GB109-36 2 Maret 2005 22:45

36 ​D​IARRHEA,​CONSTIPATION, D​ AN
​ wel ​SY
AKU​RRITABLE ​BO ​ NDROME
William J. Spruill dan William E.
Wade

Tujuan Pembelajaran dan sumber daya lainnya dapat ditemukan di

www.pharmacotherapyonline.com.

KONSEP
UTAMA

4 Bismuth
​ subsalisilat dipasarkan untuk gangguan
1 Diare
​ disebabkan oleh banyak organisme virus dan
pencernaan, mengetahui kembali ​kram perut, dan
bakteri. ​Paling sering adalah ketidaknyamanan kecil, tidak
mengendalikan diare, termasuk diare​ pada pelancong,
mengancam jiwa, dan tetapi mengandung banyak komponen yang mungkin
biasanya terbatas. beracun jika diberikan secara berlebihan.

2 Empat mekanisme patofisiologis diare telah ​dikaitkan

​ 5 Penyebab
​ sembelit yang mendasari harus diidentifikasi

dengan empat kelompok diare luas, yaitu sekretori,

​ bila memungkinkan dan tindakan korektif diambil (misalnya,
osmotik, eksudatif, dan perubahan transit usus. Tiga
mekanisme dimana penyerapan terjadi dari usus adalah perubahan
transpor aktif, difusi, dan hambatan pelarut. pola makan atau pengobatan penyakit seperti
hipotiroidisme).

3 Penatalaksanaan
​ diare berfokus pada
6 Dasar
​ ​
perawatan sembelit adalah serat makanan atau
pencegahanberlebihan ​kehilangan air dan elektrolit yang,
pencahar pembentuk massal yang menyediakan 10 hingga
perawatan makanan, menghilangkan gejala,
​ mengobati
penyebab yang dapat disembuhkan, dan mengobati 15 g / harimentah
gangguan sekunder. sera
 t.
7 ​Irritable bowel syndrome adalah salah satugas-paling
umum ​gangguanusus yang, dan ditandai denganlebih
rendah nyeri
​ perut yang, buang air besar yang terganggu,
dan kembung. Banyak manifestasi nongastrointestinal juga
ada dengan IBS. Studi terbaru telah menemukan bahwa
hipersensitivitas visceral adalah penyebab utama dalam
patofisiologi penyakit.
8 IBS
​ yang dominan diare harus dikelola dengandiet
modifikasidan obat-obatan seperti loperamide ketikadiet
perubahansaja tidak cukup untuk mengendalikan
gejala.
9 Beberapa
​ kelas obat yang terlibat dalam pengobatan
rasa sakit ​yangterkait dengan IBS, termasuk senyawa
trisiklik dan
usus-selektif calcium channel
blockers.
DIARE
Diare adalah ketidaknyamanan yang menyusahkan yang
memengaruhi sebagian besar orang di Amerika Serikat pada titik
tertentu dalam kehidupan mereka. Biasanya episode diare mulai
tiba-tiba dan mereda dalam 1 atau 2 hari tanpa pengobatan. Bab ini
berfokus terutama pada diare tidak menular, dengan hanya rujukan
minor pada diare infeksius (lihat Bab 111 tentang infeksi gas-usus).
Diare sering merupakan gejala penyakit sistemik dan tidak semua
kemungkinan penyebab diare dibahas dalam bab ini.
Untuk memahami diare, seseorang harus memiliki episode ​
definisi kondisi yang wajar; Sayangnya, literatur sangat bervariasi
dalam hal ini. Sederhananya, diare adalah peningkatan frekuensi
dan penurunan konsistensi pembuangan feses dibandingkan dengan
pola buang air besar normal seseorang. Frekuensi dan konsistensi
adalah variabel di dalam dan di antara individu. Misalnya, beberapa
orang buang air besar sesering tiga kali sehari, sedangkan yang lain
hanya buang air besar dua atau tiga kali per minggu. Diet Barat
biasanya menghasilkan tinja harian dengan berat antara 100 dan
300 g, tergantung pada jumlah bahan yang tidak dapat diserap
(terutama karbohidrat) yang dikonsumsi. Pasien dengan diare serius
dapat memiliki berat tinja harian lebih dari 300 g; Namun,
sebagian pasien sering mengalami saluran yang kecil dan berair.
Selain itu, diet kaya serat nabati, seperti yang dikonsumsi di
beberapa budaya Timur seperti di Afrika, menghasilkan tinja
dengan berat lebih dari 300 g / hari.
Diare dapat dikaitkan dengan penyakit spesifik pada testis
atau sekunder dari penyakit di luar usus. Misalnya, disentri basiler
secara langsung memengaruhi usus, sedangkan diabetes mellitus
menyebabkan episode diare neuropatik. Selain itu, diare dapat
dianggap sebagai penyakit akut atau kronis. Diare infeksius sering
akut; diare diabetes kronis. Apakah akut atau kronis, diare memiliki
penyebab patofisiologis yang sama yang membantu identifikasi
perawatan tertentu.
EPIDEMIOLOGI
Epidemiologi diare bervariasi di negara maju dan negara
berkembang.​1​-​3 ​Di Amerika Serikat, penyakit diare biasanya tidak
dilaporkan ke Centers for Disease Control and Prevention (CDC)
yang tidak terkait dengan wabah atau organisme atau kondisi yang
tidak biasa. Misalnya, sindrom defisiensi imun yang didapat
(AIDS) telah diidentifikasi dengan penyakit diare yang
berkepanjangan. Diare adalah masalah utama
aret 2005 22:45
78 ​BAGIAN 4 GANGGUAN GASTROINTESTINAL
pusat penitipan anak dan panti jompo, mungkin karena anak usia
ni dan penuaan ditambah kondisi lingkungan merupakan faktor
siko. Namun, profil epidemiologi yang tepat di Amerika Serikat
dak tersedia melalui CDC atau literatur yang diterbitkan.
Organisme virus dan bakteri menyebabkan sebagian besar
1​
diare tidak menular. Organisme bakteri penyebab umum
termasuk ​Shigella, Salmonella, Campylobacter, Staphylococcus,
dan ​Escherichia coli. ​Infeksi bakteri yang ditularkan melalui
makanan adalah masalah utama, karena beberapa episode
keracunan makanan utama telah terjadi yang dilacak pada kondisi
anitasi yang buruk di pabrik pengolahan daging. Infeksi virus akut
sebagian besar disebabkan oleh kelompok Norwalk dan rotavirus.
Di negara-negara berkembang, diare adalah penyebab utama
penyakit dan kematian pada anak-anak.​4 ​Selain itu, diare
menghasilkan beban ekonomi karena biaya yang terkait dengan
awat inap dan kehilangan produktivitas. Sekitar 1,3 miliar episode
terjadi setiap tahun dan 4 juta kematian akibat diare di
negara-negara ini. Faktor-faktor yang terkait dengan temuan ini
termasuk sanitasi yang buruk, gizi buruk, dan usia kurang dari 5
tahun. Anak-anak di negara-negara terbelakang mengalami rata-rata
tiga episode diare setiap tahun (misalnya, 2,7 episode diare / orang /
tahun di Amerika Latin) dibandingkan dengan 1 episode / orang /
tahun di Amerika Serikat dan Eropa Barat.
FISIOLOGI
Dalam keadaan puasa, 9 L cairan memasuki usus kecil proksimal
setiap hari. Dari cairan ini, 2 L dicerna melalui diet, sedangkan
sisanya terdiri dari sekresi internal. Karena kandungan makanan,
chyme duodenal biasanya hipertonik. Ketika chyme mencapai
ileum, osality menyesuaikan dengan plasma, dengan sebagian besar
lemak makanan, karbohidrat, dan protein diserap. Volume chyme
ileum berkurang sekitar 1 L / hari setelah memasuki usus besar,
yang selanjutnya dikurangi dengan penyerapan kolon hingga 100
mL setiap hari. Jika kapasitas penyerapan air usus kecil terlampaui,
chyme membebani usus besar, menyebabkan diare. Pada manusia,
daya serap usus sekitar 5 L setiap hari. Transpor cairan kolon
sangat penting untuk keseimbangan air dan elektrolit.
Penyerapan dari usus kembali ke dalam darah terjadi
oleh tiga mekanisme: transportasi aktif, difusi, dan hambatan
pelarut. Transpor aktif dan difusi adalah mekanisme transpor
natrium. Karena konsentrasi natrium luminal tinggi (142 mEq / L),
natrium berdifusi dari usus kaya natrium ke dalam sel epitel, di
mana ia dipompa secara aktif ke dalam darah dan ditukar dengan
klorida untuk mempertahankan kondisi isoelektrik melintasi epitel.
selaput.
Ion hidrogen diangkut oleh mekanisme tidak langsung
di usus kecil bagian atas. Saat natrium diserap, ion hidrogen
disekresikan ke dalam usus. Ion hidrogen kemudian bergabung
dengan ion bikarbonat untuk membentuk asam karbonat, yang
kemudian berdisosiasi menjadi karbon dioksida dan air. Karbon
dioksida mudah berdifusi ke dalam darah untuk kedaluwarsa
melalui paru-paru. Air tetap berada di chyme.
Jalur paracellular adalah rute utama pergerakan ion.
Saat ion, monosakarida, dan asam amino diangkut secara aktif,
tekanan osmotik tercipta, menarik air dan elektrolit melintasi
dinding usus. Jalur ini menyumbang sejumlah besar transportasi
ion, terutama natrium. Sodium memainkan peran penting dalam
merangsang penyerapan glukosa. Glukosa dan asam amino secara
aktif diangkut ke dalam darah melalui mekanisme transpor
bergantung natrium. Mekanisme penyerapan transpor
glukosa-natrium dan asam amino-natrium sangat penting untuk
mengobati diare.
Motilitas usus mempengaruhi absorpsi dan sekresi.
Jumlah waktu di mana konten luminal bersentuhan dengan epitel
berada di bawah kendali saraf dan hormon. Zat neurohormonal,
seperti angiotensin, vasopresin, glukokortikoid, dan aldosteron, dan
neurotransmiter juga mengatur transpor ion.
PATOFISIOLOGI
Empat mekanisme patofisiologis umum menggangguair dan
2​
keseimbanganelektrolit, menyebabkan diare, dan merupakan dasar
diagnosis dan terapi. Ini adalah (a) perubahan transpor ion aktif baik
dengan penurunan penyerapan natrium atau peningkatan sekresi
klorida; (B) perubahan motilitas usus; (c) peningkatan osmolaritas
luminal; dan (d) peningkatan tekanan hidrostatik jaringan.
Mekanisme ini telah dikaitkan dengan empat kelompok diare klinis
yang luas: sekretori, osmotik, eksudatif, dan perubahan transit usus.
Diare sekretori terjadi ketika suatu zat perangsang
meningkatkan sekresi atau mengurangi penyerapan sejumlah besar
air dan elektrolit. Zat yang menyebabkan sekresi berlebih termasuk
vasoaktif intestinal peptide (VIP) dari tumor pankreas, lemak
makanan yang tidak diserap di steatorrhea, pencahar, hormon
(seperti sekretin), racun bakteri, dan garam empedu yang
berlebihan. Banyak dari agen-agen ini merangsang adenosine
monophosphate siklik intraseluler dan menghambat Na​+​/
+​
K​ -ATPase, yang menyebabkan peningkatan sekresi. Juga, banyak
dari mediator ini menghambat penyerapan ion secara bersamaan.
Secara klinis, diare sekretori dikenali oleh volume feses yang besar
(​>​1 L / hari) dengan kandungan ion dan osmolalitas normal yang
kira-kira sama dengan plasma. Puasa tidak mengubah volume tinja
pada pasien ini.
Zat yang diserap dengan buruk mempertahankan cairan
usus, menyebabkan diare osmotik. Proses ini terjadi dengan
sindrom malabsorpsi, intoleransi laktosa, pemberian ion divalen
(misalnya, antasida yang mengandung magnesium), atau konsumsi
karbohidrat yang tidak larut dengan baik (misalnya, laktulosa).
Karena zat terlarut yang kurang larut diangkut, usus menyesuaikan
osmolalitas dengan plasma; dalam melakukan hal itu, air dan fluks
elektrolit masuk ke dalam lumen. Secara klinis, diare osmotik dapat
dibedakan dari jenis lain, karena berhenti jika pasien beralih ke
keadaan puasa.
Penyakit radang saluran pencernaan mengeluarkan lendir,
protein serum, dan darah ke dalam usus. Kadang-kadang buang air
besar hanya terdiri dari lendir, eksudat, dan darah. Diare eksudatif
mungkin mempengaruhi fungsi serap, sekretori, atau motilitas
lainnya untuk menjelaskan volume feses yang besar yang terkait
dengan gangguan ini.
Perubahan motilitas usus menghasilkan diare oleh tiga
mekanisme: pengurangan waktu kontak di usus kecil, pengosongan
prematur usus besar, dan pertumbuhan bakteri yang berlebihan.
Chyme harus dipaparkan ke epitel usus untuk periode waktu yang
cukup untuk memungkinkan proses penyerapan dan sekresi yang
normal terjadi. Jika waktu kontak ini berkurang, hasil diare. Reseksi
usus atau operasi bypass dan obat-obatan (seperti metoclopramide)
menyebabkan diare jenis ini. Di sisi lain, peningkatan waktu
pemaparan memungkinkan pertumbuhan berlebih bakteri tinja. Pola
diare usus kecil yang khas adalah gelombang yang cepat, kecil, dan
berpasangan. Gelombang ini tidak efisien, tidak memungkinkan
penyerapan, dan dengan cepat membuang chyme ke dalam usus
besar. Begitu berada di usus besar, chyme melebihi kemampuan
kolon untuk menyerap air.

