GI pharm Flashcards
cimetidine
ranitidine
famotidine
nizatidine
H2 receptor antagonists:
omeprazole and the –prazoles
MOA: Irreversible inhibition of gastric-parietal cell proton pump -prodrugs that require activation in acid environment
**PK: **take before or w/ meal; metabolized in liver by P450 enzymes
Use:
- short term treatment of gastric and duodenal ulcers (esp NSAID induced)
- GERD
- tx of choice for ZE syndrome, MEN, systemic mastocytosis
- combo therapy for H. pylori
AE: inhib P450 leads to dec. clearance warfarin, benzo’s, phenytoin; elevated Gastrin levels
octreotide
Somatostatin analog (inhibits gastric and pancreatic secretion)
Used in ZE syndrome and
Portal hypertensive bleeding
Antacids
MgOH2
AlOH2
CaCO3
MOA: Neutralize gastric acid
**Use: **
- treatment dyspeptic Sx
- may hasten ulcer healing
AE:
MgOH2: diarrhea
AlOH2: constipation
CaCO3: stimulate gastrin release and acid secretion “Acid rebound”
*don’t use in renal failure
OTC
Sucralfate
MOA: Adheres to ulcer craters and forms a protective barrier
Use: Duodenal ulcer
AE: No systemic toxicity; May bind concomitant meds
reasons for non-healing ulcers
- -non-compliance
- -H. pylori infection
- -NSAID use
- -tobacco use
- -inadequate duration therapy
- -Hypersecretory state (ZE syndrome)
- -non-peptic ulcer related disease (malignancy)
Carbechol
Bethanechol
cholinergic receptor agonists
Muscarinic receptors which when activated lead increase in intracellular Ca
enhance GI motility
Metaclopromide
MOA: Dopamine receptor antagonist, 5-HT3 antagonist, 5-HT4 agonist
Use: Symptomatic relief to pts with gastric motor failure (diabetic gastroparesis), decreases hearburn in GERD, anti-emetic (cancer),
AE:
- Somnolence, nervousness, dystonia
- -parkinsonism/tardive dyskinesia
- -galctorrhea and menstrual d/o (inc. prolactin)
Tegerserod maleate
5-HT4 partial agonist; increase GI motility
constipation predominant IBS in women
erythromycin
MOA: Motilin agonist (Motilin receptors found on smooth muscle cells, when stimulated induce and amplify MMC; potent contractile element of upper GI tract)
Use:
Diabetic gastroparesis
Intestinal pseudoobstruction
Treatment of irritable bowel syndrome
Constipation predominant: bulking agent
Diarrhea predominant: antispasmodics/anticholinergics
Constipation: prokinetics
Constipation predom in women: tegerserod maleate
treatment of gastroparesis
Metoclopramide
Erythromycin
Cisparide
Botulinum toxin (intrapyloric injection)
Treatment of pancreatic insufficienc
Treatment of pancreatic insufficiency: steatorrhea when lipase output <10% normal
1) pancreatin: alcoholic extract hog pancreas
2) pancrelipase: enriched hog pancreas prep
Dosing
–With meals
–Titrated to therapeutic effect
–Higher gastric pH enhances activity
Toxicity:
- uric acid renal stones
- lactose in pills poorly tolerated in lactose intolerant pts
Bile salt therapy
1) Chenodiol: oral therapy to dissolve gallstones but limited by diarrhea
2) Ursodiol: epimer of chenodiol w/ fewer toxicities; used to dissolve gallstones and in primary biliary cirrhosis
Metronidazole, ciprofloxacin treatment in Crohn’s diseae
- Useful in mild to moderate Crohn’s disease
- induce remission
- Adjunct treatment
Sulfasalazine
MOA: Multiple sits in inflammation cascase; inhibition leukotrienes is most imp!
