Drugs Affecting the GI System Flashcards
4 families of Antacids
Magnesium hydroxide
Aluminum hydroxide
Sodium bicarbonate
Calcium carbonate
Magnesium hydroxide
Dangerous when used in patients w/ renal failure; failing kidneys can’t excrete Mg++ and become toxic
Drugs: maalox, mylanta, Milk of magnesia
Aluminum hydroxide
Can bind with warfarin, digoxin, tetracyclines
Sodium bicarbonate
Can exacerbate heart failure, HTN, other cardiac problems; renal failure
Calcium carbonate
Can cause kidney stones
Drugs: Tums
MOA of Antacids
React w/ gastric acid to produce neutral salts or salts low in acidity to neutralize acids in the gastrointestinal (GI) tract
Antacids create a local environment that favors healing rather than stimulating cell growth & tissue repair. Thus, antacids need to be taken until the ulcer heals (usually 6-8 weeks). It is important for the practitioner to stress the need to continue antacids as directed even though pain may be relieved.
calcium carbonate (TUMS, Titralac)
Prompt-acting and prolonged but can be absorbed and cause hypercalcemia and acid rebound (by stimulating release of gastrin).
The most common side effect is constipation.
Excessive doses with calcium-containing dairy products can lead to hypercalcemia, renal insufficiency, and metabolic alkalosis (“milk-alkali syndrome” – SX HA, nausea, irritability, weakness).
Antacids Cautions
- Abdominal pain of unknown cause
- Calcium-based antacids contraindicated if patient is hypercalcemic or has renal calculi.
- Magnesium-based antacids contraindicated in patients with renal failure or renal insufficiency.
- Aluminum-based antacids should not be used in patients with renal failure on dialysis.
- Sodium content may affect patients with hypertension, congestive heart failure, or renal failure.
Side Effects of Antacids
The major side effect of antacids is altered gut motility.
Aluminum & calcium salts produce constipation; magnesium salts produce diarrhea.
Many commercial preparations are mixtures to balance effect on GI motility.
Serum electrolytes & acid-base balance may be affected, particularly by systemic antacids (sodium bicarbonate), sodium-containing drugs, and magnesium in patients with renal insufficiency.
There is usually no problem in pregnant and breast-feeding women. (Pregnancy Category A)
Elderly people with impaired renal function must use magnesium products carefully. Those with cardiovascular problems may need to avoid antacids containing sodium (e.g., Rolaids).
Magnesium-based antacids may cause diarrhea.
Antacid interactions
Separate antacid administration with other drugs by at least 2 hours.
Antacids interfere with the absorption of tetracyclines, fluoroquinolones, penicillamine, and ketoconazole.
They should NOT be used concurrently with certain enteric-coated preparations (e.g., Dulcolax Laxative). Antacids may cause breakdown of enteric coating in the stomach causing nausea & vomiting.
Signs of magnesium intoxication
(Usually due to renal insufficiency) include NV, hypotension, lethargy, confusion, and muscle weakness
Administration of antacids
Usually taken 1 to 3 hours after meals and at bedtime
Sucralfate (Carafate)
Selectively binds to ulcer tissue, acting as a barrier
Given 1 hour before meals and at bedtime but not within a half an hour of antacids.
May cause constipation.
The drug interferes with the absorption of digoxin, beta-blockers, warfarin, phenytoin, some antiarrhythmics, and fluoroquinolones.
Pregnancy category B.
Misprostol (Cytotec)
Inhibits gastric secretion, has mucosal protective qualities
Facilitates regeneration of the mucosa after NSAID-induced injury. It enhances mucous and bicarbonate secretion.
ADRs:
Diarrhea (13 to 40%)
Abdominal pain
Women – spotting & dysmenorrhea
Category X – prostaglandins stimulate uterine contractions
Off-label: cervical ripening and labor induction, as an abortifacient
Histamine 2 Receptor Antagonists (H2RAs)
Reversible competitive blockers of histamine at histamine 2 receptors located on the parietal cells of the stomach.
Highly selective. Reduce gastric acid secretion by 35% to 50%.
Are effective in alleviating symptoms and in preventing complications of peptic ulcer disease.
