18- G.I. Drugs Flashcards
esomeprazole
proton pump inhibitor
- prodrug that requires acid activation to react with and irreversibly inhibit proton pump
- do not act directly within gastric lumen, they enter parietal cells from systemic circulation (absorbed in high pH)
- dosed daily, only active for 2 hours, treatment requires 2-5 days
- liver clearance via P450 (drug interactions through CYP alterations)
- few side effects: nausea, ab. pain, constipation, flatulence, diarrhea
- increase warfarin concentrations
- decrease activation of clopidogrel
lansoprazole
proton pump inhibitor
- prodrug that requires acid activation to react with and irreversibly inhibit proton pump
- do not act directly within gastric lumen, they enter parietal cells from systemic circulation (absorbed in high pH)
- dosed daily, only active for 2 hours, treatment requires 2-5 days
- liver clearance via P450 (drug interactions through CYP alterations)
- few side effects: nausea, ab. pain, constipation, flatulence, diarrhea
- increase warfarin concentrations
- decrease activation of clopidogrel
omeprazole
proton pump inhibitor
- prodrug that requires acid activation to react with and irreversibly inhibit proton pump
- do not act directly within gastric lumen, they enter parietal cells from systemic circulation (absorbed in high pH)
- dosed daily, only active for 2 hours, treatment requires 2-5 days
- liver clearance via P450 (drug interactions through CYP alterations)
- few side effects: nausea, ab. pain, constipation, flatulence, diarrhea
- increase warfarin concentrations
- decrease activation of clopidogrel
cimetidine
H2 receptor antagonist
- block the base level of acid secretion maintained by ECL cells
- useful for nocturnal acid secretion, duodenal ulcers, and Zollinger-Ellison syndrome
- renal excretion via organic cation system
- Adverse Reactions: diarrhea, headache, drowsiness, fatigue, muscle pain
- CNS affects in elderly
- decrease pepsin and intrinsic factor output
- long term use at high doses decreases testosterone binding to androgen receptor and hydroxylation of estradiol causing galactorrhea (women) and decreased sperm count, impotence, gynecomastia (men)
famotidine
H2 receptor antagonist
- block the base level of acid secretion maintained by ECL cells
- useful for nocturnal acid secretion, duodenal ulcers, and Zollinger-Ellison syndrome
- renal excretion via organic cation system
- Adverse Reactions: diarrhea, headache, drowsiness, fatigue, muscle pain
- CNS affects in elderly
- decrease pepsin and intrinsic factor output
ranitidine
H2 receptor antagonist
- block the base level of acid secretion maintained by ECL cells
- useful for nocturnal acid secretion, duodenal ulcers, and Zollinger-Ellison syndrome
- renal excretion via organic cation system
- Adverse Reactions: diarrhea, headache, drowsiness, fatigue, muscle pain
- CNS affects in elderly
- decrease pepsin and intrinsic factor output
sucralfate
octasulfate of sucrose with Al(OH)3
- forms a sticky neutral pH polymer coating that swells and covers epithelium
- used for STRESS ulcers
- acid activated- take before food and avoid antacids/proton pump inhibitors
- adverse effects: constipation and can block absorption of other drugs through the stomach
- contraindicated in GI obstruction
aluminum hydroxide
neutralizing antacid
- neutralize pH of gastric contents
- fast acting (15 minutes), effects lasting 2-3 hours with food
- delays emptying and slows motility
- adverse effects- rebound acid secretion, constipation, nausea,
- may contribute to osteoporosis and encephalopathy with renal insufficiency, may interfere with GI absorption of other drugs
calcium carbonate
neutralizing antacid
- neutralizes pH of gastric contents
- fast acting (15 minutes), effects lasting 2-3 hours with food
- adverse effects- rebound acid secretion, hypercalcemia, may interfere with GI absorption of other drugs
magnesium hydroxide (Milk of Magnesia)
neutralizing antacids and osmotic cathartic/laxative salt
- cause inc. osmotic pressure in GI lumen causing retention of water in stool (cathartics when given at high doses)
