Gastroprotectants & Anti-emetics Flashcards
Medullary Vomiting Center
anti-emetics that work here are more effective than the CRTZ which are more effective than peripherally acting drugs
Cerenia
NK1 (neurokinin) receptor antagonist that blocks substance P in the CRTZ as well as NK1 in the GI tract
S/E: pain upon injection, bone marrow hypoplasia in dogs < 11wks old, may reduce MAC of sevo and add in visceral analgesia
Ondansetron
5HT3 (serotonin) receptor antagonist in the MVC, CRTZ, and peripheral vagal afferent input
S/E: may decrease the efficacy of tramadol, may have diarrhea, otherwise well tolerated
Famotidine, Cimentidine, Ranitidine, Nizatidine
H2 receptor antagonist - competitively inhibit (but do not completely block) gastric acid secretion by binding to histamine receptors on parietal cells and diminishes pepsin secretion
Famotidine is the strongest but the least orally bioavailable and is excreted unchanged in the urine. Unclear if dose reduction is needed in renal patients. Side effects include thrombocytopenia in people and transient increase in gastrin.
Rinetidine and Nizatidine - gastric prokinetic effects via antiacetylcholinesterase activity
Cimetidine inhibits the cytochrome p450 system and can be used in tylenol toxicity. It also reduces hepatic blood flow by 20%
Pantoprazole and Omeprazole
Proton Pump Inhibitor - noncompetitively inhibit gastric acid secretion and so are stronger than H2R antagonists. Irreversibly block the H-K-ATPase pump on the luminal side of the parietal cell and thus STOP all gastric acid secretion.
take 2-5 days to reach maximal effectiveness
Omeprazole is the prodrug and is broken down by gastric acid so it is administered encapsulated and absorbed by the duodenum. Best to administer one hour before a meal to maximize the amt of acidity and thus sequestration of the active drug in the stomach after first pass hepatic metabolism.
Side effects are uncommon but may include diarrhea. Omeprazole inhibits cytochrome p450 activity and is associated with antiplatelet activity with clopidogrel and decreased hepatic clearance of diazepam in people.
Sucralfate
Octosulfate of sucrose combined with aluminum hydroxide
coats ulcers from pepsin and bile for 6 hours. needs to be in an acidic environment
stimulates local production of prostaglandins and epidermal growth factor to encourage healing
Side effects: may lead to constipation, absorbs other drugs and so should be given on an empty stomach, only orally administered so difficult in vomiting/inappetent/aspiration risk patients
Activated charcoal
coats the lining and covers ulcers
Metoclopramide
D2 receptor antagonist that works at the CRTZ! and and 5HT3 serotonin receptor antagonist in the periphery <- usual doses we use
is also a 5HT4 agonist like cisapride but crosses the BBB and can cause extrapyridimal signs
gastric prokinetic facilitating gastric emptying and reducing gastroesophageal reflux byt tightening sphincter pressure, and relaxing the pylorus and duodenum (but no effect in the colon) but at higher doses like 0.3mg/kg/hr after a loading dose
less effective in cats than dogs b/c cats have less dopamine receptors
more effective when given as a CRI
may also increase sensitivity of the small intestine to acetylcholine
S/E: abnormal neuro/behavior, toxicity in renal disease since renally excreted
Chlorpromazine, Acepromazine
Promazine derivitives with anti-emetic properties except for vestibular disease
Anti-dopamine and anti-histamine that block the CRTZ and even MVC at high doses
Also anticholinergic, antispasmodic, and alpha antagonism
but also sedation and hypotension because of alpha antagonism
S/E: sedation, hypotension, potential for arrhythmias, maybe seizures
Misoprostol
Prostaglandin E1 analogue with antacid and mucosal protective properties in that it stimulates secretion of mucus and bicarbonate and increases gastric mucosal blood flow. It inhibits acid secretion in response to food, night, pentagastrin, and histamine. used to prevent ulceration from NSAIDs. May also enhance colonic motility
S/E: diarrhea (self limiting), uterine contraction which can cause abortion
Erythromycin
motilin receptor agonists that increases lower esophageal sphincter pressure and small and large bowel peristalsis
S/E: chronicity may lead to tolerance
Cisapride
5HT4 serotonin agonist, which is the strongest class of gastric prokinesis
good for gastroesophageal reflux by increasing gastroesophageal sphincter pressure, gastric emptying, and colonic emptying in mild to moderate cases of constipation
works along the ENTIRE GI tract but is not an anti-emetic
metabolized by the hepatic p450 cytochrome enzyme system
S/E: does not work on striated muscle and may make regurgitation worse in patient’s with megaesophagus
Cholinomimetic Drugs
class of prokinetic drugs
bethanecol, ranitidine, and nizatidine, the former which binds to muscarinic receptors wherease the two latter inhibit cholinesterase activity and seem to work best at the stomach
Serotonin antagonists
over 90% of serotonin (5HT) is located in the GI tract with the vast majority being stored in enterchromaffin cells lining the epithelium and the remainder being present in the enteric nervous system where it acts as a neurotransmitter.
There are serotonin receptors all along the intestinal epithelium
5HT1 - initiates peristaltic and secretory reflexes, no drugs yet
5HT3- activates extrinsic sensory nerves and feelings of nausea and induction of vomiting from visceral hypersensitivity, ondansetron is an antagonist
5HT4- increase presynaptic release of acetylcholine and calcitonin-gene related peptide thereby increasing transmission that leads to propulsive peristaltic and secretory reflexes, cisapride is an AGONIST but will only enhance natural/innate nerve function and will not work if nerves are damaged.
