Flash cards by Seetal K. Dhaliwal H.

S
Section V
1
Antimicrobial therapy:
Mechanism of Action Drugs
Block cell wall synthesis by inhibition of
peptidoglycan cross-linking
Penicillin, ampicillin, ticarcillin, piperacillin, imipenam,
aztreonam, cephalosporins.
Block peptidoglycan synthesis Bacitracin, vancomycin
Disrupt bacterial cell membrane Polymyxins
Block nucleotides synthesis Sulfonamides, trimethoprim
Block DNA topoisomerase Fluoroquinolones
Block mRNA synthesis Rifampin
Block protein synthesis at 50S ribosomal Chloramphenicol, Macrolides, Clindamycin, Linezolid,
Streptogamins (quinupristin, dalfopristin)
Block protein synthesis at 30S ribosomal Aminoglycosides, Tetracyclines
Bacteriostatic Erythromycin, Clindamycin, Sulfamethoxazole,
Trimethoprim, Tetracyclines, Chloramphenicol.
Bactericidal Vancomycin, Fluoroquinolones, Penicillin,
Aminoglycosides, Cephalosporins, Metronidazole.
ECSTaTiC
bacteriostatics.
Very Finely Proficient
At Cell Murder
2
2
Penicillins:
Penicillin G (IV) and Penicillin V (oral):
Binds PBP, blocks transpeptidase of cell wall cross-linking, activate autolytic enzymes.
Bactericidal for gram postive cocci and rods & gram negative cocci and spirochetes.
-lactamase sensitive. May cause hypersensitivity reactions & Hemolytic anemia.
Methicillin, Nafcillin, Dicloxacillin (penicillinase-resistant penicillins):
Narrow spectrum. -lactamase resistant due to heavier R group.
Used for S. aureus (except MRSA due to altered PBP site); Use Naf for Staph
May cause hypersensitivity reactions; methicillin interstitial nephritis.
Ampicillin, Amoxicillin (aminopenicillins):
Broad spectrum (-lactamase sensitive); Clavulanic acid/Sulbactam (penicillinase inhibitor)
enhances spectrum. AmOxicillin has greater Oral bioavailability than ampicillin.
Used in some gram positive bacteria & gram neg rods H. pylori (amoxicillin), H. influenzae, E.
coli, Listeria monocytogenes (ampicillin), Proteus mirabilis, Salmonella, enterococci & Borrelia
(amoxicillin); Ampicillin/Amoxicillin HHELPS kill enterococci & Borrelia
May cause hypersensitivity reactions, rash or pseudomembranous colitis.
Ticarcillin, carbenicillin, piperacillin (antipseudomonals):
Extended spectrum; TCP takes care of Pseudomonas; Used to kill Pseudomonas spp., and gram
neg rods; -lactamase sensitive use with clavulanic acid. Synergistic with aminoglycosides.
3
3
Cephalosporins:
1
st
generation (cefazolin, cephalexin) PEcK:
Gram positive cocci, Proteus mirabillis, E. coli, Klebsiella pneumoniae.
2
nd
generation (cefoxitin, cefaclor, cefuroxime) HEN PEcKS:
Gram positive cocci, H. influenzae, Enterobacter aerogenes, Neisseria spp., Proteus
mirabillis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
3
rd
generation (ceftriaxone, cefotaxime, ceftazidime):
Serious gram neg infections; meningitis (penetrates BBB); ceftazidine pseudomonas;
ceftriaxone gonorrhea.
:
Activity against organisms.
Toxicity:
Hypersensitivity reactions. Cross hypersensitivity with penicillins (in 5 10%).
nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in
cephalosporins with a methylthiotetrazole group i.e. cefamandole)
-lactam drugs that inhibit cell wall
synthesis but are less susceptible to
penicillinase. Bactericidal.
4
Aztreonam:
MOA: same as penicillin &
cephalosporins.
Resistant to -lactamase. No cross
allergenicity with penicillins.
Used for gram neg rods Klebsiella
spp., Pseudomonas spp., Seratia spp.
No activity against gram positive or
anaerobes.
For penicillin-allergic patients & those
with renal insufficiency who cannot
tolerate aminoglycosides.
Toxicity:
Usually nontoxic; occasionally GI
upset. No cross sensitivity with
penicillins or cephalosporins.
Imipenem/cilastin, meropenem:
MOA: same as penicillin &
cephalosporins.
Resistant to -lactamase (carbapenem).
