Gastro-intestinal Flashcards
(29 cards)
What is the mechanism of action of antacids (= AlOH, CaCO3, MgOH)
Decrease pepsin activity, bind to bile acids in the stomach, stimulate PGE2 synthesis.
Likely don’t have a strong enough buffering capacity to truly decrease the pH.
How does the efficiency of H2 antagonists / proton pump inhibitors change over time?
- H2 antagonists: efficiency decreases because of tolerance within 3 days
- Proton pump inhibitors: efficiency increases over the first 2-5 days because extra proton pumps are synthesized initially and need to be blocked as well + PPIs inhibit cytochrome P450 (-> decreased metabolism)
Why is the co-administration of H2 antagonists and PPIs not recommended
PPIs need to be in an acidic environment to inhibit the proton pump
Do PPIs / H2 antagonists need to be tapered
PPIs should be tapered if administered for > 3-4 weeks
H2 antagonists should be tapered (tolerance develops early)
Name examples of drugs whose absorption will be decreased by the use of PPIs
- Antifungals (except liquid itraconazole and fluconazole)
- Mycophenolate
Mechanism of action of cyproheptadine
5-hydroxytryptamine (5-HT2) antagonist & anti-histamine
Mechanism of action of mirtazapine
5-HT-2C receptor antagonist (-> blocks anorexic stimuli) + H1-receptor antagonist (histamine decreases appetite)
How frequently should mirtazapine be dosed in otherwise healthy cats? In dogs? What can prolong its half life?
Daily in healthy cats, potentially twice daily in dogs
Half life prolonged by older age, kidney disease, liver disease
Name 3 appetite stimulants
- Cyprohepatdine (5-HT agonist, H1 antagonist)
- Mirtazapine (5-HT-2C antagonist, H1 antagonist)
- Capromorelin (ghrelin receptor agonist)
Absorption / metabolism and mechanism of action of PPIs
- Absorbed in the duodenum (can be lysed by gastric acidity so better to give SQ initially or with bicarbonate / in enteric-coated formulation)
- First-pass hepatic metabolism
- Part of the drug not metabolized -> concentrated in parietal cells ; activated in acidic environment -> irreversible inhibition of H+/K+ transporter (proton pump)
Mechanism of action of sucralfate
Sucrose + aluminum hydroxide
Binds to epithelial cells in acidic environment, mostly at the base of erosions / ulcers -> physical barrier against pepsin and bile acids + stimulates local production of prostaglandins and epidermal growth factor
Name 1 competitive and 1 non-competitive inhibitor of gastric acid secretion
- Competitive: H2-receptor antagonists
- Non-competitive: PPIs
What H2 receptor antagonist causes marked inhibition of cytochrome P450 enzymes
Cimetidine
Mechanism of action of misoprostol
Prostaglandin E1 analog ->stimulates mucus secretion and bicarbonate secretion, increases gastric mucosal blood flow + inhibits H+ secretion from parietal cells (in response to food, gastrin, histamine)
Mechanism of action of maropitant and its different effects
Neurokinin 1 inhibitor -> blocks actions of substance P in CNS and peripherally (GI tract)
-> antiemetic
-> other: antitussive, antiinflammatory, neuroptotectant, hepatoprotectant, analgesic (visceral pain), MAC reducer in anesthesia
Mechanism / sites of action of ondansetron
5-HT3 antagonist
-> inhibits 5-HT3 receptors peripherally (in gut, responsible for vagal afferent input) and centrally (in CRTZ and medullary vomiting center)
Mechanism of action of metoclopramide
- Dopaminergic D2 receptor antagonist:
- in the gut -> increased motility
- in CRTZ -> decreased vomiting - 5-HT3 receptor antagonist:
- in CRTZ -> decreased vomiting - 5-HT4 receptor agonist:
- in the gut -> increased motility - +/- muscarinic receptor antagonist
What H2 receptor antagonist has a pro-motility effect? By what mechanism?
Ranitidine
Acetylcholinesterase inhibitor
What promazine derivatives can be used as antiemetics? What is their mechanism of action? Side effects?
Chlorpromazine, prochlorperazine
Anti-dopaminergic and anti-histamine in CRTZ (+/- medullary vomiting center)
Also alpha-adrenergic antagonists (same as acepromazine) -> can cause hypotension
+ can cause sedation
What anticholinergic agent could be used as an antiemetic
Aminopentamide
What sedative / anesthetic agents could have anti-emetic properties
- Opioids (can be both emetic and anti-emetic ; butorphanol shown to prevent vomiting)
- Propofol
What are the different types of pro-kinetic drugs and their preferential sites of actions in the GI tract
- 5-HT4 serotoninergic agonists (cisapride)
-> lower esophageal sphincter, stomach, small intestine, colon - Motilin agonists (eyrthromycin)
-> lower esophageal sphincter, stomach, small intestine +/- colon (mostly in dogs) - Cholinomimetic drugs (true cholinomimetic = betanechol / acetylcholinesterase inhibitor = ranitidine)
-> diffuse GI for betanechol, mostly stomach +/- colon for ranitidine - Metoclopramide = D2 dopaminergic antagonist and 5-HT4 serotoninergic agonist + may increase sensitivity of small intestinal smooth muscle to ACh
-> LES, stomach, duodenum
Which GI drug can moderately reduce MAC of sevoflurane during GA?
Maropitant
What is an adverse effect of metoclopramide when overdosed? Which group of patients is at risk?
Extrapyramidal signs (behaviour changes, apparent hallucinations, hyperactivity…)
Patients with renal dysfunction (excreted by kidneys)
