Gastrointestinal Agents
AGENTS FOR NAUS EA AND VOMITING
Name a major che mose nsory are a for e me sis:
Chemoreceptor trigger zone (CT Z) W he re is the C TZ found?
Area postrema of the fourth ventricle of the brain
Give e xample s of drug classe s that are e ffe ctive in the tre atme nt of nause a and vomiting:
Antihistamine-anticholinergics; benzodiazepines; butyrophenones; cannabinoids; corticosteroids; phenothiazines; substituted benzamides; 5-HT3-receptor antagonists; neurokinin receptor antagonists
Give e xample s of spe cific drugs in e ach of the following drug classe s use d in the tre atme nt of nause a and vomiting:
Antihistamine -anticholine rgics
Diphenhydramine; hydroxyzine; meclizine; cyclizine; promethazine; pyrilamine; scopolamine; trimethobenzamide Be nz odiaz e pine s Substitute d be nz amide s
Metoclopramide
5-HT3--re ce ptor antagonists Ondansetron; dolasetron; granisetron Ne urokinin re ce ptor antagonists
Aprepitant (oral); fosaprepitant (IV formulation converted to aprepitant) Do synthe tic cannabinoids have psychotropic activity?
No
How doe s me toclopramide work as an antie me tic?
Blocks dopamine receptors centrally in the CT Z
W hat is intractable e me sis le ading to de hydration and hypote nsion during pre gnancy calle d?
Hyperemesis gravidarum
W hat are the drugs of choice for tre ating e me sis during pre gnancy?
Meclizine; cyclizine; promethazine
W hat antihistamine is ofte n use d to tre at motion sickne ss?
Meclizine
W hat anticholine rgic is ofte n use d to tre at motion sickne ss?
Scopolamine
How is scopolamine normally administe re d?
As a transdermal patch to prevent systemic anticholinergic effects
W hat me dication is ofte n use d in combination re gime ns to e nhance antie me tic activity?
Dexamethasone
W hat are the side e ffe cts of cannabinoids?
Anxiety; memory loss; confusion; motor incoordination; hallucinations; euphoria; relaxation; hunger; gynecomastia W hat are the side e ffe cts of the phe nothiaz ine antie me tics?
Extrapyramidal symptoms; sedation; hypotension
W hy doe sn’t ondanse tron cause e xtrapyramidal side e ffe cts?
Blocks 5-HT3 instead of dopamine receptors in the CT Z
W hat che mothe rapy age nt has one of the highe st e me toge nic pote ntials?
Cisplatin
W hat ove r-the -counte r (O TC ) me dication can be give n in combination with me toclopramide to re duce its e xtrapyramidal side e ffe cts?
Diphenhydramine can be used for its anticholinergic properties. EPS symptoms with metoclopramide use are due to central dopamine receptor blockade, and tardive dyskinesia, if it develops, may be irreversible. T herefore, metoclopramide should only be used for short-term therapy if possible.
W hat macrolide antibiotic also has prokine tic prope rtie s for the GI tract?
Erythromycin, though tolerance to this effect develops rapidly, limiting its usefulness AGENTS FOR DIARRHEA AND CONS TIPATION
Name thre e classe s of drugs that are e ffe ctive in the tre atme nt of diarrhe a:
1. Adsorbents 2. Antimotility agents 3. Antisecretory agents
De fine adsorbe nt:
A substance offering a suitable active surface, upon which other substances may adhere to
Give e xample s of spe cific drugs in e ach of the following drug classe s use d in the tre atme nt of diarrhe a:
Adsorbe nts
Kaolin; pectin; polycarbophil; attapulgite Antimotility age nts
Diphenoxylate; loperamide; morphine Antise cre tory age nts
Bismuth subsalicylate
Give the antidiarrhe al me chanism of action for e ach of the following drug classe s:
Adsorbe nts
Adsorbs (adheres to) drugs, nutrients, toxins, and digestive juices Antimotility age nts
Decrease peristalsis by activating presynaptic opioid receptors in the enteric nervous system Antise cre tory age nts
Decrease fluid secretion in the bowel
W hat adsorbe nt can absorb 60 time s its we ight in wate r and tre at both diarrhe a and constipation?
Polycarbophil
W hat are the pote ntial side e ffe cts of bismuth subsalicylate ?
Salicylism (tinnitus, nausea, vomiting); darkening of tongue; darkening of stools; induce gout attacks in susceptible patients W hat antidiarrhe al can de cre ase te tracycline absorption if give n concomitantly?
Bismuth subsalicylate
W hat antidiarrhe al is ofte n formulate d in combination with atropine ? Diphenoxylate
W hich class of antidiarrhe als can cause paralytic ile us?
Antimotility agents
W hat me dication is ofte n use d to tre at flushing and diarrhe a se e n in carcinoid syndrome and vasoactive inte stinal pe ptide se cre ting tumors (VIPomas)?
Octreotide
W hat is octre otide ’s me chanism of action?
Synthetic analog of somatostatin which blocks release of serotonin and other vasoactive peptides; direct inhibitory effects on intestinal secretion; direct stimulatory effects on intestinal absorption
W hat are the non-antidiarrhe al use s of octre otide ? Esophageal varices; acromegaly
W hat me dication can be use d in conjunction with antibiotics to bulk stools and absorb Clostridium difficile toxins A and B in C. difficile colitis?
