatives led to the
discovery of",
" ketamine",
" </a>",
" . Ketamine is 5 to 10 percent as potent as Sernyl and is now used clinically
to induce dissociative anesthesia. Ketamine is also abused as a recreational
drug.",
" </p>",
" <p>",
" PCP's popularity as a drug of abuse peaked in the 1970s. During the late
1970s, one urban psychiatric hospital in the US found that 63 of 145 consecutive
patients sampled over a 48-hour period tested positive for PCP [",
" 5",
" </a>",
" ]. Since that time, hospital visits and poison center calls related to PCP use
have declined. Data from the American Association of Poison Control Centers
reported 713 single exposures in 2010 [",
" 6",
" </a>",
" ].",
" </p>",
" <p>",
" The basic pharmacology, clinical manifestations, and management of PCP
intoxication in adults will be reviewed here. The management of PCP poisoning in
children,",
" ketamine",
" </a>",
" poisoning, and other issues related to the management of the poisoned patient
are discussed elsewhere. (See",
" \"Phencyclidine (PCP) intoxication in children and adolescents\"",
" </a>",
" and",
" \"Ketamine poisoning\"",
" </a>",
" and",
" \"General approach to drug poisoning in adults\"",
" </a>",
" .)",
" </p>",
" PHARMACOLOGY AND CELLULAR TOXICOLOGY",
" </span>",
" — PCP, or 1-(1-phenylcyclohexyl) piperidine hydrochloride, is
a dissociative anesthetic. It is synthesized from piperidine and cyclohexanone [",
" 7",
" </a>",
" ]. It is a weak base with a pKa of 8.6 and is soluble in water and
ethanol [",
" 8",
" </a>",
" ].",
" </p>",
" <p>",
" PCP is a stable white solid with a bitter taste. It is manufactured in many
forms for recreational use, including powder, crystal, liquid, and tablets [",
" 3",
" </a>",
" ]. It has been sprinkled on leaves for ingestion, and there are reports of it
being combined with embalming fluid to enable the drug's uniform distribution in
cigarettes [",
" 9",
" </a>",
" ]. Concentrations of the drug vary in PCP tablets (1 to 6 mg) and PCP-laced
marijuana (1 to 10 mg) [",
" 10,11",
" </a>",
" ].",
" </p>",
" <p>",
" PCP has a number of analogs that may also be abused, including PHP
(rolicyclidine, phenylcyclohexylpyrrolidine), PCE (N-ethyl-1-
phenylcyclohexylamine), TCP (1-[1-(2-thienyl) cyclohexyl] piperidine), and PCC (1-
piperidinocyclohexane-carbonitrile). PCC is commonly found in street grade PCP. PCC
has the potential for increased toxicity due to the release of hydrogen cyanide
when smoked [",
" 7",
" </a>",
" ], although acute cyanide toxicity is unlikely [",
" 12",
" </a>",
" ].",
" </p>",
" <p>",
" The dose of PCP varies depending upon the amount of active drug and the route.
In general, symptoms first appear at 0.05",
" mg/kg.",
" </span>",
" Alteration of body image has been reported at 0.1",
" mg/kg",
" </span>",
" and 10 mg has been reported to cause catatonic stupor [",
" 13",
" </a>",
" ].",
" </p>",
" <p>",
" PCP is a noncompetitive antagonist of NMDA receptors [",
" 14",
" </a>",
" ]. It also stimulates sigma receptors and blocks the reuptake of biogenic
amines. Stimulation of alpha adrenergic receptors is thought to be responsible for
its sympathomimetic effects and cerebral vasospasm.",
" </p>",
" <p>",
" PCP has three primary sites of action in the central nervous system:",
" </p>",
" <p>",
" <li>",
" N-methyl-D-aspartate (NMDA) receptor complex – PCP has great affinity
for NMDA receptor complexes in the hippocampus, neocortex, basal ganglia, and
limbic system [",
" 14",
" </a>",
" ]. NMDA antagonism at these sites produces acute psychosis that mimics
schizophrenia in humans and leads to excess excitatory neurotransmitter release
(eg, glutamate, glycine, aspartate) that can cause agitation and seizures.",
" </li>",
" <li>",
" Dopamine, norepinephrine, and serotonin reuptake complex – PCP
inhibits reuptake of dopamine, norepinephrine, and serotonin in neurons [",
" 15",
" </a>",
" ]. This action contributes to the adrenergic and dopaminergic effects of PCP
intoxication.",
" </li>",
" <li>",
" Sigma receptor complex – PCP binding to the sigma receptor may
explain, in part, the psychotic, anticholinergic, and movement abnormalities seen
with intoxication [",
" 16",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" KINETICS",
" </span>",
" — The absorption, peak serum concentration, and duration of
effect vary with the route of PCP use. A retrospective study of 1000 patients found
smoking to be the most common route (72 percent), usually via laced cigarettes or
marijuana, followed by insufflation (13 percent), ingestion (12 percent), and
intravenous (IV) injection (1.5 percent) [",
" 10",
" </a>",
" ]. Smoking, insufflation, and IV or intramuscular routes produce symptoms
within two to five minutes, while oral ingestion produces symptoms in 30 to 60
minutes.",
" </p>",
" <p>",
" Smoking causes a rapid initial peak in plasma concentrations at five minutes
and a second peak at 22 minutes. The second peak may be related to delayed
absorption from the lungs. The mean half-life after smoking (24 + 7 hours) is
similar to the IV route [",
" 11",
" </a>",
" ].",
" </p>",
" <p>",
" The peak effect following ingestion is approximately 90 minutes. The duration
of action (one to three hours) is similar to the IV route [",
" 17",
" </a>",
" ]. PCP may undergo enterogastric recycling following oral doses [",
" 18",
" </a>",
" ]. Although not well absorbed in the stomach, PCP is actively secreted into
the gastric fluid, where concentrations can reach 50 times that of the serum. It is
then absorbed in the more alkaline small intestines.",
" </p>",
" <p>",
" IV injection of PCP produces an immediate effect. Following IV injection, the
duration of action is one to two hours, despite the long terminal half-life (21 + 3
hours).",
" </p>",
" <p>",
" PCP has a large volume of distribution (6.2 + 0.3",
" L/kg)",
" </span>",
" and is 65 percent protein bound [",
" 17",
" </a>",
" ]. The drug's high lipid solubility accounts for the ease with which it
crosses the blood brain barrier and enters adipose tissue [",
" 14",
" </a>",
" ]. Cerebrospinal fluid (CSF) levels are reported to be four times serum levels
due to the slightly more acidic pH of the CSF [",
" 19",
" </a>",
" ].",
" </p>",
" <p>",
" PCP displays first order kinetics with a half-life of 7 to 26 hours [",
" 20",
" </a>",
" ].",
" </p>",
" <p>",
" Elimination of PCP is principally by hepatic metabolism [",
" 17",
" </a>",
" ]. It is rapidly metabolized in the liver to hydroxylated derivatives and
excreted in the urine primarily as a mono-4-hydroxypiperidine conjugate. These
metabolites are thought to have minimal pharmacologic activity [",
" 8",
" </a>",
" ]. Approximately 5 to 10 percent is excreted unchanged in the urine [",
" 18",
" </a>",
" ]. A lower urine pH increases renal clearance, but this contributes little to
overall elimination and may be dangerous. (See",
" 'Enhanced elimination'",
" </a>",
" below.)",
" </p>",
" CLINICAL FEATURES OF OVERDOSE",
" </span>",
" </p>",
" History",
" </span>",
" — The diagnosis of phencyclidine (PCP) intoxication is made
based upon the history and clinical evaluation. Unfortunately, a clear history is
often unavailable as patients are frequently alone and exhibit alterations in
mental status. Sometimes friends or emergency medical services personnel provide
useful details. It can be helpful to know the street names for PCP, which include
angel dust, embalming fluid, killer weed, peace pill, horse tranquilizer, and hog
[",
" 21,22",
" </a>",
" ].",
" </p>",
" <p>",
" Severe poisoning can occur if a patient ingests large amounts of poorly
packaged drug to avoid discovery by the authorities (body stuffing) or a break
occurs in a container of concentrated drug that the patient has swallowed for the
purpose of illicit transport (body packing). Coingestants are common with PCP use
and may alter the clinical presentation or treatment. Marijuana cigarettes
sometimes contain PCP [",
" 9",
" </a>",
" ]. (See",
" \"Internal concealment of drugs of abuse (body packing)\"",
" </a>",
" .)",
" </p>",
" Physical examination",
" </span>",
" </p>",
" General findings",
" </span>",
" — Physical examination should begin with an assessment of the
patient's airway, breathing, circulation, and mental status. Although uncommon,
patients with large PCP ingestions may present with profound CNS and respiratory
depression requiring immediate endotracheal intubation. (See",
" 'Management'",
" </a>",
" below.)",
" </p>",
" <p>",
" PCP intoxication can produce a wide range of vital signs and physical findings
depending upon the amount ingested, the route of administration, patient
susceptibility, and the presence of coingestants. Adrenergic stimulation is
typical, but patients may exhibit central nervous system (CNS) stimulation or
depression. Most patients are alert but experience hallucinations and demonstrate
odd behavior and agitation similar to acute psychosis [",
" 10",
" </a>",
" ]. Patients may unexpectedly progress to coma, which may be prolonged. Because
of this unpredictability, vital signs and clinical assessment should be repeated
often until the patient has stabilized.",
" </p>",
" Vital signs",
" </span>",
" — Blood pressure elevation is reported in 32 to 57 percent of
patients with PCP intoxication. Systolic blood pressure correlates with elevated
plasma drug concentrations and is significantly higher than controls [",
" 23,24",
" </a>",
" ]. According to a large retrospective case series, hypertension resolves in
less than four hours in 62 percent of cases, but persists over 24 hours in 11
percent [",
" 10",
" </a>",
" ]. Spontaneous intracranial hemorrhage in association with uncontrolled
hypertension has been reported [",
" 25-27",
" </a>",
" ].",
" </p>",
" <p>",
" Tachycardia occurs in 30 to 43 percent of patients with a positive urine PCP
test [",
" 10,23",
" </a>",
" ]. In a case control study, tachycardia was more common in patients with
confirmed PCP intoxication [",
" 24",
" </a>",
" ]. Patients may be hyperthermic (2.6 to 4 percent) or hypothermic (6.4
percent) depending upon the degree of psychomotor agitation and environmental
conditions [",
" 5,10",
" </a>",
" ].",
" </p>",
" Neuropsychiatric findings",
" </span>",
" — CNS signs and symptoms are common and vary widely. Patients
may be alert with bizarre behavior, agitated or violent, or sedated and bordering
on comatose. Furthermore, these symptoms may wax and wane over time. In one case
series, 46 percent of patients were alert and oriented upon arrival to the hospital
[",
" 10",
" </a>",
" ].",
" </p>",
" <p>",
" Psychomotor agitation occurs often, with observational data suggesting a rate
between 34 and 64 percent [",
" 10,23",
" </a>",
" ]. Violence has been reported in 13 to 35 percent of patients and is more
common in single drug exposures. According to a case series of 1000 confirmed PCP-
intoxicated patients, 13 percent were involved in an altercation, of which 33
percent involved a gun or knife used to threaten others and 22 percent involved
self-inflicted wounds [",
" 10",
" </a>",
" ]. Such violent behavior may be associated with delusions of super-human
strength and diminished pain perception. Caregivers should be cautious when caring
for agitated patients with possible PCP intoxication.",
" </p>",
" <p>",
" In the same case series, psychomotor symptoms related to PCP intoxication were
grouped into major and minor patterns [",
" 10",
" </a>",
" ]. Major symptoms, including acute brain syndrome, psychosis, catatonia, and
coma, were associated with a more severe course and poorer outcomes. Complications
included trauma (16 percent of patients), rhabdomyolysis (2.2 percent), and
aspiration pneumonia (1 percent). Minor symptoms included lethargy or stupor and
combinations of bizarre behavior, violence, agitation, and euphoria in patients who
were otherwise alert and oriented. Minor symptoms were usually associated with a
less severe clinical course.",
" </p>",
" <p>",
" Acute brain syndrome, defined as disorientation combined with confusion, lack
of judgment, inappropriate affect, or loss of memory, was the most common major
symptom, reported in 37 percent of patients in one case series [",
" 28",
" </a>",
" ]. Psychosis was reported in 16.6 percent of patients in the aforementioned
series, including 63 percent of patients without coingestants. A smaller case
series reported a high rate of auditory hallucinations [",
" 5",
" </a>",
" ]. Visual and tactile hallucinations can also occur. Full recovery from
psychosis may take weeks to months [",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" In the case series cited above, catatonia was found in 11.7 percent of
patients [",
