Kaplan Section 6 - Inflammatory Drugs - Histamines, PPI's, Antacids
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| What type of cells release histamines? | mast cells and basophils
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| Histamine receptors are of which family? | Serpentine -- G coupled second messengers
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| 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
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| 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
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| What is the mechanism of H1 antagonist drugs? | competitive antagonists of histamine and therefore may be ineffective at high levels of histamine
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| Where are H1 antagonists metabolized? | in liver
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| Can H1 antagonists cross the placental barrier? | yes.
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| 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
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| What are the adverse side effects of H1 antagonists? | M block and sedation (additive with other CNS depressants), GI distress, allergic rxns
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| What is diphenhydramine? | Widely used OTC anti-H1. M block, sedation, anti-motion
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| What is promethazine? | Anti-H1 (histamine). M block, some a block, sedation, local anesthetic, anti motion.
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| What is chlorpheniramine? | antihistamine (H1); M block and antimotion; CNS stimulation
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| What is meclizine? | highly effective in antimotion; anti-histamine (H1)
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| What is hydroxyzine? | Anti-histamine (H1). M block, sedation, anti-motion. Commonly used as sedative.
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| What is loratadine? | anti-histamine (H1). M block. No CNS entry.
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| What is Fexofenadine? | anti-histamine (H1). M block. No CNS entry.
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| What drugs would you use in GI dysfxn? | H2 antagonists like cimetidine and ranitidine
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| 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.
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| Do H2-antagonists affect gastric emptying time? | no
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| What would you use H2 antagonists for? | 1. Acid peptic disease (less effective than PPI's), 2. GERD, 3. Zollinger-Ellison Syndrome
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| 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
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| Adverse effects of H2-antagonists | 1. GI distress, 2. dizziness, 3. somnolence. Elderly: slurred speech and delirium.
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| How does cimetidine affect the CYP450 system? | H2 antagonist. inhibits CYP450 --> inc effects of quinidine, phenytoin, TCA's and warfarin.
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| How does cimetidine affect androgens? | H2 antagonist. dec androgens --> gynecomastia and dec libido!
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| "prazoles" are what type of drugs? | PPI's
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| What is the mechanism of PPI's? | inhibit the K+/H+ antiporter in the parietal cell
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| What would you use PPI's for? | 1. peptic ulcer disease, 2. GERD, 3. Zollinger-Ellison syndrome
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| 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.
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| 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.
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| What is misoprostol | PGE1 analog, used for NSAID-induced GI ulcers
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| What is the mechanism of misoprostol | PGE1 analog --> cytoprotective --> inc mucus and HCO3- secretion
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| What is sucralfate? | Polymerizes on GI luminal surface to form protective gel-like coating of ulcer beds
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| When would you use sucralfate? | increase healing and decrease recurrence of ulcers
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| Why shouldn't you prescribe sucralfate with antacids? | Sucralfate polymerizes to protect ulcers. It requires acidic environment so antacids would interfere.
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| What is the mechanism of antacids? | Antacids are combo of Ca, Mg, and Al hydroxides that neutralize H+ in the gut lumen.
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| What are adverse side fx of antacids? | because decrease acidic environment in stomach, dec oral absorption of weak bases (e.eg. Quinidine), weak acids (e.g. warfarin), "azoles" (PPI's), fluoroquinilones (anti-microbial), and TCA's (via chelation)
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| What are adverse side fx of the antacid, Al(OH)3? | 1. hyPO-phosphate, 2. osteodystrophy, 3. dementia
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| What are adverse side fx of the antacid, CaCO3? | HyPERcalcemia
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| What are adverse side fx of the antacid, Mg(OH)2? | 1. HyPER-Mg --> lose deep tendon reflexes, 2. resp paralysis
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| What are adverse side fx of the antacid, NaHCO3? | "Gas"
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| What is MgSO4? | Laxative. Retains water --> inc intraluminal P
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| What is bisacodyl? | Laxative. Directly stimulates intestinal wall.
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| What is methylcellulose? | Laxative. Collects water and swells --> inc bulk in stool
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| What is docusate? | Laxative. Detergent --> stool softener
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| Why would you want to give mineral oil to a constipated patient? | lubricant - works as a laxative
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| What is lactulose? | Laxative. hyperosmotic (also indicated for systemic encephalopathy)
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