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GI Drugs
Pharmacology 208
77
Pharmacology
Graduate
02/15/2010

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Cards

Term
Where are the gastrin containing cells?
Definition
Antrum
Term
Where are enterochromaffin-like cells?
Definition
fundus
Term
What is the secreted by ECL cells?
Definition
histamine
Term
What stimulates histamine release in ECL cells?
Definition
Gastrin/CCK-B and ACh/M1
Term
What is released by parietal cells?
Definition
HCl
Term
What inhibits histamine release at ECL?
Definition
somatostatin
Term
What stimulates the release of HCl at parietal?
Definition
ACh/M3, histamine/H2, gastrin/CCK-B
Term
Risk factors of peptic ulcer disease (9)
Definition
coffee, alcohol, tobacco, salicylates, NSAIDs, heredity, age, H. pylori, stress
Term
Heartburn and GERD risk factors (3)
Definition
hiatal hernia, weakened esophageal sphincter pressure, overweight
Term
Rx of peptic acid disease (4)
Definition
reduce gastric acid secretion, enhance mucosal defense, neutralize gastric acid, eradicate H. pylori
Term
Sites of action for treatment of peptic acid dx
Definition
H2 receptor, proton pump, lumen, mucosa
Term
H2 antagonists
Definition
ranitidine, famotidine
Term
H2 antagonists mechanism
Definition
Directly block histamine-stimulated gastric acid secretion – antagonists at histamine H2 receptors, Blunt parietal cell responses to ACh and gastrin
Term
H2 antagonists toxicity
Definition
Very low toxicity – but reduce dose in renal dysfunction
Term
H2 antagonists efficacy
Definition
Up to 90% inhibition of nocturnal gastric acid secretion, gastric and duodenal ulcers, GERD
Term
H2 antagonist half-life
Definition
2-3 hrs
Term
H2 antagonist adverse effects
Definition
Cimetidine only: antiandrogenic properties and binding to microsomal P450
Term
Famotidine use
Definition
famotidine with long-term NSAID therapy reduces the number of ulcers
Term
H2 antagonist use
Definition
famotidine with long-term NSAID therapy reduces the number of ulcers, prophylaxis after acute event to prevent recurrence
Term
Omeprazole basics
Definition
Proton Pump inhibitor, Irreversible inhibition of parietal cell proton pump (H+/K+-ATPase) results in prolonged 90-98% inhibition of gastric acid secretion
Term
PPI mechanism
Definition
weak base accumulates in acidic parietal cells then protonated form of drug binds covalently to enzyme – are acid labile so need enteric coating to get past stomach
Term
Why is zegredid special?
Definition
combines omeprazole with bicarb to allow for more rapid absorption
Term
PPI metabolism
Definition
P450
Term
PPI tolerance
Definition
well-tolerated, but nausea, diarrhea, and dizziness can occur
Term
PPI use
Definition
better during the day, but does have nocturnal application
Term
PPI efficacy
Definition
ulcers and GERD, first choice in Zollinger-Ellison Syndrome
Term
PPI availability
Definition
OTC, except for zegredid poor choice for occasional heartburn
Term
PPI safety
Definition
no indication of gastric carcinoid tumors, 50% increase in pneumonia in one study – possibly to more bacterial aspiration from less acidic stomach, nor increased risk of heart attack or other heart complications
Term
Antacid types
Definition
Mg(OH)2, Al(OH)2, CaCO3
Term
antacid absorption
Definition
poor, stay in GI and directly neutralize acid
Term
antacid adverse effects
Definition
Mg-diarrhea, Al and Ca-constipation
Term
antacid efficacy
Definition
occasional heartburn
Term
Antacid drug interactions
Definition
can increase or decrease the absorption of many classes of drugs, changes dissolution rate of gastric emptying
Term
Al or Ca drug interaction
Definition
decreased absorption of TCN, isoniazid, ketoconazole
Term
Antacid pH altering
Definition
increase in urinary pH alters elimination or acidic (salicylates) and basic (quinidine) drugs
Term
H. pylori treatment
Definition
a PPI plus clarithromycin with metronidazole or amoxicillin, sometimes also use bismuth-containing compounds
Term
Sucralfate, bismuth subsalicylate muchanism
Definition
forms paste-like gel at low pH that adheres to positively charge proteins of epithelial cells as ulcer craters, coating actions protects cells against acid and pepsin attack
Term
Pepto counter-indication
Definition
can adsorb other drugs, e.g. TCN, phentoin, digoxin, so what 2 hrs before admin; do not co-admin with antacids
Term
What type of drug is metoclopramide?