Use: -mild to moderate UC (maintaining remission)
AE: Due to sulfa component…
–Dose related malaise, nausea, abdominal pain
–Impaired folic acid absorption (supplements needed)
–Reversible decrease in sperm count
–Severe skin reactions, rarely (Stevens-Johnson syndrome)
–Bone marrow suppression
Sulfasalazine: 5-ASA linked with sulfapyridine which is digested in colon
Melsalamine
coated 5-ASA which slows release
Use: Mild to moderate UC
–Asacol (works distal colon)
–Pentasa (works jejunum thru colon)
–Enemas (local delivery distal colitis and rectal disease)
AE: lacks sulfa component and assoc. toxicities
Glucocorticoids
Treatment of choice for severe IBD (Abdominal pain, fever, leukocytosis, rectal bleeding)
-used short-term to achieve remission
Budesonide (maintenance use in crohns disease)
Azathioprine, 6-mercaptopurine
MOA–Suppress lymphocyte proliferation
Use: 2nd line therapy for severe or steroid resistant IBD
-useful for maintaining remission (slow onset action)
AE: Bone marrow suppression, pancreatitis, drug induced malignancy
*TPMT testing for slow metabolizers
Cyclosporine
MOA: Calcineurin inhibitor, suppresses pro-inflammatory transcription factors
Use: –For severe UC not responding to steroids
AE–Use limited by toxicity
•Renal insufficiency
•Hypertension
TNF-alpha inhib
Binds TNFa which is known to be increased in mucosa of crohn’s pts
-used for inducing and maintaining remission in Crohns disease
Bulk forming agents
-pysillium
carboxymethylcellulose
-methylcellulose
MOA: hydrophilic colloids form gel in large intestine, distending and stimulating peristalsis
Use: Chronic constipation, chronic diarrhea, diarrhea w/ incontinence, diarrhea in IBS
Contraind: : GI obstruction or perforation, gastric retention, undiagnosed abd. Pain, vomiting, appendicitis, toxic colitis, ileus, megacolon; avoid in pts with swallowing difficulities, severely swollen colon, watch Na, K, aspartame
AE: Bloating, flatulence, abdominal cramps (diminish with time)
Other: Adsorb other oral meds, separate by 1 hr
- *Osmotic/Saline/Hyperosmotic**
- magnesium citrate/hydroxide
- polyethylene glycol/Electrolyte solutions
- lactulose
- sorbitol
MOA: Non-adsorbable/non-digestable salts or sugars hold water in intestine by osmotic force; distends intestine and stimulates peristalsis
Use: constipation (chronic), evacuation of colon prior to radiologic/endoscopic procedures, sugars—hepatic encephalopathy, prompt evacuation in 1-3hrs,
Contraind: GI obstruction or perforation, gastric retention, undiagnosed abd. Pain, vomiting, appendicitis, toxic colitis, ileus, megacolon, ulcerative colitis, diverticulitis, colostomy/ileostomy, Severe renal insufficiency, heart block, rectal bleeding
AE:
- magnesium salts: hypermagnesia if renal insuff, cramping/pain
- sodium salts: hyperphosphatemia, hypocalcemia if reanl insuff
- PEG/ES: nausea, vomiting, cramps, bloating, abd. Fullness
- sugars: gas, bloating, distension
Interactions:
- Mg(OH): may dec. absorption of antibiotics and cause premature release of enteric coated meds
- PEG/ES: oral meds given 1 hr before start may be not be absorbed
-watch hydration
- *Surfactants (stool softeners)**
- anioninc surfactants
- detergents: docusate, dioctyl sodium sulfosucinate
MOA: Anionic surfactants become emulsified w/ stool, softening it and making passage easier
Use: Stool softener, Adjunct therapy for hemorrhoids
ContraInd: GI obstruction or perforation, gastric retention, undiagnosed abd. Pain, vomiting, appendicitis, toxic colitis, ileus, megacolon, fecal impaction/intestinal obstruction, acute abdominal pain, don’t use with mineral oil Mild
AE: abdominal cramping
Interactions: May inc. mineral oil absorption and toxicity (don’t give together)
Other: take with a full glass of water, no laxative action, do not use for >1wk, does not work after constipation occurs
- *Lubricants**
- mineral oil
MOA: Penetrates and lubricates feces for easier passage, prevents water reabsorption
Use: Fecal impaction, post-MI/surgery/partum to avoid straining
ContraInd: GI obstruction or perforation, gastric retention, undiagnosed abd. Pain, vomiting, appendicitis, toxic colitis, ileus, megacolon, diverticulitis, UC, colostomy, ileostomy
AE: Risk aspiration in debilitated pts, incontinence/anal leakage, malabsorption fat soluble vitamins, chronic intestinal hypomotility
Interactions: Docusate, may decrease fat soluble vitamin absorption
Other: Some absorption when given orally, no absorption as enema
- *Irritant/Stimulant/Contact**
- anthraquinones—cascara sagrada (bark)
- senna/sennosides: Cassia plant leaves
- aloe: lily family leaf
- castor oil/ricinoleic acid
- diphenylmethane: bisacodyl (ducolax)
MOA: Contact irritant effects on enterocytes, enteric neurons, and muscle,accumulation water and electrolytes and stimulate intestinal motility
Use: Constipation, preparation for surgery, delivery, GI exam
ContraInd: Rectal bleeding, N/V, acute abdomen or bowel obstruction, appendicitis, or gastroenteritis
*not for chronic use
AE: Anthraquinones: cathartic colon, cramps, severe diarrhea, dependency, tachyphylaxis
- castor oil: damage microvilli and inc. intestinal permeability, AVOID, cramping