" 28",
" </a>",
" ]. In another series, approximately 6 percent of patients were reported to be
wandering in public and 56 percent of them had disrobed [",
" 10",
" </a>",
" ]. Catatonia is typically of short duration with 85 percent of cases resolving
by 24 hours [",
" 1",
" </a>",
" ].",
" </p>",
" <p>",
" Lethargy or stupor was reported in 3.8 percent of patients [",
" 28",
" </a>",
" ]. Coma was reported in 11 percent of patients, with the duration of
unconsciousness ranging from 30 minutes to seven days. A smaller case series
reported that 50 percent of patients developed a decreased level of consciousness
at some time during their clinical course [",
" 23",
" </a>",
" ].",
" </p>",
" <p>",
" Horizontal, vertical, or rotatory nystagmus is common with reported rates
ranging from 57 to 89 percent of cases (",
0/31/507\">",
" table 1",
" </a>",
" ) [",
" 10,24",
" </a>",
" ]. Other potential CNS effects include dystonic reactions, tardive dyskinesia,
and athetosis, but these are rare. Symptoms such as ataxia, dysarthria, nausea, and
vomiting may also occur.",
" </p>",
" Complications",
" </span>",
" — Fatalities in the setting of PCP intoxication are uncommon
and most are secondary to trauma. Other causes include hyperthermia, respiratory
arrest, and intracranial hemorrhage.",
" </p>",
" <p>",
" Treating clinicians should be aware of the potential for multiple serious
complications in patients with PCP intoxication. These occur most often with large
ingestions and may include:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Rhabdomyolysis",
" </li>",
" <li>",
" Seizures",
" </li>",
" <li>",
" Hypoglycemia",
" </li>",
" <li>",
" Prolonged comatose state",
" </li>",
" </ul>",
" </p>",
" <p>",
" Rhabdomyolysis developed in 2.2 percent of patients in one series of 1000
patients [",
" 28",
" </a>",
" ] and hemodialysis was necessary in 0.3 percent. In another case series, 40
percent of patients with PCP-associated rhabdomyolysis (defined as myoglobinuria
and a creatinine phosphokinase concentration above 16,000",
" IU/L)",
" </span>",
" developed acute renal failure [",
" 29",
" </a>",
" ].",
" </p>",
" <p>",
" Seizures occur infrequently, with estimates ranging from 2.6 to 6 percent of
cases [",
" 5,10,30",
" </a>",
" ]. Status epilepticus has been reported.",
" </p>",
" <p>",
" Prolonged psychiatric illness may stem from an underlying condition or drug
effect. Psychiatric evaluation should be obtained after a period of observation
confirms the patient is medically stable. A retrospective review performed at a
psychiatric facility found that 20 patients with new-onset PCP-induced psychosis
needed shorter hospitalizations (average 4.8 days; range 1 to 9) compared with 20
patients with new-onset functional psychosis (13.9 days; range 3 to 41) [",
" 31",
" </a>",
" ]. However, there are reports of patients with PCP-induced psychosis requiring
up to four to six weeks for full recovery.",
" </p>",
" DIFFERENTIAL DIAGNOSIS",
" </span>",
" — Due to the variable presentation of PCP intoxication, the
differential diagnosis is considerable. Other toxicologic causes that should be
entertained in cases of altered mental status, hallucinations, and excessive
adrenergic activity include sympathomimetics, anticholinergic toxicity, other
hallucinogens (LSD, mescaline, and psilocybin), ethanol or sedative hypnotic drug
withdrawal, neuroleptic malignant syndrome (NMS), serotonin syndrome, and
salicylate toxicity (",
3/43/3773\">",
" table 2",
" </a>",
" and",
1/11/1214\">",
" table 3",
" </a>",
" ). (See",
" </a>",
" and",
" \"Evaluation of abnormal behavior in the emergency department\"",
" </a>",
" and",
" \"Methamphetamine intoxication\"",
" </a>",
" and",
" \"Anticholinergic poisoning\"",
" </a>",
" and",
" \"Intoxication from LSD and other common hallucinogens\"",
" </a>",
" and",
" \"Management of moderate and severe alcohol withdrawal syndromes\"",
" </a>",
" and",
" \"Serotonin syndrome\"",
" </a>",
" and",
" \"Salicylate (aspirin) poisoning in adults\"",
" </a>",
" .)",
" </p>",
" <p>",
" Medical illness must also be considered. Altered mental status and vital sign
abnormalities should lead to careful evaluation for central nervous system
infections (encephalitis, meningitis) and sepsis. Metabolic etiologies such as
hypoglycemia, hyponatremia, hyperthyroidism, and hypoxia are easily assessed and
should be investigated. Occult head trauma can cause acute changes in mental
status. Patients without apparent medical or toxicologic illness who remain
symptomatic should be evaluated for possible psychosis. (See",
" \"Clinical features and diagnosis of acute bacterial meningitis in adults\"",
" </a>",
" and",
" \"Diagnosis of delirium and confusional states\"",
" </a>",
" .)",
" </p>",
" LABORATORY EVALUATION",
" </span>",
" </p>",
" General testing",
" </span>",
" — Routine laboratory evaluation of the poisoned patient
should include the following:",
" </p>",
" <p>",
" <li>",
" An electrocardiogram, to assess for cardiac conduction abnormalities",
" </li>",
" <li>",
" Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration
in mental status",
" </li>",
" <li>",
" Acetaminophen",
" </a>",
" and salicylate levels, to rule out these common coingestions",
" </li>",
" <li>",
" Pregnancy test in women of childbearing age",
" </li>",
" </ul>",
" </p>",
" <p>",
" Several other laboratory studies are indicated in the setting of PCP
intoxication, including creatine kinase, urine myoglobin, and liver transaminases.
Further testing is performed based upon clinical assessment. As examples, BUN and
creatinine are obtained if rhabdomyolysis or other potential causes of renal
failure are suspected, while a CT of the head and evaluation of cerebrospinal fluid
may be needed in the setting of a persistently altered mental status.",
" </p>",
" <p>",
" The most common laboratory abnormalities associated with PCP intoxication
include an elevated creatine kinase (70 percent), elevated liver transaminases (50
percent), hyperuricemia (24 percent), and hypoglycemia (22 percent) [",
" 10",
" </a>",
" ].",
" </p>",
" Testing for PCP",
" </span>",
" — Serum and urine tests to determine PCP concentrations are
available at some hospitals. However, the results of such tests are generally not
available with sufficient speed to be of use during acute management.",
" </p>",
" <p>",
" Serum concentrations were once widely available, but with the decreased
prevalence of PCP, most labs offer qualitative testing only. Qualitative testing is
more helpful than quantitative concentrations since serum levels do not correlate
well with brain concentrations or clinical toxicity [",
" 23,24",
" </a>",
" ]. Confirmatory testing using gas chromatography with mass spectroscopy is
performed on rare occasions when definitive drug identification is needed [",
" 32",
" </a>",
" ].",
" </p>",
" <p>",
" The US National Institute on Drug Abuse (NIDA) guidelines for federal
workplace drug testing uses a cutoff urine PCP concentration of 25",
" ng/mL.",
" </span>",
" Urine toxicology screens may remain positive for several weeks. In one series
of chronic users, urine screens remained positive for an average of 14 days [",
" 33",
" </a>",
" ]. CSF testing has been reported in two cases with concentrations one to four
times the serum levels [",
" 19",
" </a>",
" ].",
" </p>",
" <p>",
" Multiple causes of false positive urine tests have been reported and the
potential adverse medicolegal consequences of such results are profound. Drugs
capable of causing a false positive urine test include",
" ketamine",
" </a>",
" [",
" 34",
" </a>",
" ],",
" dextromethorphan",
" </a>",
" [",
" 32,35",
" </a>",
" ],",
" diphenhydramine",
" </a>",
" [",
" 36",
" </a>",
" ],",
" venlafaxine",
" </a>",
" [",
" 37",
" </a>",
" ], and",
" tramadol",
" </a>",
" [",
" 38",
" </a>",
" ].",
" </p>",
" MANAGEMENT",
" </span>",
" </p>",
" Airway, breathing, and circulation",
" </span>",
" — Initial stabilization including a rapid assessment of the
airway, breathing, and circulation is important. Airway protection with
endotracheal intubation and mechanical ventilation was necessary in 1.2 percent of
patients in one large case series [",
" 28",
" </a>",
" ]. We suggest avoiding",
" succinylcholine",
" </a>",
" when performing rapid sequence intubation in patients with known or suspected
PCP intoxication who exhibit significant psychomotor agitation or hyperthermia
because of the risk of exacerbating rhabdomyolysis-related hyperkalemia.",
" </p>",
" <p>",
" Some clinicians believe that PCP intoxication may increase airway secretions
and the risk of laryngospasm, but such cases are likely to be extremely uncommon.",
" </p>",
" <p>",
" Patients with concerning clinical findings (eg, stupor, hyperthermia) are
placed on a cardiac monitor, given supplemental oxygen, and have intravenous access
established. Abnormal vital signs are addressed immediately, and advanced life
support measures are instituted as needed. Further acute interventions are based
upon clinical findings, as quantitative testing for PCP is generally unavailable
and unhelpful. (See",
" </a>",
" and",
" \"Advanced cardiac life support (ACLS) in adults\"",
" </a>",
" .)",
" </p>",
" Sedation",
" </span>",
" — Rapid control of psychomotor agitation is the cornerstone
of successful management. Physical restraints may be necessary initially and
several staff members are often needed to control patients agitated from PCP.
Thereafter, chemical sedation is essential to control agitation, prevent or treat
hyperthermia, perform a thorough physical examination, and obtain necessary
studies.",
" </p>",
" <p>",
" Little evidence exists to guide the use of sedatives in the management of PCP
intoxication. Based upon observational reports and broad clinical experience, we
believe benzodiazepines are the preferred agents to achieve chemical sedation.",
" </p>",
" <p>",
" We treat severely agitated patients immediately with intravenous (IV)
benzodiazepines (",
" lorazepam",
" </a>",
" 4 mg IV or",
" diazepam",
" </a>",
" 5 to 10 mg IV). These doses can be repeated every eight to ten minutes based
upon patient response.",
" </p>",
" <p>",
" Butyrophenones (eg,",
" droperidol",
" </a>",
" 2.5 mg or",
" haloperidol",
" </a>",
" 5 mg) may be used as adjunctive therapy when benzodiazepines do not adequately
control symptoms [",
" 39",
" </a>",
" ]. These doses may be repeated. Some clinicians prefer to avoid butyrophenones
because they are purported to lower the seizure threshold and impair heat
dissipation in hyperthermic patients. However, there are no high quality studies in
humans to support such claims.",
" </p>",
" <p>",
" Although IV administration of sedatives and antipsychotics is strongly
preferred in severely intoxicated patients, intramuscular (IM) injection may be
used if IV access is unavailable. IM injection may provide sufficient sedation to
allow definitive care, including placement of IV catheters.",
" Midazolam",
" </a>",
" (5 mg IM) or",
" droperidol",
" </a>",
" (10 mg IM) may be used in such situations.",
" </p>",
" <p>",
" In the rare case of severe refractory psychomotor agitation or status
epilepticus, treatment with a barbiturate or a",
" propofol",
" </a>",
" infusion may be necessary. Endotracheal intubation and mechanical ventilation
are commonly required in such instances.",
" </p>",
" <p>",
" We treat mildly or moderately intoxicated patients with benzodiazepines and a
quiet environment.",
" Lorazepam",
" </a>",
" 1 to 2 mg IV or",
" diazepam",
" </a>",
" 2 to 5 mg IV may be adequate, and should be repeated as needed. Small
observational studies suggest that sensory deprivation (dark, quiet room; hands
covered) may decrease agitation [",
" 40",
" </a>",
" ].",
" </p>",
" Treatment of complications",
" </span>",
" — Once adequate sedation is achieved, the patient with PCP
intoxication should be carefully examined for secondary injuries. PCP intoxication
often leads to bizarre behavior, hallucinations, delusions of physical prowess, and
a diminished perception of pain. As a result, PCP abuse is often associated with
trauma. A large case series reported injuries in 13 percent of patients, 22 percent
of which were self-inflicted [",
" 10",
" </a>",
" ].",
" </p>",
" <p>",
" Other major potential complications of PCP intoxication include hyperthermia,
seizures, rhabdomyolysis, and hypertension. Hyperthermia typically improves with
adequate sedation, but external cooling and, in a small number of severe refractory
cases, even paralysis and mechanical ventilation may be necessary. Hypertension is
typically transient and rarely requires pharmacologic intervention beyond sedation.
