Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + TEST TAKING TIPS Download Section PDF Listen +++ ++ Test Taking Tips The most commonly tested mechanism of actions of drugs are succinylcholine (vs other paralytics), imatinib, fluoroquinolones, warfarin, and corticosteroids. Don't over-memorize intricate details of exotic drug classes. + MECHANICS Download Section PDF Listen +++ +++ What are some basic drug properties? ++ Absorption, distribution, metabolism, elimination +++ What is first-order kinetics? ++ Drug dose determines quantity eliminated (dose-dependent elimination) +++ What is zero-order kinetics? ++ Also known as Hoffman elimination: constant drug quantity eliminated per unit time +++ What is the primary role of the P450 system? ++ Primary drug oxidizers +++ What are some of the inducers of the P450 system? ++ Cigarette smoke, phenobarbital, rifampin, ethanol, INH, phenytoin, etc +++ What are some of the inhibitors of the P450 system? ++ Grapefruit, erythromycin, nelfinavir, itraconazole, etc ++ FIGURE 5-1. Drug administration by continuous intravenous infusion (upper panel) or intermittent intravenous bolus (lower panel). Attainment of steady-state plasma concentration (Cpss) occurs after 3 to 5 half-lives, regardless of the dosing regimen. Peak and trough fluctuations around Cpss are aimed to each be within the therapeutic range (therapeutic but subtoxic plasma levels). (Reproduced from Hall JB, Schmidt GA, Wood LDH. Principles of Critical Care. 3rd ed. http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) Graphic Jump LocationView Full Size||Download Slide (.ppt) +++ What is half-life of a drug? ++ Purpose of dosing by half-life is to achieve steady-state concentration. Typical drugs reach steady state after 5 half-lives +++ What is a Phase I reaction? ++ Nonsynthetic reaction, for example, oxidation/reduction, NOT conjugation +++ What is a Phase II reaction? ++ Synthetic reaction, for example, conjugation, methylation, sulfation, etc + GASTROINTESTINAL Download Section PDF Listen +++ +++ ESOPHAGUS +++ What are some treatments for achalasia? ++ Calcium channel blockers, long-acting nitrates, botulinum toxin injections +++ What is the management for esophageal varices bleeding? ++ Vasopressin (splanchnic vasoconstrictor at V1 receptors, increases factor VIII and VWF via extrarenal V2 receptors). Propanolol/Nadolol (preventative role; inhibits B2 adrenergic splanchnic vasodilation). Nitrates (reduce portal venous pressure) +++ What are some treatment options for reflux disease? ++ Selective H2 blockers (cimetidine, ranitidine, etc) = 24-hour acid reduction by 70%. Proton pump inhibitors (pantoprazole, omeprazole, etc) = 10% rebound hyperacidity after discontinuing due to hypergastrinemia + STOMACH Download Section PDF Listen +++ +++ What are the D2 agonists motility agents and how do they work? ++ Domperidone and metoclopramide, they increase lower esophageal sphincter (LES) tone, increase antrum contraction, increase small bowel peristalsis (beware of extrapyramidal symptoms [EPS] and tardive side effects) +++ How does erythromycin work as motility agent? ++ Motilin agonists, it amplifies Phase III activity via migrating motor complex +++ What are the general categories of antiemetics? ++ Serotonin receptor antagonist (ondansetron) Compazine (ill-defined μ-opiate agonists [MOA]) Nonselective antihistamine/H1 blocker (Phenergan) Substance P antagonist (aprepitant) +++ How do you treat peptic ulcer disease? ++ See H2 blockers and proton pump inhibitors (PPIs) above Misoprostol (prostaglandin E2) increases mucin production, decreases intracellular cyclic AMP (cAMP), and therefore acid reduction—used in "type 5" ulcers Sucralfate = sucrose plus aluminum hydroxide (coats gastric lining, resists pepsin) Bismuth (adjunct to antibiotics in setting of Helicobacter pylori) +++ What is the treatment for Helicobacter pylori? ++ PPI plus 2 antibiotics (usually Clarithromycin plus either amoxicillin or metronidazole) Bismuth occasionally used as adjunct. (Note: Gastric mucosa-associated lymphoid tissue [MALT] can be treated by Helicobacter pylori eradication) +++ What chemotherapeutic agent is used for gastrointestinal stromal tumors (GIST)? ++ Imatinib (Gleevec): tyrosine kinase inhibitor at Philadelphia chromosome + SMALL BOWEL Download Section PDF Listen +++ +++ List of medications used in the management of inflammatory bowel disease. ++ Corticosteroids, Sulfasalazine, Mesalamine, Metronidazole, immunosuppression (azathioprine, 6-mercaptopurine, cyclosporine, methotrexate) + COLON Download Section PDF Listen +++ +++ Bowel preparations ++ Magnesium based (mag-citrate, mag-hydroxide, mag-sulfate, etc) Phosphate based (fleets phospha-soda, sodium phosphate, etc) Both exert main mechanism of action by osmotic draw of fluid into bowel lumen phosphate preparations moderately absorbed, caution in renal impairment Lactulose, sorbitol, mannitol: all act by osmotic MOA Polyethylene glycol (Golytely, Miralax): nonabsorbable long-chain polyethylene glycol molecules. Bowel mixed with isotonic electrolyte solutions to prevent metabolic derangement + INTRA-OP Download Section PDF Listen +++ +++ Used to relax the sphincter of Oddi in setting of common bile duct stones and also for intestinal smooth muscle