PEMERIKSAAN ETIOLOGI DARI STOOL
Karakteristik feses penting dalam menilai etiologi diare. Deskripsi
frekuensi, volume, konsistensi, dan warna memberikan petunjuk
diagnostik. Misalnya, diare yang dimulai di usus kecil
menghasilkan feses yang banyak, encer atau berlemak (berminyak),
dan berbau busuk; mengandung partikel makanan yang tidak
tercerna; dan biasanya bebas dari darah kotor. Diare kolon muncul
sebagai gerakan kecil, pucat, dan terkadang berdarah atau berlendir.
Tenesmus rektal dengan flatus menyertai diare usus besar.
GB109-36 2 Maret 2005 22:45
BAB 36 DIARRHEA, KONSTIPASI, DAN SISTEM BOWEL YANG TIDAK DIRITRIT ​679
TABEL 36-1. ​Presentasi Klinis Diare
TABEL 36-2. ​Obat-obatan yang
Menyebabkan Diare
Umum ​r ​Biasanya, episode diare akut mereda dalam 72 jam setelah
onset,
sedangkan diare kronis sering melibatkan serangan selama periode
waktu yang lama. ​Tanda ​r dan gejala ​timbulnya mendadak mual,
​
muntah, sakit perut, sakit kepala, demam, ​r, menggigil
​ dan malaise.
Buang air besar yang sering dan tidak pernah berdarah, dan diare
jam. ​Intermiten periumbilikalis atau lebih rendah
berlangsung ​r 12-60
​
nyeri kuadran kanan dengan kram
dan usus terdengar suara adalah karakteristik dariusus ​r
penyakitkecil. ​Ketika rasa sakit hadir dalam diare usus besar,
itu adalahmencekam,
sensasisakit dengan tenesmus (mengejan, tinja tidak efektif dan
menyakitkan). Nyeri melokalisasi ke daerah hipogastrik,kanan
bawah atau ​r kuadran,
​ atau daerah sakral. ​Pada diare kronis,
riwayat serangan sebelumnya, penurunan berat badan,
anoreksia, dan kelemahan kronis adalah temuan penting. ​fisik
r Pemeriksaan
​ ​Biasanya menunjukkan hyperperistalsis
dengan borborygmi dan
kelembutan umum atau lokal. ​Laboratorium r​ ​tes ​studi
analisisStool termasuk pemeriksaan untuk mikroorganisme, darah,
​
lendir, lemak, osmolalitas, pH, elektrolit dan mineral ​r konsentrasi,
​
dan budaya. ​Tes tinja kit yang berguna untuk mendeteksi virus
rotavirus. ​Pengujian serologis
gastrointestinal, ​r khususnya
​
antibodi menunjukkan peningkatan titer selama3 hingga 6 hari ​rr
periode, tetapi tes ini tidak praktis dan tidak spesifik.
Kadang-kadang, total volume tinja harian juga ditentukan.
Langsung visualisasi endoskopi dan biopsi dari usus besar dapat
dilakukan untuk menilai adanya kondisi seperti kolitis atau ​r.
kanker ​Studi radiografi sangat membantu dalamneoplastik dan
inflamasi
kondisi.
PRESENTASI KLINIS
Tabel 36-1 menguraikan presentasi klinis diare sementara Tabel
36-2 menunjukkan penyebab diare yang diinduksi oleh obat. Obat
pencahar Antasida yang
mengandung magnesium
Antineoplastik Auranofin
(garam emas) Antibiotik
Klindamisin Tetrasiklin
Sulfonamida Antibiotik
spektrum luas Antihipertensi
Reserpine
Guanethidine
Methyldopa
Guanabenz
Cholinergik
Bethanechol Neostigmine Agen
kardiak Quinidineobat-obatan.
sangat penting dalamdiare yang diinduksi. Banyak agen, termasuk
antibiotik dan obat-obatan lain, menyebabkan diare, atau lebih
jarang, kolitis pseudomembran. Penyalahgunaan pencahar yang
dilakukan sendiri untuk menurunkan berat badan sangat populer.
Perilaku neurotik atau psikotik menyebabkan penyalahgunaan
pencahar. Efek samping obat (misalnya, efek samping quinidine)
sering muncul sebagai diare.
Sebagian besar diare akut sembuh sendiri, mereda dalam 72
jam. Namun, bayi, anak-anak kecil, orang tua, dan orang-orang
yang lemah memiliki risiko untuk kejadian yang tidak wajar dan
mematikan dalam diare yang berkepanjangan atau banyak.
Kelompok-kelompok ini berisiko mengalami gangguan air,
elektrolit, dan asam-basa, dan berpotensi kolaps dan kematian
kardiovaskular. Prognosis untuk diare kronis tergantung pada
penyebabnya; misalnya, diare akibat diabetes mellitus dan
 berkurang sepanjang hidup. tujuanadalah untuk (a) mengelola diet; (b)
mencegahair,berlebihan
gangguanlistrik, dan asam-basa yang; (C) memberikan bantuan
►​PENGOBATAN: gejala; (d) mengobati penyebab yang dapat disembuhkan; dan (e)
mengelola gangguan sekunder yang menyebabkan diare (Gambar
Diare
36-1 dan 36-2).
Dokter harus memahami dengan jelas bahwa diare, seperti
■
batuk, dapat menjadi mekanisme pertahanan tubuh untuk
PENCEGAHA
menghilangkan zat atau patogen yang berbahaya. Respons
N terapeutik yang benar tidak harus menghentikan diare dengan
segala cara.

Penyakit diare virus akut sering terjadi di pusat penitipan anak dan
rumah perawatan. Karena kontak orang-ke-orang adalah
mekanisme penyebaran penyakit virus, teknik isolasi harus dimulai.
Untuk infeksi bakteri, parasit, dan protozoa, penanganan makanan
yang ketat, sanitasi, air, dan praktik kebersihan lingkungan lainnya
dapat mencegah transmisi. Jika diare adalah sekunder dari penyakit
lain, mengendalikan kondisi primer diperlukan. Antibiotik dan
bismuth subsalisilat dianjurkan untuk mencegah diare, bersamaan
dengan pengobatan air minum dan kehati-hatian dengan konsumsi
sayuran segar.
■ ​HASIL YANG
DIINGINKAN
■ ​MANAJEMEN NONFARMAKOLOGI
Manajemen
diet adalah prioritas pertama dalam pengobatan diare. Kebanyakan
dokter merekomendasikan untuk menghentikan konsumsi makanan
padat dan produk susu selama 24 jam. Namun, puasa adalah nilai
yang patut dipertanyakan, karena modalitas perawatan ini belum
secara luas dihentikan. Pada diare osmotik, manuver ini
mengendalikan masalah. Jika mekanismenya keluar, diare tetap
ada. Untuk pasien yang mengalami

Jika pencegahan tidak berhasil dan diare terjadi,terapeutik

3​
GB109-36 2 Maret 2005 22:45
680 ​BAGIAN 4 GANGGUAN GASTROINTESTINAL
Diare
Riwayat dan pemeriksaan fisik
Diare akut Diare
kronik
GAMBAR 36-1. ​Rekomendasi untuk mengobatiakut
(<3 hari)
(> 14 hari)
diare. Ikuti langkah-langkah ini: (1) Lakukan riwayat lengkap dan pemeriksaan fisik. (2) Apakah diarenya akut atau kronis? Jika diare
kronis, lihat Gambar 36-2.
Tidak ada demam atau gejala sistemik
. Gbr. 36-2
(3) Jika diare akut, periksa adanya demam dan / atau tanda dan gejala sistemik (yaitu, pasien toksik). Jika penyakit sistemik
(demam, anoreksia, atau penurunan volume), periksa untuk memeriksa
tinja untuk WBC / RBC / ova dan parasit ​merupakan sumber infeksi. Jika positif untuk diare infeksius, gunakan obat antibiotik /
anthelmintik yang tepat dan terapi simtomatik. Jika negatif untuk penyebab infeksi, gunakan
Negatif Positif ​hanya pengobatan simtomatik. (4) Jika tidak ada temuan sistemik, maka gunakan terapi simtomatik berdasarkan
keparahan vol-.
Terapi simtomatik.

