Pharmacology Of The Upper GI Flashcards
When does acid production peak for stomach?
Peaks before breakfast, lunch, and dinner, and then in the evening while you sleep
Antacids
- MOA
- examples
- indications
- contraindications
Hydroxide and/or carbonate salts that directly neutralize stomach acid (no receptor required)
Examples:
1) Al(OH)3 (gaviscon)
2) Mg(OH)2 (milk of magnesia)
3) CaCO3 (tums)
Indications: mild GERD and dyspepsia
Contraindications: none (but dose spreading with other meds as the altered pH can reduce drug absorption of other drugs or chelate to them
Antacids side effects:
- Carbonate-based salts —> belching due to CO2 production
- Calcium-containing —> hypercalcemia —> calculi formation
- Aluminum containing —> constipation and hypophosphatemia (it binds to phosphate)
- Magnesium containing —> diarrhea due to limited absorption
Can take Aluminum and Magnesium ones together to offset the effects
H2 Receptor antagonists
- examples
- MOA
- dosing pattern and excretion organ
- indications
- complications
- the tidine drugs (randtidine)
- famotidine is most potent dosed at 20mg Bid or 40mg HS
- competitively block H2 receptors
- reduces acid production put to 60-70% because vagal and gastrin pathways still available due to food-related stimulus
- most effective in reduction of nocturnal acid secretion
- typically taken orally (can also be done IM and IV) with an oral bioavailability of 50% (except nizatidine due to minimal 1st pass metabolism) with peak absorptions at 1-3 hours
- twice daily administration and eliminated renally
- indications:
1) GERD
2) peptic ulcer disease
3) dyspepsia
4) prevention of bleeding from stress-related gastritis
Complications:
- none, but does cross placenta and breast into milk - no known harm to fetus
Common H2 receptor antagonist side effects
Diarrhea or constipation
Headache
Drowsiness/fatigue
Muscle pain
Rare Sid effects of H2 receptor antagonists
Confusion/agitation
Delirium/hallucinations
Slurred speech
Gynecomastia/galactrorrhea (cimetidine only)
Blood dyscrasias (very rare)
Proton pump inhibitors
- examples
- MOA
- dosing regime and why?
- indications
- contraindications
The prazole drugs (omeprazole)
- irreversible in activation of proton pumps common to all triggers of gastric acid secretion
- can decrease H+ secretion by 90-98%
- restoration of acid requires new proton pump synthesis —> 18-24 hours and as such, usually dosed once daily
- selective for parietal cell proton pumps
Indications:
- gastric and duodenal ulcer (H. Pylori and NSAID induced)
- GERD
- prevention of bleeding from stress-related gastritis
Gastric hypersecretory conditions (e.g. gastrinoma (Zollinger-Ellison syndrome))
Contraindications - none
Side effects of PPIs
Nausea
Diarrhea or constipation
Abdominal pain
Flatulence
Also some more rare side effects:
- acute kidney injury
- enteric infections
- structural and functional changes in the gastric mucosa (such as benign bumps that go away one discontinuing meds)
Other options for acid reduction
Antimuscarinics - pirenzipine - utile, effective, but side effects (dry mouth and blurred vision)
Gastrin receptor antagonists - proglumide (pathway is inhibited at pH <2.5, better off targeting other pathways
Treatment for H Pylori
14 days of PPI + clarithromycin and amoxicillin or metronidazole
6 weeks of PPI alone
Misoprostol
- describe the MOA
- direct effects on what cells?
- describe the pharmacokinetics
- indications
- contraindications
- side effects
- is a Prostaglandin E1 analogue and emulates endogenous PGE2
- direct effects:
1) inhibitory of parietal cells
2) Stimulatory of mucous cells - has a short half life requiring frequent dosing and has no impact on P450 enzymes
- implicated for NSAID-induced ulcers
- contraindicated in pregnancy as it can induce strong uterine contractions
- side effects - all due to ability of PGE1/2 to stimulate GI/uterine smooth muscle
1) diarrhea
2) abdominal cramping
3) uterine contractions
Sucralfate
- what is it?
- MOA
- describe the pharmacokinetics
- indications
- contraindications
- side effects
Is an Al(OH3)-sucrose sulfate complex
- acid released an ionic sulfate sucrose that binds too charged proteins in ulcer forming viscous sticky protective barrier
- also causes indirect stimulate of PGE2 production
- has a localized action (minimally systemic absorption) with a short effect (6 hours) and needs to be taken on empty stomach
- indicated in gastric and duodenal ulcers
- has no contraindications
Side effects:
- Al3+ induced constipation
- may reduce absorption of some other drugs via direct binding or impaired membrane crossing
Bismuth Subsalicyclate
- MOA
- describe pharmacokinetics
- indications
- contraindications
- side effects
Coats ulcers forming physical protective barrier
- increased PGE2, HCO3 and mucus production
- Antimicrobial against H. Pylori
- reduces stool frequency (via salicylate effects on PG/Cl secretion)
Dissociates in stomach acting locally - only salicylate substantially absorbed
Indicated as adjuvant to triple therapy to H. Pylori ulcers as well as in acute diarrhea
Contraindications:
- children with viral infections —> Reye’s syndrome
- allergies to ASA (30mL - 325mg tablet)
Side effects:
- black stool due to reaction with hydrogen sullied in colon and may be confused with GI bleeding
- blackening of the tongue
- constipation
Prokinetic drugs
- two types and their differences
- MOA
- pharmacokinetics
- indications
- contraindications
- side effects
Metoclopramide and domperidone
- both are dopamine D2 receptor antagonists
- metoclopromaide has addition agonist activity at serotonin (5-HT) receptors
- relieve basal dopamine inhibition of upper GI tract, stimulating peristalsis and facilitating gastric emptying
- Metoclopromide is available in oral and parenteral formulations (domperidone has higher 1st past metabolism)
- short duration of action (1-2 hours) and metabolized in the liver
- indicated in GERD, impaired gastric emptying (gastroparesis), nausea and vomiting, and postpartum lactation stimulation
- contraindicated in situations where GI motility is harmful
Side effects:
- GI cramping
- diarrhea
- hyperprolactinemia
- metoclopromide crossed BBB causing dystopias, Parkinson’s-like syndromes, tardive dyskinesia, drowsiness, restlessness, insomnia and anxiety (and these are all more prominent in elders and children)
Ondansetron
- MOA
- indications
- side effects
Is an anti-emetic drug
MOA:
- antagonist of Serotonin 5-HT3 receptors —> vagal afferent S, chemoreceptor trigger zone, and vomiting center
Indications:
- chemotherapy-induced nausea and vomiting
- post-operative and post-radiation nausea and vomiting
Side effects:
- headache
- dizziness
- constipation
Not very effective in reducing motion sickness
