CHAPTER 62 Drugs Used in the Treatment of Gastrointestinal Diseases 1079

SUMMARY Drugs Used Primarily for Gastrointestinal Conditions

Pharmacokinetics,
Subclass, Drug Mechanism of Action Effects Clinical Applications Toxicities, Interactions

DRUGS USED IN ACID-PEPTIC DISEASES

Proton pump Irreversible blockade of H+/ Long-lasting reduction of Peptic ulcer, gastroesophageal Half-lives much shorter than
inhibitors (PPIs), eg, K+-ATPase pump in active stimulated and nocturnal reflux disease, erosive gastritis duration of action low toxicity
omeprazole, parietal cells of stomach acid secretion reduction of stomach acid may
lansoprazole reduce absorption of some drugs
and increase that of others

H2-receptor blockers, eg, cimetidine: Effective reduction of nocturnal acid but less effective against stimulated secretion; very safe, available over the counter (OTC).
Cimetidine, but not other H2 blockers, is a weak antiandrogenic agent and a potent CYP enzyme inhibitor
Sucralfate: Polymerizes at site of tissue damage (ulcer bed) and protects against further damage; very insoluble with no systemic effects; must be given four times daily
Antacids: Popular OTC medication for symptomatic relief of heartburn; not as useful as PPI and H2 blockers in peptic diseases

DRUGS STIMULATING MOTILITY

Metoclopramide D2-receptor blocker removes Increases gastric emptying Gastric paresis (eg, in diabetes) Parkinsonian symptoms due to
inhibition of acetylcholine and intestinal motility antiemetic (see below) block of central nervous system
neurons in enteric nervous (CNS) D2 receptors
system

Domperidone: Like metoclopramide, but less CNS effect; not available in USA
Cholinomimetics: Neostigmine often used for colonic pseudo-obstruction in hospitalized patients
Macrolides: Erythromycin useful in diabetic gastroparesis but tolerance develops

LAXATIVES
Magnesium hydrox- Osmotic agents increase Usually causes evacuation Simple constipation; bowel Magnesium may be absorbed and
ide, other water content of stool within 46 h, sooner in prep for endoscopy (especially cause toxicity in renal impairment
nonabsorbable salts large doses polyethylene glycol (PEG)
and sugars solutions)

Bulk-forming laxatives: Methylcellulose, psyllium, etc: increase volume of colon, stimulate evacuation
Stimulants: senna, cascara; stimulate activity; may cause cramping
Stool surfactants: Docusate, mineral oil; lubricate stool, ease passage
Chloride channel activators: Lubiprostone, prostanoic acid derivative, stimulates chloride secretion into intestine, increasing fluid content; linaclotide, guanylyl cyclase-C
agonist, stimulates chloride secretion by CFTR
Opioid receptor antagonists: Alvimopan, methylnaltrexone; block intestinal -opioid receptors but do not enter CNS, so analgesia is maintained

ANTIDIARRHEAL DRUGS
Loperamide Activates -opioid receptors Slows motility in gut with Nonspecific, noninfectious Mild cramping but little or no CNS
in enteric nervous system negligible CNS effects diarrhea toxicity

Diphenoxylate: Similar to loperamide, but high doses can cause CNS opioid effects and toxicity
Colloidal bismuth compounds: Subsalicylate and citrate salts available. OTC preparations popular and have some value in travelers diarrhea due to adsorption of toxins
Kaolin + pectin: Adsorbent compounds available OTC in some countries

DRUGS FOR IRRITABLE BOWEL SYNDROME (IBS)

Alosetron 5-HT3 antagonist of high Reduces smooth muscle Approved for severe diarrhea- Rare but serious constipation
potency and duration of activity in gut predominant IBS in women ischemic colitis infarction
binding

Anticholinergics: Nonselective action on gut activity, usually associated with typical antimuscarinic toxicity
Chloride channel activator: Lubiprostone (see above); useful in constipation-predominant IBS in women; linaclotide (see above): useful in adults with
constipation-predominant IBS