Refractory hypertension can be treated with short acting agents such as
nitroglycerine or",
" nitroprusside",
" </a>",
" that can be titrated to effect. Cardiac monitoring and frequent reexamination
are essential in patients with any significant complication. (See",
" \"Severe hyperthermia (heat stroke) in adults\"",
" </a>",
" and",
" \"Status epilepticus in adults\"",
" </a>",
" and",
" \"Treatment of specific hypertensive emergencies\"",
" </a>",
" and",
" \"Prevention and treatment of heme pigment-induced acute kidney injury (acute
renal failure)\"",
" </a>",
" .)",
" </p>",
" <p>",
" Animal studies suggest that antipsychotic medications can block PCP mediated
behavioral effects [",
" 41",
" </a>",
" ]. Clinical trials in humans are needed before this approach can be
recommended.",
" </p>",
" Decontamination",
" </span>",
" — Most patients survive PCP intoxication uneventfully with
supportive care; decontamination is generally unnecessary in isolated ingestions.
However, decontamination with",
" activated charcoal",
" </a>",
" (AC) may be useful if a massive ingestion or a potentially dangerous
coingestant is present and treatment is started within one hour of ingestion.
Patients who ingest large amounts of PCP to avoid police detection (body stuffers)
or to transport drug for distribution (body packers) may sustain massive
ingestions. Any potential benefit from AC must be weighed against the risk of
aspiration, especially given the potential for altered mental status and seizures
with severe PCP intoxication. AC is given in a dose of 1",
" g/kg",
" </span>",
" (maximum 50 g).",
" </p>",
" <p>",
" We do NOT typically use multi-dose",
" activated charcoal",
" </a>",
" (MDAC) in patients with PCP intoxication. MDAC provides a theoretical benefit
because of the extensive enterohepatic recirculation of PCP. Dogs treated with AC
following oral doses of PCP demonstrated decreased duration of anesthesia,
seizures, and death [",
" 42",
" </a>",
" ]. Giving rats activated charcoal following an oral dose of PCP significantly
elevated the lethal dose (LD50) of PCP [",
" 42",
" </a>",
" ]. However, there is no evidence of clinical benefit in humans, and the
potential for aspiration exists whenever AC is given.",
" </p>",
" <p>",
" We do NOT suggest the use of nasogastric suction in patients with PCP
intoxication. Nasogastric suction is theoretically beneficial when performed soon
after ingestion due to the high concentration of PCP in the stomach's acidic
environment. However, it has no proven benefit and may cause electrolyte
abnormalities, aspiration, and unwanted difficulty in agitated patients.",
" </p>",
" <p>",
" Whole bowel irrigation is NOT routinely recommended. It should only be used in
patients who have ingested potentially lethal amounts of PCP, as may occur with
body stuffers or body packers. (See",
" \"Internal concealment of drugs of abuse (body packing)\"",
" </a>",
" .)",
" </p>",
" Enhanced elimination",
" </span>",
" — Neither urine acidification nor charcoal hemoperfusion
should be used in the treatment of PCP intoxication.",
" </p>",
" <p>",
" Although some toxicologists have proposed urinary acidification as a means of
increasing PCP clearance [",
" 18",
" </a>",
" ], this process increases total drug clearance by only one percent [",
" 3,11",
" </a>",
" ]. Moreover, acidification increases the potential for systemic acidosis,
worsening rhabdomyolysis and renal damage, and precipitation of uric acid leading
to nephrolithiasis [",
" 43",
" </a>",
" ].",
" </p>",
" <p>",
" In a study of dogs loaded with 5",
" mg/kg",
" </span>",
" of PCP, charcoal hemoperfusion failed to reduce the number of seizures,
duration of coma, or tissue concentration compared with control animals [",
" 44",
" </a>",
" ]. Only 2 percent of the parent compound was recovered. The authors concluded
that PCP's high volume of distribution, high lipid solubility, and low plasma
concentration make removal by hemoperfusion ineffective.",
" </p>",
" DISPOSITION",
" </span>",
" — Due to the variable course of PCP toxicity, even patients
without severe symptoms or complications benefit from some period of observation.
Patients presenting early following an ingestion may be asymptomatic initially but
should be observed for at least six hours. Patients with mild symptoms presenting a
few hours after the onset of intoxication generally recover within several hours.
Such patients may be discharged provided the effects of intoxication have resolved
and the patient remains symptom-free during a brief (one to two hours) period of
observation.",
" </p>",
" <p>",
" Any patient with significant complications (eg, rhabdomyolysis, coma, status
epilepticus) or severe symptoms (eg, uncontrolled hypertension, hyperthermia)
should be admitted to an intensive care setting. Patients with less severe but
persistent symptoms should be admitted to an appropriate ward for further
monitoring and treatment.",
" </p>",
" <p>",
" Psychiatric evaluation should be obtained where appropriate, once medical
problems have been addressed. Chronic abusers may benefit from treatment for
substance abuse. (See",
" \"Substance use disorders: Principles for recognition and assessment in
general medical care\"",
" </a>",
" .)",
" </p>",
" FUTURE CONSIDERATIONS",
" </span>",
" — Supportive care remains the cornerstone of the management
of PCP toxicity. However, the use of monoclonal antibodies to reverse toxicity is
being studied and may provide an alternative approach in the future [",
" 45,46",
" </a>",
" ]. Monoclonal anti-phencyclidine Fab antibody fragments successfully reversed
PCP-induced locomotor effects in a rat model [",
" 45",
" </a>",
" ]. These antibodies are not able to cross the blood brain barrier and directly
reverse receptor binding. However, the antibodies decrease the concentration of
free PCP and alter its pharmacokinetics.",
" </p>",
" PEDIATRIC CONSIDERATIONS",
" </span>",
" — The clinical presentation of PCP intoxication is different
in infants and young children than in adolescents or adults. The diagnosis and
management of children with PCP intoxication is reviewed separately. (See",
" \"Phencyclidine (PCP) intoxication in children and adolescents\"",
" </a>",
" .)",
" </p>",
" ADDITIONAL RESOURCES",
" </span>",
" — Regional poison control centers in the United States are
available at all times for consultation on patients who are critically ill, require
admission, or have clinical pictures that are unclear (1-800-222-1222). In
addition, some hospitals have clinical",
" and/or",
" </span>",
" medical toxicologists available for bedside consultation",
" and/or",
" </span>",
" inpatient care. Whenever available, these are invaluable resources to help in
the diagnosis and management of ingestions or overdoses. The World Health
Organization provides a listing of international poison centers at its website:",
" <a class=\"external\"
href=\"file://www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html\">"
,
" www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html",
" </a>",
" </p>",
" </span>",
" </p>",
" <p>",
" <li>",
" Phencyclidine (ie, PCP) is a dissociative anesthetic that is abused
primarily for its hallucinatory effects. Significant toxicity is rare but
potentially serious. The drug's onset of action is rapid, but the duration of
action is generally brief (one to four hours). (See",
" 'Pharmacology and cellular toxicology'",
" </a>",
" above and",
" 'Kinetics'",
" </a>",
" above.)",
" </li>",
" <li>",
" Symptoms of PCP intoxication vary depending upon the route of exposure,
dose, and coingestants, and may include altered mental status (from comatose to
profound psychomotor agitation), hallucinations, hypertension, tachycardia, and
multidirectional nystagmus. Severe complications may include traumatic injuries,
rhabdomyolysis, hyperthermia, and seizures. (See",
" 'Clinical features of overdose'",
" </a>",
" above.)",
" </li>",
" <li>",
" Due to the variable presentation of PCP intoxication, the differential
diagnosis is considerable. It is reviewed in the text. (See",
" 'Differential diagnosis'",
" </a>",
" above.)",
" </li>",
" <li>",
" Quantitative drug concentrations have little role in the management of acute
toxicity. Qualitative testing is available, but false positives are frequent.
Results may remain positive for weeks. (See",
" 'Testing for PCP'",
" </a>",
" above.)",
" </li>",
" <li>",
" Rapid control of psychomotor agitation is the cornerstone of successful
management. Physical restraints may be necessary initially and several staff
members are often needed to control patients agitated from PCP. Chemical sedation
should be administered as rapidly as possible. Decontamination and other aspects of
management are discussed above. (See",
" 'Management'",
" </a>",
" above.)",
" </li>",
" <li>",
" In patients with PCP-related psychomotor agitation who require sedation, we
suggest the use of benzodiazepines (",
" Grade 2C",
" </a>",
" ). We treat severely agitated patients immediately with intravenous (IV)
benzodiazepines (",
" lorazepam",
" </a>",
" 4 mg IV or",
" diazepam",
" </a>",
" 5 to 10 mg IV). These doses can be repeated every eight to ten minutes based
upon patient response. In severely intoxicated patients, intramuscular (IM)
injection may be used initially if IV access is unavailable.",
" Midazolam",
" </a>",
" (5 mg IM) may be used in such situations. (See",
" 'Sedation'",
" </a>",
" above.)",
" </li>",
" <li>",
" We treat mildly or moderately intoxicated patients with benzodiazepines and
a quiet environment.",
" Lorazepam",
" </a>",
" 1 to 2 mg IV or",
" diazepam",
" </a>",
" 2 to 5 mg IV may be adequate, and may be repeated as needed. (See",
" 'Sedation'",
" </a>",
" above.)",
" </li>",
" <li>",
" Patients with significant symptoms should be admitted to a monitored
setting. Due to the relatively short duration of action, patients with mild
symptoms are candidates for a period of observation and discharge. Patients whose
medical symptoms resolve but have persistent behavioral issues should undergo a
psychiatric evaluation. (See",
" 'Disposition'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" </a>",
" .",
" </div>",
" <h1>",
" REFERENCES",
" </h1>",
" <li>",
" Pali, MJ, Tharratt, RS, Albertson, TE. Phencyclidine and its congeners. In:
Critical Care Toxicology, 1st, Brent, J, Wallace, KL, Burkhart, KK, et al (Eds),
Mosby, Philadelphia 2005. p.777.",
" </li>",
" <li>",
" CHEN G, ENSOR CR, RUSSELL D, BOHNER B. The pharmacology of 1-(1-
phenylcyclohexyl) piperidine-HCl. J Pharmacol Exp Ther 1959; 127:241.",
" </a>",
" </li>",
" <li>",
" Olmedo, R. Phencyclidine and ketamine. In: Goldfrank's Toxicologic
Emergencies, 8th, Flomenbaum, NE, Goldfrank, LR, Hoffman, RS, et al (Eds), McGraw-
Hill, New York 2006. p.1231.",
" </li>",
" <li>",
" Wright HH, Cole EA, Batey SR, Hanna K. Phencyclidine-induced psychosis:
eight-year follow-up of ten cases. South Med J 1988; 81:565.",
" </a>",
" </li>",
" <li>",
" Yago KB, Pitts FN Jr, Burgoyne RW, et al. The urban epidemic of
phencyclidine (PCP) use: clinical and laboratory evidence from a public psychiatric
hospital emergency service. J Clin Psychiatry 1981; 42:193.",
" </a>",
" </li>",
" <li>",
" American Association of Poison Control Centers. file://www.aapcc.org/
(Accessed on November 15, 2011).",
" </li>",
" <li>",
" Shesser R, Jotte R, Olshaker J. The contribution of impurities to the acute
morbidity of illegal drug use. Am J Emerg Med 1991; 9:336.",
" </a>",
" </li>",
" <li>",
" Liden CB, Lovejoy FH Jr, Costello CE. Phencyclidine. Nine cases of
poisoning. JAMA 1975; 234:513.",
" </a>",
" </li>",
" <li>",
" Holland JA, Nelson L, Ravikumar PR, Elwood WN. Embalming fluid-soaked
marijuana: new high or new guise for PCP? J Psychoactive Drugs 1998; 30:215.",
" </a>",
" </li>",
" <li>",
" McCarron MM, Schulze BW, Thompson GA, et al. Acute phencyclidine
intoxication: incidence of clinical findings in 1,000 cases. Ann Emerg Med 1981;
