Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology
Section VI λ Drugs for Inflammatory and Related Disorders
H2 Antagonists (e.g., Cimetidine, Ranitidine, Famotidine)
λMechanisms of action:
–Suppress secretory responses to food stimulation and nocturnal secretion of gastric acid via their ability to decrease (indirectly) the activity of the proton pump.
–Also partially antagonize HCl secretion caused by vagally or gastrininduced release of histamine from ECL-like cells (GI mast cells)
–No effects on gastric emptying time
λUses:
–PUD (overall less effective than proton pump inhibitors)
–Gastroesophageal reflux disease (GERD)
–Zollinger-Ellison syndrome
λSide effects:
–Cimetidine is a major inhibitor of P450 isoforms → drug interaction via ↑ effects
–Cimetidine →↓ androgens → gynecomastia and ↓ libido
Proton Pump Inhibitors
λMechanism of action:
–Omeprazole and related “–prazoles” are irreversible, direct inhibitors of the proton pump (K+/H+ antiport) in the gastric parietal cell
λUses:
–More effective than H2 blockers in peptic ulcer disease (PUD)
–Also effective in GERD and Zollinger-Ellison syndrome
–Eradication regimen for H. pylori
Misoprostol
λMechanism of action: PGE1 analog, which is cytoprotective →↑ mucus and bicarbonate secretion and ↓ HCl secretion
λUses: Previously for NSAID-induced ulcers, but PPIs are now used
Sucralfate
λMechanism of action: polymerizes on gastrointestinal luminal surface to form a protective gel-like coating of ulcer beds. Requires acid pH (antacids may interfere)
λUses: ↑ healing and ↓ ulcer recurrence
Bismuth Subsalicylate
λMechanism of action: like sucralfate, binds selectively to ulcer, coating it, and protecting it from acid and pepsin
λCombined with metronidazole and tetracycline to eradicate H. pylori (BMT regimen)
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Section VI λ Drugs for Inflammatory and Related Disorders
Chapter Summary
λThe H2 histamine antagonists (e.g., cimetidine and ranitidine) are used to suppress the secretion of gastric acid. The mechanism of action is illustrated in Figure VI-2-1. The clinical uses and adverse effects are discussed.
λOmeprazole and the other “–prazole” proton-pump inhibitors are more powerful inhibitors of gastric secretion than are the antagonists. Their clinical uses and adverse reactions are considered.
λMisoprostol is a cytoprotective prostaglandin E1 analog.
λSucralfate forms a protective gel, covering gastrointestinal ulcers. Bismuth subsalicylate behaves similarly.
λAntacids neutralize preformed protons.
λFigure VI-2-2 illustrates the number of complex factors impinging upon the emetic (vomiting) center. The antiemetic drugs are listed.
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Drugs Acting on Serotonergic Systems |
3 |
Learning Objectives
Demonstrate understanding of drug actions on 5HT receptors
Describe treatment options for migraine headaches
λSerotonin (5-hydroxytryptamine, 5HT) is an autacoid synthesized and stored in gastrointestinal cells, neurons, and platelets. Metabolized by MAO type A, its metabolite 5-hydroxyinolacetic acid (5HIAA) is a marker for carcinoid.
λOf the seven receptor subtype families, all are G-protein coupled, except 5HT3, which is coupled directly to an ion channel.
DRUG ACTIONS ON 5HT RECEPTORS
5HT1(a–h)
λFound in the CNS (usually inhibitory) and smooth muscle (excitatory or inhibitory)
λDrug: buspirone
–Partial agonist at 5HT1a receptors → anxiolytic (generalized anxiety disorder [GAD])
λDrug: sumatriptan and other triptans
–Agonist at 5HT1d receptors in cerebral vessels →↓ migraine pain
–Side effects of “–triptans”: possible asthenia, chest or throat pressure or pain
5HT2(a–c)
λFound in CNS (excitatory)
λIn periphery, activation → vasodilation, contraction of gastrointestinal, bronchial, and uterine smooth muscle, and platelet aggregation
λDrugs:
–Olanzapine and other atypical antipsychotics: antagonist at 5HT2a receptors in CNS →↓ symptoms of psychosis
–Cyproheptadine
º5HT2 antagonist used in carcinoid, other gastrointestinal tumors, and postgastrectomy; also used for anorexia nervosa; serotonin syndrome
ºHas marked H1-blocking action: used in seasonal allergies
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