- neutralize pH of acid contents
- fast acting (15 minutes) lasting effects 2-3 hours with food
- stimulates gastric emptying and motility
- adverse effects- rebound acid secretion, may interfere with GI absorption of other drugs
- CONTRAINDICATED IN RENAL DISEASE
misoprostol
prostaglandin analog
- short acting (3 hours)
- only used to prevent NSAID-induced injury
- adverse effects: diarrhea, exacerbate inflammatory bowel disease, increase uterine contractions
pirenzepine
M1 antagonist (uncommon in USA)
-blocks neurotransmission in the intramural ganglia resulting in less vagal stimulation of parietal and ECL cells
can reduce basal acid production 40-50%
-significant anticholinergic side effects
bethanechol
prokinetic agent
- aim is to selectively activate M2 and M3 receptors
- does not activate coordinated motility so it is not a front line approach
- side effects- bradycardia, flushing, diarrhea, cramps, salivation, blurred vision
cisapride
prokinetic agent
- 5-HT4 receptor agonist and adenylate cyclase stimulant
- used for GERD and gastroparesis
- adverse effects- fatal cardiac arrhythmias (strict FDA distribution)
erythromycin
prokinetic agent
- motilin agnoist
- macrolide antibiotic
- causes gastric dumping
- can improve gastric emptying with ileus, scleroderma, and pseudo-obstructions
- FAST DUMPS can be painful, not recommended for chronic use
metoclopramide
prokinetic agent
- general dopamine receptor antagonist
- increases lower esophageal sphincter tone and upper GI motility
- can relieve GERD symptoms but does not promote healing
- used for N/V in dysmotility, laxative
- adverse effects- EPS, dystonias, tardive dyskinesia with chronic use
neostigmine
prokinetic agent
- AChE inhibitor
- can be used acutely to counter an ilues
tegaserod
prokinetic agent
- serotonin partial agnoist in the gut used for females with irritable bowel syndrome
- can improve lower bowel motility if cases with chronic constipation and bloating
- adverse effects- fatal cardiac arrhythmias (strict FDA distribution)
magnesium citrate
osmotic cathartic/laxative salt
- cause inc. osmotic pressure in GI lumen causing retention of water in stool (cathartics when given at high doses)
- small amount absorbed but given at high enough dose to overcome absorption
- Mg may stimulate CCK and inc. motility
- should be avoided in those with renal insufficiency, cardiac disease, electrolyte abnormalities, or with diuretic use
magnesium sulfate
osmotic cathartic/laxative salt
- cause inc. osmotic pressure in GI lumen causing retention of water in stool (cathartics when given at high doses)
- small amount absorbed but given at high enough dose to overcome absorption
- Mg may stimulate CCK and inc. motility
- should be avoided in those with renal insufficiency, cardiac disease, electrolyte abnormalities, or with diuretic use
polyethylene glycol (GoLYTELY)
osmotic cathartic/laxative alcohol
- non-absorbable and cause water retention in stool
- actually cathartics that act as laxatives at lower doses
lactulose (Cephulac)
osmotic laxative
-used for constipation assoc. with opioid use and vincristine
-bacterial fermentation drops luminal pH and can trap NH4, which is inc. in patients with hepatic disease
+++can reduce efficacy but may be beneficial in those with hepatic disease
mannitol
osmotic cathartic/laxative
- inc. osmotic pressure in GI lumen stimulates peristalsis
- used for constipation assoc. with opioid use and vincristine
sorbitol
osmotic cathartic/laxative
- inc. osmotic pressure in GI lumen stimulates peristalsis
- used for constipation assoc. with opioid use and vincristine
docusate (Colace)
stool wetting agent
- surfactant that allows mixing of fatty substances and water in stool
- effective as softeners but do NOT inc. frequency of defecation (may inc. frequency but only d/t inc. ease of passing stool)
bisacodyl (Dulcolax)
irritant laxative
- used orally or rectally
- induces moderate inflammation leading to reduced water absorption (inc. water in stool) and inc. motility