Treat: gastric & duodenal ulcers, GERD, Zollinger-Ellison Syndrome (hypersecretion of gastric acid -> peptic ulcers), aspiration pneumonitis (cimetidine), heartburn, acid indigestion, sour stomach
Cimetidine (Tagamet)
H2RA
Cimetidine (Tagamet) – 1st drug.
Interactions with theophylline, warfarin, and phenytoin; not used much.
Large doses -> may develop central effects such as severe agitation, slurred speech, confusion, & delirium. This is especially applicable to the elderly or subjects with renal impairment. This CNS effect is generally not seen with the other H2 antagonists
Ranitidine (Zantac)
H2RA
Occasional reversible hepatitis or hepatocellular disorders have occurred.
Famotidine (Pepcid)
H2RA
Nizatidine (Axid)
H2RA
Hepatocellular injury may occur
Precautions, contraindications, ADRs of H2RAs
Cautious use in renal impairment
Pregnancy category B
Ranitidine and famotidine use approved in children
ADRs:
Gynecomastia and impotence-especially with cimetidine
Mental confusion, agitation, psychosis, depression, and disorientation
Elevating gastric pH increases risk of pneumonia
Agranulocytosis, granulocytopenia, thrombocytopenia, and aplastic anemia
–prazole
Proton Pump Inhibitors (PPIs)
Omeprazole (Prilosec) Lansoprazole (Prevacid) Dexlansoprazole (Kapidex) Pantoprazole (Protonix) Rabeprazole (Aciphex) Esomeprazole Magnesium (Nexium (#1))
PPIs
Decrease in acid secretion lasts for up to 72 hours after each dose.
Short-term treatment of active gastric ulcers, active duodenal ulcers
Erosive esophagitis
Symptomatic GERD
Active peptic ulcers w/ H. pylori infection
Long-term treatment of hypersecretory states such as Zollinger-Ellison syndrome
Discontinuation of PPIs may result in acid rebound.
Extensively metabolized in the liver; use cautiously in patients with hepatic dysfunction and the elderly
PPIs and Children
Esomeprazole, omeprazole, and lansoprazole approved for short-term use in children as young as 1 year.
Pantoprazole and rabeprazole not approved in children less than 12 years.
PPIs and Pregnancy
Pregnancy category B or C.
Congenital anomalies have been reported: Use with caution.
ADRs of PPIs
Abdominal pain, Diarrhea, N/V
Increased risk of pneumonia
Long term use – increased risk of fractures due to decreased Ca absorption
Rebound hypersecretion
Hypomagnesemia
Long-term suppression of acid may allow bacteria overgrowth in the gut including Clostridium difficile.
Black Box Warning for Omeprazole
Clopidogrel (Plavix) has a Black Box warning regarding interactions with Omeprazole.
Bismuth Subsalicylate (Pepto-Bismol)
Absorbent anti-diarrheal.
Effective for preventing traveler’s diarrhea. It acts not only as an adsorbent.
Can be used to treat H-Pylori.
Remember, bismuth subsalicylate will likely cause black stool and sometimes a black tongue.
Diphenoxylate (opioid) and loperamide (Imodium) are narcotic derivatives that are relatively free of analgesic, euphoric or abuse-promoting effects but have a predominant effect on the gut. They decrease propulsive movements, allowing more time for water to be absorbed from fecal contents. Are generally for management of acute diarrhea of nonspecific origin, or chronic diarrhea caused by inflammatory bowel disease, or traveler’s diarrhea.
diphenoxylate with atropine is Lomotil & it contains a sub therapeutic dose of atropine to produce unpleasant effects if taken in overdose, thus discourages abuse. Side effects of Lomotil include drowsiness, dry mouth, abdominal cramps & dizziness. Euphoria has been reported.
Diphenoxylate with atropine (Lomotil)
Opiate anti-diarrheal.
Narcotic derivative. Relatively free of analgesic, euphoric or abuse-promoting effects but have a predominant effect on the gut.
Decrease propulsive movements, allowing more time for water to be absorbed from fecal contents.
Generally for management of acute diarrhea of nonspecific origin, or chronic diarrhea caused by inflammatory bowel disease, or traveler’s diarrhea.