Imipenem is broad spectrum:
Administered with ciLASTIN to
inactivation in renal tubules.
Used for gram positive cocci, gram ned
rods, & anaerobes. DOC for
Enterobacter.
The significant side effects limit use to
life threatening infections, or after drugs
have failed. Meropenem, however, has
reduced risk of seizures & is stable to
dihydropeptidase I.
Toxicity:
GI distress, skin rash, & CNS toxicity
(seizures) at high plasma levels.
With Imipenem, the kill is LASTIN with ciLASTIN.
5
Vancomycin:
MOA: inhibits cell wall mucopeptide
formation by binding D-ala D-ala.
Resistance occurs when aa change from
D-ala D-ala to D-ala D-lac.
Used for serious, gram-positive multi-
drug resistant organisms;
S. aureus, C. difficile -
pseudomembranous colitis.
Toxicity:
Nephrotoxicity, Ototoxicity,
Thrombophlebitis, diffuse flushing
red man syndrome (can large
prevent by pretreatment with
antihistamines and slow infusion rate).
Well tolerated in general does NOT
have many problems.
Protein synthesis
inhibitors:
Buy AT 30, CCELL (sell) at 50
30S inhibitors:
Aminoglycosides (bactericidal)
Tetracycline (bacteriostatic)
50S inhibitors:
Chloramphenicol, Clindamycin
(bacteriostatic)
Erythromycin & other macrolides
(bacteriostatic)
Lincomycin (bacteriostatic)
Linezolid (variable)
6
Aminoglycosides:
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin bactericical.
Inhibits formation of initiation complex & cause misreading of mRNA. Require O2
for uptake cannot kill anaerobes Mean GNATS canNOT kill anaerobes
Used for severe gram neg rod infections. Synergistic with -lactam antibiotics.
Neomycin for bowel surgery.
Nephrotoxicity (especially when used with cephalosporins). Ototoxicity (especially
when used with loop diuretics). Terotogen.
Macrolides:
Erythromycin, Azithromycin, Clarithromycin bacteriostatic.
Inhibits protein synthesis by blocking translocation; bind to the 23 rRNA of the
50S ribosomal subunit.
Used for URIs, pneumonias, STDs gram positive cocci, Mycoplasma, Legionella,
Chlamydia, Neisseria.
Prolonged QT interval (especially erythromycin), GI discomfort (most common
cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes.
Increases serum concentration of theophyllines, oral anticoagulants.
7
7
Tetracyclines:
Tetracycline, doxycycline, democlocycline, minocycline.
Binds 30S & prevents attachment of aminoacyl-tRNA; limited CNS
penetration. Doxycycline is fecally eliminated & is safe in renal failure
patients. Must NOT take with milk, antacids, or iron-containing preparations
because divalent cations inhibit absorption in gut.
Used in Vibrio cholerae, Acne, Chlamydia, Ureaplasma Urealyticum,
Mycoplasma pneumoniae, Tularemia, H. pylori, Borrelia burdorferi (Lyme
disease) & Ricketssia.
Toxicity:
GI distress, dicoloration of teeth & inhibition of bone growth in children,
photosensitivity.
Contraindicated in pregnancy.
VACUUM The BedRoom.
8
Chloramphenicol:
Inhibits 50S
peptidlytransferase.
Used in meningitis (H.
influenzae, N. meningitidis, S.
pneumoniae).
Conservative owing to toxicities.
Toxicity:
Anemia (dose dependent), aplastic
anemia (dose dependent), gray
baby syndrome (in preemies due to
lack of liver UDP-glucuronyl
transferase)
Clindamycin:
Blocks peptide bond
formation at 50S subunit.
Treats anaerobes above the
diaphragm Bacteroides
fragilis, Clostridium
perfringens.
Toxicity:
Pseudomembranous colitis (C.
difficile overgrowth), fever,
diarrhea.
9
Sulfonamides:
Sulfamethoxazole (SMX),
sulfisoxazole, sulfadiazine.
PABA antimetabolites inhibit
dihydropteroate synthetase.
Used in gram positive, gram neg,
Nocardia, Chlamydia. Triple Sulfas
or SMX for simple UTI.
Toxicity:
Hypersensitive reactions, hemolysis if
G6PD deficiency, nephrotoxicity
(tubointerstitial nephritis),
photosensitivity, kernicterus, displace
other drugs from albumin (i.e.
warfarin)
Trimethoprim:
Inhibits bacterial dihydrofolate
reductase.
Used with sulfonamides (TMP-
SMX), causing sequential block of
folate synthesis.