Gunakanantibiotik yang tepat ​penipisan ume, cairan oral atau parenteral / elektrolit, ​terapi simtomatik dan ​agen tidiarrheal (lihat Tabel
36-4), dan diet .
Berlangsung> 14 hari
Diagnosis
a. Obati penyebab spesifik
Demam atau gejala sistemik
Terapi simtomatik a. Penggantian cairan / elektrolit b. Loperamide,
 diphenoxylate, atau absorbent c. Diet
mual dan / atau muntah, diet rendah residu yang ringan dan mudah dicerna harus diberikan selama 24 jam. Jika muntah hadir dan
diare kronis kronis
dengan antiemetik (lihat Bab 35 tentang mual dan muntah), tidak ada yang diminum. Saat buang air besar berkurang, diet hambar
dimulai. Pemberian makan harus dilanjutkan pada anak-anak dengan diare bakteri akut. Anak-anak yang diberi makan memiliki
lebih sedikit morbiditas dan mortalitas, terlepas apakah mereka menerima cairan rehidrasi oral atau tidak. Studi tidak tersedia di
lansia atau dalam kelompok berisiko tinggi lainnya untuk menentukan nilai pemberian makanan berkelanjutan pada diare bakteri.
■ ​AIR DAN
ELEKTROLIT Rehidrasi dan pemeliharaan air dan elektrolit adalah tujuan perawatan utama sampai episode diare berakhir. Jika
volume pasien habis, rehidrasi harus diarahkan untuk mengganti air dan elektrolit ke komposisi tubuh normal. Kemudian
komposisi air dan elektrolit dipertahankan dengan mengganti kehilangan. Banyak pasien tidak akan mengalami penurunan
volume dan oleh karena itu hanya akan memerlukan cairan perawatan dan terapi elektrolit. Parenteral dan enteral
Tidak ada diagnosis,
rute dapat digunakan untuk memasok air dan elektrolit. Jika muntah ​terapi simtomatik
dan dehidrasi tidak parah, pemberian makan enteral adalah metode yang lebih murah dan disukai. Di Amerika Serikat, banyak
persiapan rehalasi oral komersial tersedia (Tabel 36-3).
Karena kekhawatiran tentang hipernatremia, dokter terus dirawat di rumah sakit dan memperbaiki defisit cairan dan elektrolit
secara intravena pada dehidrasi parah. Solusi oral sangat dianjurkan.​5​,​6 ​Di negara-negara berkembang, Solusi Reformasi Mulut
Organisasi Kesehatan Dunia (WHO-ORS) menyelamatkan kehidupan jutaan anak setiap tahun.
Selama diare, usus kecil mempertahankan kemampuannya untuk secara aktif mengangkut monosakarida seperti glukosa. Glukosa
secara aktif membawa natrium dengan air dan elektrolit lainnya. Karena WHO-ORS memiliki konsentrasi natrium yang tinggi,
dokter AS enggan menggunakannya pada anak-anak yang bergizi baik. Namun studi komparatif terkontrol menggambarkan hasil
yang lebih baik dengan WHO-ORS daripada dengan cairan parenteral.​7 ​Asam amino meningkatkan transportasi natrium dan
bertindak sebagai ​penyebab yang mungkin:
a. Infeksi usus b. Penyakit radang usus
c. Malabsorpsi d.hormon sekretoris
Tumore. Narkoba, tiruan f. Gangguan motilitas
Pilih studi diagnostik yang tepat Misalnya, a. Biakan tinja / ovum /
parasit / WBC / RBC / lemak b. Sigmoidoskopi c. Biopsi usus
a. Hidrasi penuh b. Menghentikanberpotensi menyebabkan
obat yangc. Sesuaikan diet d. Loperamide atau
absorben
GAMBAR 36–2. ​Rekomendasi untuk mengobati diare kronis. Ikuti langkah-langkah ini: (1) Lakukan anamnesis dan pemeriksaan
fisik yang cermat. (2) Banyak kemungkinan penyebab diare kronis. Ini dapat diklasifikasikan ke dalam infeksi usus (bakteri atau
protozoa), penyakit radang (penyakit Crohn atau kolitis ulserativa), malabsorpsi (intoleransi laktosa), tumor hormon sekretorik (tumor
karsinoid usus atau VIPoma), obat (antasid), tiruan (pencahar), faktual (pencahar) penyalahgunaan), atau gangguan gerak (diabetes
mellitus, sindrom iritasi usus, atau hipertiroidisme). (3) Jika diagnosisnya tidak pasti, beberapa studi diagnostik yang sesuai harus
dipesan. (4) Setelah didiagnosis, pengobatan direncanakan untuk penyebab yang mendasari dengan terapi antidiare simtomatik. (5)
Jika tidak ada penyebab spesifik yang dapat diidentifikasi, terapi simtomatik ditentukan.
Sejarah dan pemeriksaan fisik

GB109-36 2 Maret 2005 22:45

BAB 36 DIARRHEA, KONSTIPASI, DAN SINDROMI BOWEL IRRITABEL ​681

TABEL 36–3. ​Solusi Rehidrasi Lisan

a​ b​ b​ b​
WHO-ORS​ Pedialyte​ (Ross) Rehydralyte​ (Ross) Infalyte (Mead Johnson) Resolusi​ (Wyeth)

b​ c​
Osmolalitas (mOsm / L) 333 249 304 200 269 Karbohidrat​ (g / L) 20 25 25 30​ 20 Kalori (kal / L) 85 100 100 126 80 Elektrolit (mEq / L)
Sodium 90 45 75 50 50 Kalium 20 20 20 25 20 Klorida 80 35 65 45 50 Sitrat - 30 30 34 34 Bikarbonat 30 - - - - Kalsium - - - - 4
Magnesium - - - - 4 Sulfat - - - - - Fosfat - - - - 5
Organisasi​
Kesehatan Dunia Rehidrasi Oral Solution.
b​ ​
Karbohidrat adalah glukosa. c​ Padatan sirup beras
adalah sumber karbohidrat.
5 mL (keduanya adalahdiresepkan
agen antisekresi. Para peneliti telah menambahkan glisin ke dalam
ORS dalam upaya untuk menciptakan "super-ORS." Laporan,
bagaimanapun, mengecewakan, karena glisin menyebabkan diare
osmotik dan diuresis dalam konsentrasi eksperimental.
Larutan oral berbasis beras adalah substrat aktif
hiposmotik yang mengelusi glukosa tanpa meningkatkan tinja atau
keluarnya urin. Pizarro dkk.​7 ​melaporkan rehidrasi efektif bayi
dengan diare akut menggunakan larutan berbasis beras. Mereka
juga melaporkan penurunan produksi tinja dan penyerapan serta
retensi cairan dan elektrit yang lebih besar. Singkatnya, solusi
rehidrasi oral adalah pengobatan yang menyelamatkan nyawa bagi
jutaan orang yang menderita di negara berkembang. Penerimaan di
negara maju kurang antusias; Namun, keuntungan dari produk ini
dalam mengurangi rawat inap dapat membuktikan penggunaannya
sebagai alternatif yang hemat biaya, menghemat jutaan dolar dalam
pengeluaran perawatan kesehatan.
■ ​TERAPI FARMAKOLOGI
Berbagai obat telah digunakan untuk mengobati serangan diare
(Tabel 36-4). Obat-obat ini dikelompokkan ke dalam beberapa
kategori: antimotilitas, adsorben, senyawa antisekresi, antibiotik,
enzim, dan mikroflora usus. Biasanya obat ini tidak bersifat kuratif
tetapi paliatif.
■ ​OPIAT DAN DERIVATIF
MEREKA
Optiat dan turunan opioid (a) menunda transit konten intraluminal
atau (b) meningkatkan kapasitas usus, memperpanjang kontak dan
penyerapan. Enkephalins, zat opioid endogen, mengatur pergerakan
cairan melintasi mukosa dengan merangsang proses penyerapan.
Keterbatasan penggunaan opiat mencakup potensi kecanduan
(kekhawatiran nyata dengan penggunaan jangka panjang) dan
memburuknya diare pada diare infeksi tertentu.
Sebagian besar opiat bertindak melalui mekanisme perifer
dan sentral dengan pengecualian loperamide, yang hanya bertindak
perifer. Loperamide bersifat antisekresi; itu menghambat
protein-ikatan kalmodulin, mengendalikan sekresi klorida.
Loperamide, tersedia dalam bentuk kapsul 2-mg atau larutan 1 mg /
GB109-36 2 Maret 2005 22:45
682 ​BAGIAN 4 GANGGUAN
produk yang tidak), disarankan untuk menangani diare akut dan
kronis. Dosis dewasa biasanya pada awalnya 4 mg per oral, diikuti
oleh 2 mg setelah setiap tinja, hingga 16 mg / hari. Digunakan
dengan benar, agen ini memiliki efek samping yang jarang seperti
pusing dan sembelit. Jika diare itu bersamaan dengan demam tinggi
atau feses berdarah, pasien harus dirujuk ke dokter. Selain itu, diare
yang berlangsung selama 48 jam setelah memulai pemberian lop
eramide memerlukan perhatian medis. Loperamide juga dapat
digunakan untuk diare pada pelancong. Ini sebanding dengan
bismuth subsalisilat untuk pengobatan gangguan ini.​8
Diphenoxylate tersedia dalam bentuk tablet 2,5 mg dan
sebagai larutan 2,5 mg / 5 mL. Sejumlah kecil atropin (0,025 mg)
dimasukkan untuk mencegah penyalahgunaan. Pada orang dewasa,
ketika diminum 2,5 sampai 5 mg tiga atau empat kali sehari, tidak
melebihi dosis total 20 mg setiap hari, difenoksilat jarang bersifat
toksik. Beberapa pasien mungkin mengeluh atropinisme
(penglihatan kabur, mulut kering, dan keraguan berkemih). Seperti
loperamide, itu tidak boleh digunakan pada pasien yang berisiko
enteritis bakteri dengan ​Escherichia coli, Shigella, a​ tau ​Salmonella.
Difenoksin, turunan difenoksilat, juga dikombinasikan
dengan atropin dan memiliki kegunaan yang sama, tindakan
pencegahan, dan efek samping. Dipasarkan sebagai tablet 1-mg,
dosis dewasa adalah 2 mg pada awalnya diikuti oleh 1 mg setelah
setiap tinja yang longgar, tidak melebihi 8 mg / hari.
Paregoric, tingtur opium, dipasarkan sebagai larutan 2 mg / 5
mL dan diindikasikan untuk menangani diare akut dan kronis. Ini
tidak banyak ditentukan hari ini karena potensi penyalahgunaannya.
■ ​ADSORBEN
Adsorben digunakan untuk menghilangkan gejala. Produk-produk
ini, banyak yang tidak memerlukan resep, tidak beracun, tetapi
efektivitasnya tetap tidak terbukti. Adsorben tidak spesifik dalam
aksi mereka; mereka menyerap nutrisi, racun, obat-obatan, dan jus
pencernaan. Pemberian bersama dengan obat lain mengurangi
ketersediaan hayati. Panel review over-the-counter Administrasi
Makanan dan Obat merekomendasikan polycarbonophil hanya
sebagai adsorben yang efektif.
Polycarbophil menyerap 60 kali beratnya dalam air dan dapat
digunakan untuk mengobati diare dan sembelit. Ini adalah produk
non-resep dan dijual sebagai tablet kunyah 500 mg. Produk
hidrofilik yang tidak terserap ini aman dan dapat dikonsumsi empat
kali sehari, hingga 6 g / hari pada orang dewasa.
 GASTROINTESTINAL TABEL 36-4. ​Sediaan Antidiare yang Dipilih
Bentuk DosisDosis Dewasa
Antimotilitas
Dipenoksilat 2,5 mg / tablet 5 mg empat kali sehari; jangan melebihi 20 mg / hari
2,5 mg / 5 mL Loperamide 2 mg / kapsul Awalnya 4 mg, kemudian 2 mg setelah masing-masinglonggar
tinja; jangan melebihi 16 mg / hari 1 mg / 5 mL Paregoric 2 mg / 5 mL (morfin) 5-10 mL 1–4 kali sehari Opium tingtur 5 mg / mL
(morfin) 0,6 mL empat kali sehari Difenoxin 1 mg / tablet Dua tablet, lalu satu tablet setelah setiap
tinja; hingga 8 tablet / hari ​Adsorben
campuran Kaolin-pektin 5,7 g kaolin + 130,2 mg pektin / 30 mL 30-120 mL setelah masing-masing tinja longgar Polycarbophil 500
mg / tablet Kunyah 2 tablet empat kali sehari atau setelah setiap
tinja longgar; jangan melebihi 12 tablet / hari Attapulgite 750 mg / 15 mL 1200-1500 mg setelah setiap buang air besar
300 mg / 7,5 mL
gerakan atau setiap 2 jam; hingga 9000 750 mg / tablet
mg / hari 600 mg / tablet 300 mg / tablet ​Antisecretory
Bismuth subsalicylate 1050 mg / 30 mL Dua tablet atau 30 mL setiap 30 menit hingga 1 jam sebagai
262 mg / 15 mL dibutuhkan hingga 8 dosis / hari 524 mg / 15 mL 262 mg / tablet Enzim (laktase) 1250 unit laktase netral / 4 tetes
3–4 tetes diambil dengan susu atau produk susu
3300 FCC unit laktase per tablet 1 atau 2 tablet seperti di atas Penggantian bakteri (​Lactobacillus acidophilus, Lactobacillus
bulgaricus​)
2 tablet atau 1 paket granul 3 hingga 4 kali sehari; berikan dengan susu, jus, atau air ​Octreotide ​0,05 mg / mL Awal: 50 mcg secara
subkutan
0,1 mg / mL 1-2 kali per hari dan dosis titrasi berdasarkan0,5 mg / mL
indikasihingga 600 mcg / hari dalam 2-4 dosis terbagi
■ ​AGEN ANTISECRETORY Subalicylateantisekresi
bismuth tampaknya memiliki efek, antiinflamasi, dan antibakteri. Sebagai produk yang tidak diresepkan, produk ini digunakan
untuk gangguan pencernaan, meredakan kram perut, dan mengendalikan diare, termasuk diare. Kekuatan dosis subsalisilat bismut
adalah tablet kunyah 262 mg, 262 mg / 5 mL cairan, dan 524 mg / 15 mL cair. Dosis dewasa yang biasa adalah 2 tablet atau 30
mL setiap 30 menit hingga 1 jam hingga 8 dosis per hari.
Bismuth subsalisilat mengandung banyak komponen yang mungkin ​
4​ beracun jika diberikan secara berlebihan untuk mencegah
atau mengobati diare. Misalnya, bahan aktif adalah salisilat, yang dapat berinteraksi dengan antikoagulan atau dapat menghasilkan
salisilisme (tinitus, mual, dan muntah). Bismuth mengurangi penyerapan tetrasiklin dan dapat mengganggu studi radiografi
gastrointestinal tertentu. Pasien mungkin mengeluhkan lidah dan tinja menjadi gelap dengan pemberian berulang. Salisilat dapat
menyebabkan serangan gout pada individu yang rentan.
Suspensi bismut subsalisilat telah dievaluasi dalam pengobatan diare sekretori etiologi infeksius. Dalam dosis 30 mL setiap 30
menit selama delapan dosis, tinja yang tidak berbentuk berkurang dalam 24 jam pertama. Bismuth subsalisilat juga efektif untuk
mencegah diare pada pelancong.
Octreotide, analog octapeptide sintetik dari satiostatin endogen, diresepkan untuk pengobatan simtomatik tumor karsinoid dan
tumor yang mensekresi peptida intestinal vasoaktif (VIPomas).​9 ​Tumor karsinoid usus metastatik mengeluarkanberlebihan
zat vasoaktif dalam jumlah, termasuk histamin, bradikinin, serotonin, dan prostaglandin. Tumor karsinoid primer terjadi di seluruh
saluran pencernaan, dengan sebagian besar di ileum. Tanda dan gejala dominan yang dialami oleh pasien dengan tumor ini
disebabkan oleh konsentrasi 5-hydroxytryptophan dan serotonin yang berlebihan. Totalitas efek klinis mereka disebut ​sindrom
​ erangan vasomotor paroksismal mencirikan sindrom karsinoid, terutama kemerahan mendadak pada wajah dan leher
karsinid. S
ungu. Serangan-serangan ini sering disebabkan oleh ledakan emosi atau oleh konsumsi makanan atau alkohol. Beberapa pasien
mengalami diare berair yang keras dengan kram perut. Awalnya, diare dapat ditangani dengan berbagai agen seperti kodein,
difenoksilat, siprohepadin, metisergida, fenoksibenzamin, atau metildopa. Baru-baru ini, octreotide telah menjadi obat pilihan.
Octreotide blocks the release of serotonin and many other active peptides and has been effective in controlling diarrhea and
flushing. It is reported to have direct inhibitory effects on intestinal secretion and stimulatory effects on intestinal absorption.
Non–gastrin-secreting adenomas of the pancreas are tumors associated with profuse watery diarrhea. This condition has been
referred to as Verner-Morrison syndrome, WDHA (watery diarrhea, hypokalemia, and achlorhy- dria) syndrome, pancreatic
cholera, watery diarrhea syndrome, and VIPoma. Excessive secretion of VIP from a retroperitoneal or pan- creatic tumor produces
most of the clinical features. Excessive VIP is isolated in about half of patients, along with numerous other peptide hormones
(peptide histidine methionine [PHM], serotonin,