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 1080 S ion X Special Topics

ect

Pharmacokinetics,
Subclass, Drug Mechanism of Action Effects Clinical Applications Toxicities, Interactions

ANTIEMETIC DRUGS
Ondansetron, other 5-HT3 blockade in gut and Extremely effective in First-line agents in cancer Usually given IV but orally active in

5-HT3 antagonists CNS with shorter duration of preventing chemotherapy- chemotherapy; also useful for prophylaxis 49 h duration of
binding than alosetron induced and postoperative postop emesis action very low toxicity but may
nausea and vomiting slow colonic transit

Aprepitant NK1-receptor blocker in CNS Interferes with vomiting Effective in reducing both early Given orally IV fosaprepitant

reflex no effect on 5-HT, and delayed emesis in cancer available fatigue, dizziness,
dopamine, or steroid chemotherapy diarrhea CYP interactions
receptors

Corticosteroids: Mechanism not known but useful in antiemetic IV cocktails

Antimuscarinics (scopolamine): Effective in emesis due to motion sickness; not other types

Antihistaminics: Moderate efficacy in motion sickness and chemotherapy-induced emesis

Phenothiazines: Act primarily through block of D2 and muscarinic receptors

Cannabinoids: Dronabinol is available for use in chemotherapy-induced nausea and vomiting, but is associated with CNS marijuana effects

DRUGS USED IN INFLAMMATORY BOWEL DISEASE (IBD)
5-Aminosalicylates, Mechanism uncertain may Topical therapeutic action Mild to moderately severe Sulfasalazine causes sulfonamide

eg, mesalamine in be inhibition of eicosanoid systemic absorption may Crohns disease and ulcerative toxicity and may cause GI upset,
many formulations inflammatory mediators cause toxicity colitis myalgias, arthralgias,
Sulfasalazine myelosuppression other

aminosalicylates much less toxic

Purine analogs and Mechanism uncertain may Generalized suppression of Moderately severe to severe GI upset, mucositis

antimetabolites, eg, promote apoptosis of immune processes Crohns disease and ulcerative myelosuppression purine
6-mercaptopurine, immune cells Methotrexate colitis analogs may cause hepatotoxicity,
methotrexate blocks dihydrofolate but rare with methotrexate at the
reductase low doses used

Anti-TNF antibodies, Bind tumor necrosis factor Suppression of several Infliximab: Moderately severe to Infusion reactions reactivation of

eg, infliximab, and prevent it from binding aspects of immune severe Crohns disease and latent tuberculosis increased risk
others to its receptors function, especially Th1 ulcerative colitis others of dangerous systemic fungal and
lymphocytes approved in Crohns disease bacterial infections

Corticosteroids: Generalized anti-inflammatory effect; see Chapter 39

PANCREATIC SUPPLEMENTS
Pancrelipase Replacement enzymes from Improves digestion of Pancreatic insufficiency due to Taken with every meal may

animal pancreatic extracts dietary fat, protein, and cystic fibrosis, pancreatitis, increase incidence of gout
carbohydrate pancreatectomy

Pancreatin: Similar pancreatic extracts but much lower potency; rarely used

BILE ACID THERAPY FOR GALLSTONES
Ursodiol Reduces cholesterol Dissolves gallstones Gallstones in patients refusing May cause diarrhea

secretion into bile or not eligible for surgery

DRUGS USED TO TREAT VARICEAL HEMORRHAGE

Octreotide Somatostatin analog May alter portal blood flow Patients with bleeding varices Reduced endocrine and exocrine

mechanism not certain and variceal pressures or at high risk of repeat pancreatic activity other
bleeding endocrine abnormalities GI upset

Beta blockers: Reduce cardiac output and splanchnic blood flow; see Chapter 10

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 CHAPTER 62 Drugs Used in the Treatment of Gastrointestinal Diseases 1081