10:237.",
" </a>",
" </li>",
" <li>",
" Cook CE, Brine DR, Jeffcoat AR, et al. Phencyclidine disposition after
intravenous and oral doses. Clin Pharmacol Ther 1982; 31:625.",
" </a>",
" </li>",
" <li>",
" Tschirgi T. Phencyclidine: A hidden risk of illicit drug use. Pharm Alert
1990; 19:1.",
" </a>",
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" <li>",
" Aniline O, Pitts FN Jr. Phencyclidine (PCP): a review and perspectives. Crit
Rev Toxicol 1982; 10:145.",
" </a>",
" </li>",
" <li>",
" Javitt DC, Zukin SR. Recent advances in the phencyclidine model of
schizophrenia. Am J Psychiatry 1991; 148:1301.",
" </a>",
" </li>",
" <li>",
" Akunne HC, Reid AA, Thurkauf A, et al. [3H]1-[2-(2-
thienyl)cyclohexyl]piperidine labels two high-affinity binding sites in human
cortex: further evidence for phencyclidine binding sites associated with the
biogenic amine reuptake complex. Synapse 1991; 8:289.",
" </a>",
" </li>",
" <li>",
" Wolfe SA Jr, De Souza EB. Sigma and phencyclidine receptors in the brain-
endocrine-immune axis. NIDA Res Monogr 1993; 133:95.",
" </a>",
" </li>",
" <li>",
" Cook CE, Brine DR, Quin GD, et al. Phencyclidine and phenylcyclohexene
disposition after smoking phencyclidine. Clin Pharmacol Ther 1982; 31:635.",
" </a>",
" </li>",
" <li>",
" Aronow R, Done AK. Phencyclidine overdose: an emerging concept of
management. JACEP 1978; 7:56.",
" </a>",
" </li>",
" <li>",
" Donaldson JO, Baselt RC. CSF phencyclidine. Am J Psychiatry 1979;
136:1341.",
" </a>",
" </li>",
" <li>",
" Jackson JE. Phencyclidine pharmacokinetics after a massive overdose. Ann
Intern Med 1989; 111:613.",
" </a>",
" </li>",
" <li>",
" Caravatti, EM. Hallucinogenic drugs. In: Medical Toxicology, 3rd, Dart, RC,
Caravatti, EM, McGuigan, MA, et al (Eds), Lippincott, Williams, and Wilkins,
Philadelphia 2004. p.1106.",
" </li>",
" <li>",
" Milhorn HT Jr. Diagnosis and management of phencyclidine intoxication. Am
Fam Physician 1991; 43:1293.",
" </a>",
" </li>",
" <li>",
" Bailey DN. Phencyclidine abuse. Clinical findings and concentrations in
biological fluids after nonfatal intoxication. Am J Clin Pathol 1979; 72:795.",
" </a>",
" </li>",
" <li>",
" Barton CH, Sterling ML, Vaziri ND. Phencyclidine intoxication: clinical
experience in 27 cases confirmed by urine assay. Ann Emerg Med 1981; 10:243.",
" </a>",
" </li>",
" <li>",
" Bessen HA. Intracranial hemorrhage associated with phencyclidine abuse. JAMA
1982; 248:585.",
" </a>",
" </li>",
" <li>",
" Eastman JW, Cohen SN. Hypertensive crisis and death associated with
phencyclidine poisoning. JAMA 1975; 231:1270.",
" </a>",
" </li>",
" <li>",
" Crosley CJ, Binet EF. Cerebrovascular complications in phencyclidine
intoxication. J Pediatr 1979; 94:316.",
" </a>",
" </li>",
" <li>",
" McCarron MM, Schulze BW, Thompson GA, et al. Acute phencyclidine
intoxication: clinical patterns, complications, and treatment. Ann Emerg Med 1981;
10:290.",
" </a>",
" </li>",
" <li>",
" Akmal M, Valdin JR, McCarron MM, Massry SG. Rhabdomyolysis with and without
acute renal failure in patients with phencyclidine intoxication. Am J Nephrol 1981;
1:91.",
" </a>",
" </li>",
" <li>",
" Kessler GF Jr, Demers LM, Berlin C, Brennan RW. Letter: Phencyclidine and
fatal status epilepticus. N Engl J Med 1974; 291:979.",
" </a>",
" </li>",
" <li>",
" Carls KA, Ruehter VL. An evaluation of phencyclidine (PCP) psychosis: a
retrospective analysis at a state facility. Am J Drug Alcohol Abuse 2006; 32:673.",
" </a>",
" </li>",
" <li>",
" Budai B, Iskandar H. Dextromethorphan can produce false positive
phencyclidine testing with HPLC. Am J Emerg Med 2002; 20:61.",
" </a>",
" </li>",
" <li>",
" Simpson GM, Khajawall AM, Alatorre E, Staples FR. Urinary phencyclidine
excretion in chronic abusers. J Toxicol Clin Toxicol 1982; 19:1051.",
" </a>",
" </li>",
" <li>",
" Hoffman, RJ, Saddock, V, Nelson, L. Effect of ketamine on phencyclidine
immunoassays (abstract). J Toxicol Clin Toxicol 2001; 39:523.",
" </a>",
" </li>",
" <li>",
" Schier J. Avoid unfavorable consequences: dextromethorpan can bring about a
false-positive phencyclidine urine drug screen. J Emerg Med 2000; 18:379.",
" </a>",
" </li>",
" <li>",
" Levine BS, Smith ML. Effects of diphenhydramine on immunoassays of
phencyclidine in urine. Clin Chem 1990; 36:1258.",
" </a>",
" </li>",
" <li>",
" Santos PM, López-García P, Navarro JS, et al. False positive
phencyclidine results caused by venlafaxine. Am J Psychiatry 2007; 164:349.",
" </a>",
" </li>",
" <li>",
" Hull MJ, Griggs D, Knoepp SM, et al. Postmortem urine immunoassay showing
false-positive phencyclidine reactivity in a case of fatal tramadol overdose. Am J
Forensic Med Pathol 2006; 27:359.",
" </a>",
" </li>",
" <li>",
" Giannini, AJ, Nageotte, C, Loiselle, RH, et al. Comparison of
chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine
psychosis: DA-2 receptor specificity. J Toxicol Clin Toxicol 1984-1985; 22:573.",
" </a>",
" </li>",
" <li>",
" COHEN BD, LUBY ED, ROSENBAUM G, GOTTLIEB JS. Combined sernyl and sensory
deprivation. Compr Psychiatry 1960; 1:345.",
" </a>",
" </li>",
" <li>",
" Grayson B, Idris NF, Neill JC. Atypical antipsychotics attenuate a sub-
chronic PCP-induced cognitive deficit in the novel object recognition task in the
rat. Behav Brain Res 2007; 184:31.",
" </a>",
" </li>",
" <li>",
" Picchioni AL, Consroe PF. Activated charcoal--a phencyclidine antidote, or
hog in dogs. N Engl J Med 1979; 300:202.",
" </a>",
" </li>",
" <li>",
" Barton CH, Sterling ML, Vaziri ND. Rhabdomyolysis and acute renal failure
associated with phencyclidine intoxication. Arch Intern Med 1980; 140:568.",
" </a>",
" </li>",
" <li>",
" Allen WR, O'Barr TP, Corby DG. Hemoperfusion of phencyclidine in the dog.
Int J Artif Organs 1985; 8:101.",
" </a>",
" </li>",
" <li>",
" Hardin JS, Wessinger WD, Proksch JW, Owens SM. Pharmacodynamics of a
monoclonal antiphencyclidine Fab with broad selectivity for phencyclidine-like
drugs. J Pharmacol Exp Ther 1998; 285:1113.",
" </a>",
" </li>",
" <li>",
" Lacy HM, Gunnell MG, Laurenzana EM, Owens SM. Engineering and
characterization of a mouse/human chimeric anti-phencyclidine monoclonal antibody.
Int Immunopharmacol 2008; 8:1.",
" </a>",
" </li>",
" </ol>",
" </div>",
" </div>",
" </div>",
" </span>",
" |",
" </span>",
" </a>",
" |",
" </span>",
" Release: 21.3 - C21.34",
" </span>",
" <br/>",
" Licensed to:",
" Morehouse School of Medicine",
" </span>",
" </span>",
" |",
" </span>",
" Support Tag: [1105-194.187.108.93-F5F47B5EFB-S473950.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
" </a>",
" </div>",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <ul>",
" <li>",
" <span>",
" </span>",
" </a>",
" </li>",
" INTRODUCTION",
" </a>",
" </li>",
" PHARMACOLOGY AND CELLULAR TOXICOLOGY",
" </a>",
" </li>",
" KINETICS",
" </a>",
" </li>",
" CLINICAL FEATURES OF OVERDOSE",
" </a>",
" </li>",
" History",
" </a>",
" </li>",
" Physical examination",
" </a>",
" </li>",
" - General findings",
" </a>",
" </li>",
" - Vital signs",
" </a>",
" </li>",
" - Neuropsychiatric findings",
" </a>",
" </li>",
" Complications",
" </a>",
" </li>",
" </a>",
" </li>",
" LABORATORY EVALUATION",
" </a>",
" </li>",
" General testing",
" </a>",
" </li>",
" Testing for PCP",
" </a>",
" </li>",
" MANAGEMENT",
" </a>",
" </li>",
" Airway, breathing, and circulation",
" </a>",
" </li>",
" Sedation",
" </a>",
" </li>",
" Treatment of complications",
" </a>",
" </li>",
" Decontamination",
" </a>",
" </li>",
" Enhanced elimination",
" </a>",
" </li>",
" DISPOSITION",
" </a>",
" </li>",
" FUTURE CONSIDERATIONS",
" </a>",
" </li>",
" PEDIATRIC CONSIDERATIONS",
" </a>",
" </li>",
" ADDITIONAL RESOURCES",
" </a>",
" </li>",
" </a>",
" </li>",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"EM/313\" rel=\"outline_link\">",
" GRAPHICS",
" View All",
" </a>",
" </div>",
" </h1>",
" <ul>",
" <div class=\"openRelatedGraphics\" id=\"EM/313|TAB\">",
" TABLES",
" </a>",
" </div>",
" </li>",
1\">",
" Poisons causing nystagmus",
" </a>",
" </li>",
2\">",
" Causes of delirium and confusion",
" </a>",
" </li>",
3\">",
" Drugs that cause or prolong delirium",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <ul>",
" Advanced cardiac life support (ACLS) in adults",
" </a>",
" </li>",
" Anticholinergic poisoning",
" </a>",
" </li>",
" Clinical features and diagnosis of acute bacterial meningitis in adults",
" </a>",
" </li>",
" Diagnosis of delirium and confusional states",
" </a>",
" </li>",
" Evaluation of abnormal behavior in the emergency department",
" </a>",
" </li>",
" General approach to drug poisoning in adults",
" </a>",
" </li>",
" Internal concealment of drugs of abuse (body packing)",
" </a>",
" </li>",
" Intoxication from LSD and other common hallucinogens",
" </a>",
" </li>",
" Ketamine poisoning",
" </a>",
" </li>",
" Management of moderate and severe alcohol withdrawal syndromes",
" </a>",
" </li>",
" Methamphetamine intoxication",
" </a>",
" </li>",
" Phencyclidine (PCP) intoxication in children and adolescents",
" </a>",
" </li>",
" Prevention and treatment of heme pigment-induced acute kidney injury (acute
renal failure)",
" </a>",
" </li>",
" Salicylate (aspirin) poisoning in adults",
" </a>",
" </li>",
" Serotonin syndrome",
" </a>",
" </li>",
" Severe hyperthermia (heat stroke) in adults",
" </a>",
" </li>",
" Status epilepticus in adults",
" </a>",
" </li>",
" Substance use disorders: Principles for recognition and assessment in
general medical care",
" </a>",
" </li>",
" Treatment of specific hypertensive emergencies",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_17_6426="Epidemiology, clinical manifestations, diagnosis, and natural
history of uterine leiomyomas (fibroids)";
" </div>",
" </noscript>",
" <br>",
" <sup>",
" ®",
" </sup>",
" <br>",
" </a>",
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
here to print\">",
" Print",
" </a>",
" |",
" </span>",
" Back",
" </a>",
" </div>",
" </div>",
" Epidemiology, clinical manifestations, diagnosis, and natural history of
uterine leiomyomas (fibroids)",
" </div>",
" <div>",
" </a>",
" Author",
" </a>",
" <br/>",
" Elizabeth A Stewart, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" Section Editor",
" </a>",
" <br/>",
" Robert L Barbieri, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" Deputy Editor",
" </a>",
" <br/>",
" Sandy J Falk, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" Disclosures",
" </a>",
" </div>",
" <span>",
" </span>",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" </span>",
" Oct 2013.",
" |",
" </span>",
" </span>",
" Jun 1, 2012.",
" </div>",
" INTRODUCTION",
" </span>",
" — Uterine leiomyomas (fibroids or myomas) are the most common
pelvic tumor in women [",
" 1-3",
" </a>",
" ]. They are benign monoclonal tumors arising from the smooth muscle cells of
the myometrium. They arise in reproductive age women and typically present with
symptoms of abnormal uterine bleeding or pelvic",
" pain/pressure.",
" </span>",
" Uterine fibroids may also have reproductive effects (eg, infertility, adverse
pregnancy outcomes).",
" </p>",
" <p>",
" The epidemiology, clinical manifestations, diagnosis, and natural history of
uterine leiomyomas are reviewed here. Treatment of uterine leiomyomas, leiomyoma
histology and pathogenesis, differentiating leiomyomas from uterine sarcomas, and
leiomyoma variants are discussed separately. (See",
" \"Overview of treatment of uterine leiomyomas (fibroids)\"",
" </a>",
" and",
" \"Histology and pathogenesis of uterine leiomyomas (fibroids)\"",
" </a>",
" and",
" \"Differentiating uterine leiomyomas (fibroids) from uterine sarcomas\"",
" </a>",
" and",
" \"Variants of uterine leiomyomas (fibroids)\"",
" </a>",
" .)",
" </p>",
" TERMINOLOGY AND LOCATION",
" </span>",
" — Fibroids are often described according to their location in
the uterus, although many fibroids have more than one location designation (",
" <a class=\"graphic graphic_figure graphicRef53241 \" href=\"UTD.htm?