Contains a subtherapeutic dose of atropine to produce unpleasant effects if taken in overdose, thus discourages abuse. Side effects of Lomotil include drowsiness, dry mouth, abdominal cramps & dizziness.
Euphoria has been reported.
Loperamide (Imodium)
Opiate anti-diarrheal.
Narcotic derivative. Relatively free of analgesic, euphoric or abuse-promoting effects but have a predominant effect on the gut.
Decrease propulsive movements, allowing more time for water to be absorbed from fecal contents.
Generally for management of acute diarrhea of nonspecific origin, or chronic diarrhea caused by inflammatory bowel disease, or traveler’s diarrhea.
Diphenoxin with atropine (Motofen)
Opiate anti-diarrheal.
Kaolin and pectin
Absorbent anti-diarrheal.
Bowel disease
Loperamide QID may be used as adjunct therapy.
Chronic infantile diarrhea
Bismuth subsalicylate
Traveler’s diarrhea
Bismuth subsalicylate with each meal and at bedtime to prevent traveler’s diarrhea
If diarrhea develops
Bismuth subsalicylate every 30 minutes (maximum 8 doses) for up to 48 hours
Loperamide 4 mg then 2 mg after every stool (maximum 8 mg/day)
Chronic infantile diarrhea
Bismuth Subsalicylate (Pepto-Bismol)
Traveler’s diarrhea
Bismuth Subsalicylate (Pepto-Bismol) with each meal and at bedtime to prevent traveler’s diarrhea If diarrhea develops, Bismuth Subsalicylate (Pepto-Bismol) every 30 minutes (maximum 8 doses) for up to 48 hours Loperamide (Imodium) 4 mg then 2 mg after every stool (maximum 8 mg/day)
Severe diarrhea with fever and dysentery
Treated with antibiotic alone (eg. metronidazole); antimotility agents are contraindicated.
Cholera, shigella
TMP/SMX
Giardia, amebiasis
Metronidazole
Clostridia
Vancomycin
Metronidazole, or
Fidaxomicin
Traveler’s diarrhea
Colistin sulfate (Coly-Mycin S) may be used in children For travelers diarrhea caused by E coli or shigella.
Doxycycline
Azithromycin, or
Ciprofloxacin
Can also treat with Rifaximin (Xifaxan)
Crofelemir (Fyulyzaq)
Delayed-release tablets are indicated for the treatment of HIV-related diarrhea.
Inhibits calcium-activated chloride channels. The drug is minimally absorbed.
Antiemetics
Antihistamines Phenothiazines Sedative hypnotics Cannabinoids 5-HT3 receptor antagonists (Serotonin Antagonist)
5-HT3 receptor antagonists (Serotonin Antagonist)
Block serotonin on vagal nerve terminals and in the chemoreceptor trigger zone.
Chemotherapy induced nausea/vomiting (CINV)
N/V associated with radiation therapy
N/V associated w/ viral gastritis (off label)
Pregnancy related N/V (off label)
Post anesthesia N/V
Adverse Effects
Headache, Diarrhea, Dizziness
Prolonged QT interval -> inc risk of torsades
Use cautiously in the following situations:
Patients w/ bradycardia
Patients w/ heart failure
Patients w/ electrolyte abnormalities
Ondansetron [Zofran]
5-HT3 receptor antagonists (Serotonin Antagonist)
Granisetron [Kytril HCl]- [Sancuso transdermal]
5-HT3 receptor antagonists (Serotonin Antagonist)
Dolasetron [Anzemet]
5-HT3 receptor antagonists (Serotonin Antagonist)
Palonosetron [Aloxi]
5-HT3 receptor antagonists (Serotonin Antagonist)
Antihistamines
Strong anticholinergic effects as well as histamine1-blocking effects.
ADRs:
Drowsiness
Anticholinergic effects of dry mouth, blurred vision, and urinary retention
Phenothiazines
Block dopamine receptors in the chemoreceptor trigger zone.
(Stimulation of dopamine receptors cause nausea and vomiting by increasing impulses to the NTS and the dorsal vagal complex.)
ADRs:
Produce extrapyramidal symptoms (EPS). Contraindicated in Parkinson’s disease.