- safe but overdose causes catharsis
- do not chew tabs or mix with milk/antacids to ensure reaches small intestine intact and avoid gastric irritation
castor oil
misc. laxative
- general smooth muscle stimulant used as laxative (can also induce labor)
- made from ricinus communis which produces ricin (deadly) and oil full of triglyceride and ricinoleic acid
- ricinoleic acid speeds motility of small bowel
glycerin
misc. laxative
- suppository that acts as hydroscopic agent and lubricant
- inc. water retention stimulates peristalsis and evacuation reflex
- rectal administration can produce bowel movement within an hour
- cannot be given orally because will not have efficacy
methylcellulose
bulk-forming laxative
- fiber based material, not broken down or absorbed
- bulk material stimulates peristalsis/mass action
- great for regular/soft stools
- may exacerbate intestinal obstructions and may absorb other drugs
- can also function as anti-diarrheal to dec. symptoms of watery stool
polycarbophil
bulk-forming laxative
- fiber based material, not broken down or absorbed
- bulk material stimulates peristalsis/mass action
- great for regular/soft stools
- may exacerbate intestinal obstructions and may absorb other drugs
- can also function as anti-diarrheal to dec. symptoms of watery stool
psyllium
bulk-forming laxative
- fiber based material, not broken down or absorbed
- bulk material stimulates peristalsis/mass action
- great for regular/soft stools
- may exacerbate intestinal obstructions and may absorb other drugs
- can also function as anti-diarrheal to dec. symptoms of watery stool
alosetron (Lotronex)
antidiarrheal agent
- 5-HT3 ANTAGONIST used for diarrhea predominant IBS
- generally produce effects opposite of 5-HT4 agonists
- may reduce visceral sensitivity by reducing sensory and vagal nerve signaling
- can produce serious constipation and potentially fatal ischemic colitis
- only used after failing other therapies
bismuth subsalicylate (Pepto-Bismol)
antidiarrheal agent
-bismuth
++99% unabsorbed and eliminated in feces
++has anti-secretory, anti-inflammatory, anti-microbial activities
++commonly used in H-Pylori treatments
-salicylate released in acidic environment
++NSAID absorbed systemically
-Mg-Al silicate (clay) (bulk forming effects)
diphenoxylate (Lomotil)
antidiarrheal agent
- opioid receptor agonists (Piperidine derivative)
- Difenoxin is active metabolite
- can have CNS effects
- packaged with sub-therapeutic doses of atropine to discourage abuse
loperamide (Imodium)
antidiarrheal agent
- mu-opioid receptor antagonist that inhibits bowel motility
- 40-50x more potent then morphine
- no CNS effects
octreotide (Sandostatin)
antidiarrheal agent
- parenteral derivative of somatostatin (natrual peptide that inhibits pancreatic secretions)
- used to combate secretory diarrhea of hormone secreting tumors, post-surgical gastric dumping syndrome, and diarrhea assoc. with chemo
- used to rest pancreas in pancreatitis
- reduces secretion of serotonin, gastrin, insulin, and secretin
- S/FX: nausea, bloating
- long-term therapy may result in gallstones
Chlopromazine (Thorazine)
antiemetic: DA receptor antagonist/Phenothiazine
-MOA: targets D2 receptors in CTZ and H1 receptors.
+effective for motion sickness
-Adverse effects: parkinson-like Sx and EPS with long-term use
+may lead to dissociative dysphoria
cyclizine (Marezine)
antiemetic: Antihistamine: H1 receptor antagonist
- MOA: act primarily in the brainstem and vestibular apparatus
- Effective for motion sickness.
- cross BBB so cause sedation.
- also has anticholinergic effects (effective in abdmonial CA).
diphenhydramine (Benadryl)
antiemetic: Antihistamine: H1 receptor antagonist
- MOA: act primarily in the brainstem and vestibular apparatus
- Effective for motion sickness.
- cross BBB so cause sedation.
dimenhydrinate (Dramamine)
antiemetic: Antihistamine: H1 receptor antagonist
- MOA: act primarily in the brainstem and vestibular apparatus
- Effective for motion sickness.
- cross BBB so cause sedation.