30/16/30978\">",
" figure 1",
" </a>",
" and",
" <a class=\"graphic graphic_picture graphicRef80897 graphicRef59079 \"
href=\"UTD.htm?42/46/43752\">",
" picture 1A-B",
" </a>",
" ):",
" </p>",
" <p>",
" <li>",
" Intramural myomas – These leiomyomas develop from within the uterine
wall. They may enlarge sufficiently to distort the uterine cavity or serosal
surface. Some fibroids can be transmural and extend from the serosal to the mucosal
surface.",
" </li>",
" <li>",
" Submucosal myomas – These leiomyomas derive from myometrial cells just
below the endometrium. These neoplasms often protrude into the uterine cavity. The
extent of this protrusion is described by the European Society of Hysteroscopy
classification system and is clinically relevant for predicting outcomes of
hysteroscopic myomectomy [",
" 4",
" </a>",
" ]. A type 0 fibroid is completely intracavitary, type I has less than 50
percent of its volume in the uterine wall, whereas a type II has 50 percent or more
of its volume in the uterine wall (",
26/32/27143\">",
" figure 2",
" </a>",
" ). Types 0 and I are hysteroscopically resectable, although significant
hysteroscopic expertise may be needed to resect type I masses. (See",
" \"Hysteroscopic myomectomy\", section on 'Myometrial penetration'",
" </a>",
" .)",
" </li>",
" <li>",
" Subserosal myomas – These leiomyomas originate from the myometrium at
the serosal surface of the uterus. They can have a broad or pedunculated base (",
" <a class=\"graphic graphic_diagnosticimage graphicRef63661 \"
href=\"UTD.htm?8/34/8737\">",
" image 1",
" </a>",
" ) and may be intraligamentary (ie, extending between the folds of the broad
ligament).",
" </li>",
" <li>",
" Cervical myomas – These leiomyomas are located in the cervix, rather
than the uterine corpus.",
" </li>",
" </ul>",
" </p>",
" PREVALENCE",
" </span>",
" — Uterine leiomyomas are the most common pelvic tumor in
women, as noted above [",
" 1-3",
" </a>",
" ]. A hysterectomy study found myomas in 77 percent of uterine specimens [",
" 5",
" </a>",
" ].",
" </p>",
" <p>",
" The epidemiology of leiomyomas parallels the ontogeny and life cycle changes
of the reproductive hormones estrogen and progesterone. Although the growth of
fibroids is responsive to gonadal steroids, these hormones are not necessarily
responsible for the genesis of the tumors. (See",
" \"Histology and pathogenesis of uterine leiomyomas (fibroids)\", section on
'Steroid hormones'",
" </a>",
" .)",
" </p>",
" <p>",
" Leiomyomas have not been described in prepubertal girls, but they are
occasionally noted in adolescents. Myomas are clinically apparent in approximately
12 to 25 percent of reproductive age women and noted on pathological examination in
approximately 80 percent of surgically excised uteri [",
" 2,5,6",
" </a>",
" ]. In hysterectomy specimens sectioned at 2-mm intervals, premenopausal women
had an average 7.6 fibroids [",
" 5",
" </a>",
" ]. Most, but not all, women have shrinkage of leiomyomas at menopause.",
" </p>",
" RISK FACTORS",
" </span>",
" </p>",
" Race",
" </span>",
" — The incidence rates of fibroids are typically found to be
two- to three-fold greater in black women than in white women [",
" 1,7,8",
" </a>",
" ]. In one study, the estimated cumulative incidence of fibroids of any size,
including very small tumors, by age 50 was >80 percent for black women and
almost 70 percent for white women [",
" 1",
" </a>",
" ]. Clinically relevant fibroids (uterine enlargement greater than or equal to
nine weeks size, fibroid greater than or equal to 4 cm, or submucosal fibroid) are
detectable by transvaginal sonography in approximately 50 percent of black women in
the menopausal transition and 35 percent of white women in the menopausal
transition [",
" 1",
" </a>",
" ].",
" </p>",
" <p>",
" The etiology of the increased incidence of leiomyomas in black women is
unknown. It cannot be explained by known factors that vary by race [",
" 8",
" </a>",
" ]. There have been studies that correlated the presence of fibroids in African
American women with polycystic ovarian syndrome [",
" 9",
" </a>",
" ] and self-reported experience of racism [",
" 10",
" </a>",
" ].",
" </p>",
" <p>",
" The natural history of leiomyomas also differs by race. Most white women with
symptomatic fibroids are in their 30s or 40s; however, black women develop symptoms
on average four to six years younger and may even present with disease in their 20s
[",
" 11,12",
" </a>",
" ]. In addition, it appears that fibroids grow at a slower rate after age 35 in
white women, but not in black women [",
" 13",
" </a>",
" ]. Compared with white women, black women experience more severe disease based
on their symptoms in a proposed severity algorithm and have more extensive disease
at the time of hysterectomy [",
" 11,12",
" </a>",
" ].",
" </p>",
" <p>",
" The rate of hysterectomy for fibroids is greater among black women than among
white women (38 versus 16 per 10,000 women) [",
" 14",
" </a>",
" ]. Also, among women undergoing hysterectomy, black women appear to have
surgery at a younger age, have larger uteri, and more severe anemia [",
" 11,12",
" </a>",
" ].",
" </p>",
" <p>",
" Data are mixed regarding whether Latina women have an increased risk of
uterine myomas compared with non-Latina white women [",
" 8,14",
" </a>",
" ]. The risk was 1.3-fold in a prospective study of 133,000 women [",
" 14",
" </a>",
" ]. Some of this variation may be accounted for whether black Latina women are
included in the analysis.",
" </p>",
" Menstrual history and parity",
" </span>",
" — Early menarche (<10 years old) is associated with an
increased risk of developing fibroids. This may largely account for the early onset
of disease in black women in whom menarche is generally earlier than in white women
[",
" 11,15-18",
" </a>",
" ]. Additionally, prenatal exposure to diethylstilbestrol is associated with an
increased risk of fibroids, supporting the role of early hormonal exposure in
pathogenesis [",
" 19",
" </a>",
" ]. In white women, a specific polymorphism in the transcription factor HMGA2
appears to be linked to both uterine leiomyomas and shorter adult height,
suggesting that early menarche may be a key influence [",
" 16",
" </a>",
" ].",
" </p>",
" <p>",
" Parity (having one or more pregnancies extending beyond 20 weeks) decreases
the chance of fibroid formation [",
" 20-22",
" </a>",
" ]. It has been hypothesized that the postpartum remodeling of the uterus may
have the effect of clearing smaller fibroids [",
" 23",
" </a>",
" ]. Recent studies supported this hypothesis with the finding that over a third
of women with a single fibroid identified during pregnancy had none on postpartum
ultrasound, and almost 80 percent of fibroids were smaller following pregnancy [",
" 24",
" </a>",
" ]. In some cohorts, early age at first birth decreases risk and a longer
interval since last birth increases risk [",
" 15",
" </a>",
" ].",
" </p>",
" Hormonal contraception",
" </span>",
" — Use of low dose oral contraceptives (OCs) does not cause
fibroids to grow, therefore administration of these drugs is not contraindicated in
women with fibroids [",
" <a class=\"abstract\" href=\"UTD.htm?6/17/6426/abstract/15,20,25-27\">",
" 15,20,25-27",
" </a>",
" ]. One possible exception was reported by the Nurses' Health Study, which
suggested OC use increased the risk of leiomyomas in women with early exposure to
OCs (13 and 16 years old) [",
" 22",
" </a>",
" ].",
" </p>",
" <p>",
" Long acting progestin-only contraceptives (eg, depot medroxyprogesterone)
protect against development of leiomyomas [",
" 15,27,28",
" </a>",
" ]. However, recent studies of postpartum fibroid regression suggest that these
agents inhibit fibroid regression when used in the postpartum period [",
" 29",
" </a>",
" ].",
" </p>",
" Ovulation induction agents",
" </span>",
" — There are isolated reports of leiomyoma enlargement in
women treated with",
" clomiphene",
" </a>",
" [",
" 30,31",
" </a>",
" ]. However, both cases reported occurred in the era before clinical use of
ultrasound and the only presurgical assessment of the size of fibroids was pelvic
examination and culdoscopy. Given the frequency of ultrasound monitoring in
conjunction with current fertility treatments and the dearth of case reports, the
association of fibroid growth with agents for ovulation induction is unlikely [",
" 32",
" </a>",
" ].",
" </p>",
" Obesity",
" </span>",
" — Most studies show a relationship between fibroids and
increasing body mass index; however, a relationship with increased body mass index,
weight gain as an adult, or body fat varies between studies. The relationship is
complex and is likely modified by other factors, such as parity, and may be more
related to change in body habitus as an adult [",
" 25,33-37",
" </a>",
" ].",
" </p>",
" Diet, caffeine, and alcohol use",
" </span>",
" — Significant consumption of beef and other reds meats (1.7-
fold) or ham (1.3-fold) is associated with an increased relative risk of fibroids
and consumption of green vegetables (0.5-fold) and fruit (especially citrus fruit)
with a decreased risk [",
" 38,39",
" </a>",
" ]. One report suggested that consumption of dairy products, but not soy
products, is inversely related to fibroid risk in black women [",
" 40",
" </a>",
" ]. Dietary consumption of carotenoids is not associated with a change in risk
for uterine leiomyoma [",
" 41",
" </a>",
" ]. Recent data suggest that consumption of dairy products is inversely
associated with leiomyoma risk in black women [",
" 40",
" </a>",
" ]. There was no confounding effect of soy consumption, which is often a
substitute for dairy products in lactose intolerant women [",
" 40",
" </a>",
" ]. Dietary vitamin A from animal sources may also be associated with decreased
fibroid risk [",
" 39",
" </a>",
" ]. Increases in dietary glycemic index or load are associated with a weak
increase in fibroid risk in some women [",
" 42",
" </a>",
" ].",
" </p>",
" <p>",
" Consumption of alcohol, especially beer, appears to increase the risk of
developing fibroids [",
" 43",
" </a>",
" ].",
" </p>",
" <p>",
" Caffeine consumption is not a risk factor.",
" </p>",
" Smoking",
" </span>",
" — Smoking decreases the risk of having fibroids through an
unknown mechanism. Smoking does not appear to affect estrogen metabolism [",
" 20,44",
" </a>",
" ].",
" </p>",
" Heredity",
" </span>",
" — Studies imply a familial predisposition to leiomyomas in
some women. (See",
" \"Histology and pathogenesis of uterine leiomyomas (fibroids)\", section on
'Genetics'",
" </a>",
" .)",
" </p>",
" Other factors",
" </span>",
" — Hypertension is associated with an increased leiomyoma
risk. The risk is related to increased duration or severity of hypertension [",
" 45",
" </a>",
" ]. Environmental phthalate exposure appears to be linked to an increased risk
of fibroids, especially in women with concomitant endometriosis [",
" 46",
" </a>",
" ].",
" </p>",
" <p>",
" Several measures of uterine infection appear to be associated with an
increased risk of leiomyomas. This is consistent with the hypothesis that uterine
injury may lead to leiomyoma formation [",
" 45,47",
" </a>",
" ].",
" </p>",
" CLINICAL MANIFESTATIONS",
" </span>",
" — Symptoms attributable to uterine myomas can generally be
classified into three distinct categories:",
" </p>",
" <p>",
" <li>",
" Abnormal uterine bleeding",
" </li>",
" <li>",
" Pelvic pressure and pain",
" </li>",
" <li>",
" Reproductive dysfunction",
" </li>",
" </ul>",
" </p>",
" <p>",
" Although the majority of myomas are small and asymptomatic, many women with
fibroids have significant problems that interfere with some aspect of their lives
and warrant therapy. These symptoms are related to the number, size, and location
of the neoplasms. Myomas can occur as single or multiple tumors and range in size
from microscopic to tens of centimeters. The size of the myomatous uterus is
described in menstrual weeks, as with the gravid uterus. As an example, a 20-week
size myomatous uterus is not unusual, and is often associated with heavy menses,
increasing abdominal girth, and a sense of abdominal fullness similar to
pregnancy.",
" </p>",
" </span>",
" — Abnormal uterine bleeding is the most common symptom.