Combination used for recurrent
UTIs, Shigella, Salmonella,
Pneumocystis jiroveci pneumonia.
TMP Treats Marrow Poorly
Toxicity:
Megaloblastic anemia,
leukopenia, granulocytopenia.
May alleviate with supplemental
folinic acid.
10
Fluoroquinolones:
Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin,
enoxacin & nalidic acid (a quinolone).
Used for gram neg rods of urinary and GI tracts (including Pseudomonas),
Neisseria, & some gram positive organisms.
Toxicity:
GI upset, superinfections, skin rashes, headache, dizziness. Contraindicated in
pregnancy & children damages cartilage. Tendonitis & tendon rupture in adults, leg
cramps & myalgia in kids.
Inhibit DNA gyrase
(topoisimerase II). Must not be
taken with antacids. Bactericidal.
FluoroquinoLONES hurt your BONES
Metronidazol:
Treats Giardia, Entamoeba, Trichomonas, Gardenella vaginalis, Anaerobes
(Bacteriodes, Clostridium). Used with bismuth & amoxicillin (or tetracycline) for
triple therapy of H. Pylori.
Toxicity:
Disulfiram-like reaction with alcohol; headache, metallic taste.
Forms toxic metabolites in bacterial cell that damage DNA.
Bactericidal & antiprotozoal.
GAP METRO
11
Polymixins:
Bind to cell membrane of bacteria & disrupt their osmotic properties. Polymyxins
are cationic, basic proteins that act like detergents.
Used for resistant gram negative infections.
Toxicity:
Neurotoxicity, acute renal tubular necrosis.
Polymyxin B, polymyxin E.
MYXins MIX up membranes.
Antimicrobial drugs:
Bacterium Prophylaxis Treatment
M. tuberculosis Isoniazid ifampin, soniazid, yrazinamide,
thambutol ( for treatment)
M. avium-intracellulare Azithromycin Azithromycin, rifampin, ethambutol,
streptomycin
M. leprae NA Dapsone, rifampin, clofazimine
12
Anti-TB drugs
INH-SPIRE (inspire):
Isoniazid (INH), Streptomycin, Pyrazinamide, Rifampin, Ethambutol.
Cycloserine (2
nd
line therapy)
Ethambutol optic neuropathy (red-green color blindness). For other drugs
hepatotoxicity.
Isoniazid (INH): Injures Neurons & Hepatocytes
Synthesis of mycolic acids.
Causes neurotoxicity & hepatotoxicity. Pyridoxine (Vit B
6
) prevents neurotoxicity.
Rifampin:
Inhibits DNA-dependent RNA polymerase.
Delays resistant to dapsone when used for leprosy. Used for meningococcal
prophylaxis & chemoprophylaxis in contacts of children with Haemophilus influenzae
type B.
Minor hepatotoxicity & drug interactions ( CYP450); orange body fluids
(nonhazardous side effect).
Rifampins 4 Rs:
RNA polymerase inhibitor
Revs up microsomal P-450
Red/Orange body fluids
Rapid resistance if used alone
13
Antifungal therapy:
14
Amphotericin B:
Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of
electrolytes.
Used for Cryptococcus, Blactomyces, Coccidioides, Aspergillus, Histoplasma,
Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not
cross BBB.
May cause fever/chills (shake & bake), hypotension, nephrotoxicity,
arrhythymias, anemia, IV phlebitis (amphoterrible). Hydration reduces
nephrotoxicity. Liposomal amphotericin reduces toxicity.
Nystatin:
Binds ergosterol disrupting fungal membranes. Too toxic for systemic use.
Swish and swallow for oral Candidiasis (thrush); topical for diaper rash or
vaginal candidiasis.
15
15
Azoles:
Inhibits fungal sterol (ergosterol) synthesis.
Used for systemic mycoses. Fluconazole for Cryptococcal meningitis in AIDS
(can cross BBB), & candidal infections of all types (i.e. yeast infections).
Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans;
hypercortisolisms. Clotrimoxazole & miconazole for topical fungal infections.
Toxicity causes hormone synthesis inhibition (gynecomastia), liver dysfunction
(inhibits CYP450), fever, chills.
Flucytosine:
Inhibits DNA synthesis by conversion to 5-fluorouracil.
Used in systemic fungal infections (candidiasis, cryptococcus) in combination with
amphotericin B.
Causes nausea, vomiting, diarrhea and bone marrow suppresion.
16
16
Terbinafine:
Inhibits fungal enzyme squalene epoxidase.