- salt of diphenhydramine and chlorotheophyllinate (think theophylline)
dolasetron (Anzemet)
antiemetic: SE receptor (5HT-3) ) antagonist
- Acts centerally at CTZ and STN
- Act peripherally in the intestine.
- t1/2=7-9’
- excretion through liver
- Useful in chemotherapy and emesis promoting states.
- Adverse Rxn: constipation, diarrhea, HA, and light-headedness
hydroxyzine (Vistaril)
antiemetic: Antihistamine: H1 receptor antagonist
- MOA: act primarily in the brainstem and vestibular apparatus
- Effective for motion sickness.
- cross BBB so cause sedation.
granisetron (Kytril)
antiemetic: SE receptor (5HT-3) ) antagonist
- Acts centerally at CTZ and STN
- Act peripherally in the intestine.
- t1/2= 9-11.6’
- excretion through liver
- Useful in chemotherapy and emesis promoting states.
- Adverse Rxn: constipation, diarrhea, HA, and light-headedness
ondansetron (Zofran)
antiemetic: SE receptor (5HT-3) ) antagonist
- Acts centerally at CTZ and STN
- Act peripherally in the intestine.
- t1/2= 3.9’
- excretion through liver
- Useful in chemotherapy and emesis promoting states.
- Adverse Rxn: constipation, diarrhea, HA, and light-headedness
paleondansetron (Aloxi)
antiemetic: SE receptor (5HT-3) ) antagonist
- Acts centerally at CTZ and STN
- Act peripherally in the intestine.
- t1/2= 40’
- only given IV
- highest affinity for 5HT-3 of this class.
- excreted by kidneys
- Useful in chemotherapy and emesis promoting states.
- Adverse Rxn: constipation, diarrhea, HA, and light-headedness
prochlopromazine (Compazine)
antiemetic: DA receptor antagonist/Phenothiazine
-MOA: targets D2 receptors in CTZ and H1 receptors.
+effective for motion sickness
-Adverse effects: parkinson-like Sx and EPS with long-term use
+may lead to dissociative dysphoria
promethazine (Phenergen)
antiemetic: Antihistamine: H1 receptor antagonist
- MOA: act primarily in the brainstem and vestibular apparatus
- Effective for motion sickness.
- cross BBB so cause sedation.
Scopoloamine
antiemetic: Anticholinergic
-MOA: muscarinic cholinergic antagonist.
+minimal CTZ effects
-effective for motion sickness (vestibular apparatus) and PONV
- Adverse rxn: sedation, dry mouth, blurred vision. May precipitate outburst of uncontrolled behavior when combined with pain of anxiety (remember atropine excitation).
6-mercaptopurine
purine antagonist (Thiopurine)
- MOA: metabolized to 6-thioguanine leading to the prevention of DNA synthesis by targeting rapidly proliferating cells.
- effective for UC and Crohn’s
- Adverse rxn: pancreatitis, fever, rash, arthraligias, NV, and bone marrow depression.
adalimumab (Humira)
human antibody (TNF-alpha antibody)
- somewhat less effective
- maintain remission for UC and Crohn’s
- adverse rxn: increased risk for respiratory infection
azathioprine (Imuran)
thiopurine
- prevention of DNA synthesis by targeting rapidly proliferating cells.
- effective for UC and Crohn’s
- Adverse rxn: pancreatitis, fever, rash, arthraligias, NV, and bone marrow depression.
budesonide (entocort)
glucocorticosteroid
-effective for IBD 2/2 antiinflammatory and immune effects.
-Adverse rxn: immunosupression, endocrine dysfunction, steroid psychosis, etc
-200x as potent as hydrocortisone but only 10% bio-availability and most is removed via 1st pass effect
+effective for topical Tx inside the bowel
infliximab (Remicade)
humanized antibody (TNF-alpha antibody)
- somewhat less effective
- maintain remission for UC and Crohn’s
- adverse rxn: increased risk for respiratory infection
prednisone (Deltasone)
glucocorticosteroid
- effective for IBD 2/2 antiinflammatory and immune effects.
- Adverse rxn: immunosupression, endocrine dysfunction, steroid psychosis, etc
