GI Drugs Flashcards
Aluminum Hydroxde
Antacid
MOA: neutralization of low gastric pH protects esophageal mucosa from reflux corrosion
SE: constipation
Magnesium Hydroxide
Antacid
MOA: neutralization of low gastric pH protects esophageal mucosa from reflux corrosion
SE: osmotic diarrhea (can become life threatening if someone abuses the drug)
Calcium Carbonate
Antacid
MOA: neutralization of low gastric pH protects esophageal mucosa from reflux corrosion
SE: CO2 causes belching and can lead to metabolic alkalosis (milk alkali syndrome)
Antacid Drug Interactions
Decreased absorption of coadministgered tetracyclines, fluoroquinolones, itraconazole and iron
H2 Receptor Antagonist (names)
Prototype: Cimetidine
2nd generation: Ranitidine, Famotidine, Nizatidine (no anti-adrogenic or CNS adverse effects)
H2 Antagonists
MOA: selective competitive inhibition at the parietal H2 Gs receptor
Effect: suppress basal gastric acid secretion w/ modest effect on meal stimulated secretion
Use: GERD, PUD, nonulcer dyspepsia, prophylaxis against stress-related gastritis
Cimetidine SEs
Sx’s: gynecomastia, galactorrhea, male impotence (acts as nonsteroidal anti-androgen and prolactin stimulant); confusion, dizziness and HAs; B12 deficiency and myelosuppression in long term use
Interactions: CYP450 inhibition causing increased serum concentration of Warfarin, Diazepam and Phenytoin
Proton Pump inhibitors
MOA: irreversibly bind and inhibit H-K ATPase in gastric parietal cells
Effect: suppress basal and meal stimulated gastric acid production
Use: pts that fail 2x daily H2RA therapy, severe GERD, PUD (H. pylori, NSAID ulcers), gastrinoma, nonulcer dyspepsia,
SEs: diarrhea, abd pn, HA
Proton Pump Inhibitors (names)
“-prazole” drugs
Omeprazole / Esomeprazole / Lansoprazole / Rabeprazole / Pantoprazole
Omeprazole SEs
CYP450 inhibition, will inhibit metabolism of Warfarin, Diazepam and Phenytoin
CYP2C19 inhibitors
Omeprazole / Esomeprazole / lansoprazole
*Clopidogrel requires CYP2C19 to convert it to active form so these drugs are CI in a pt taking Clopidogrel
H. pylori Eradication
Triple therapy (10-14d): Clarithromycin + Amoxicillin + PPI orrrr Clarithromycin + Metronidazole + PPI
Quadruple therapy (14d): Bismuth Subsalicylate + Metronidazole + Tetracycline + PPI
Misoprostol
PGE1 analog
MOA: binds EP3 receptor stimulating Gi pathway
Effect: decreased gastric acid secretion, stimulates mucus and bicarbonate secretion, enhances mucosal blood flow
Use: prevention of NSAID-induced ulcers; diarrhea, abd pn
*CI in pregnancy
Sucralfate
Salt of sucrose + sulfate aluminum hydroxide
MOA: forms viscous paste that binds selectively to ulcers forming a physical barrier
Effect: stimulates mucosal prostaglandin and HCO3- secretion
Use: initial management of GERD in pregnancy
Bismuth Subsalicylate
Use: suppresses H. pylori
SE: dark stools, salicylate toxicity in combo w/ other salicylate products
CI: pts w/ ESRD
Prokinetic Agents
M1 agonists
Effect: enhance contractions in relatively uncooradinated fashion that produces little or no net propulsive activity
(Bethanechol / Neostigmine - not currently indicated for tx GI motility disorders)
Erythromycin
Motility receptor agonist
Effect: downregulation of motility receptors leading to early tolerance so its use is limited to short courses
Use: DM gastroparesis
Cisapride
MOA: 5-HT4 agonist, 5-HT3 antagonist, direct smooth muscle stimulant
Use: was used for GERD and gastroparesis (no longer used in US bc it has potential to cause ventricular arrhythmias)
Metoclopramide