Anticholinergic effects
Hypotension
Sedation
Cannabinoids
Work in the CNS to prevent nausea and vomiting associated with cancer chemotherapy. CINV (2nd line therapy).
Potential unpleasant effects such as temporal disintegration, dissociation, depersonalization, & dysphoria. Contraindicated in patients w/ psychiatric disorders.
Tachycardia & hypotension -> use cautiously in patients with CV history.
Drowsiness -> do not combine w/ ETOH, sedatives, or CNS depressants.
Dronabinol (Marinol)
Cannabinoid
Stimulation of appetite in patients w/ AIDS induced anorexia.
Use with caution in patients with seizure disorders.
Nabilone (Cesamet)
Cannabinoid
Cyclizine (Marezine)
Antihistamine
meclizine (Antivert)
Antihistamine
May be useful in treating vertigo of motion sickness or vertigo of vestibular origin.
buclizine (Bucladin-S)
Antihistamine
dimenhydrinate (Dramamine)
Antihistamine
May be useful in treating vertigo of motion sickness or vertigo of vestibular origin.
Prochlorperazine (Compazine)
Phenothiazine
Promethazine (Phenergan)
Phenothiazine
Metoclopramide
"Prokinetic" or "promotility" drug, which increases lower esophageal sphincter pressure and improves esophageal peristalsis. It stimulates motility of the upper GI tract without increasing secretions from the pancreas or having an effect on gall bladder motility. Treat: N/V (IV) Diabetic gastroparesis (oral) GERD (oral) Hiccups (off label)
Metoclopramide Warnings/ADRs
Black Box Warning: Risk of developing tardive dyskinesia. Use cautiously in patients with a history of depression.
Depression may occur, including suicidal ideation.
Contraindicated in GI hemorrhage, mechanical obstruction, new surgery on the GI tract, or perforation. Diarrhea.
Hypoglycemia in patients with diabetes.
Pregnancy Category B
Six Classes of Laxatives
Stimulants Osmotics Bulk-producing laxatives Lubricants Surfactants Hyperosmolar laxatives
Cascara
Stimulant Laxative
Irritate the intestinal mucosa or stimulate the nerve endings of the intestinal smooth muscle.
Senna
Stimulant Laxative
Irritate the intestinal mucosa or stimulate the nerve endings of the intestinal smooth muscle.
Bisacodyl
Stimulant Laxative
Irritate the intestinal mucosa or stimulate the nerve endings of the intestinal smooth muscle.
Castor Oil
Stimulant Laxative
Irritate the intestinal mucosa or stimulate the nerve endings of the intestinal smooth muscle.
Magnesium Hydroxide
Osmotic Laxative
Magnesium Citrate
Osmotic Laxative
Sodium Phosphate
Osmotic Laxative
Polyethylene Glycol
Osmotic Laxative
Psyllium
Bulk-producing laxative
Decreased absorption of digoxin, warfarin, & salicylates if taken within 2 hours of fiber or bulk forming laxatives
Methylcellulose
Bulk-producing laxative
Decreased absorption of digoxin, warfarin, & salicylates if taken within 2 hours of fiber or bulk forming laxatives
Polycarbophil
Bulk-producing laxative
Decreased absorption of digoxin, warfarin, & salicylates if taken within 2 hours of fiber or bulk forming laxatives
Mineral Oil
Lubricant Laxative
Docusate(s)
Surfactants
Detergent action allows water & fat to penetrate the stool, making it softer & easier to eliminate.
Also stimulate electrolyte & fluid secretion from intestinal muscoal cells.
Glycerine
Hyperosmolar laxative
Given as a suppository evacuates the colon in 15-60 minutes.
Local osmotic effect draws water into the rectum, stretching the rectum and stimulating defecation.
Glycerin helpful for bowel retraining.
Lactulose
Hyperosmolar laxative ADRs: Abdominal distention, gas, & abdominal cramps N/V Diarrhea Hypokalemia Hypovolemia Increased glucose levels
All laxatives are contraindicated…
In the presence of nausea, vomiting, undiagnosed abdominal pain, or if bowel obstruction is suspected/diagnosed
Linaclotide [Linzess]
Chronic Idiopathic Constipation
It acts on the lumen of the intestinal epithelium to cause increased secretion of chloride and bicarbonate into the intestine which results in increased intestinal fluid and accelerated transit.