Heavy",
" and/or",
" </span>",
" prolonged menses is the typical bleeding pattern with myomas [",
" 48",
" </a>",
" ]. Intermenstrual bleeding and postmenopausal bleeding are",
" <strong>",
" NOT",
" </strong>",
" characteristic of myomas and should be investigated to exclude endometrial
pathology. (See",
" \"Evaluation of the endometrium for malignant or premalignant disease\"",
" </a>",
" .) Heavy uterine bleeding may be responsible for associated problems, such as
iron deficiency anemia, social embarrassment, and lost productivity in the work
force.",
" </p>",
" <p>",
" The presence and degree of uterine bleeding are determined, in large part, by
the location of the fibroid; size is of secondary importance. (See",
" 'Terminology and location'",
" </a>",
" above.) Submucosal myomas that protrude into the uterine cavity (eg, types 0
and I) (",
26/32/27143\">",
" figure 2",
" </a>",
" ) are most frequently related to significant menorrhagia [",
" 2,4,49",
" </a>",
" ]. However, women with intramural myomas also commonly experience heavy or
prolonged menstrual bleeding. The mechanism(s) of profuse menses are unclear, but
may include both microscopic and macroscopic abnormalities of the uterine
vasculature, impaired endometrial hemostasis, or molecular dysregulation of
angiogenic factors [",
" 50",
" </a>",
" ].",
" </p>",
" </span>",
" </p>",
" Bulk-related symptoms",
" </span>",
" — The myomatous uterus is irregularly shaped, in contrast to
the pregnant uterus, and can cause specific symptoms due to pressure from myomas at
particular locations. As examples, urinary frequency, difficulty emptying the
bladder, and, rarely, urinary obstruction can all occur with fibroids; symptoms
sometimes arise when an anterior fibroid presses directly on the bladder or a
posterior fibroid pushes the entire uterus forward. Silent, ureteric compression
leading to renal hydronephrosis is rare [",
" 51",
" </a>",
" ]. Fibroids that place pressure on the rectum can result in constipation. Back
pain may, on occasion, be related to the presence of myomas, but other possible
causes should be considered. Very large uteri may compress the vena cava and lead
to increase in thromboembolic risk [",
" 52-54",
" </a>",
" ]. At least one study suggests the risk of venous thromboembolism is likely to
be the presenting complaint associated with an enlarged uterus rather than a
postsurgical complication [",
" 52",
" </a>",
" ].",
" </p>",
" Dysmenorrhea",
" </span>",
" — Dysmenorrhea is also reported by many women with fibroids.
This pain in many women appears to be correlated with heavy menstrual flow",
" and/or",
" </span>",
" passage of clots.",
" </p>",
" Dyspareunia",
" </span>",
" — It is controversial whether women with fibroids in any
location are more likely to experience dyspareunia than women without fibroids [",
" 55,56",
" </a>",
" ]. However, among women with fibroids, anterior or fundal fibroids are the
most likely to be associated with deep dyspareunia. Number and size of fibroids do
not appear to influence the incidence or intensity of dyspareunia.",
" </p>",
" Leiomyoma degeneration or torsion",
" </span>",
" — Infrequently, fibroids cause acute pain from degeneration
(eg, carneous or red degeneration) or torsion of a pedunculated tumor. Pain may be
associated with a low grade fever, uterine tenderness on palpation, elevated white
blood cell count, or peritoneal signs. The discomfort resulting from degenerating
fibroids is self-limited, lasting from days to a few weeks, and usually responds to
nonsteroidal antiinflammatory drugs. Pelvic magnetic resonance imaging with
gadolinium can be useful to make the diagnosis of degeneration since degenerating
fibroids do not have enhancement following contrast administration [",
" 57",
" </a>",
" ]. If acute pain is the sole indication for surgery, other disease processes,
such as endometriosis and renal colic, or rare diagnoses such as pelvic
tuberculosis, should be carefully excluded [",
" 58,59",
" </a>",
" ]. (See",
" \"Pathogenesis, clinical features, and diagnosis of endometriosis\"",
" </a>",
" .)",
" </p>",
" Effects on reproduction",
" </span>",
" — Leiomyomas that distort the uterine cavity (submucosal or
intramural with an intracavitary component) result in difficulty conceiving a
pregnancy and an increased risk of miscarriage [",
" 60",
" </a>",
" ]. In addition, leiomyomas have been associated with adverse pregnancy
outcomes (eg, placental abruption, fetal growth restriction, and preterm labor and
birth). These issues are discussed in detail separately. (See",
" \"Reproductive issues in women with uterine leiomyomas (fibroids)\"",
" </a>",
" and",
" \"Pregnancy in women with uterine leiomyomas (fibroids)\"",
" </a>",
" .)",
" </p>",
" Other",
" </span>",
" — Infrequently, a leiomyoma will present with transcervical
prolapse, resulting in ulceration or infection.",
" </p>",
" <p>",
" Rare symptoms of fibroid tumors that appear to be related to ectopic hormone
production include:",
" </p>",
" <p>",
" <li>",
" Polycythemia from autonomous production of erythropoietin [",
" 61",
" </a>",
" ]",
" </li>",
" <li>",
" Hypercalcemia from autonomous production of PTHrP [",
" 62",
" </a>",
" ]",
" </li>",
" <li>",
" Hyperprolactinemia [",
" 63",
" </a>",
" ]",
" </li>",
" </ul>",
" </p>",
" DIAGNOSIS",
" </span>",
" — The presumptive diagnosis of uterine myomas is usually
based upon the finding of an enlarged, mobile uterus with an irregular contour on
bimanual pelvic examination. Typically, an ultrasound is used to confirm the
diagnosis and exclude the possibility of another type of uterine mass or an adnexal
mass.",
" </p>",
" Pelvic examination",
" </span>",
" — A thorough pelvic examination should be performed. On
bimanual pelvic examination, an enlarged, mobile uterus with an irregular contour
is consistent with a leiomyomatous uterus. The size, contour, and mobility of the
uterus should be noted, along with any other findings (eg, adnexal mass, cervical
mass). These findings are helpful to follow changes in the uterus over time and to
aid surgical planning (eg, plan transverse or vertical incision).",
" </p>",
" <p>",
" Infrequently, on speculum exam, a prolapsed submucosal fibroid may be visible
at the external cervical os. These should be removed and are distinguished from a
large endocervical or endometrial polyp by the firm consistency of the tissue and
by pathologic evaluation. (See",
" \"Prolapsed uterine leiomyoma (fibroid)\"",
" </a>",
" .)",
" </p>",
" Imaging",
" </span>",
" — When a myoma is suspected based upon symptoms or pelvic
examination findings, imaging or hysteroscopy are useful to exclude the possibility
of another type of uterine mass or an adnexal mass. (See",
" 'Differential diagnosis'",
" </a>",
" below.) Computed tomography has little clinical utility in delineating the
position of fibroids relative to the endometrium or myometrium [",
" 64",
" </a>",
" ].",
" </p>",
" Ultrasound",
" </span>",
" — Transvaginal ultrasound has high sensitivity (95 to 100
percent) for detecting myomas in uteri less than 10 weeks' size. Localization of
fibroids in larger uteri or when there are many tumors is limited [",
" 65",
" </a>",
" ]. This is the most widely used modality due to its availability and cost-
effectiveness.",
" </p>",
" <p>",
" Saline infusion sonography (sonohysterography) improves characterization of
the extent of protrusion into the endometrial cavity by submucous myomas and allows
identification of some intracavitary lesions not seen on routine ultrasonography
(",
" <a class=\"graphic graphic_diagnosticimage graphicRef51266 \" href=\"UTD.htm?
11/28/11715\">",
" image 2",
" </a>",
" ). (See",
" \"Saline infusion sonohysterography\"",
" </a>",
" .)",
" </p>",
" Diagnostic hysteroscopy",
" </span>",
" — Diagnostic hysteroscopy can be performed in the office with
a flexible or rigid hysteroscope. When the entire fibroid is visualized arising
from a pedicle, or has a broad base, the lesion is hysteroscopically classified as
intracavitary. However, when the fibroid abuts the endometrium or protrudes into
the myometrium, the depth of penetration cannot be ascertained hysteroscopically.
Additionally, hysteroscopy less accurately predicts the size of the myoma compared
with ultrasound and sonohysterography [",
" 66",
" </a>",
" ].",
" </p>",
" Magnetic resonance imaging",
" </span>",
" — Magnetic resonance imaging is the best modality for
visualizing the size and location of all uterine myomas and can distinguish among
leiomyomas, adenomyosis, and adenomyomas. Due to the expense of this modality, its
use is best reserved for surgical planning for complicated procedures. It may also
be useful in differentiating leiomyomas from leiomyosarcomas, and before uterine
artery embolization since imaging patterns predict uterine artery embolization
outcome [",
" 67,68",
" </a>",
" ].",
" </p>",
" Hysterosalpingography",
" </span>",
" — A hysterosalpingogram (HSG) is a good technique for
defining the contour of the endometrial cavity. It has poor ability to visualize
the rest of the myometrium and can falsely identify an intramural fibroid impinging
on the uterine cavity as a submucosal fibroid. It is typically used to visualize
myomas only when a HSG is needed to evaluate tubal patency in women with
infertility. (See",
" \"Hysterosalpingography\"",
" </a>",
" .)",
" </p>",
" </span>",
" — A normal nonpregnant uterus weighs approximately 70 g. The
differential diagnosis of an enlarged uterus includes both benign and malignant
conditions:",
" </p>",
" <p>",
" <li>",
" Uterine adenomyosis or adenomyoma",
" </li>",
" <li>",
" Leiomyoma variant",
" </li>",
" <li>",
" Pregnancy",
" </li>",
" <li>",
" Hematometra",
" </li>",
" <li>",
" Uterine sarcoma",
" </li>",
" <li>",
" Uterine carcinosarcoma",
" </li>",
" <li>",
" Endometrial carcinoma",
" </li>",
" <li>",
" Metastatic disease (typically from another reproductive tract primary)",
" </li>",
" </ul>",
" </p>",
" <p>",
" The following sections will review aspects of these conditions that are
relevant to distinguishing them from leiomyomas and uterine sarcoma.",
" </p>",
" Benign conditions",
" </span>",
" </p>",
" Adenomyosis or adenomyoma",
" </span>",
" — Among the etiologies of a uterine mass, adenomyoma is the
most likely to resemble a leiomyoma on pelvic imaging and intraoperative
examination. Diffuse adenomyosis can also cause uterine enlargement without the
presence of a discrete mass.",
" </p>",
" <p>",
" Similar to leiomyomas or uterine sarcoma, adenomyomas typically present with
abnormal uterine bleeding. One characteristic that may distinguish adenomyomas from
leiomyomas or sarcoma is the presence of dysmenorrhea as a prominent symptom.