Cholestyramine, a nonabsorbable binding agent W hat type s of me dications cause constipation?
Opioid analgesics; anticholinergics; calcium-containing antacids; aluminum-containing antacids; calcium channel blockers; clonidine; iron; sodium polystyrene sulfonate
Give e xample s of drug classe s that are e ffe ctive in the tre atme nt of constipation:
Bulk forming agents; irritants and stimulants; stool softeners
Give e xample s of spe cific drugs in e ach of the following drug classe s use d in the tre atme nt of constipation:
Bulk forming age nts
Methylcellulose; psyllium; bran; magnesium-containing salts; polyethylene glycol O smotic laxative s
Lactulose; magnesium hydroxide (milk of magnesia); sorbitol; magnesium citrate; sodium phosphate; polyethylene glycol Irritants and stimulants
Cascara; senna; aloe; bisacodyl Stool softe ne rs
Mineral oil; docusate (oral or enema, trade name: Colace); glycerin suppository C l− channe l activators
Lubiprostone (Amitiza)
Give the me chanism of action for e ach of the following drug classe s:
Bulk-forming age nts
Form gels in large intestine which causes water retention and intestinal distention, thereby increasing peristaltic activity O smotic laxative s
Nonabsorbable compounds which draw fluid into the colon to maintain osmotic neutrality Irritants and stimulants
Irritate gut lining which subsequently increases peristalsis Stool softe ne rs
Surfactants that become emulsified with stool, thereby softening feces C l channe l activators
Activate CIC-2 Cl− channels in the apical membrane of intestinal cells increasing fluid and intestinal motility without altering serum Na+ or K+ levels. T he effects are localized to the GI tract, increase fluid secretion into the intestinal lumen, and accelerate fecal transit.
W hat are the pote ntial side e ffe cts of bisacodyl?
Abdominal cramping; atonic colon CLINICAL VIGNETTES
A 50-ye ar-old woman is in the surgical inte nsive care unit (IC U) status post right middle ce re bral arte ry he morrhagic stroke . She is be ing me chanically ve ntilate d. He r morning laboratorie s come back with a plate le t count of 50,000 (normal 150,000-450,000). Give n he r history, she is not on de e p ve nous thrombosis (DVT) prophylaxis with he parin. W hat othe r prophylactic me dication, commonly e mploye d in a critical care se tting, may be re sponsible for he r drop in plate le t count?
Patients in ICUs are routinely put on DVT and GI prophylaxis given the prolonged immobility and high physiologic stress of intensive care. Pharmacologic DVT prophylaxis is not appropriate in this patient, and mechanical methods such as sequential compression stockings should be used instead. However, this patient was most likely started on omeprazole for prevention of stress-induced gastric ulcers. Omeprazole can cause thrombocytopenia. T his patient should be switched to a different GI prophylactic medication. Esomeprazole, the S-enantiomer of omeprazole, while controversial as to whether or not it is more effective to inhibit stomach acid secretion, does not carry the same risk of lowering platelets.
A 60-ye ar-old woman with a past me dical history of rhe umatoid arthritis (RA) and chronic iron de ficie ncy ane mia is found to have blood in he r stool.
C olonoscopy is ne gative , but a gastric ulce ration is discove re d upon uppe r e ndoscopy. Afte r succe ssful tre atme nt of the ulce r, what me dication could be adde d to the patie nt’s re gime n to pre ve nt a re pe at ulce r or gastric pe rforation?
Patients with a chronic inflammatory disease such as RA are often successful in relieving their pain symptoms with long-term treatment with NSAIDs. However, this therapy can lead to gastric ulceration and chronic gastrointestinal bleeding that can lead to iron deficiency anemia. T his anemia is often overlooked in patients with chronic autoimmune disorders as anemia of chronic disease. All GI bleeding must be considered colon cancer until proven otherwise, especially in patients older than 50 years, but once ruled out the next most likely location in this patient is a gastric ulcer due to disruption of the gastric mucosa by long-term NSAID administration. Because of the patient’s RA, NSAID cessation is difficult. In patients such as this, addition of misoprostol, a prostaglandin analog, may be appropriate.
An 86-ye ar-old woman with a history of chronic constipation is tre ate d with lactulose with good re lie f of he r constipation. Howe ve r, she complains of painful abdominal cramps and e mbarrassing flatus and wishe s to try anothe r me dication. W hat laxative has a similar me chanism of action to lactulose and will not cause large e le ctrolyte imbalance s, making it safe to use in this e lde rly patie nt?
Polyethylene glycol (PEG) is an osmotic laxative used in high concentration formulas as a bowel cleanser prior to endoscopic procedures. It is effective in lower concentrations for treatment of chronic constipation. Unlike lactulose and sorbitol, it is not metabolized by colonic bacteria, decreasing colonic gas formation. It does not cause large fluid or electrolyte shifts. T herefore, unlike magnesium citrate, sodium phosphate, or magnesium hydroxide, PEG does not carry a risk for electrolyte disturbances, making it an ideal choice for elderly patients and/or patients with renal insufficiency.