GB109-36 March 2, 2005 22:45

 CHAPTER 36 DIARRHEA, CONSTIPATION, AND IRRITABLE BOWEL SYNDROME
683

Lactobacillus ​preparations replace colonic microflora. This suppos-

somatostatin, gastrin, and glucagon). Surgical tumor dissection is
edly restores normal intestinal function and suppresses the growth
the treatment of choice. In nonsurgical candidates, the profuse
of pathogenic microorganisms. However, a dairy product diet
watery diarrhea and other symptoms commonly encountered are
containing 200 to 400 g of lactose or dextrin is equally effective in
managed with octreotide.
producing recolonization of normal flora. The dosage varies
The dose of octreotide varies with the indication, disease depending on the brand used and lactobacillus preparations should
sever- ity, and patient response.​9 ​For managing diarrhea and be administered with milk, juice, water, or cereal. Intestinal flatus is
flushing as- sociated with carcinoid tumors in adults, the initial the primary patient complaint experienced with this modality.
dosage range is 100 to 600 mcg/day in two to four divided doses
Anticholinergic drugs such as atropine block vagal tone
subcutaneously for 2 weeks. For controlling secretory diarrhea of
and prolong gut transit time. Drugs with anticholinergic properties
VIPomas, the dosage range is 200 to 300 mcg/day in two to four
are present in many nonprescription products. Their value in
divided doses for 2 weeks. Some patients may require higher doses
controlling diarrhea is questionable and limited due to side effects.
for symptomatic control. Patients responding to these initial doses
To stop di- arrhea, clinicians have been falsely taught to dose
may be switched to Sando- statin LAR Depot, a long-acting
anticholinergics until they decrease salivary and sweat secretion.
octreotide formulation. This product consists of microspheres
Angle-closure glau- coma, selected heart diseases, and obstructive
containing the drug. Initial doses consist of 20 mg given
uropathies are relative contraindications to the use of
intramuscularly intragluteally at 4-week intervals for 2 months. It is
anticholinergic agents.
recommended that during the first 2 weeks of ther- apy the
Lactase enzyme products are helpful for patients
short-acting formulation also be administered subcutaneously. At
experiencing diarrhea secondary to lactose intolerance. Lactase is
the end of 2 months, patients with good symptom control may have
required for
the dose reduced to 10 mg every 4 weeks, while those without suffi-
carbohydrate digestion. When a patient lacks this enzyme, eating
cient symptom control may have the dose increased to 30 mg every
dairy products causes an osmotic diarrhea. Several products are
4 weeks. For patients experiencing recurrence of symptoms on the
available for use each time a dairy product, especially milk or ice
10-mg dose, dosage adjustment to 20 mg should be made. It is not
cream, is consumed.
uncommon for patients with carcinoid tumors or VIPomas to expe-
rience periodic exacerbation of symptoms. Subcutaneous octreotide
for several days should be reinstituted in these individuals. In so- CLINICAL CONTROVERSY
called carcinoid crisis, octreotide is given as an intravenous Long-term use of oral opiates is not routinely
infusion at 50 mcg/h for 8 to 24 hours. recommended for several pharmacologic reasons. Some
Because octreotide inhibits many other gastrointestinal opioids such as mor- phine and codeine have the
hor- mones, it has a variety of intestinal side effects. With tendency to cause constipation by slowing down the
prolonged use, gallbladder and biliary tract complications such as peristaltic action of the bowels, which can also result in a
cholelithiasis have been reported. About 5% to 10% of patients functional ileus. This effect can be min- imized by
complain of nausea, di- arrhea, and abdominal pain. Local injection administering laxatives and/or stool softeners in patients
pain occurs with about an 8% incidence. With high doses, who require longer-term opiate therapy. Prokinetic agents
octreotide may reduce dietary fat absorption, leading to steatorrhea. may also be helpful in treating opiate-related consti-
Two other somatostatin analogs, lanreotide and pation.
10 ​
vapreotide, have been studied.​ Lanreotide is indicated for patients
with carcinoid tumors in a dose of 30 mg intramuscularly (as a
depot) every 14 days. If necessary the dose can be increased to 30 ■ ​INVESTIGATIONAL
mg intramuscu- lar every 7 to 10 days. Vapreotide is an orphan DRUGS
drug that is indicated for pancreatic and gastrointestinal fistulas.
Many experimental drugs have been used to control diarrhea. Phe-
nothiazines, ​β-​ blockers, nonsteroidal anti-inflammatory drugs, cal-
■ ​MISCELLANEOUS cium channel blockers, and ​α​-adrenergic agonists are only a few
PRODUCTS
 agents under investigation in either animals or humans. NifalatideIARRHEA
is
an enkephalin analog that delays the onset of castor oil–induced
diarrhea and decreases stool frequency. Dizziness and dry mouth ost patients with acute diarrhea experience mild to moderate dis-
are frequent side effects. Enkephalinase inhibitors (eg, acetorphan
ess. In the absence of moderate to severe dehydration, high fever,
or racecadotril) are other therapeutic options that reduce nd blood or mucus in the stool, this illness is usually self-limiting
hypersecre- tion of water and electrolytes into the intestinal lumen.
ithin 3 to 7 days. Mild to moderate acute diarrhea is usually
Prostaglandin inhibitors, aspirin and its analogs, and indomethacinanaged on an outpatient basis with oral rehydration, symptomatic
are safe and effective in childhood gastroenteritis; studies eatment,
in and diet. Elderly persons with chronic illness and infants
animals support in- domethacin use in enteropathogen secretory ay require hospitalization for parenteral rehydration and close
states such as ​Vibrio cholerae i​ nfection. onitoring.
Vaccines are a new therapeutic frontier in controlling■ S ​ EVERE
infectious diarrheas, especially in developing countries.​11​,​12 ​CholeraDIARRHEA
vaccine, which is available in the United States in the parenteral
form of whole- cell inactivated bacteria, yields some protection butIn the urgent/emergent situation, restoration of the patient's vol-
is not totally effec- tive and does not prevent transmission.ume status is the most important outcome. Toxic patients (fever,
However, live oral vaccine is thought to be protective against ​V.dehydration, hematochezia, or hypotension) require hospitalization,
cholerae​. Oral ​Shigella ​vaccine, al- though effective under fieldintravenous fluids and electrolyte administration, and empiric an-
conditions, requires five doses and repeat booster doses, therebytibiotic therapy while awaiting culture and sensitivity results. With
limiting its practicality for use in developing nations. With abouttimely management, these patients usually recover within a few
1,500 serotypes for ​Salmonella,​ a vaccine is not currently available.days.
There are three parenteral typhoid vaccine formu- lations available
in the United States. In addition, an oral vaccine of ​S. typhi ​(Tyza)
is now available and is administered in 4 doses on days 1, 3, 5, and
7, to be completed at least 1 week before exposure. Rotavirus
vaccine is effective in infants and children, and is adminis- tered as CONSTIPATI
a three–oral dose sequence. ON

