Gastrointestinal Drugs Flashcards
Examples - Antiemetic Drugs
- maropitant
- ondansetron
- metoclopramide
- promazine derivatives (ACP, CPZ)
NEUROKININ-1 RECEPTOR ANTAGONISTS
-Ex: maropitant
MOA: Blocks action of substance P in CNS and at peripheral NK-1 receptors in GI tract
Peripheral, Central Effects
Other Effects of NK1 R antagonists
Bone marrow hypoplasia in puppies younger than 11 weeks old
Other effects beyond antiemesis: Anti-inflammatory, Neuroprotectant, hepatoprotectant, MAC reduction/ visceral analgesia, anti-tumor
5-HT3 R Antagonists
Ex: ondansetron
MOA: Competitive serotonin receptor antagonists (peripheral in intestines if PO and centrally within CRTZ and medullary vomiting center if injected)
Peripheral, Central Effects
5-HT3 R Antagonist - metabolism
Metabolized by liver P-450 enzymes, then eliminated in urine and bile
5-HT3 R Antagonists - AEs
Adverse effects: Minimal; May cause in humans constipation/ diarrhea/ somnolence/ prolonged QT interval; May decrease efficacy of tramadol
Potential for Serotonin Syndrome
Metoclopramide
Antiemetic MOA: Dopamine antagonist + Serotonin receptor antagonist (5-HT3 antag.)
Prokinetic MOA: Dopamine antagonist +/- Increased sensitivity of SI smooth mm to ACh
Cats are thought to have a paucity of dopamine receptors – this is why it seems less effective
Central emetogens, peripheral and central for pro kinetic activity
Effects of Metoclopramide
Blocks CRTZ: antiemetic at 1-2 mg/kg q24h
Gastric prokinetic activity to facilitate gastric emptying and decreases GER requires higher doses like LD 0.4mg/kg followed by 0.3 mg/kg/h
Metoclopramide Excretion
Excreted by kidneys so use care in patients with substantially decreased GFR»_space; Renal dysfunction allows for high blood levels»_space; Extrapyramidal signs with hyperactivity/ frenzied behavior
Also risk of serotonin syndrome
Promazine Derivatives: ACP, CPZ
MOA: Antidopaminergic (D2) + Antihistamine effects that block the CRTZ and at higher doses also the medullary vomiting center
CENTRAL EFFECTS
Effects of Promazine Derivatives
Also alpha blockers but antiemetic effects are typically achieved at doses lower than those needed to produce sedation and hypotension
Can produce brady- or tachy-cardia but are antiarrhythmic;
May potentiate extrapyramidal effects of metoclopramide (so use caution and maybe don’t use both together)
Risk of serotonin syndrome
Prokinetic Drugs
- 5-HT4 R Agonists
- Cholinomimetic Drugs
- Motilin R Agonists
Gastric Protectants
- H2 R Antagonists
- PPIs
- Sucralfate
5-HT4 SEROTONERGIC AGONISTS (EX-CISAPRIDE)
Most effective class of prokinetic drugs in vet med (more effective than metoclopramide at treating GER and delayed gastric emptying)
Uses: Treat GER, poor gastric emptying, and chronic constipation; Increases gastroesophageal sphincter pressure; Increases SI motility
Limitations of 5-HT4 R Agonists
Does NOT work on striated muscle, so will not enhance esophageal motility in megaesophagus and in fact may make regurg worse in those patients because it increase LES tone
Cholinomimetic Drugs
Ex: ranitidine, bethanechol
Ranitidine MOA
Inhibits acetylcholinesterase»_space; Promote gastric emptying (minimal colonic motility)
Also H2 R antagonism
Anticholinergics
–Scopalamine (effective for motion sickness in people, less so in vet med), atropine
–Block M1 R - vomiting caused by vestibular stimulation, stimulation of CTRZ
Not practical for many causes of vomiting in vet med, significant SE
Scopolamine: excitement in many animals, esp cats
Glucocorticoids (steroids)
Block PGE2 production
Motilin R Agonists
MOA: Stims motilin receptors»_space; Promotes SI and LI peristalsis + Increases LES pressure
Erythromycin only
Other macrolides have different carbon structure, unable to bind to motion R
PERIPHERAL EFFECT
Misoprostol
Prostaglandin E analog»_space; Enhances colonic motility to treat patients with nonresponsive constipation
Stims secretion of mucus and bicarb
Increases gastric mucosal BF
Acts directly on parietal cells to inhibit acid secretion
PERIPHERAL EFFECTS
Adverse Effects of misoprostol
Diarrhea; Uterine contraction which can cause abortion
Gastroprotectants - Usage
typically indicated to heal existing gastric ulcers but are not effective at preventing ulceration when the cause still exists.
While drugs that decrease gastric acid secretion are NOT antiemetic (eg have no effect on CRTZ or MVC), can lessen nausea with an antidyspeptic effect
Causes of GI Ulceration
Gastric hypoxia and hypoperfusion (d/t hypotensive shock, SIRS, severe life-threatening illness) with or without steroids or NSAID use
Hyperacidity from gastrinoma or MCT may cause gastric ulcers but more commonly duodenal
Liver failure / FB may also cause gastric ulcers
NSAID GI Ulceration - locations in horses
stomach, RDC - anywhere
NSAID GI Ulceration - location in camelids
third compartment
NSAID GI Ulceration - dogs
antrum, proximal duodenum
NSAID GI Ulceration - ruminants
Abomasum
HISTAMINE-2 RECEPTOR ANTAGONISTS (H2RAS) EX- FAMOTIDINE, CIMETIDINE
MOA: Block histamine receptor on gastric parietal cell to competitively inhibit gastric acid secretion (vs PPIs which are noncompetitive) –> more effective at decreasing gastric acid secretion
Onset of action is almost immediate
HISTAMINE-2 RECEPTOR ANTAGONISTS (H2RAS) EX- FAMOTIDINE, CIMETIDINE Metabolism
First pass hepatic metabolism with PO admin; cimetidine/ ranitidine metabolized by liver but famotidine excreted almost completely unchanged in urine
Cimetidine: CYP450 inhibition
Cimetidine’s Effects on Hepatic CYP450
Markedly inhibits hepatic P450 enzymes:
decreases metabolism of lidocaine/ theophylline/ metronidazole/ etc»_space; Toxicity (famotidine barely affects this at all)
Cimetidine also decreases hepatic BF by about 20%
Cimetidine is associated with more AE, uncommon with ranitidine or famotidine
PPIs: omeprazole, pantoprazole
Somewhat effective as prophylactic against NSAID-induced GUE (gastric ulceration and erosion), but not completely effective
MOA: Irreversibly inhibit H-K ATPase on luminal side of parietal cell»_space; Stops secretion of H+ ions into gastric lumen
Non-competitive inhibition
PPI Onset of Action
2-5 days before maximal acid suppression occurs, but the immediate effects may still be superior to those of famotidine, and suppression of acid continues for a few days after admin d/t irreversible inhibition of the proton pump enzyme
Can decrease GER during GA but will not prevent it
AEs PPIs
Diarrhea; Inhibit P-450 enzymes (omep»_space; pantop)
Sucralfate
Aluminum hydroxide compound that binds to epithelial cells in the acidic environment of stomach
Physical barrier to ulcer to protect ulcer from acids
Stims local production of prostaglandins, binding to epidermal growth factor (to encourage mucosal repair)