P R E P A R A T I O N S A V A I L A B L E
Generic Name Available As Generic Name Available As
ANTACIDS Promethazine Generic, Phenergan, others
*
Aluminum hydroxide gel Generic, AlternaGEL, others Scopolamine Transderm Scop
*
Calcium carbonate Generic, Tums, others Trimethobenzamide Generic, Tigan, others
Combination aluminum Generic, Maalox, Mylanta, Gaviscon, SELECTED ANTI-INFLAMMATORY DRUGS USED IN
hydroxide and magnesium Gelusil, others GASTROINTESTINAL DISEASE (SEE ALSO CHAPTER 55)
hydroxide preparations* Adalimumab Humira
H 2 HISTAMINE RECEPTOR BLOCKERS Balsalazide Colazal
Cimetidine Generic, Tagamet, Tagamet HB* Budesonide Entocort, Uceris
Famotidine Generic, Pepcid, Pepcid AC,* Pepcid Certolizumab Cimzia
Complete* Golimumab Symponi
Nizatidine Generic, Axid, Axid AR* Hydrocortisone Cortenema, Cortifoam,
Ranitidine Generic, Zantac, Zantac 75* ProctofoamHC
SELECTED ANTICHOLINERGIC DRUGS Infliximab Remicade
Atropine Generic Mesalamine 5-ASA
Belladonna alkaloids tincture Generic Oral: Asacol
Dicyclomine Generic, Bentyl, others Rectal: Rowasa, Canasa
Glycopyrrolate Generic, Robinul Methylprednisolone Medrol Enpack
Hyoscyamine Anaspaz, Levsin, others Olsalazine Dipentum
Scopolamine Generic, Transderm Scop Sulfasalazine Generic, Azulfidine
PROTON PUMP INHIBITORS SELECTED ANTIDIARRHEAL DRUGS
Esomeprazole magnesium Nexium Bismuth subsalicylate* Pepto-Bismol, others
Esomeprazole strontium Difenoxin Motofen
*
Omeprazole Generic, Prilosec, Prilosec OTC Diphenoxylate Generic, Lomotil, others
Omeprazole-sodium bicarbonate Zegerid Loperamide* Generic, Imodium
Lansoprazole Generic, Prevacid BULK-FORMING LAXATIVES *
Dexlansoprazole Dexilant Methylcellulose Generic, Citrucel
Pantoprazole Generic, Protonix Psyllium Generic, Serutan, Metamucil, others
Rabeprazole Generic, Aciphex OTHER SELECTED LAXATIVE DRUGS
MUCOSAL PROTECTIVE AGENTS Alvimopan Entereg
Sucralfate Generic, Carafate Bisacodyl* Generic, Dulcolax, others
DIGESTIVE ENZYMES Cascara sagrada* Generic
Pancrelipase Creon, Pancrease, Zenpep, Pertyze, Docusate* Generic, Colace, others
Ultresa Lactulose Generic, Chronulac, Cephulac,
DRUGS FOR MOTILITY DISORDERS & SELECTED ANTIEMETICS others
5-HT 3 -RECEPTOR ANTAGONISTS Linaclotide Linzess
Alosetron Lotronex Lubiprostone Amitiza
Dolasetron Anzemet Magnesium hydroxide (milk of Generic
magnesia, Epsom Salt)*
Granisetron Generic, Kytril
Methylnaltrexone bromide Relistor
Ondansetron Generic, Zofran
Polycarbophil* Equalactin, Mitrolan, FiberCon,
Palonosetron Aloxi
FiberLax
OTHER MOTILITY AND ANTIEMETIC AGENTS
Polyethylene glycol electrolyte CoLyte, GoLYTELY, HalfLytely,
Aprepitant Emend solution Moviprep, others
Dronabinol Generic, Marinol Senna* Senokot, ExoLax, others
Fosaprepitant Emend, Emend IV Sodium Phosphate Fleets Phospho-soda, OsmoPrep,
Metoclopramide Generic, Reglan, others Visicol
Nabilone Cesamet DRUGS THAT DISSOLVE GALLSTONES
Prochlorperazine Generic, Compazine Ursodiol Generic, Actigall, URSO
*
Over-the-counter formulations.

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