onstipation is a commonly encountered medical condition in the

■ ​EVALUATION OF THERAPEUTIC nited States for which many patients initiate self-treatment. One
OUTCOMES ason constipation continues to be a frequent problem in this coun-
y is lack of adequate dietary fiber. Another unfortunate problem is
at many people have misconceptions about normal bowel
■ ​GENERAL OUTCOMES
nction, and think that daily bowel movements are required for
MEASURES alth and well being. Others believe that the lack of a daily bowel
ovement contributes to the accumulation of toxic substances or is
Therapeutic outcomes are directed toward key symptoms, signs, sociated with various somatic complaints. These misconceptions
and laboratory studies. Constitutional symptoms usually improveften lead to the inappropriate use of laxatives by the general
within 24 to 72 hours. Monitoring for changes in the frequency and
ublic.
char- acter of bowel movements on a daily basis in conjunction
Constipation does not have a single, generally agreed upon
with vital signs and improvement in appetite are of utmost
definition. When using the term, the lay public or health care pro-
importance. Also, the clinician needs to monitor body weight,
essional may be referring to several difficult-to-quantify variables:
serum osmolality, serum electrolytes, complete blood cell counts,
bowel movement frequency, stool size or consistency, and such
urinalysis, and culture results (if appropriate).
symp- toms as the sensation of incomplete defecation. Stool
requency is most often used to describe constipation; however, the
GB109-36 March 2, 2005 22:45
frequency of bowel movements used to define constipation is not
well established. Normal people pass at least three stools per week.
Some of the definitions of constipation used in clinical studies
include (a) less than three stools per week for women and five
stools per week for men despite a high-residue diet, or a period of
684 ​SECTION 4 GASTROINTESTINAL DISORDERS more than 3 days without a bowel movement; (b) straining at stool
greater than 25% of the time and/or two or fewer stools per week;
or (c) straining at defecation and less than one stool daily with
■ ​ACUTE
minimal effort. These varying definitions demonstrate the difficulty
 in characterizing this problem.
An international committee defined and classified
constipa- tion on the basis of stool frequency, consistency, and
difficulty of defecation.​13​,1​ 4 ​Functional constipation is defined as
two or more of the following complaints present for at least 12
months in the absence of laxative use: (a) straining at least 25% of
the time; (b) lumpy or hard stools at least 25% of the time; (c) a
feeling of incomplete evacuation at least 25% of the time; or (d)
two or fewer bowel movements in a week. Rectal outlet delay is
defined as anal blockage more than 25% of the time and prolonged
defecation or manual disimpaction when necessary.
EPIDEMIOLOG
Y more fre- quently.
As many as 40% of patients older than 65 years of age report
experi- encing constipation.​15 ​The results from 42,375 participants
of the Na- tional Health Interview Survey on Digestive Disorders
demonstrated that there is not an age-related increased incidence of
infrequent bowel movements; however, there is an age-related
increased incidence of laxative use.​16 ​The frequency of subjects
reporting two or fewer bowel movements per week was 5.9% for
those younger than 40 years of age; 3.8% for subjects 60 to 69
years of age; and 6.3% for subjects older than 80 years of age. In a
prospective study of 3166 people
older than 65 years of age in a Florida community,​17 ​26% of women recognized to have antimotility properties.
and 15.8% of men reported recurrent constipation. Factors found to
correlate with self-reported constipation were age, sex (higher fre- ch 2, 2005 22:45
quency in females), total number of drugs taken, abdominal pain,
and hemorrhoids.
increasing age. Table 36–5 lists common causes of constipation in
specific disease states.
DRUG-INDUCED
CONSTIPATION
Use of drugs that inhibit the neurologic or muscular function of the
GI tract, particularly the colon, may result in constipation (Table
36–6). The majority of cases of drug-induced constipation are
caused by opiates, various agents with anticholinergic properties,
and antacids containing aluminum or calcium. With most of the
agents listed in Table 36–6, the inhibitory effects on bowel function
are dose dependent, with larger doses clearly causing constipation
Opiates have effects on all segments of the bowel, but
effects are most pronounced on the colon. The major mechanism by
which opiates produce constipation has been proposed to be
prolongation of intestinal transit time by causing spastic,
nonpropulsive contrac- tions. An additional contributory
mechanism may be an increase in electrolyte absorption.
All opiate derivatives are associated with constipation, but
the degree of intestinal inhibitory effects seems to differ between
agents. Orally administered opiates appear to have greater
inhibitory ef- fects than parenterally administered products. Orally
administered enkephalins (endogenous opiate-like polypeptides) are

PATHOPHYSIOLOG CHAPTER 36 DIARRHEA, CONS

Y 685

Constipation is not a disease, but a symptom of an underlying

5​
TABLE 36–5. ​Possible Causes of
disease or problem. Approaches to the treatment of constipation Constipation
should begin with attempts to determine its cause. Disorders of the TABLE 36–6. ​Drugs Causing
GI tract (irritable bowel syndrome or diverticulitis), metabolic Constipation
disorders (diabetes), or endocrine disorders (hypothyroidism) may
be involved. Constipation commonly results from a diet low in fiber Conditions Possible Causes
or from use of constipating drugs such as opiates. Finally, it is
GI disorders Irritable bowel syndrome
believed that con- stipation may sometimes be psychogenic in
Diverticulitis Upper GI tract diseases Anal and rectal
origin.​18 ​Each of these causes is discussed in the following sections.
diseases Hemorrhoids Anal fissures Ulcerative proctitis
Constipation is a frequently reported problem in the Tumors Hernia Volvulus of the bowel Syphilis Tuberculosis
elderly, probably the result of improper diets (low in fiber and Helminthic infections Lymphogranuloma venereum
liquids), di- minished abdominal wall muscular strength, and Hirschsprung's disease Metabolic and Diabetes mellitus with
possibly diminished physical activity. However, as previously neuropathy
stated, the frequency of bowel movements is not decreased with endocrine disorders Hypothyroidism
normal aging. In addition, diseases that may cause constipation, Panhypopituitarism Pheochromocytoma
such as colon cancer and di- verticulitis, are more common with Hypercalcemia Enteric glucagon excess
 Pregnancy Depressed gut motility
including proctoscopy, sigmoidoscopy,
Increased fluid absorption from colon Decreased physical
colonoscopy, or barium enema, may be necessary to determine
activity Dietary changes Inadequate fluid intake Low dietary
fiber Use of iron salts Neurogenic causes CNS diseases the ​r presence of colorectal pathology. ​Thyroid function studies
​
Trauma to the brain (particularly the medulla) Spinal cord injury CNS
tumors Cerebrovascular accidents Parkinson's disease Psychogenic may be performed to determine the ​r presence
​ of metabolic or
causes Ignoring or postponing urge to defecate
endocrine disorders. ​With laxative abuse, fluid and electrolyte
Psychiatric
diseases Drug-induced See Table 36–6 imbalances (most
commonly hypokalemia), protein-losing gastroenteropathy
with hypoalbuminemia may be present.

Agents with anticholinergic properties inhibit bowel

function by parasymp atholytic actions on innervation to many
regions of the GI tract, particularly the colon and rectum. Many troglycerin, and amitriptyline.​22 ​Serum chloride and aspartate
types of drugs possess anticholinergic action, and these agents are amino- transferase, as well as alcohol consumption, are negatively
used commonly in both hospitalized and nonhospitalized patients. related to constipation.
One study demonstrated that amitriptyline, diphenhydramine, and
thioridazine use were asso- ciated with laxative needs in 800
nursing home patients.​15 CLINICAL
In patients older than 65 years of age, drugs that correlate PRESENTATION
most often with constipation are anticholinergics, aspirin,
furosemide, ni- Table 36–7 shows the general clinical presentation of
Analgesic constipation.
s
Inhibitors of prostaglandin synthesis
Opiates Anticholinergics
►​TREATMENT:
Antihistamines Antiparkinsonian agents (eg, benztropine or
trihexaphenidyl) Phenothiazines Tricyclic antidepressants Constipation
Antacids containing calcium carbonate or aluminum hydroxide
Barium sulfate Calcium channel blockers Clonidine Diuretics ■ ​GENERAL APPROACH TO
(non–potassium-sparing) Ganglionic blockers Iron
TREATMENT
preparations Muscle blockers (​D​-tubocurarine,
succinylcholine) Nonsteroidal anti-inflammatory agents
Polystyrene sodium sulfonate
The patient should be asked about the frequency of bowel
movements and the chronicity of constipation. Constipation
occurring recently in an adult may indicate significant colon
TABLE 36–7. ​Clinical Presentation of pathology such as malignancy; constipation present since early
Constipation infancy may be indicative of neuro- logic disorders. The patient
also should be carefully questioned about
usual diet and laxative regimens. Does the patient have a diet con-
Signs ​r and
​ symptoms ​It is important to ascertain whether the
sistently deficient in high-fiber items and containing mainly highly
patient perceives the problem ​as infrequent bowel movements, refined foods? What laxatives or cathartics has the patient used to
at- tempt relief of constipation? The patient should be questioned
stools of insufficient size, a feeling ​r of
​ fullness, or difficulty and pain about other concurrent medications, with interest focused on agents
on passing stool. ​ that might cause constipation.
Signs and symptoms include hard, small or dry
For most patients complaining of constipation, a thorough
stools, bloated phys- ical examination is not required after it is established that
stomach, cramping abdominal pain and discomfort, straining or constipation
grunting, sensation of blockade, fatigue, headache, and nausea

and vomiting. ​Laboratory ​r tests

​ ​A series of examinations,
GB109-36 March 2, 2005 22:45
686 ​SECTION 4 GASTROINTESTINAL DISORDERS
TABLE 36–8. ​Constipation Treatment Algorithm

History ​r ​Stool frequency ​r ​Stool consistency ​r ​Difficulty of defecation Possible

