Gastrointestinal Flashcards
Amoxicillin
Antibiotic
Low resistance/toxicity
Clarithromycin
Antibiotic
Has shown increasing resistance
Metronidazole
Antibiotic
For patients who have penicillin allergies
Anaerobic-specific
Tetracycline
Antibiotic
Used in bismuth-based quadruple therapy
(bismuth subsalicylate + metronidazole + tetracycline + PPI or H2RA)
Bismuth subsalicylate
Antibiotic
Colloidal suspension in MgAl silicate clay
Salicylate is absorbed (anti-secretory, anti-inflammatory)
Bismuth is excreted in feces (antibacterial activity against HP, binds E. coli enterotoxins)
Use: PUD, diarrhea, nausea, cramping
Adverse: black discoloration of stool and tongue (bismuth sulfide), salicylism (tinnitus), Reye’s syndrome
Aluminum hydroxide-magnesium hydroxide
Antacid
Alkaline compound that neutralizes gastric acid (raises stomach pH to ~5)
Acid-neutralizing capacity (ANC) unit
Rapid onset, short duration
Mg2+: diarrhea (stimulates peristalsis)
Al3+: smooth muscle relaxation (counters peristalsis)
Not well absorbed and don’t generate CO2
Use: relieve mild sx of dyspepsia and GERD
Interferes with absorption of other drugs
Cimetidine
H2RA
Block acid secretin from parietal cells
Indirectly decreases gastrin and ACh-induced acid secretion
Competitive inhibitors of H2 receptors (highly selective)
Prophylaxis
Use: PUD (short term) , GERD (nocturnal), Aspiration pneumonitis
Adverse: very well tolerated, endocrine effects, CNS effects, pneumonia (bacterial colonization of stomach)
Inhibits multiple CYP isoforms
Omeprazole
PPI
NOT ACTIVATED IN LUMEN
ABSORBED IN SI
Prodrug. Irreversibly inhibits H+/K+/ATPase.
Activated within parietal cells
Take 30 minutes before meals. (stimulate acid-formation within parietal cells)
Reduce acid secretions by 95% within 2 hours. Can persist for 2-3 days (irreversible)
Enteric coated formulation (bypass acidic environment), absorbed at alkaline pH.
CYP 2C19, 3A4
Asian variant of 2C19 –> slow metabolism, potential toxicity
Use: PUD, GERD, Zollinger-Ellison (gastrinoma), NSAID-assc ulcers in pts who continue NSAID use
Adverse: well tolerated, n, constipation/diarrhea, flatulence, pneumonia, decreased Ca absorption
Interacts with warfarin, diazepam, cyclosporine, clopidogrel
Rebound hypersecretion of stomach acid
Sucralfate
Mucosal protectant
Sulfate sucrose and aluminum hydroxide
Forms gel at pH<4
Binds necrotic tissue (barrier to acid and pepsin)
Not absorbed, no acid-neutralizing activity, no acid-reduction
Take on empty stomach 1h before meals
Use: duodenal and stress ulcers
Lower risk of nosocomial pneumonia
Adverse: constipation, reduced absorption of other drugs
Misoprestol
Prostaglandin (PGE1) analog
Substitues for PG when synthesis is inhibited by NSAIDs
Reduces acid secretion from parietal cells
Promotes bicarb and mucus secretion from epithelial cells
Use: prevent gastric ulcers in pts using NSAIDs for long-term therapy, in combo with mifepristone (RU-486) to induce abortion (uterine contraction)
Adverse: dose-dependent diarrhea
DO NOT USE DURING PREGNANCY
Psyllium
Laxative (bulk-forming)
Group III (slow onset–1-3 days, soft stool)
MOA: non-digestible/non-absorbable, swell with water –> viscous solution –> stretches GI wall –> peristalsis
Use: temporary treatment of mild constipation
Adverse: administered with full glass of H2O to prevent impaction
Bisacodyl
Laxative (stimulant (irritant))
Group II (intermediate latency–6-12 hours, semi-fluid stool)
MOA: stimulate (irritate) GI motility, increase H2O and electrolytes within lumen
Oral or rectal administration
Use: opioid-induced constipation, constipation from slow intestinal transit
Widely used and frequently misused/abused
Adverse: proctitis (long term)
Methylnaltrexone
Laxative
Antagonist (mu)
Treat opioid-induced constipation
Quaternary derivative of naltrexone with reduced ability to cross BBB
Docusate sodium
Laxative (surfactant–stool softener)
Group III (slow onset–1-3 days, soft stool)
MOA: lower surface tension –> water penetration
May decrease water absorption by intestinal wall
Use: mild constipation, take with full glass of water
Magnesium hydroxide
Laxative (osmotic)
Group I (rapid action–2-6 hours, watery stool)
MOA: osmotic action drawing H2O into lumen –> stool swelling –> stretching
TAKE ON EMPTY STOMACH
Use: Low dose = group II effect, High dose = group I effect (colonoscopy), purge to remove ingested toxins/evacuate dead parasites