- diphenylmethane: mucosal damage, cramping, inflammation w/ suppositories
Interacionts:-antacids/milk (GI upset)
Other: Anthraquinones: digested by colonic bacteria to active form, onset 6-12hrs
- Castor oil: hydrolyzed to ricinoleic acid, stim fluid secretion and speeds GI transit, quick onset
- diphenylmethanes: require hydrolysis to active form, stimulates enteric nerves, contact effects
Methylnaltrexone
MOA: Peripheral opiod receptor antagonist,does not cross BBB
Use: Opioid induced constipation
ContraInd: mechanical GI obstruction
AE: Diarrhea, abdominal pain, dizziness, could inc. pain
Other: Subcutaneous injection, Pregnancy category B
Alvimopan
MOA: Competitive antagonist at peripheral mu opioid rectpor, slow dissociation (does not reverse analgesia of central opioid agonists)
Use: Post-operative ileus, in hospital use only
ContraIndications Therapeutic doses or opioids used more than 7 consecutive days
AE: Dyspepsia, hypokalemia, urinary retention
Interactions: Drugs that inhibit p-glycoprotein (amiodarone, diltiazem, cyclosporine, itraconazole, quinidine, spironolactone, verpamil)
Other:
- not P450 substrate
- is a substrate for p-glycoprotein
- pregnancy category B
Lubiprostone
MOA: Agonist at GI CLC-2 Cl- channels, inc. production of chloride rich intestinal fluids w/o affecting Na/K levels
Use: Chronic idiopathic constipation in adults, IBS w/ constipation (F>18), no restriction in length of use
ContraInd: Chronic diarrhea, diarrhea predominant IBS, mechanical GI obstruction
AE: Nausea, diarrhea, abdominal pain
Other: Poor systemic absorption
linaclotide
MOA: Guanylate cyclase C agonist→inc. cGMP
Use: Chronic idiopathic constiation in adults, IBS w/ constipation
ContraInd: Mechanical GI obstruction, not for use in pediatric pts (<17yo)
AE: Severe diarrhea, abd pain, flatulence, abd distension
Other:
- Not metabolized by P450 or p-glycoprotein
- minimal systemic exposure
- pregnancy category C
- *Narcotic analog**
- phenylpiperidine
- loperamide (Imodium)
- diphenoxylate
- atropine
- diphenoxin
- paregoric
MOA: Stimulate opiate receptors in myenteric plexus→ delayed intestinal transit and reduced secretion
Use: Acute, nonspecific diarrhea; loperamide for chronic diarrhea
ContraInd:
- -“septic” pts
- -toxic megacolon
- -ulcerative colitis
- -pseudomembranous colitis
- -diarrhea d/t organisms that penetrate wall (toxigenic E. coli, salmonella, shigella)
AE: Constipation, distension, bloating, nausea, vomiting, CNS depression, drowsiness, dizziness, fatigue, toxic megacolon
Interactions: **Diphenoxylate/Atropine: **
- inc CNS depression w/ alcohol, barbituates, CNS depressants
- w/ MOAI hypertensive crisis -avoid atropine in pediatric pts and pts w/ hepatic impairment
Bismuth subsalicylate (pepto bismol)
MOA: Bind bacterial toxins, absorb fluid in gut, anti-secretory effects in infectious diarrhea, anti-inflammatory
Use: diarhhea, traveler’s diarrhea
ContraInd: Hypersensitivity to salicylates, children <16 w/ viral infection, chronic use in pts w/ renal failure,
AE: Temporary black tongue stools, high doses w/ enteritis→bismuth or salicylate toxicity
Interactions: Bind other drugs, take oral meds 1 hr before or 4hrs after
Octreotide
MOA: Somatostain analog, hyperpolarizes gut neurons, dec. Ach release and slows peristalsis; prevents release of secretion inducing NT (VIP, serotonin)
Use: *severe refractory diarrhea (Eg. AIDS, endocrine tumor related—carcinoid, VIPoma)
ContraInd: Hypersensitivity to drugs or components
AE: Gallbladder stasis, inhibition of pancreatic secretions, injection site irritation, nausea, diarrhea, abd. pain
Interactions: Dec. plasma levels of cyclosporine
- *Anticholinergics**
- atropine
- belladonna alkaloids
Cholinergic receptors, dec intestinal muscle tone and peristalsis, slowed movement fecal matter thru GI tract
Sucralfate (carafate)
MOA: Topical mucosal protective agents, Forms ulcer-adherent complex at ulcer site and acts as protective barrier, stimulate mucosal PG and bicarb secretion, bind EGFR and FRGR
Use: Treatment of duodenal and gastric ulcers Aluminum may accumulate w/ dec. renal function
Interactions: *requires acidic pH for activation so don’t co-administer w/ antacids, H2 receptor antagonists, PPI, can inhibit absorption of other meds
Misoprostol
MOA: Systemic mucosal protective agents, Misoprostol Inhibits gastric acid secretion and stimulates secretion of mucin and bicarb and improving mucosal blood flow
Use: Prevention of NSAID induced gastric ulcers or mucosal injury
ContraInd: Pregnancy category X (miscarriage due to uterine contraction stimulation), hx of allergy to prostaglandins, IBS
AE: Dose dependent diarrhea, cramping, nausea, headache (resolve in 1-2wks)
Interactions: Reduced availability when taken w/ antacids,
does not affect P450 No dose adjustment for elderly or impaired renal function
Anatacids
MOA: Anatacids Neutralize gastric acid
Use: Relief GI Sx
ContraInd: Caution in pts w/ renal failure
AE: Constipation, diarrhea
Interactions: LOTS! Dec. absorption
- Imp: theophyline, fluoroquinolone, antibiotics, tetracycline, isoniazid, ketoconazole, iron