​ causes ​r ​Diet deficient in high-fiber items and

consisting mainly of

highly refined foods ​r ​GI disorders ​r ​Metabolic and endocrine disorders r​ ​Pregnancy ​r ​Neurogenic ​r ​Psychogenic ​r ​Drug-Induced ​r

Laxative abusers ​Symptoms seen with chronic constipation ​r ​Fluid and electrolyte imbalances (hypokalemia) ​r ​Protein-losing

gastroenteropathy with hypoalbuminemia ​r ​Syndromes resembling colitis ​Select appropriate diagnostic studies ​r P
​ rotoscopy ​r

Sigmoidoscopy ​r C ​ arium enema ​Diagnosis

​ olonoscopy ​r B
1. Treat specific cause 2. No diagnosis, symptomatic therapy
A. Bulk-forming agents B. Dietary modification C. Alter lifestyle (exercise) D. Increase fluid intake E. Discontinue potential drug
inducer
(a) is not a chronic problem, (b) is not accompanied by signs of sig- nificant GI disease (eg, rectal bleeding or anemia), and (c)
does not cause severe discomfort. In these circumstances, the patient may be referred directly to the first-line therapies for
constipation described in the next section (mainly bulk-forming laxatives and dietary fiber with occasional use of saline or
stimulant laxatives). Table 36–8 presents a general treatment algorithm for the management of constipation.
The proper management of constipation requires a number of ​
6​ different modalities; however, the basis for therapy should be
dietary modification. The major dietary change should be an increase in the amount of fiber consumed daily. In addition to dietary
man- agement, patients should be encouraged to alter other aspects of their lifestyles if necessary. Important considerations are to
encourage pa- tients to exercise (achieved even by brisk walking after dinner) and to adjust bowel habits so that a regular and
adequate time is made to re- spond to the urge to defecate. Another general measure is to increase fluid intake. This is generally
recommended and believed beneficial, although there is little objective evidence to support this measure.
If an underlying disease is recognized as the cause of consti- pation, attempts should be made to correct it. GI malignancies may
be removed via surgical resection. Endocrine and metabolic derange- ments should be corrected by the appropriate methods. For
example, when hypothyroidism is the cause of constipation, cautious institu- tion of thyroid-replacement therapy is the most
important treatment measure.
As discussed earlier, many drug substances may cause consti- pation. If a patient is consuming medications well known to cause
constipation, consideration should be given to alternative agents. For
some medications (eg, antacids), nonconstipating alternatives exist. If no reasonable alternatives exist to the medication thought to
be re- sponsible for constipation, consideration should be given to lowering the dose. If a patient must remain on constipating
medications, then more attention must be given to general measures for prevention of constipation, as discussed in the next
section.
■ ​NONPHARMACOLOGIC THERAPY
■ ​DIETARY MODIFICATION AND BULK-FORMING AGENTS
The most important aspect of therapy for constipation for the major- ity of patients is dietary modification to increase the amount
of fiber consumed. Fiber, the portion of vegetable matter not digested in the human GI tract, increases stool bulk, retention of
stool water, and rate of transit of stool through the intestine. The result of fiber therapy is an increased frequency of defecation.
Also, fiber decreases intraluminal pressures in the colon and rectum, which is thought to be beneficial for diverticular disease and
for irritable bowel syndrome. The specific physiologic effects of fiber are not well understood. Patients should be advised to
include at least 10 g of crude fiber in their daily diets.​19 ​Fruits, vegetables, and cereals have the highest fiber content. Bran, a
by-product of milling of wheat, is often added to foods to increase fiber content. Raw bran is generally 40% fiber. Medicinal
products, often called “bulk-forming agents,” such as psyllium hydrophilic colloids, methylcellulose, or polycarbophil, have
properties similar to those of dietary fiber and may be taken as tablets, powders, or granules (Table 36–9). A trial of dietary
modification with high-fiber content should be continued for at least 1 month before effects on bowel func- tion are determined.
Most patients begin to notice effects on bowel
TABLE 36–9. ​Dosage Recommendations for Laxatives and Cathartics
Agent Recommended Dose
Agents that cause softening of feces in 1–3 days ​Bulk-forming agents
Methylcellulose 4–6 g/day Polycarbophil 4–6 g/day Psyllium Varies with product Emollients
Docusate sodium 50–360 mg/day Docusate calcium 50–360 mg/day Docusate potassium 100–300 mg/day Lactulose 15–30 mL
 orally Sorbitol 30–50 g/day orally Mineral oil 15–30 mL orally ​Agents that result in soft or semifluid stool in 6–12 h ​Bisacodyl
(oral) 5–15 mg orally Phenolphthalein 30–270 mg orally Cascara sagrada Dose varies with formulation Senna Dose varies with
formulation Magnesium sulfate (low dose) ​<1 ​ 0 g orally ​Agents that cause watery evacuation in 1–6 h ​Magnesium citrate 18 g 300
mL water Magnesium hydroxide 2.4–4.8 g orally Magnesium sulfate (high dose) 10–30 g orally Sodium phosphates Varies with salt
used Bisacodyl 10 mg rectally Polyethylene glycol-electrolyte
preparations
4L

GB109-36 March 2, 2005 22:45

CHAPTER 3 6 DIARRHEA, CONSTIPATION, AND IRRITABLE BOWEL SYNDROME

687

function 3 to 5 days after beginning a high-fiber diet, but some
patients may require a considerably longer period of time. Patients
should be cautioned that abdominal distention and flatus may be
particularly troublesome in the first few weeks of fiber therapy,
particularly with high bran consumption. In most cases these
problems resolve with continued use.
Bulk-forming laxatives have few adverse effects. The
only major caution in the use of bulk-forming laxatives is that
obstruction of the esophagus, stomach, small intestine, and colon
has been reported when the agents have been consumed without
sufficient fluid or in patients with intestinal stenosis.
■ ​DRUG REGIMENS OF
CHOICE
Treatment and prevention of constipation should consist of bulk-
forming agents in addition to dietary modifications that increase di-
etary fiber.​23 ​A variety of products are available that provide
adequate bulk. Whichever agent is chosen, it should be used daily
and continued indefinitely in most patients, particularly those with
chronic consti- pation. Bulk-forming agents available in
combination with diphenyl- methane or anthraquinone derivatives
should not be used on a routine basis.​For most persons with acute

constipation, infrequent use (less than

■ products is acceptable. Acute con- stipation may be relieved by the
SURGERY
In a small percentage of patients presenting with complaints of con-
stipation, surgical procedures are necessary due to the presence of
colonic malignancies or GI obstruction from a number of other
causes. In each case, the involved segment of intestine may be
resected or re- vised. Surgery may be required in some endocrine
disorders causing constipation, such as pheochromocytoma, which
requires removal of a tumor.
■
BIOFEEDBAC
K
The majority of patients with constipation related to pelvic floor
dysfunction can benefit from electromyogram-guided biofeedback
therapy.​19 ​The value of biofeedback in children with chronic consti-
pation has not been well demonstrated.​20
■ ​PHARMACOLOGIC
THERAPY
​ every few weeks) of laxative
use of a tap-water enema or a glycerin suppository; if neither is
effective, the use of oral sorbitol, low doses of diphenylmethane or
anthraquinone laxatives, or saline laxatives (eg, milk of magnesia)
may provide relief. If laxative treatment is required for longer than
1 week, the person should be advised to consult a physician to
determine if there is an underlying cause of constipation that
requires treatment with other modalities.
For some bedridden or geriatric patients, or others with
chronic constipation, bulk-forming laxatives remain the first line of
treat- ment, but the use of more potent laxatives may be required
relatively frequently. Fiber should be avoided in bedridden patients
who are cognitively impaired.​19 ​When other than bulk-forming
laxatives are used, they should be administered in the lowest
effective dose and as infrequently as possible to maintain regular
bowel function (more than three stools per week). Agents that may
be used in these situ- ations include diphenylmethane and
anthraquinone derivatives, milk of magnesia, and sorbitol or
lactulose. Mineral oil should be avoided,
particularly in bedridden patients, because of the risk of aspiration
and lipoid pneumonia. Some patients with chronic constipation may
present with fecal impactions. Before vigorous oral laxatives can be
used, the impaction needs to be removed using mechanical
methods, including tap water or saline enemas and digital Emollient laxatives are ineffective in treating constipation,
extraction. but are used mainly to prevent this condition. They may be helpful
In the hospitalized patient without GI disease, constipation in situations in which straining at stool should be avoided, such as
may be related to the use of general anesthesia and/or opiate after recovery from myocardial infarction, with acute perianal
substances. Most orally or rectally administered laxatives may be disease, or after rectal surgery. It is unlikely that these agents would
used in these sit- uations. For prompt initiation of bowel be very effective in preventing constipation if major causative
evacuation, either a tap-water enema, glycerin suppository, or oral factors (eg, heavy opiate use, uncorrected pathology, or inadequate
milk of magnesia are recom- mended. dietary fiber) are not concurrently addressed.
With infants and children, constipation may occur commonly. Although docusates are generally safe, a few adverse effects
In patients with persistent problems, the underlying etiology may be have been noted. They may increase the intestinal absorption of
neurologic, metabolic, or secondary to anatomic abnormalities. agents administered concurrently and alter toxic potential.
Management of constipation in this age group should consist of
dietary modification with an emphasis on high-fiber foods. ch 2, 2005 22:45
For acute constipation in most age groups, a tap-water enema
or glycerin suppository may be helpful. Occasional use of milk of
magnesia or an anthraquinone laxative in low doses is justified as
well.
88 ​SECTION 4 GASTROINTESTINAL DISORDERS