However, dysmenorrhea is a common gynecologic symptom and may be present in some
women with leiomyomas. In addition, adenomyosis and fibroids often occur in the
same woman, making differentiation more difficult.",
" </p>",
" <p>",
" Adenomyomas are generally more difficult to excise than leiomyomas. Leiomyomas
are typically separated from the adjacent myometrium by a pseudocapsule. With
adenomyomas, there is typically no tissue plane between the adenomyoma and the
myometrium. Uterine sarcomas are also likely to be difficult to excise.",
" </p>",
" <p>",
" The diagnosis of uterine adenomyosis is discussed separately. (See",
" \"Uterine adenomyosis\", section on 'Diagnosis'",
" </a>",
" .)",
" </p>",
" Leiomyoma variant",
" </span>",
" — There are a number of leiomyoma variants that manifest some
facets of malignancy, yet lack others. For example, they may metastasize, but not
be locally invasive and be histologically benign. These lesions appear to be
exceedingly rare. (See",
" \"Variants of uterine leiomyomas (fibroids)\"",
" </a>",
" .)",
" </p>",
" Other etiologies",
" </span>",
" — Pregnancy is readily distinguishable from other uterine
masses with measurement of a serum human chorionic gonadotropin",
" and/or",
" </span>",
" pelvic sonography. (See",
" \"Clinical manifestations and diagnosis of early pregnancy\", section on
'Diagnosis'",
" </a>",
" .)",
" </p>",
" <p>",
" Hematometra, a collection of blood within the uterine cavity, occurs most
often following after an intrauterine procedure",
" and/or",
" </span>",
" in women with cervical stenosis and is diagnosed with pelvic imaging. (See",
" \"Overview of pregnancy termination\", section on 'Hematometra'",
" </a>",
" .)",
" </p>",
" <p>",
" Adenomatoid tumors are an uncommon type of mass of the female reproductive
tract that can be seen in the myometrium or in the adnexa (the most common place is
actually next to the fallopian tube) [",
" 69",
" </a>",
" ]. They are mesothelial proliferations and are not histologically related to
adenomyosis. They may grossly mimic leiomyomas. ",
" </p>",
" <p>",
" In addition, fibroids must be differentiated from other etiologies of abnormal
uterine bleeding (see",
" \"Terminology and evaluation of abnormal uterine bleeding in premenopausal
women\"",
" </a>",
" and",
" \"Postmenopausal uterine bleeding\"",
" </a>",
" ), pelvic pain (see",
" \"Clinical features and diagnosis of pelvic inflammatory disease\"",
" </a>",
" ), and infertility (see",
" \"Overview of infertility\"",
" </a>",
" ).",
" </p>",
" Malignant disease",
" </span>",
" </p>",
" Sarcoma",
" </span>",
" — Uterine sarcomas are rare. The incidence was 3 to 7 per
100,000 United States (US) population from 1989 to 1999 [",
" 70",
" </a>",
" ], based upon data from the Surveillance, Epidemiology and End Results (SEER)
US national cancer database. The median age at diagnosis is approximately 60 years
old. The three most common types of uterine sarcomas are clinically
indistinguishable: leiomyosarcoma, endometrial stromal sarcoma, and
undifferentiated endometrial sarcoma. The prognosis of sarcoma varies somewhat by
histologic type, but, in general, the prognosis is poor compared to other
gynecologic malignancies. (See",
" \"Differentiating uterine leiomyomas (fibroids) from uterine sarcomas\"",
" </a>",
" .)",
" </p>",
" Carcinosarcoma",
" </span>",
" — Uterine carcinosarcomas are rare and highly aggressive
tumors with a poor prognosis. The incidence of carcinosarcomas in US women age 35
years or older is approximately 1 to 4 per 100,000 US population. The median age at
diagnosis is approximately 62 to 67 years old.",
" </p>",
" <p>",
" Historically, uterine carcinosarcoma was classified as a type of uterine
sarcoma, and was termed malignant mixed müllerian tumor or mixed mesodermal
sarcoma. However, these tumors are now classified as carcinomas since they derive
from a monoclonal cancer cell that exhibits sarcomatous metaplasia, rather than a
mixture of carcinoma and sarcoma. In addition, the epidemiology, risk factors, and
clinical behavior associated with carcinosarcoma also suggest a closer relationship
to endometrial carcinoma than to sarcoma. (See",
" \"Clinical features, diagnosis, staging, and treatment of uterine
carcinosarcoma\", section on 'Epidemiology and risk factors'",
" </a>",
" and",
" \"Clinical features, diagnosis, staging, and treatment of uterine
carcinosarcoma\", section on 'Pathology'",
" </a>",
" .)",
" </p>",
" Endometrial carcinoma",
" </span>",
" — Endometrial carcinoma may also result in abnormal uterine
bleeding and a uterine mass. However, the diagnosis is typically made with
endometrial sampling and imaging usually shows a thickened endometrium; if a mass
is present, it is generally confined to the endometrium, except in women with
advanced disease.",
" </p>",
" NATURAL HISTORY",
" </span>",
" </p>",
" Premenopausal women",
" </span>",
" — With modern pelvic imaging, we have achieved an increased
appreciation of the variability of growth and shrinkage of leiomyomas",
" <strong>",
" </strong>",
" among women of reproductive age [",
" 13,71,72",
" </a>",
" ]. Prospective studies have found that between 7 to 40 percent of fibroids
regress over six months to three years [",
" 13,71",
" </a>",
" ]. In one prospective study of 64 women (mean age 44 years) with fibroids, the
average growth rate was 1.2 cm in diameter over 2.5 years (range 0.9 to 6.8 cm) [",
" 71",
" </a>",
" ]. As an example, a study that followed 72 women with a total of 262 fibroids
with magnetic resonance imaging reported a median growth rate of 9 percent at six-
month follow-up. [",
" 13",
" </a>",
" ]. There was wide variation in the growth of individual fibroids across all
study participants (range -89 percent to +138 percent) and for different fibroids
within each woman. Another example was a prospective study in which 36 women with a
total of 101 fibroids were evaluated with magnetic resonance imaging at three-month
intervals for one year [",
" 73",
" </a>",
" ]. Increase in volume of ≥30 percent in a three-month period was found in
37 myomas; rapid growth was more likely in tumors that were ≤5 cm in diameter.",
" </p>",
" Postmenopausal women",
" </span>",
" — Relief of menstrual bleeding symptoms related to fibroids
occurs at the time of menopause, when menstrual cyclicity stops and steroid hormone
levels wane. Most, but not all, women have shrinkage of leiomyomas at menopause.",
" </p>",
" Women on hormone therapy",
" </span>",
" — Use of postmenopausal hormone therapy may cause some women
with leiomyomas to continue to have symptoms after menopause. The risk of symptoms
may depend, in part, on the location of the fibroid (higher if submucosal [",
" 74",
" </a>",
" ]) and type of estrogen preparation (higher with transdermal estrogen in some
studies [",
" 75,76",
" </a>",
" ], but not others [",
" 77",
" </a>",
" ]).",
" </p>",
" <p>",
" A systematic review including five randomized controlled trials found that
postmenopausal hormone therapy was associated with some myoma growth, but this
typically occurred without clinical symptoms [",
" 78",
" </a>",
" ]. These findings were confirmed in a subsequent prospective study [",
" 79",
" </a>",
" ]. Thus, the presence of leiomyomas is not a contraindication to use of
postmenopausal hormone therapy and postmenopausal hormone therapy does not lead to
development of new symptomatic fibroids in most women. (See",
" \"Postmenopausal hormone therapy: Benefits and risks\", section on 'Uterine
leiomyomas'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" </span>",
" — UpToDate offers two types of patient education materials,
“The Basics” and “Beyond the Basics.” The Basics patient
education pieces are written in plain language, at the 5",
" <sup>",
" th",
" </sup>",
" to 6",
" <sup>",
" th",
" </sup>",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" <sup>",
" th",
" </sup>",
" to 12",
" <sup>",
" th",
" </sup>",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
“patient info” and the keyword(s) of interest.)",
" </p>",
" <p>",
" <li>",
" Basics topics (see",
" \"Patient information: Uterine fibroids (The Basics)\"",
" </a>",
" )",
" </li>",
" <li>",
" Beyond the Basics topics (see",
" \"Patient information: Uterine fibroids (Beyond the Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" </span>",
" </p>",
" <p>",
" <li>",
" Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in
women (cumulative incidence by age 50 of >80 percent for black women and almost
70 percent for white women). The incidence of leiomyomas parallels the life cycle
changes of the reproductive hormones estrogen and progesterone. (See",
" 'Prevalence'",
" </a>",
" above and",
" 'Race'",
" </a>",
" above.)",
" </li>",
" <li>",
" Leiomyomas are benign monoclonal tumors arising from the smooth muscle cells
of the myometrium. Fibroids are often described according to their location in the
uterus (submucosal, intramural, subserosal, cervical). (See",
" 'Prevalence'",
" </a>",
" above.)",
" </li>",
" <li>",
" Symptoms attributable to uterine myomas can generally be classified into
three distinct categories: abnormal uterine bleeding, pelvic pressure and pain,
reproductive dysfunction. (See",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </li>",
" <li>",
" The presumptive diagnosis of uterine myomas is usually based upon the
finding of an enlarged, mobile uterus with an irregular contour on bimanual pelvic
examination. Typically, an imaging study is used to confirm the diagnosis and
exclude the possibility of another type of uterine mass or an adnexal mass. (See",
" 'Diagnosis'",
" </a>",
" above.)",
" </li>",
" <li>",
" Transvaginal ultrasound is the most widely used imaging modality for
evaluating fibroids due to its availability and cost-effectiveness. Saline infusion
sonography (sonohysterography) improves characterization of the extent of
protrusion into the endometrial cavity by submucous myomas and allows
identification of some intracavitary lesions not seen on routine ultrasonography.