MOA: 5-HT4 agonist, vagal and central 5-HT3 antagonist, DA antagonist
Effect: increases LES tone, stimulates natural and small intestinal contractions
Use: gastroparesis, anti-emetic, previously used for GERD sx relief
SE: extrapyramidal effects d/t DA antagonism (more common in young ppl @ high doses), galactorrhea by blocking inhibitory effect of DA on prolactin release
Scopolamine
Antimuscarinic
Use: prevention and tx of motion sickness, post-op N/V
H1 Antagonists
Diphenhydramine / Meclizine / Cyclizine
MOA: act on vestibular afferents as well as brainstem
Use: motion sickness and post-op emesis
5-HT3 Antagonists
Ondansetron / Granisetron
MOA: antagonize receptors in vagal afferents, STN, CTZ and AP
Use: DOC for prophylaxis against chemo induced N/V, hyperemesis gravidarum, post-op N
SE: constipation, diarrhea, HA< lightheadedness
Arepitant
NK1 antagonist
MOA: antagonist of NK1 receptors for substance P
Use: prophylaxis against delayed cancer induced N/V
Administration: PO incombo w/ dexamethasone and 5-HT3 receptor antagonist
Metabolism: CYP3A4 metabolism and may affect metabolism of Warfarin and oral contraceptives
Promethazine / Droperidol
D2 antagonists
MOA: D2 antagonism at CTZ
Use: motion sickness
SE: extrapyramidal effects
Dexamethasone / Methylprednisone
Corticosteroids
Effect: suppression of peritumoral inflammatoin and prostaglandin production
Use: adjuvants in tx of nause in
pt’s w/ metastatic ca
Dronabinol
Cannabinoid
MOA: stimulates CB1 subtype of cannabinoid receptors on neurons in/around vomiting center in brainstem
Use: prophylactic in pt’s receiving chemo when other meds arent effective
SEs: palpitations, tachycardia, vasodilation, hypotension, conjunctival injection, paranoid rxns
Lorazepam / Alprazolam / Diazepam
Effect: facilitate GABAa action in CNS by increasing frequency of Cl- channel opening
Use: adjuncts d/t sedative, amnesiac, anti-anxiety effects
SE: CNS depression and dependence
Methylcellulose / Psyllium / Bran
Bulk-forming laxatives
MOA: nondigestible colloids absorb water to form bulky soft jelly that distended the colon to promote peristalsis
CI: immobile pt’s and those in long-term opioids therapy
Castor Oil
MOA: directly stimulate enteric nervous system to increase motility
Metabolism: broken down to ricinoleic acid in small intestine
CI: pregnancy (bc it may cause uterine contractions)
Senna
Stimulant laxative
SE: chronic use may lead to melanosis coli (brown pigment of colonic mucosa)
Docusate / Glycerine
Stool softener
MOA: surfactants which allow water to penetrate and soften formed stool in the bowel
Mineral Oil
Lubricant laxative
CI: not given with Ducosate as mineral oil will be absorbed into stool thereby negating its laxative effect
Osmotic Laxatives
Lactulose / Magnesium Hydroxide / Magnesium Sulfate
MOA: nonabsorbable sugars or slots exert osmotic pull to retain water
Lactulose
Metabolized by colonic bacteria and can lead to severe flats w/ cramping
Magnesium Salts
Shouldn’t be used fro prolonged periods in persons w/ renal insufficiency bc they may cause hypermagnesemia
Polyethylene Glycol (PEG)
Osmotic laxative
MOA: water soluble polymer that generates high osmotic pressure in gut lumen
Use: complete bowel prep before GI endoscopy, preferred for management of chronic constipation
Lubiprostone
MOA: stimulates type 2 Cl- channels of small intestine
Effect: increases secretion of Cl- resulting in 👆🏽intestinal mobility
Use: chronic constipation and IBS w/ predominant constipation
SE: diarrhea
CI: children