Adverse: substantial dehydration, electrolyte imbalance, Mg2+ can cause toxicity in patients with impaired renal function
Lactulose
Laxative (osmotic)
Group I (rapid action–2-6 hours, watery stool )
MOA: osmotic action drawing H2O into lumen –> stool swelling –> stretching
TAKE ON EMPTY STOMACH
Use: Low dose = group II effect, High dose = group I effect (colonoscopy), purge to remove ingested toxins/evacuate dead parasites
Treat hepatic encephalopathy, reduce plasma ammonia levels (via acid trapping NH3 produced by bacteria in non–absorbable NH4+)
Titrate dose to achieve 2-3 soft stools/day
Adverse: substantial dehydration, electrolyte imbalance
Loperamide
Antidiarrheal
Opioid
MOA: myenteric opiate receptors –> reduce secretory activity (delta) and GI motility (mu)
Loperamide: 40-50x more potent diarrheal than morphine
PK: well absorbed (oral), poor penetration of BBB
Adverse: constipation
Diphenoxylate
Antidiarrheal
Opioid
MOA: myenteric opiate receptors –> reduce secretory activity (delta) and GI motility (mu)
PK: well absorbed (oral), high oral doses can cause morphine-like subjective responses (schedule V) (contain atropine [dysphoria] to discourage abuse)
Bismuth subsalicylate
Antidiarrheal
Reduce stool frequency and liquidity
Salicylate inhibition of intestinal prostaglandin and chloride secretion
Ondansetron
Antiemetic
5-HT3 receptor antagonist
MOA: most effective antiemetic agent, enhanced efficacy by corticosteroids
PK: IV administration, long duration, cleared by CYP3A4, 1A2, 2D6
Use: minimize/prevent emesis from CINV and radiation, hyperemesis of pregnancy, postoperative nausea (vagal stimulation)
NOT EFFECTIVE FOR MOTION SICKNESS OR DELAYED CINV NAUSEA
Adverse: well-tolerated
Aprepitant
Antiemetic Substance P receptor (NK1) antagonist Blocks NK1 receptors in brain (STN and area pastrami) PK: 3A4, induces 2D6 Use: delayed nausea Adverse: well tolerated
Metoclopramide
Prokinetic
MOA: dopamine D2 receptor antagonist
D2 receptor stimulation –> inhibits motility –> reduces ACh release (myenteric plexus)
Blockage of this = increased motility
Effects confined to upper GI trat, increases lower esophageal sphincter tone
Relieves n/v by antagonism of D2-R in CTZ
Use: n/v (GI dysmotility syndromes, migraines), GERD, gastroparesis
Adverse: extrapyramidal effects (parkonsonism), Tardive dyskinesia, hyperprolactinemia
Alosetron
IBS
5-HT3 receptor antagonist
MOA: decrease GI motility, inhibits unpleasant visceral afferent sensations
Use: diarrhea-predominant IBS (FEMALE patients only)
Adverse: severe constipation (10%), life-threatening ischemic colitis (THIS SHIT IS DANGEROUS)
DO NOT USE IN CONSTIPATION-DEPENDENT IBS
LAST LINE AGENT
Sulfasalazine
IBD
Mesalamine (5-ASA)-based therapy
Prodrug: azo (N=N) bond cleaved by intestinal flora –> 5-ASA
Topical (non-systemic) action on luminal surface of colon
MOA unclear: does not involve COX inhibition
Use: induce and maintain remission in UC
Adverse: due to sulfapyridine metabolite, GI problems, HA, arthralgia, myalgia, myelosuppression
Infliximab
IBD
Anti-TNF-based therapy
MOA: chimeric monoclonal Ab against TNF-alpha (cytokine–> immune/inflammatory response)
IV infusion slowly with antihistamines or anti-infl agents (prevent infusion reactions)
Maintains remission in patients with Crohn’s disease; closes fistulas
Adverse (serious): neutropenia, INFECTION (TB), heart failure, MALIGNANCY (Lymphomas), pulmonary disease, demyelinating disease, cutaneous reactions, allergic reactions
Psyllium
Laxative (Bulk forming)
Creates a stretch to simulate peristalsis
Group III: slow onset (1-3 days), soft-formed stool
MOA: non-digestible/non-absorbale, swell with water –> viscous solution –> softer + increased volume –> stretch
Use: mild constipation (temporary)
Adverse: give with full glass of water (prevent impaction)
Bisacodyl
Laxative (stimulant)
Irritates colonic mucosa to stimulate peristalsis.
Group II: intermediate latency (6-12h), semi-fluid stools
MOA: stimulate (irritate) GI motility, increase water/electrolytes within lumen
Oral or rectal suppository (rapid onset)
Use: opioid-induced constipation, constipation from slow intestinal transit
WIDELY USED AND MISUSED/ABUSED
Adverse: proctitis (long-term use)
Methylnaltrexone
Laxative Antagonist at mu receptor Treat opioid-induced constipation Quaternary derivative of naltrexone Reduced ability to cross BBB
Docusate sodium
Laxative (surfactant)
Stool softener. Pulls water into stool to create a stretch.