■ ​DRUG
CLASSES
UBRICANTS
The traditional classification system for laxatives and cathartics by
suspected mode of action is not very useful, as this is not clearly ineral oil is the only lubricant laxative in routine use. This agent,
understood for many agents. In general, most of these products in- btained from petroleum refining, acts by coating stool and
duce bowel evacuation by one or more of the mechanisms lowing for easier passage. It inhibits colonic absorption of water,
ereby
associated with the etiology of diarrhea, including active electrolyte increasing stool weight and decreasing stool transit time.
secretion, decreased water and electrolyte absorption, increased ineral oil may be given orally or rectally in a dose of 15 to 45
intraluminal osmolarity, and increased hydrostatic pressure in the L. Generally, the effect on bowel function is noted after 2 or 3
gut. Laxatives convert the intestine from primarily an organ that ays of use.
absorbs water and electrolytes to an organ that secretes these Mineral oil is helpful in situations similar to those
substances. ggested for docusates: to maintain a soft stool and to avoid
raining for relatively short periods of time (a few days to 2
The various classes of laxatives are discussed in this section.
eeks); however, it possesses a much greater potential for adverse
These agents are divided into three general classifications: (a) those
causing softening of feces in 1 to 3 days (bulk-forming laxatives, fects and its routine use should be discouraged. Mineral oil may
do- cusates, and lactulose); (b) those that result in soft or semifluidabsorbed systemically and can cause a foreign-body reaction in
stool in 6 to 12 hours (diphenylmethane derivatives and mphoid tissue. Also, in debilitated or recumbent patients, mineral
anthraquinone deriva- tives); and (c) those causing water l may be aspirated, causing lipoid pneumonia.​21 ​Mineral oil may
crease the absorption of fat-soluble vitamins (A, D, E, and K)
evacuation in 1 to 6 hours (saline cathartics, castor oil, and
polyethylene glycol-electrolyte lavage solution). ith chronic use by causing retention in the GI tract. Finally, even
hen given orally, mineral oil may leak from the anal sphincter,
using pruritus and soiling of clothing.
■ ​EMOLLIENT
LAXATIVES
​LACTULOSE AND
Emollient laxatives are surfactant agents, docusate in its various
ORBITOL
salts, which work by facilitating mixing of aqueous and fatty
materials within the intestinal tract. They may increase water and
actulose is a disaccharide that is used orally or rectally. It is
electrolyte secretion in the small and large bowel. These products
etabo- lized by colonic bacteria to low-molecular-weight acids,
are generally given orally, although docusate potassium has alsosulting in an osmotic effect whereby fluid is retained in the
been used rectally. These products result in a softening of stools 22 ​
lon.​ The fluid retained in the colon lowers the pH and increases
within 1 to 3 days of therapy.
lonic peristalsis. Lactulose is generally not recommended as a
first-line agent for the treatment of constipation because it is costly reversible after anthraquinones have been discontinued for 3 to 6
and not necessarily more effective than such agents as sorbitol or months.
milk of magnesia. It may be justified as an alternative for acute
constipation, and has been particu- larly useful in elderly patients.
Occasionally, the use of lactulose may result in flatulence, cramps, ■ ​SALINE
diarrhea, and electrolyte imbalances.​27 ​Sorbitol, a monosaccharide, CATHARTICS
exerts its effect by osmotic action and has been recommended as a
primary agent in the treatment of func- tional constipation in Saline cathartics are composed of relatively poorly absorbed ions
cognitively intact patients.​19 ​It is as effective as lactulose and much such as magnesium, sulfate, phosphate, and citrate, which produce
less expensive. their effects primarily by osmotic action in retaining fluid in the GI
tract. Magnesium stimulates the secretion of cholecystokinin, a
hormone that causes stimulation of bowel motility and fluid
secretion. These agents may be given orally or rectally. A bowel
■ ​DIPHENYLMETHANE
movement may result within a few hours after oral doses and in 1
DERIVATIVES hour or less after rectal administration.
These agents should be used primarily for acute evacuation
The two commonly used diphenylmethane derivatives are bisacodyl
of the bowel, which may be necessary before diagnostic
and phenolphthalein. Bisacodyl exerts its therapeutic effect by stim-
examinations, after poisonings, and in conjunction with some
ulating the mucosal nerve plexus of the colon. Phenolphthalein is
anthelmintics to eliminate parasites. Such agents as milk of
thought to inhibit active glucose and sodium absorption, resulting in
magnesia (an 8% suspension of magnesium hydroxide) may be used
fluid accumulation in the colon by osmotic action. With both of
occasionally (every few weeks) to treat constipation in otherwise
these agents, significant interpatient variability exists with dosing.
healthy adults. Saline cathartics should not be used on a routine
A dose that causes no effect in one patient may result in excessive
basis. The enema formulations of these agents may be useful in
cramping and fluid evacuation in others. With phenolphthalein, a
fecal impactions.
small portion of the dose undergoes enterohepatic recirculation,
which may result in a prolonged laxative action. As with most laxatives, these agents may cause fluid and
elec- trolyte depletion. Also, magnesium or sodium accumulation
These agents are not recommended for regular daily
may occur when magnesium-containing cathartics are used in
use. Their use is acceptable intermittently (every few weeks) to
patients with renal dysfunction or when sodium phosphate is used in
treat constipa- tion or as a bowel preparation before diagnostic
patients with congestive heart failure.
procedures in which cleansing of the colon is necessary. These
agents may sometimes cause severe abdominal cramping as well as
significant fluid and electrolyte imbalances with chronic use. They
■ ​CASTOR
should not be used for patients in whom appendicitis is a possibility
(perforation of the appendix may result) or during pregnancy or OIL
lactation. Finally, pa- tients using phenolphthalein-containing
laxatives should be cautioned that their urine might turn pink. Castor oil is metabolized in the GI tract to an active compound, ri-
cinoleic acid, which stimulates secretory processes, decreases glu-
■ ​ANTHRAQUINONE
cose absorption, and promotes intestinal motility, primarily in the
DERIVATIVES
small intestine. Castor oil usually results in a bowel movement
within 1 to 3 hours of administration. Because the agent has such a
Anthraquinone derivatives include cascara sagrada, sennosides, and
strong purgative action, it should not be used for the routine
casanthrol. Gut bacteria metabolizes these agents to their active
treatment of constipation.
com- pounds, but the exact mechanisms of action are not
understood. Effects are limited to the colon, and stimulation of
Auerbach's plexus may be involved. Recommendations for the use
■
of these agents are similar to those for the diphenylmethane
derivatives. In most cases, intermittent use is acceptable; daily use
GLYCERIN
should be strongly discouraged.
Glycerin is usually administered as a 3-g suppository and exerts its
Most of the concerns with the use of diphenylmethane
effect by osmotic action in the rectum. As with most agents given as
derivatives apply to the anthraquinone derivatives. In addition, the
suppositories, the onset of action is usually less than 30 minutes.
anthraquinone derivatives may cause melanosis coli, an
Glycerin is considered a very safe laxative, although it may occa-
accumulation of dark pig- ment, mainly in the cecum and rectum,
sionally cause rectal irritation. Its use is acceptable on an
that is evident after 4 to 13 months of use. A pathologic effect of
intermittent basis for constipation, particularly in children.
melanosis coli has not been demonstrated, and it appears to be
 of these agents is without adverse consequences. Abuse of laxatives
GB109-36 March 2, 2005 22:45 has occurred tradi- tionally in persons trying to maintain daily
bowel function, but more recently has extended to others who use
laxatives for the purpose of controlling weight. In either case, the
consistent abuse of strong laxatives and cathartics may lead to
serious illness.
Laxative abuse AND
CHAPTER 36 DIARRHEA, CONSTIPATION, for the purpose BOWEL
IRRITABLE of maintaining
SYNDROMEdaily
689 bowel func- tion begins with misconceptions about the frequency,
quantity, or consistency of stools. With the use of strong purgatives,
the colon may be so thoroughly cleansed that a bowel movement
■ ​POLYETHYLENE may not oc- cur normally until a few days later. This delay
GLYCOL-ELECTROLYTE LAVAGE reinforces the need for more purgatives and the cycle of laxative
SOLUTION dependence is begun. Eventually the patient may require daily
in a bowel movement within 30 minutes. Soap-suds enemas are nolaxatives to maintain bowel function.
longer recommended as their use may result in proctitis or colitis. The laxative abuser may present with contradictory
findings of diarrhea and weight loss. In addition, long-term abusers
Whole-bowel irrigation with polyethylene glycol-electrolyte lavage of laxatives tend to have vomiting, abdominal pain, lassitude,
solution (PEG-ELS) has become popular for colon cleansing before weakness, thirst, edema, and bone pain (caused by osteomalacia).
diagnostic procedures or colorectal operations. With prolonged use of laxatives a number of serious illnesses may
Four liters of this solution is administered over 3 hours to arise. These include fluid and electrolyte imbalances (including
obtain complete evacuation of the GI tract. The solution is not acid-base imbalances and hypokalemia), protein-losing
recommended for the routine treatment of constipation and its use gastroenteropathy with hypoalbumin- emia, and syndromes
should be avoided in patients with intestinal obstruction. resembling colitis.
The determination of laxative abuse syndrome can be
difficult because many laxative abusers vigorously deny laxative
■ ​OTHER
use. Middle- aged women tend to be the most common laxative
AGENTS abusers. The chronic laxative abuse problem should be addressed
by a combination of measures, including psychiatric evaluation,
Tap-water enemas may be used to treat simple constipation. The ad- dietary modification with reliance on bulk-forming laxatives, and
ministration of 200 mL of tap water by enema to an adult often specific guidelines to the patient for the withdrawal of stimulant
results laxatives.
■ A variation of laxative abuse is seen in persons who use
PREVENTIO them as a means of weight loss. It appears from the medical
N literature and daily news sources that this type of abuse is on the
increase. Treatment of patients who abuse laxatives in this way has
proven very difficult.
For certain groups of patients, such as those recovering from
myocardial infarction or rectal surgery, straining at defecation is to
be avoided. The basis of preventive therapy in these patients should EVALUATION OF THERAPEUTIC
be bulk-forming laxatives. Additionally, the use of docusate is OUTCOMES
popular, although its effectiveness is debated. In pregnant patients,
constipation may result because of alterations in anatomy or iron The ultimate goal of treatment for constipation is alteration of
supplementation. As described earlier, bulk-forming laxatives and lifestyle (particularly diet) to prevent further episodes of
docusates should be the first line of prevention. constipation. Short-
term goals include alleviation of acute constipation with relief from
symptoms. For patients with chronic constipation, the goals are
more long-term and include use of proper diet and decreased
LAXATIVE ABUSE reliance on laxatives. Effective treatment of constipation requires
SYNDROME the patient to become more knowledgeable about the causes of
constipation, proper diet, and appropriate use of laxatives.
Misconceptions about normal bowel patterns and the effect of laxa-
tives have contributed to a syndrome of laxative abuse that is
relatively common in the United States. The availability of
laxatives as choco- lates or gums conveys to the public that the use IRRITABLE BOWEL
 SYNDROME
gns ​rrrrrr and
​ symptoms ​Lower abdominal pain Abdominal
Irritable bowel syndrome (IBS) is one of the most common
gastroin- testinal disorders encountered in clinical practice, oating and distention Diarrhea symptoms, ​>​3 stools/day
affecting as many as 20% of adults, and is more common in
xtreme urgency Mucus passage Constipation symptoms, ​<3 ​
women. This latter point is probably a consequence of women
ools/wk, straining, incomplete ​r evacuation
being more likely than men to report their symptoms to the medical ​ ​
Psychological
community. Although a benign disorder, IBS is chronic and
mptoms such as depression and anxiety
recurring in nature.
ongastrointestinal ​rrr ​symptoms ​Urinary symptoms