Definition
prokinetic agent
Term
Metoclopramide mechanism (4)
Definition
enhances release of ACh in myenteric plexus, improves intestinal smooth muscle response to ACh, increases esophageal clearance and improved tone in esophageal sphincter, increased intestinal motility
Term
Metoclopramide adverse effects
Definition
has DA D2 receptor antagonist activity that can cause extrpyramidal (Parkinson-like) symptoms and tardive dyskinesia
Term
Metoclopramide use
Definition
antiemetic for cancer patients
Term
What can cause constipation?
Definition
can be the result of reduced colonic motility and/or increased hardness of intestinal contents
Term
Constipation and dietary rx
Definition
add fiber and plenty of water to improve bulk and consistency of feces
Term
What is the laxative effect?
Definition
Results in excretion of soft stool
Term
What is laxative cathartic effect?
Definition
More intense effect with greatly increased intestinal activity and watery stool – e.g. for a colonoscopy
Term
Laxative contraindications
Definition
Cramps, colic, nausea, vomiting, other symptoms of appendicitis, undiagnosed abdominal pain
Term
What type of drug is lubiprostone?
Definition
stimulant laxative
Term
lubiprostone efficacy
Definition
idiopathic chronic constipation: abdominal pain, bloating, straining, hard stools with no known cause; more common in elderly females
Term
lubiprostone mechanism
Definition
increases intestinal fluid secretion>>increased number of bowel movements
Term
lubiprostone adverse effects
Definition
diarrhea, abdominal pain, distention
Term
lubiprostone use
Definition
chronic
Term
Mg(OH)2 laxative mechanism
Definition
admin as a hypertonic solution which increases osmotic pressure within lumen>>stimulation of peristalsis
Term
Mg(OH)2 catharsis
Definition
evacuation in less than 3 hours
Term
What is loperamide?
Definition
antidiarrheal agent, opioids with low abuse potential because they are very poorly absorbed
Term
Loperamide mechanism
Definition
slows intestinal transit time due to stimulation of mu opioid receptors in intestinal smooth muscle, muscarinic antagonist
Term
Loperamide adverse effects
Definition
constipation, toxic megacolon, can cross BBB and cause CNS toxicity
Term
Loperamide counter-indication
Definition
patients with UC or acute bacillary/amoebic dysentary
Term
Physiology of nausea and vomiting
Definition
In the CNS, both the vomiting center in the brainstem and the Chemoreceptor Trigger Zone (CTZ) which sits just outside the blood brain barrier have high concentrations of 5-HT3 receptors. These areas also receive input from the vagal system. Activation of these centers, as occurs in cancer chemotherapy or after general anesthesia, results invomiting and nausea.
Term
What is ondansetron?
Definition
antinausea and vomiting
Term
Ondanestron mechanism
Definition
blocks 5-HT3 receptors
Term
Ondansetron use
Definition
before chemo or surgery
Term
Ondansetron admin
Definition
IV or orally, little effect on muscarinic or dopaminergic receptors
Term
Ondansetron synergy
Definition
addition of dexmethasone (corticosteroid) or aprepitan (neurokinin 1 receptor)
Term
What is tegaserod?
Definition
Rx for IBS-C or chronic idiopathic constipation (CIC)
Term
tegaserod mechanism
Definition
5-HT4 receptor agonist stimulates submucosal and myenteric plexi to release ACh and other transmitters, resulting in more rapid transit through stomach and intestines.
Term
tegaserod adverse effects
Definition
diarrhea, but generally resolves after several days of treatment; heart attack, stroke and unstable angina
Term
tegaserod problems
Definition
taken off general market by FDA, if physician decides drug is necessary for IBS-C or CIC (chronic idiopathic constipation) then can prescribe for these conditions only in women younger than 55 who have no known heart disease
Term
What is alosetron?
Definition
antidiarrheal
Term
Alosetron mechanism
Definition
5-HT3 receptor antagonist alosetron, which is FDA approved only for women with diarrhea-predominant IBS; decresed colonic motility via enteric and CNS blockade of 5-HT3 receptors
Term
alsetron adverse effects
Definition
constipation, serious but rare (0.3%) is ischemic colitis which can be fatal
Term
sulfaslazine basics
Definition
UC and Chrohn’s, 5-aminosalicylic acid (5-ASA)
Term
sulfasalazine mechanism
Definition
interferes with intermediates in inflammatory pathways, topical 5-ASA is effective
Term
sulfasalazine adverse effects
Definition
up to 40% of patients cannot tolerate: nausea, HA, HS, bone marrow suppression
Term
sulfasalazine admin
Definition
enemas and suppositories used for lesions near anus in Chrohn’s, different formulations based on location of lesions
Term
Azathioprine mechanism
Definition
IBD, immunosuppression, purine anti-metabolite
Term
Azathoiprine adverse effects
Definition
bone marrow suppression, rashes, fever, nausea
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