Contraindicated in children, or suspected mechanical GI obstruction.
Lubiprostone [Amitiza]
Chronic Idiopathic Constipation
Methylnaltrexone [Relistor]
Opioid-induced constipation
Mu opioid antagonist that binds to Mu receptors in the GI tract.
NOT a laxative.
Treatment of inflammatory bowel diseases (UC, Chron’s) 5 Basic Classes of Medications
Aminosalicylates Antibiotics Corticosteroids Immunomodulators Biologic Therapies
sulfasalazine
Aminosalicylate
mesalamine
Aminosalicylate
olsalazine
Aminosalicylate
balsalazide
Aminosalicylate
Aminosalicylates for IBD
Used for both ulcerative colitis and Crohn’s disease; however, they are much more effective for ulcerative colitis and are being used less often for Crohn’s disease
Antibiotics for IBD
Used selectively in patients with Crohn’s disease
Used in patients with IBD who develop infection with Clostridium difficile
Effective in treating fistulas and fissures in Crohn’s disease
azathioprine
Immunomodulator
cyclosporine
Immunomodulator
6-mercaptopurine,
Immunomodulator
methotrexate
Immunomodulator
Biologic Therapies
anti-TNF
anti-Integrins
adalimumab
Biologic therapy to treat UC, Chron’s
golimumab
Biologic therapy to treat UC
infliximab
Biologic therapy to treat UC, Chron’s
vedolizumab
Biologic therapy to treat UC, Chron’s
certolizumab pegol
Biologic therapy to treat UC, Chron’s
Orlistat
Lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats.
Pregnancy Category B
The drug may be taken with each main meal.
ADRs: oily evacuation, flatus, fecal urgency, and fecal incontinence.
Diethylpropion
Nonamphetamines, but CNS stimulants that suppress appetite by increasing the availability of NE in the brain.
Indicated only for short term (3 months or less) use.
Tolerance can develop; abuse may occur, and the drugs cause increased alertness, decreased fatigue, nervousness & insomnia. Peripheral effects are tachycardia, angina pain & hypertension.
Phentermine
Nonamphetamines, but CNS stimulants that suppress appetite by increasing the availability of NE in the brain.
Indicated only for short term (3 months or less) use.
Tolerance can develop; abuse may occur, and the drugs cause increased alertness, decreased fatigue, nervousness & insomnia. Peripheral effects are tachycardia, angina pain & hypertension.
Phentermine with topiramate (Qnexa)
Once-daily, controlled-release, combination weight-loss product approved as an adjunct to diet and exercise for chronic weight management of obese or overweight patients with weight-related comorbidities.
PHEN/TPM is modestly effective and a viable option for patients interested in losing weight.
Side effects that were reported in >5% of patients included paresthesias, dizziness, dysgeusia, insomnia, constipation, and dry mouth.
Topiramate and zonisamide [Zonegran]
Weight reduction.
High incidence of adverse effects; most common were altered taste, constipation, diarrhea, dry mouth, headache, fatigue, N/V, somnolence, speech problems, impaired attention, memory problems, anxiety, and depression.
PUD Treatment, Triple Therapy
PPI plus
Clarithromycin or Metronidazole
Amoxicillin
Treat for 10 to 14 days
PUD Treatment, Quadruple Therapy
PPI plus Metronidazole Tetracycline Bismuth Subsalicylate Treat for 14 days.
Usually used as second-line therapy in patients who fail first-line therapy.
PUD Treatment, Levofloxacin-based Triple Therapy
PPI twice daily
Levofloxacin
Amoxicillin
Treat for 10 to 14 days.
Second-line or rescue therapy.
Common ADRs of PUD Treatment
Treatment regimens using metronidazole (Flagyl) or clarithromycin (Biaxin) cause a metallic taste in the mouth.
Alcoholic beverages (eg, beer, wine) should be avoided while taking metronidazole; the combination can cause skin flushing, headache, nausea, vomiting, sweating, and a rapid heart rate.
Bismuth causes the stool to become black and may cause constipation.
Many of the regimens cause diarrhea and stomach cramps