PATHOPHYSIOLOG atigue Dyspareunia Other

​ ​rrr concurrent
​ conditions
Y
bromyalgia Functional dyspepsia Chronic fatigue syndrome
educed health-related quality of life
Although the exact pathophysiogic abnormalities with IBS are still
being actively investigated, it is currently thought that IBS results
from altered somatovisceral and motor dysfunction of the intestine
from a variety of causes. Abnormal central nervous system
processing of afferent signals may lead to visceral hypersensitivity, CLINICAL
with the specific nerve pathway affected determining the exact PRESENTATION
symptomatology ex- pressed. This visceral hypersensitivity is a
neuroenteric phenomenon that is independent of motility and Irritable bowel syndrome presents as either diarrhea-predo-
7​
psychological disturbances.​23 ​Fac- tors known to contribute to these
minant or constipation-predominant disease and can be defined as
alterations include genetics, motil- ity factors, inflammation,
lower abdominal pain, disturbed defecation (constipation, diar-
colonic infections, mechanical irritation to local nerves, and
rhea, or an alternating pattern of both), and bloating in the absence
psychological factors.
of structural or biochemical factors that might explain these
symptoms (Table 36–10).
SEROTONIN-TYPE In the past, diagnosis of IBS was based upon
RECEPTORS entification of the primary complaints of the patient and
xcluding other medical condi-
The enteric nervous system contains a significant percentage of theTABLE 36–11. ​Symptom-Based Criteria for IBS
body's 5-hydroxytryptamine (serotonin, 5-HT).​24 ​Two types of sero-
The Manning
tonin exists within the gut: serotonin type 3 (HT​3​) and serotoninCriteria​23
Chronic or recurrent abdominal pain for at least 6 months and two
type 4 (HT​4​), which are responsible for secretion, sensitization, and
​ or
motility.​25 ​Previous studies show that there is an increase in the more of the following:
postprandial levels of 5-HT in those who suffer from diarrhea-1. Abdominal pain relieved with defecation 2. Abdominal pain
predominant IBS when compared with nonsufferers.​24 ​Thereforeassociated with more frequent stools 3. Abdominal pain associated
stimulation and antagonism of these serotonin receptors has becomewith looser stools 4. Abdominal distention 5. Feeling of incomplete
a focused area for research on new drug therapies for both diarrhea-evacuation after defecation 6. Mucus in stools ​Rome II diagnostic
and constipation-predominant disease. criteria for IBS​26 ​At least 12 weeks, which need not be consecutive,
in the preceeding 12
GB109-36 March 2, 2005 22:45 months, of abdominal discomfort or pain that has two of
three features:
1. Relieved with defecation; and/or 2. Onset
associated with a change in frequency of stool;
and/or 3. Onset associated with a change in form
(appearance) of
690 ​SECTION 4 GASTROINTESTINAL DISORDERS
stoo
l
TABLE 36–10. ​Clinical Presentation of IBS
 receptors to treat constipation-predominant and
diarrhea-predominant IBS, respectively. However, both
drugs are currently only in- dicated for women. Efficacy
and safety in men has not been established because the
tions having a similar clinical presentation. Currently, the diagnosis
nitial manufacturer's sponsored clin- ical trials contained
of IBS is based upon the use of either the symptom-based
nsufficient numbers of men with IBS to provide the
Manning​23 ​or Rome II​26 ​criteria outlined in Table 36–11.
necessary statistical power to prove efficacy and safety.
Additional diagnostic steps that can be taken includeOngoing studies should determine if these drugs are
sigmoid- oscopy or colonoscopy; examination of the stool for occult ndicated in men.
blood and ova and parasites; complete blood cell count; erythrocyte Alosetron was withdrawn from the US market in
sedimenta- tion rate; and serum electrolytes. In some cases, 2000 due to serious adverse effects including severe
radiographic imaging studies, such as computed tomography scans constipation and ischemic colitis that did not appear in the
or barium swallows or enemas, may also be necessary if the initial clinical trials. Its use is now limited to an
findings of the above assessment are not typical for IBS.​28 FDA-approved restricted use program in lower initial
doses, and requires extensive post- marketing
surveillance. Results of these trials are necessary to
definitively determine alosetron's true safety profile, espe-
►​TREATMENT: Irritable Bowel cially with regard to its association with or causation of
Syndrome fatal ischemic colitis.

■ ​GENERAL APPROACH TO
TREATMENT ■ ​CONSTIPATION-PREDOMINANT
DISEASE

The treatment approach to IBS is based upon the predominant

symp- toms and their severity (Fig. 36–3). Milder, less frequent In the constipation-predominant patient, dietary fiber may be bene-
episodes can be managed with dietary restrictions and a higher-fiber ficial. Patients should be instructed to begin with 1 tablespoonful of
diet with ad- dition of bulk-forming laxatives if necessary. More fiber with 1 meal daily and gradually increase the dose to include
persistent disease may require prn use of various antispasmodic or fiber with 2 and 3 meals a day until the desired outcome is
antidiarrheal agents such as loperamide. Lastly, the severest forms achieved. Endpoints that the patient should aim for include bulkier
of this disease may call for pharmacologic agents directed and more easily passed stools. For patients unable to tolerate dietary
specifically at the underlying neu- rohormonal imbalance, such as bran, bulk- ing agents such as psyllium may be substituted.​27
Laxative use is not encouraged in these patients, and it should only
the 5-HT​4 ​agonists such as tegaserod or
​ the 5-HT​3 ​receptor
be used in the smallest dose for the least amount of time in cases of
severe constipation.
antagonists such as alosetron.
The 5-HT​4 ​agonist tegaserod is the first therapy approved
CLINICAL CONTROVERSY
by the
​ FDA specifically for the treatment of
The newer serotonin receptor agonists and antagonists constipation-predominant
tegaserod and alosetron act on GI-specific serotonin
GB109-36 March 2, 2005 22:45
CHAPTER 36 DIARRHEA, CONSTIPATION, AND IRRITABLE BOWEL SYNDROME ​691
Diagnosis of irritable bowel syndrome
Symptomatic treatment including stress management and patient education
Add psychotherapeutic behavior modifications, including stress reduction, and consider antidepressants for associated pain symptoms
intolerance should be considered in certain patients; however, the prevalence of this condition may be exaggerated.
Herbal medicines or teas often contain senna, which may produce diarrhea. In patients with disease persistence following dietary
modi- fication, loperamide may be used for episodic management of urgent diarrhea, or in situations in which the patient wishes
to avoid the possi- bility of an acute onset of symptoms.​29 ​This drug decreases intestinal transit, enhances water and electrolyte
absorption, and strengthens rectal sphincter tone. Some patients may require continuous therapy, and careful dosage titration can
usually be undertaken to prevent the development of constipation. Cholestyramine may be useful in pa-
Constipation predominant Diarrhea predominant
tients with diarrhea related to idiopathic bile acid malabsorption or following cholecystectomy.​28
 Diarrhea-predominant IBS caused by excessive stimulation of the 5-HT​3 receptor
​ can be relieved by the drug alosetron. Alosetron
Increase dietary fiber and fluid intake
Lactose-free, caffeine-free diet. Counsel patient on other diarrhea- inducing foods and drugs to avoid
was the first truly effective treatment for diarrhea-predominant IBS. However, in November 2000 it was voluntarily withdrawn
from the market due to severe GI adverse effects, including 113 reported cases of serious constipation and 8 cases of possible
ischemic colitis and death. This decision was met with a great public outcry, as many
Add bulk-forming laxatives and
Add loperamide or other consider antispasmodic
antispasmodic agents
who had suffered for years had experienced relief for the first time. Because this drug was highly effective in many patients, the
FDA approved restricted use of alosetron in June 2002. Alosetron is now available via an FDA-approved restricted use program in
conjunction
Add serotonin-4 agonist (eg, tegaserod)
with GlaxoSmithKline as detailed at http://www.lotronex.com. It is now indicated, in lower initial doses of 1 mg daily, for women
with diarrhea-predominant symptoms of greater than 6 months' duration that are not relieved by conventional therapy. Health care
providers must utilize extreme caution in therapy with this drug, and must follow strict FDA-mandated guidelines.
■ ​PAIN IN IBS
FIGURE 36–3. ​A general stepwise approach to the management of both constipation- and diarrhea-predominant irritable bowel
syndrome.
Select patients with IBS suffer significant pain associated with ​
9​ their disease. Data supporting the use of antispasmodic agents in
31​,​32 ​
these patients are conflicting.​ In these cases, a trial of low-dose IBS.​28 ​Tegaserod is a serotonin derivative that activates 5-HT​4

recep- ​tors on the neurons in the gastrointestinal tract, increasing GI motility and decreasing visceral sensations. It is approved as
2-mg or 6-mg doses given twice daily 30 minutes prior to a meal with water for up to 12 weeks.​29 ​Stimulation of the 5-HT​4

receptors by tegaserod in- creases

​ gastric secretions and promotes motility, with improvement in symptoms generally occurring
within the first week of therapy. Cur- rently this therapy is only approved for use in women, as efficacy and safety in men has not
been established due to inadequate numbers of
antidepressant therapy is indicated, especially if pain is associated with eating. Both tricyclic antidepressants and serotonin
reuptake in- hibitors produce analgesia, and may relieve depressive symptoms if present. Preprandial doses of drugs containing
anticholinergic proper- ties may suppress pain (and/or diarrhea) associated with an overactive postprandial gastrocolonic
response. Tricyclic antidepressants should be avoided in patients with pain and constipation. In addition, psy- chotherapy,
including cognitive behavioral therapy, relaxation ther- apy, and hypnotherapy have been shown to decrease IBS symptoms.​33
men enrolled in clinical trials to date.​30 ​In addition, length of effective therapy has only been approved for 12 weeks.​37 ​However,
recent evi- dence suggests that tegaserod may provide safe and effective therapy for up to 12 months.​30 ​Diarrhea was the most
common adverse effect,

■ ​DRUG CLASSES CURRENTLY UNDER INVESTIGATION ​FOR THE TREATMENT OF IBS ​resulting in
drug discontinuation in 1.6% of study subjects.
Numerous agents are currently undergoing investigation for the man-
■ ​DIARRHEA-PREDOMINANT DISEASE
agement of IBS.​33 ​Selective blockade of the muscarinic M​3 ​receptors as
​ well as ​β​3​-adrenoceptor agonists have been shown to alter
For patients in whom diarrhea is the primary
gut motility without affecting the cardiovascular system.​34 ​However, two ​8 ​
complaint, avoid- ​
ance of certain food products may be necessary. Caffeine, al-
Add serotonin-3 antagonists (eg, alosetron)
recently tested compounds, zamifenacin and darifenacin have shown limited efficacy to date.​35 ​cohol, and artificial sweeteners
(sorbitol, fructose, and mannitol)
Other compounds being evaluated include neurokinin 1 and are known to irritate the gut and produce a laxative effect. Lactose
neurokinin 3 receptor antagonists, gut-selective calcium channel

GB109-36 March 2, 2005 22:45

692 ​SECTION 4 GASTROINTESTINAL DISORDERS

blockers, cholecystokinin A receptor antagonists, and agents capa- ble of stimulating motilin receptors (motilinomimetics).​36

■ ​EVALUATION OF THERAPEUTIC OUTCOMES

IBS is usually classified as constipation-predominant, diarrhea- predominant, or IBS with abdominal pain and bloating. Therapeutic goals
in IBS should focus on the patient's primary complaint. Dietary and drug therapy goals should focus on end-organ treatment to relieve
abdominal pain (antispasmodic drugs) or disturbed bowel habits (an- tidiarrheals and bulk-forming agents). Additionally, severe symptoms
from central nervous system dysregulation should be treated with an- tidepressants, psychotherapy, relaxation/stress management, cogni-
tive behavior treatment, and/or hypnosis aimed at specific affective disorders.​36 ​Lastly, the serotonin receptor agonists and antagonists can
be used in carefully selected patients whose symptoms are not ade- quately controlled with other agents. The American Gastroenterology
Association recommends that patients with severe IBS consider psy- chological treatments such as psychotherapy, relaxation/stress man-
agement, and/or cognitive behavior treatment.

ABBREVIATIONS

HT: serotonin IBS: irritable bowel syndrome ORS: oral rehydration solution PEG-ELS: polyethylene glycol-electrolyte lavage
solution PHM: peptide histidine methionine VIP: vasoactive intestinal peptide

Review Questions and other resources can be found at ​www.pharmacotherapyonline.com.

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