Pharmacology Flashcards
Histamine is released in the stomach by __(a)__ cells in response to __(b)__?
a) Enterochromaffin-like Cells (ECLs)
b) ACh released by the Vagus nerve
Gastrin is released by G cells in the _____.
antrum (of stomach).
Effect of Histamine release in the stomach?
Histamine triggers the release of acid by the Parietal Cells via H2 receptors
ACh, from the Vagus nerve has what effects on stomach cells?
- Release of HCl from Parietal cells
(directly via M3 receptors & indirectly via Histamine release on H2 receptors) - Release of Mucus & Bicarbonate from Superficial Epithelial cells
Gastrin effect on stomach cells?
Causes the release of HCl from Parietal cells
via CCK2 receptors
Prostaglandins effect on stomach cells?
PGE2 inhibits release of HCl from Parietal cells
(via EP3 receptors)
PGI2 causes release of Mucous & Bicarbonate from Superficial Epithelial Cells
(via EP3 or EP? receptors)
(they also increase blood flow to stomach)
NO effect on stomach?
Increases blood flow to stomach
H2-blockers: side effects?
Very rare - mostly seen w/ Cimetidine
• Headache, dizziness, myalgia
• CNS AEs possible in elderly with impaired renal or hepatic function
• Confusion, hallucinations, etc.
• Drug Interactions – cimetidine inhibits CYP1A2, CYP2C19, CYP2D6, CYP3A4
• Antiandrogenic – cimetidine inhibits DHT binding to androgen receptor → impotence, loss of libido, gynecomastia
– Inhibit estradiol metabolism & increases prolactin levels
• All - ↓doses in mod. to severe renal dysfunction
H2-receptor Antagonist: effects?
- ↓ Volume & [H+] of gastric secretion
- ↓ Basal acid secretion
- ↓ Gastrin & ACh stimulated secretion
• ↓ Food stimulated acid secretion – Modest
4 H2-receptor antagonists?
Cimetidine, Ranitidine, Famotidine, Nizatidine
Most potent H2-receptor Antagonist?
Famotidine
also longest effect
*available PO & IV
H2-Receptor Antagonists - Indications?
- Rx for gastric & duodenal ulcers
- Zollinger-Ellison syndrome
- GERD
- Erosive esophagitis
- OTC – heartburn, acid indigestion, etc.
PPI - inhibition is reversible or irreversible?
Irreversible
PPIs - effects?
- ↓↓ Acid secretion (basal & stimulated)
- N/C in volume of secretion
- ↑↑Gastrin secretion – hyperplasia of ECL cells
IV formulations available for which of the PPIs?
esomeprazole, pantoprazole, & lansoprazole
PPIs - Indications?
• GERD – erosive esophagitis treat/prevention
• PUD
– H pylori associated ulcers healing/ treatment
– NSAID-induced ulcers
– Prevention of rebleeding from peptic ulcers
• Dyspepsia – OTC – omeprazole, lansoprazole
– Limited to 14 day Tx no more than 3 times/yr
- Prevention of stress ulcers in ICU patients – IV
- Hypersecretory conditions – Zollinger- Ellison
PPIs- adverse effects?
Very safe drugs! AEs in small % of patients
- GI (nausea, diarrhea, colic, constipation)
- CNS (headache, dizziness, somnolence)
- Skin rash
- ↑↑ Liver enzymes
• Potential DDI
– CYP2C19 & CYP3A4 – Clopidogrel, warfarin, methotrexate, tacrolimus
– Drugs with pH dependent absorption
PPIs - safety warnings?
- PPI Symptom relief does not rule out gastric Ca
- PPI use may increase risk of C. difficile infection
- Prolong use of high does may be associated with ↑ risk of osteoporosis-related bone fracture of the hip, wrist or spine.
- Rare cases of life threatening hypomagnesemia have been reported in after prolonged use.
- Cases of vitamin B12 deficiency have been reported with prolonged use.
Misoprostol - MOA?
- ↑ Secretion of Mucus & Bicarbonate from superficial epithelial cells
- ↓ Acid secretion
Misoprostol - contraindications?
Pregnancy
Misoprostol - Uses?
- Used to prevent of NSAID-induced ulcers
* Available in combination with NSAIDs
Misoprostol - adverse effects?
Diarrhea, colic
Sucralfate - Effect
sadf