Used to treat dermatophytoses (especially onychomycosis).
Caspofungin:
Inhibits cell wall synthesis by inhibiting synthesis of -glucan.
Used to treat invasive aspergillosis.
Causes GI upset, flushing.
Griseofulvin:
Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing
tissues (nails).
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea,
ringworm).
Teratogenic, carcinogenic, confusion, headaches, CYP450 & warfarin metabolism.
17
17
Antiviral Chemotherapy:
18
Amantadine:
Blocks viral penetration/uncoating (M2 protein); may buffer pH of endosome. Also
causes the release of DA from intact nerve terminals.
Prophylaxis & treatment of Influenza A; Parkinsons disease.
Toxicity ataxia, dizziness, slurred speech.
Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, so
not used.
Amantadine blocks influenza A & rubellA & causes problems with the cerebellA.
Rimantidine is a derivative with fewer side effects. Does not cross BBB.
Zanamivir, oseltamivir:
Inhibits Influenza neuraminidase, decreasing the release of progeny virus.
Treatment of both Influenza A and B.
19
Acyclovir:
Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog.
Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA
polymerase by chain termination.
Used for HSV, VZV, EBV, HSV-induced mucocutaneous & genital lesions as well as
for encephalitis. Prophylaxis in immunocompromised patients. For herpes zoster,
use famciclovir. No effects on latent forms of HSV and VZV.
Generally well tolerated. Resistance develops when lack thymidine kinase.
Ribavirin:
Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP
dehydrogenase.
Used for RSV & chronic Hepatitis C.
Causes hemolytic anemia. Severe teratogen.
20
Ganciclovir:
5-monophosphate formed by a CMV viral kinase of HSV/VZV thymidine kinase.
Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits
viral DNA polymerase.
Used for CMV, especially in immunocompromised patients.
Toxicity leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to
host enzymes than acyclovir.
Resistance develops if mutated CMV DNA polymerase of lack viral kinase.
Foscarnet:
Viral DNA polymerase inhibitor that binds pyrophosphate-bindinig site of the
enzyme. Does not require activation by viral kinase.
Used for CMV retinitis in immunocompromised patients when Ganciclovir fails &
for acyclovir-resistant HSV.
Causes nephrotoxicity.
Resistance develops with mutated DNA polymerase.
21
HIV therapy:
Protease Inhibitors:
Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir.
Toxicity GI intolerance (nausea, diarrhea), hyperglycemia, lipodystrophy, thromocytopenia
(indinavir).
Reverse transcriptase inhibitors:
Nucleosides (Zidovudine [ZDV/AZT], didanosine [ddI], zalcitabine [ddC], stavudine [d4T],
lamivudine [3TC], abacavir): Have you dined (vudine) with my nuclear (nucleosides) family?
Non-nucleosides (Nevirapine, Efavirenz, Delavirdine): Never Ever Deliver nucleosides.
Toxicity: bone marrow suppression (neutropenia, anemia), peripheral neuropathy, lactic acidosis
(nucleosides), rash (non-nucleosides), megaloblastic anemia (ZDV), pancreatitis (ddI). GM-CSF &
erythropoietin can be used to reduce bone marrow suppression.
Part of HAART. Used when CD4 <500 cells/mm
3
or high viral load. ZDV as prophylaxis during
pregnancy to reduce fetal transmission.
Fusion inhibitors: ENFUVIRTIDE
Binds gp41, inhibits fusion with CD4 cells.
Toxicity: hypersensitivity reactions, reactions at SC injection site, risk bacterial pneumonia.
Used in persistent viral replication infections despite antiretroviral therapy and in combination
with other drugs.
22
22
Interferons:
Glycoproteins from human leukocytes that block various stages of viral RNA & DNA
synthesis. Induce ribonuclease that degrades viral mRNA.
IFN- chronic Hepatis B & C, and Kaposis sarcoma;
IFN- MS;
IFN- NADPH oxidase deficiency.
Toxicity: Neutropenia
Antibiotics to avoid in pregnancy:
Sulfonamides kernicterus
Aminoglycosides ototoxicity
Fluoroquinolones cartilage damage
Erythromycin acute cholestatic hepatitis in moms (and
clarithromycin embryotoxic)
Metronidazole mutagenesis
Tetracycline discolored teeth & inhibition of bone growth
Ribavirin teratogenic
Griseofulvin teratogenic
Chloramphenicol gray baby
SAFE Moms Take
Really Good Care
23
23