Alvimopan / Methylnaltrexone
Selective mu-opioid receptor antagonists
MOA: dont cross BBB so act at level of the gut to maintain normal motility in pt’s w/ acute or chronic use of opioid analgesics
Loperamide
Opioid agonist MOA: activates present-tic mu-opioid receptors in entered nervous system to inhibit ACh release and decreases gut peristalsis Use: IBS w/ diarrhea predominance *low potential for addiction CI: children and pt's w/ severe colitis
Dioxyphenolate
Opioid agonist
MOA: activates present-tic mu-opioid receptors in entered nervous system to inhibit ACh release and decreases gut peristalsis
*can cross CNS at higher doses
CI: children and pt’s w/ severe colitis
Octreotide
Somatostatin analog
Effect: decrease pancreatic exocrine fxn
Use: secretory diarrhea d/t neuroendocrine tumors, diarrhea 2° to vagotomy, dumping syndrome, short bowel syndrome, AIDS
SE: steatorrhea (can lead to fat-soluble vitamin deficiency), gallstones (d/t decreased gallbladder contractility)
Bismuth Subsalicylate
MOA: coating and salicylate component
Effect: decreases fluid secretion in the enteric trace
Use: traveler’s diarrhea
Aminosalicylates
Sulfasalazine / Balsalazide / Mesalamine
MOA: 5-aminosalicylates acid (5-ASA) at high concentrations at target sites given PO or suppository/enema depending on the site of dz
Use: long term maintenance of IBD remission
Sulfasalazine
5-ASA linked to sulfapyridine by an ago bond
(Only partially absorbed in jejunum after PO administration)
SE: HA, arthralgia, myalgia, BM suppression, HS rxns
Balsalazide
5-ASA linked to inert unabsorbed carrier molecule
*delivers max amts to colon
Mesalamine
5-ASA packaged in microgranules taht release the active drug into desired portion of gut
Glucocorticoids
Prednisone / Prednisolone / Budesonide
Effects: interaction w/ intracellular glucocorticoid response elements, inhibition of phospholipase A2 and COX, inhibition of NF-κB
Prednisone / Predisonolone
Intermediate duration of action which allows for once daily dosing
Hydrocortisone
Administered via enema for sigmoid and rectal iBD flares
Budesonide
High rate of first pass metabolism when given PO which decreases the rate of systemic SEs compared to other systemic corticosteroids
Mercaptopurine / Azathioprine
Immunosuppressive purines
MOA: steroid sparing effect
Use: IBD remission
SE (toxicity): N/V, hepatotoxicity and BM suppression
CI: administered w/ allopurinol bc it reduces xanthine oxide activity which can increase serum concentrations of these purines
Methotrexate
MOA: inhibits dihydrofolate reductase to decrease thymidine and purine production
Effect: reduces IL-1 effects
SE: BM suppression, megaloblastic anemia, mucositis (folate supplementation is recommended)
Anti-TNF-α Drugs
Infliximab / Adalimumab
MOA: bind and inactivate TNF
Effect: suppress pro-inflammatory response
Use: acute and chronic IBD
Infliximab
Use: moderate-severe colitis that isn’t responsive to Mesalamine or steroids
Natalizumab
Anti-integrin
MOA: monoclonal Ab targeting integrity on circulating inflammatory cells
Effect: disruption of leukocyte vascular wall adhesion and subsequent tissue migration
Use: moderate-severe unresponsive Crohn’s dz
SE: infusion rxns, opportunistic infections, reactivation of JC virus resulting in PML
Pancrelipase
MOA: combination of amylase, lipase and proteases given PO with each meal
Use: exocrine pancreas insufficiency (CF, chronic pancreatitis)
SE: diarrhea, abd pn, hyperuricosuria, renal stones, colic strictures
Alosetron
5-HT3 antagonist
Use: diarrhea IBS