(See",
" 'Imaging'",
" </a>",
" above.)",
" </li>",
" <li>",
" Relief of symptoms related to fibroids usually occurs at the time of
menopause, when menstrual cyclicity stops and steroid hormone levels wane. Most,
but not all, women have shrinkage of leiomyomas at menopause. Use of postmenopausal
hormone therapy may cause some women with leiomyomas to continue to have symptoms
after menopause. Hormone therapy may be associated with an increase in size of
existing myomas, but not with the development of new myomas. (See",
" 'Postmenopausal women'",
" </a>",
" above and",
" 'Women on hormone therapy'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" </a>",
" .",
" </div>",
" <h1>",
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" </a>",
" </li>",
" </ol>",
" </div>",
" </div>",
" </div>",
" </span>",
" |",
" </span>",
" </a>",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" Licensed to:",
" </span>",
" </span>",
" |",
" </span>",
" Support Tag: [0603-190.111.122.2-168C04E0CB-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
" </a>",
" </div>",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <ul>",
" <li>",
" <span>",
" </span>",
" </a>",
" </li>",
" INTRODUCTION",
" </a>",
" </li>",
" TERMINOLOGY AND LOCATION",
" </a>",
" </li>",
" PREVALENCE",
" </a>",
" </li>",
" RISK FACTORS",
" </a>",
" </li>",
" Race",
" </a>",
" </li>",
" Menstrual history and parity",
" </a>",
" </li>",
" Hormonal contraception",
" </a>",
" </li>",
" Ovulation induction agents",
" </a>",
" </li>",
" Obesity",
" </a>",
" </li>",
" Diet, caffeine, and alcohol use",
" </a>",
" </li>",
" Smoking",
" </a>",
" </li>",
" Heredity",
" </a>",
" </li>",
" Other factors",
" </a>",
" </li>",
" CLINICAL MANIFESTATIONS",
" </a>",
" </li>",
" </a>",
" </li>",
" </a>",
" </li>",
" - Bulk-related symptoms",
" </a>",
" </li>",
" - Dysmenorrhea",
" </a>",
" </li>",
" - Dyspareunia",
" </a>",
" </li>",
" - Leiomyoma degeneration or torsion",
" </a>",
" </li>",
" Effects on reproduction",
" </a>",
" </li>",
" Other",
" </a>",
" </li>",
" DIAGNOSIS",
" </a>",
" </li>",
" Pelvic examination",
" </a>",
" </li>",
" Imaging",
" </a>",
" </li>",
" - Ultrasound",
" </a>",
" </li>",
" - Diagnostic hysteroscopy",
" </a>",
" </li>",
" - Magnetic resonance imaging",
" </a>",
" </li>",
" - Hysterosalpingography",
" </a>",
" </li>",
" </a>",
" </li>",
" Benign conditions",
" </a>",
" </li>",
" - Adenomyosis or adenomyoma",
" </a>",
" </li>",
" - Leiomyoma variant",
" </a>",
" </li>",
" - Other etiologies",
" </a>",
" </li>",
" Malignant disease",
" </a>",
" </li>",
" - Sarcoma",
" </a>",
" </li>",
" - Carcinosarcoma",
" </a>",
" </li>",
" - Endometrial carcinoma",
" </a>",
" </li>",
" NATURAL HISTORY",
" </a>",
" </li>",
" Premenopausal women",
" </a>",
" </li>",
" Postmenopausal women",
" </a>",
" </li>",
" - Women on hormone therapy",
" </a>",
" </li>",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" </a>",
" </li>",
" </a>",
" </li>",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"OBGYN/5486\" rel=\"outline_link\">",
" GRAPHICS",
" View All",
" </a>",
" </div>",
" </h1>",
" <ul>",
" <div class=\"openRelatedGraphics\" id=\"OBGYN/5486|DiagnosticImage\">",
" <a href=\"#\" title=\"DIAGNOSTIC IMAGES\">",
" DIAGNOSTIC IMAGES",
" </a>",
" </div>",
" </li>",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?8/34/8737\"
title=\"diagnostic image 1\">",
" Pedunculated fibroid",
" </a>",
" </li>",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?11/28/11715\"
title=\"diagnostic image 2\">",
" Submucosal fibroid",
" </a>",
" </li>",
" <div class=\"openRelatedGraphics\" id=\"OBGYN/5486|FIG\">",
" <a href=\"#\" title=\"FIGURES\">",
" FIGURES",
" </a>",
" </div>",
" </li>",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?30/16/30978\"
title=\"figure 1\">",
" Fibroid anatomy",
" </a>",
" </li>",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?26/32/27143\"
title=\"figure 2\">",
" Submucosal leiomyoma position",
" </a>",
" </li>",
" <div class=\"openRelatedGraphics\" id=\"OBGYN/5486|PIC\">",
" <a href=\"#\" title=\"PICTURES\">",
" PICTURES",
" </a>",
" </div>",
" </li>",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?41/47/42740\"
title=\"picture 1A\">",
" Leiomyoma uterus A",
" </a>",
" </li>",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?13/0/13315\"
title=\"picture 1B\">",
" Leiomyoma uterus B",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <ul>",
" Clinical features and diagnosis of pelvic inflammatory disease",
" </a>",
" </li>",
" Clinical features, diagnosis, staging, and treatment of uterine
carcinosarcoma",
" </a>",
" </li>",
" Clinical manifestations and diagnosis of early pregnancy",
" </a>",
" </li>",
" Differentiating uterine leiomyomas (fibroids) from uterine sarcomas",
" </a>",
" </li>",
" Evaluation of the endometrium for malignant or premalignant disease",
" </a>",
" </li>",
" Histology and pathogenesis of uterine leiomyomas (fibroids)",
" </a>",
" </li>",
" Hysterosalpingography",
" </a>",
" </li>",
" Hysteroscopic myomectomy",
" </a>",
" </li>",
" Overview of infertility",
" </a>",
" </li>",
" Overview of pregnancy termination",
" </a>",
" </li>",
" Overview of treatment of uterine leiomyomas (fibroids)",
" </a>",
" </li>",
" Pathogenesis, clinical features, and diagnosis of endometriosis",
" </a>",
" </li>",
" Patient information: Uterine fibroids (Beyond the Basics)",
" </a>",
" </li>",
" Patient information: Uterine fibroids (The Basics)",
" </a>",
" </li>",
" Postmenopausal hormone therapy: Benefits and risks",
" </a>",
" </li>",
" Postmenopausal uterine bleeding",
" </a>",
" </li>",
" Pregnancy in women with uterine leiomyomas (fibroids)",
" </a>",
" </li>",
" Prolapsed uterine leiomyoma (fibroid)",
" </a>",
" </li>",
" Reproductive issues in women with uterine leiomyomas (fibroids)",
" </a>",
" </li>",
" Saline infusion sonohysterography",
" </a>",
" </li>",
" Terminology and evaluation of abnormal uterine bleeding in premenopausal
women",
" </a>",
" </li>",
" Uterine adenomyosis",
" </a>",
" </li>",
" Variants of uterine leiomyomas (fibroids)",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_17_6427="Alkaline diuresis in poisons";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=PULM
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PULM
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"figure\">",
" Agents for which alkaline diuresis may enhance elimination",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td>",
" 2,4-D chlorphenoxyacetic acid (herbicide)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Chlorpropamide",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Salicylates",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Diflunisal",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Fluoride",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Methotrexate",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1_start\">",
" Barbiturates",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Phenobarbital",
" </td>",
" </tr>",
" <tr>",
" Primidone",
" </td>",
" </tr>",
" <tr>",
" Barbital",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Sulfonamides",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6428="Methods of summarizing studies in systematic reviews";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" </a>",
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Methods of summarizing studies in systematic reviews",
" </div>",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" Approach",
" </td>",
" Main model",
" </td>",
" Comments",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Qualitative systematic review",
" </td>",
" <td>",
" Qualitative description of evidence",
" </td>",
" <td>",
" May be most appropriate if large degree of heterogeneity among studies.",
" </td>",
" </tr>",
" <tr>",
" <td rowspan=\"2\">",
" Meta-analysis overall estimate",
" </td>",
" <td>",
" Fixed effects model",
" </td>",
" <td>",
" Assumes a single truth across populations and homogeneity among studies.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Random effects model",
" </td>",
" <td>",
" Incorporates between-study heterogeneity. Wider confidence interval than
fixed effects model when heterogeneity is present.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Meta-analysis of multiple interventions simultaneously",
" </td>",
" <td>",
" Network meta-analysis (mixed or multiple treatment comparison)",
" </td>",
" <td>",
" Estimates relative effects of multiple interventions against each other,
even if no individual study analyzed a comparison between 2 or more specific
interventions.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Meta-analysis subgroup analyses",
" </td>",
" <td>",
" Fixed or random effects models",
" </td>",
" <td>",
" May explain heterogeneity. Subject to ecological fallacy. May not be
possible due to limited reported data. Arbitrary selection of subgroups may result
in spurious findings.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Meta-regression",
" </td>",
" <td>",
" Regression across studies",
" </td>",
" <td>",
" May explain heterogeneity. Subject to ecological fallacy. May not be
possible due to limited reported data.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Individual patient data meta-analysis",
" </td>",
" <td>",
" Multivariate regression across individuals",
" </td>",
" <td>",
" Allows most complete analysis of data and evaluation of heterogeneity.
Costly and resource-intensive.",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6429="Oral antibiotics human bites";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=ID
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=ID
" Print",
" </a>",
" </a>",
" Email",
" </a>",
" </div>",
" </div>",
" Empiric oral antibiotic therapy for human bites",
" </div>",
" <tr>",
" Antibiotic",
" </td>",
" Dosing for adults",
" </td>",
" Dosing for children",
" </td>",
" </tr>",
" <tr>",
" <td>",
" <p>",
" Agent of choice:",
" </p>",
" <p>",
" Amoxicillin-clavulanate",
" </p>",
" </td>",
" <td>",
" 875/125 mg twice daily",
" </td>",
" <td>",
" 20 mg/kg per dose (amoxicillin component) two times daily (maximum 875 mg
amoxicillin and 125 mg clavulinic acid per dose)*",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\" colspan=\"3\">",
" Alternate empiric regimens include:•",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist2_start\" colspan=\"3\">",
" One of the following agents with activity against",
" <em>",
" Eikenella",
" </em>",
" :",
" </td>",
" </tr>",
" <tr>",
" Doxycycline Δ",
" </td>",
" <td class=\"sublist_other\">",
" 100 mg twice daily",
" </td>",
" Not recommended in children <8 years of age",
" </td>",
" </tr>",
" <tr>",
" Trimethoprim-sulfamethoxazole Δ",
" </td>",
" 1 double strength tablet twice daily",
" </td>",
" 4-5 mg/kg (trimethoprim component) per dose twice daily (maximum 160 mg
trimethoprim per dose)",
" </td>",
" </tr>",
" <tr>",
" Penicillin VK",
" </td>",
" 500 mg four times daily",
" </td>",
" 12.5 mg/kg per dose four times daily (maximum 500 mg per dose)",
" </td>",
" </tr>",
" <tr>",
" Cefuroxime",
" </td>",
" 500 mg twice daily",
" </td>",
" 10 mg/kg per dose twice daily (maximum 500 mg per dose)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist2\" colspan=\"3\">",
" Fluoroquinolones (one of the following):",
" </td>",
" </tr>",
" <tr>",
" Ciprofloxacin",
" </td>",
" 500 to 750 mg twice daily",
" </td>",
" Use with caution in children <18 years of age",
" </td>",
" </tr>",
" <tr>",
" Moxifloxacin",
" </td>",
" 400 mg once daily",
" </td>",
" Use with caution in children <18 years of age",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent2\" colspan=\"3\">",
" <strong>",
" PLUS",
" </strong>",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist2_start\" colspan=\"3\">",
" One of the following agents with anaerobic activity:",
" </td>",
" </tr>",
" <tr>",
" Metronidazole",
" </td>",
" 500 mg three times daily",
" </td>",
" 10 mg/kg per dose three times daily (maximum 500 mg per dose)",
" </td>",
" </tr>",
" <tr>",
" Clindamycin Δ",
" </td>",
" 450 mg three times daily",
" </td>",
" 10 mg/kg per dose three times daily (maximum 450 mg per dose)",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\" colspan=\"3\">",
" The following agents have poor activity against",
" <em>",
" Eikenella",
" </em>",
" and should be avoided:",
" </td>",
" </tr>",
" <tr>",
" Cephalexin",
" </td>",
" </tr>",
" <tr>",
" Dicloxacillin",
" </td>",
" </tr>",
" <tr>",
" Erythromycin",
" </td>",
" </tr>",
" </table>",
" </div>",
" * In patients with infected bite wounds, the clinician may increase the does
to 45 mg/kg per dose (amoxicillin component) twice daily (maximum 875 mg
amoxicillin and 125 mg clavulinic acid per dose).",
" <br>",
" • The preferred regimen for pencillin allergic pediatric patients is
trimethoprim-sulfamethoxazole OR cefuroxime PLUS clindamycin (depending on liquid
drug availability and palatability).",
" <br>",
" Δ May also be active against MRSA (check susceptibility testing).",
" </br>",
" </br>",
" </div>",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var title_f6_17_6430="Contents: Peds psychosocial emergencies";
var content_f6_17_6430=[" <script type=\"text/javascript\">",
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" Child abuse: Anatomy and pathogenesis of retinal hemorrhages after
abusive head trauma",
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var title_f6_17_6431="Circadian rhythm of plasma ACTH";
" ©2013 UpToDate",
" <sup>",
" ®",
" </sup>",
" </div>",
" <a href=\"?imageKey=ENDO
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" Circadian rhythm of adrenocorticotropin (ACTH) secretion",
" </div>",
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" </div>",
" Top panel: Pulse analysis of plasma ACTH concentrations in samples obtained at
10-minute intervals for 24 hours. The line represents the plasma ACTH concentration
at any moment as predicted by a computer-generated deconvolution program. Bottom
panel: Computer-calculated ACTH secretion rate at any moment. The circadian rhythm
in plasma ACTH concentrations and, therefore, of cortisol secretion and plasma
cortisol concentrations is a function of the variation in the amplitude, not the
frequency, of ACTH secretory pulses. To convert pg/mL to pmol/L, multiply by
0.22.",
" </div>",
" Data from: Veldhuis JD, Iranmanesh A, Johnson ML, et al. Amplitude, but not
frequency, modulation of adrenocorticotropin secretory bursts gives rise to the
nyctohemeral rhythm of the corticotropic axis in man. J Clin Endocrinol Metab
1990; 71:452.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");

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var title_f6_17_6416="First degree AV block III";

var content_f6_17_6416=[" <div id=\"graphicsToolbar\">",

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