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USMLE - Pharm

Kaplan Section 6 - Inflammatory Drugs - Histamines, PPI's, Antacids

What type of cells release histamines? mast cells and basophils
Histamine receptors are of which family? Serpentine -- G coupled second messengers
What happens with activation of H1 receptors? 1. NO --> inc capillary dilation --> dec BP, 2. inc cap permeability --> inc edema, 3. IP3 and DAG release --> inc bronchiolar smooth muscle contraction, 4. inc activation of peripheral nociceptive receptors --> inc pain and pruritis, 5. dec AV nodal cond
What happens with activation of H2 receptors? 1. inc gastric acid secretion --> inc GI ulcers, 2. inc SA nodal rate --> positive inotropy (contractility) and automaticity
What is the mechanism of H1 antagonist drugs? competitive antagonists of histamine and therefore may be ineffective at high levels of histamine
Where are H1 antagonists metabolized? in liver
Can H1 antagonists cross the placental barrier? yes.
What are anti-histamines (H1) used for? 1. allergic rxns, 2. motion sickness, 3. N and V in pregnancy, 4. preoperative sedation, 5. OTC sleep aid and cold medication
What are the adverse side effects of H1 antagonists? M block and sedation (additive with other CNS depressants), GI distress, allergic rxns
What is diphenhydramine? Widely used OTC anti-H1. M block, sedation, anti-motion
What is promethazine? Anti-H1 (histamine). M block, some a block, sedation, local anesthetic, anti motion.
What is chlorpheniramine? antihistamine (H1); M block and antimotion; CNS stimulation
What is meclizine? highly effective in antimotion; anti-histamine (H1)
What is hydroxyzine? Anti-histamine (H1). M block, sedation, anti-motion. Commonly used as sedative.
What is loratadine? anti-histamine (H1). M block. No CNS entry.
What is Fexofenadine? anti-histamine (H1). M block. No CNS entry.
What drugs would you use in GI dysfxn? H2 antagonists like cimetidine and ranitidine
How do H2-antagonists work? 1. block H2 receptor. Suppress secretory responses to food stimulation & nocturnal secretion of gastric acid via ability to indirectly decrease activity of proton pump. 2. partially antagonize HCl secretion caused by vagal stimulation or by gastrin.
Do H2-antagonists affect gastric emptying time? no
What would you use H2 antagonists for? 1. Acid peptic disease (less effective than PPI's), 2. GERD, 3. Zollinger-Ellison Syndrome
What is Zollinger-Ellison Syndrome? increased levels of gastrin produced --> excess HCl released in stomach --> peptic ulcers (95%). Often cause is tumor (gastrinoma) of duodenum or pancreas
Adverse effects of H2-antagonists 1. GI distress, 2. dizziness, 3. somnolence. Elderly: slurred speech and delirium.
How does cimetidine affect the CYP450 system? H2 antagonist. inhibits CYP450 --> inc effects of quinidine, phenytoin, TCA's and warfarin.
How does cimetidine affect androgens? H2 antagonist. dec androgens --> gynecomastia and dec libido!
"prazoles" are what type of drugs? PPI's
What is the mechanism of PPI's? inhibit the K+/H+ antiporter in the parietal cell
What would you use PPI's for? 1. peptic ulcer disease, 2. GERD, 3. Zollinger-Ellison syndrome
What are adverse effects of PPI's? dec bioavailability of drugs that require acidity for oral absorption (because PPI's decrease acidity) -- e.g. drugs like fluoroquinolones and ketoconazole.
How do PPI's affect the CYP450 system? inhibits CYP450 --> dec elimination of diazepam (BZ, seizures and muscle relaxation), phenytoin (anticonvulsant, blocks fast Na channels), warfarin.
What is misoprostol PGE1 analog, used for NSAID-induced GI ulcers
What is the mechanism of misoprostol PGE1 analog --> cytoprotective --> inc mucus and HCO3- secretion
What is sucralfate? Polymerizes on GI luminal surface to form protective gel-like coating of ulcer beds
When would you use sucralfate? increase healing and decrease recurrence of ulcers
Why shouldn't you prescribe sucralfate with antacids? Sucralfate polymerizes to protect ulcers. It requires acidic environment so antacids would interfere.
What is the mechanism of antacids? Antacids are combo of Ca, Mg, and Al hydroxides that neutralize H+ in the gut lumen.
What are adverse side fx of antacids? because decrease acidic environment in stomach, dec oral absorption of weak bases ( Quinidine), weak acids (e.g. warfarin), "azoles" (PPI's), fluoroquinilones (anti-microbial), and TCA's (via chelation)
What are adverse side fx of the antacid, Al(OH)3? 1. hyPO-phosphate, 2. osteodystrophy, 3. dementia
What are adverse side fx of the antacid, CaCO3? HyPERcalcemia
What are adverse side fx of the antacid, Mg(OH)2? 1. HyPER-Mg --> lose deep tendon reflexes, 2. resp paralysis
What are adverse side fx of the antacid, NaHCO3? "Gas"
What is MgSO4? Laxative. Retains water --> inc intraluminal P
What is bisacodyl? Laxative. Directly stimulates intestinal wall.
What is methylcellulose? Laxative. Collects water and swells --> inc bulk in stool
What is docusate? Laxative. Detergent --> stool softener
Why would you want to give mineral oil to a constipated patient? lubricant - works as a laxative
What is lactulose? Laxative. hyperosmotic (also indicated for systemic encephalopathy)
Created by: christinapham
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