Group III: slow onset (1-3 days), soft-formed stool
MOA: lowers surface tension –> penetration of water
May decrease water absorption by intestinal wall
Use: mild constipation, take with full glass of water
Magnesium hydroxide
Laxative (osmotic)
Pulls water into colon.
Group I: rapid action (2-6h), watery consistency
MOA: poorly absorbed salts/sugars. Draw water into intestinal lumen–> stool swelling –> stretch
TAKE ON EMPTY STOMACH
Low dose: mild to mod constipation
High dose: fluid evacuation of bowel (surgical prep)
Adverse: dehydration, electrolyte imbalance, systemic absorption of Mg2+ –> toxicity (if impaired renal fxn)
Lactulose
Laxative (osmotic)
Group I: rapid action (2-6h), watery consistency
Group I: rapid action (2-6h), watery consistency
MOA: poorly absorbed salts/sugars. Draw water into intestinal lumen–> stool swelling –> stretch
TAKE ON EMPTY STOMACH
Low dose: mild to mod constipation
High dose: fluid evacuation of bowel (surgical prep)
Use: 1st line prevention/tx of HEPATIC ENCEPHALOPATHY (reduces plasma NH4 level via acid-trapping NH3. makes NH4+ which cannot be absorbed)
Titrated to achieve 2-3 soft stools per day
Adverse: dehydration, electrolyte imbalance
Loperamide
Antidiarrheal
OTC
MOA: myenteric opiate receptor agonist (reduces secretory activity–delta; and GI motility–mu)
40-50x more potent antidiarrheal than morphine
PK: well-absorbed (oral); poor penetration of BBB
Adverse: constipation
Diphenoxylate
Antidiarrheal
Prescription
MOA: myenteric opiate receptor agonist (reduces secretory activity–delta; and GI motility–mu)
PK: well absorbed (oral); high doses –> morphine-lke response (schedule V); contains atropine (dysphoria) to discourage abuse
Adverse: constipation
Bismuth subsalicylate
Antidiarrheal
Reduces stool frequency and liquidity
Salicylate inhibition of intestinal prostaglandin and chloride secretion
Ondansetron
Antiemetic (SETRON)
5-HT3 receptor antagonist
MOA: most effective antiemetics, enhanced by corticosteroids
PK: IV administration (prophylaxis), long duration, cleared by 3A4, 1A2, 2D6
Use: minimize/prevent emesis from CINV and radiation, hyperemesis of pregnancy, postoperative nausea (vagal stimulation)
NOT EFFECTIVE AGAINST MOTION SICKNESS OF DELAYED CINV NAUSEA
Aprepitant
Antiemetic
Substance P receptor (NK1) antagonist
Blocks NK1 receptors in brain (STN, area postrema)
PK: 3A4 kinetics, 2D6 induction
Use: delayed nausea, improves efficacy of other anti-emetics used for CINV
Metoclopramide
Prokinetic
Acts “upstream” of ACh. Coordinated GI motility/transit.
MOA: dopamine D2 receptor antagonist
D2 stimulation –> inhibits motility + reduces ACh release –> increased GI motility
Effects confined to upper GI tract. Increases LES tone.
Relieves n/v by antagonism of D2 receptors in CTZ
Use: n/v (GI dismotility syndromes, migraine), GERD, gastroparesis
Adverse: extrapyrimidal effects (parkinsonian), Tardive dyskinesia, hyperprolactinemia
Alosetron
IBS (SETRON: don’t confuse with antiemetic)
MOA: antagonist 5-HT3 receptors
Decrease GI motility –> inhibits unpleasant visceral afferent sensations
Use: diarrhea-predominant IBS (female patients only)
Adverse: severe constipation (10%), life-threatening ischemic colitis
DO NOT USE IN CONSTIPATION-DEPENDENT IBS
LAST LINE AGENT
Sulfasalazine
IBD (UC)
Mesalamine (5-ASA) based therapy
Prodrug azo (N=N) bond cleaved by intestinal flora –> 5-ASA
5-ASA: topical (non-systemic), luminal surface of colon
Does not involve COX inhibition
Use: induce/maintain remission in mild to mod UC
Also used in Crohn’s (unclear efficacy)
Adverse: systemic due to absorption of sulfapyridine metabolite, GI problems, HA, arthralgias, myalgia, myelosuppression
Infliximab
IBD (Crohns)
Anti-TNF-based therapy
MOA: chimeric monoclonal Ab against cytokine TNF-alpha. (TNF-alpha promotes immune/infl responses)
IV slow infusion with antihistamines/anti-infl agents
Induces/maintains remission of Crohn’s; closes fistulas
Adverse (serious): neutropenia, INFECTION (TB), heart failure, MALIGNANCY (lymphomas), pulmonary disease, demyelinating disease, cutaneous reaction, allergic reactions