relaxation to accommodate sizers/staplers: ++ Glucagon +++ What dyes can be used to evaluate integrity of viscus, ureter, etc? ++ Methylene blue, indigo carmine +++ This can be used as an adjunct to determine intestinal perfusion: ++ Fluorescein +++ This agent aids in sentinel lymph node biopsy (some patients have severe anaphalytic reaction, risk less than 1%): ++ Lymphazurin + PANCREAS Download Section PDF Listen +++ +++ Pancreatic enzyme replacement: ++ Pancreatin Lipase, protease, amylase formulations (viokase, ku zyme, pancrease, Creon, Ultrase) +++ What prophylaxis may be used in the setting of necrotizing pancreatitis (controversial)? ++ Adequate penetrance of pancreas tissue: imipenem, third-generation cephalosporins, piperacillin, mezlocillin, fluoroquinolones, metronidazole +++ What drugs are implicated in pharmacologic pancreatitis? ++ Anti-inflammatories: Sulfasalazine, Sulindac, Salicylates Immunosuppressants: Azathioprine, 6-mercaptopurine Diuretics: diazoxide, ethacrynic acid, furosemide, thiazides Antibiotics: Didanosine, metronidazole, tetracycline, nitrofurantoin, pentamidine, Trimethoprim-sulfamethoxazole + ENDOCRINE Download Section PDF Listen +++ +++ List the antihyperthyroid agents: ++ Thionamides: Methimazole and Propothiouracil: inhibit oxidation of iodide to iodine. PTU, as well, prevents T4 to T3 conversion >Agranulocytosis most common serious adverse side effect of thionamides Ionic inhibitors: Lugol iodine (potassium iodide): inhibits thyroglobulin proteolysis as well as TH release. May reduce gland vascularity if resection planned Radioactive ablation (I131) electron-generating concentration of isotope leads to cytotoxicity Imaging Technetium 99, Iodine123, PET (fluorodeoxyglucose), SestaMIBI Hormone replacement Levothyroxine, liothyronine advantage of liothyronine is lessened suppression of TRH/TSH axis +++ What is the treatment of hypercalcemia? ++ IVF rehydration Loop diuretic Bisphosphonates (Pamidronate, Zoledronic acid) Vitamin D analogues (calcitriol, doxercalciferol, cinacalcet) +++ How do you treat hypoparathyroid tetany (severe hypocalcemia)? ++ IV calcium gluconate, oral calcium, vitamin D, magnesium +++ What is the Cosyntropin test? ++ 0.25 mg Cosyntropin IV, after 30 minutes rise in cortisol to minimum 20 mcg/dL +++ What is the treatment of adrenal insufficiency? ++ Glucocorticoid = hydrocortisone Mineralocorticoid = fludrocortisone Sex steroid replacement: DHEA (primarily in women) +++ Which medications may suppress ACTH secretion? ++ Metyrapone, octreotide, ketoconazole +++ Treatment includes administration of K+ sparing diuretic (spironolactone): ++ Hyperaldosteronism +++ Treated preoperatively with α-adrenergic blockade (phenoxybenzamine) calcium channel blockers can be used as adjunct but avoid β-blockers: ++ Pheochromocytoma + VASCULAR Download Section PDF Listen +++ +++ Medications indicated for claudication: ++ Cilostazol: cellular phosphodiesterase inhibitor Pentoxyfylline: increases RBC pliability/flexibility +++ List the antiplatelets: ++ Aspirin: irreversible block of thromboxane production Dipyridamole: increases platelet cAMP Ticlodipine and Clopidogrel: inhibits ADP-induced aggregation Glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tinofiban) +++ List the anticoagulants: ++ Heparin-inhibits antithrombin—dose-dependent half-life: 100, 400, 800 u/kg = 1, 2.5, 5 hours Low-molecular-weight heparin (enoxaparin, dalteparin, etc) Direct thrombin inhibitor (lepirudin, bivalirudin, argatroban). Caution lepirudin in renal failure (use argatroban), dose reduces argatroban in liver failure (use lepirudin). Ximelagatran = first approved oral thrombin inhibitor Factor Xa inhibitors (danaparoid, fondaparinux) 24-hour half-life Warfarin—inhibits Vitamin K-dependent cofactors: II, VII, IX, X, C, and S +++ List the available thrombolytics and their functions: ++ Plasminogen: enhances fibrinolysis Streptokinase: binds plasminogen enhancing conversion to plasmin Tissue plasminogen activator: self-explanatory Aminocaproic acid: potential antidote in case of overdose. Competes for lysine-binding sites and blocks interaction of plasmin with fibrin +++ How does protamine work? Dosage? ++ Binds heparin ionically. Dose = 1 to 1.5 mg/100 units reduce as time after heparin administration increases. Half-life is unknown. + CENTRAL NERVOUS SYSTEM/ANESTHESIA Download Section PDF Listen +++ +++ Functions via the GABA receptor (agonists): ++ Benzodiazepines/Barbiturates +++ It induces hypnotic state, has a caloric content of 1.1 kcal/mL (lipid), and is contraindicated in patients with egg allergy: ++ Propofol +++ Opioids work via which receptors? ++ μ, κ, δ +++ What are the conscious altering medications? ++ Ketamine—increases intracerebral pressure; do not use in head injury Etomidate—large infusions adrenal suppressing +++ Name the depolarizing paralytic agent: ++ Succinylcholine (risk of malignant hyperthermia—stop drug, give dantrolene. Patients with atypical pseudocholinesterases can have unusual prolonged duration of action) +++ What are the nondepolarizing agents? ++ Competitive acetylcholine inhibitors (rocuronium, pancuronium, mivacurium, cis-atracurium, etc). Cis-atracurium undergoes Hoffman elimination, making it safe in patients with liver/renal dysfunction +++ What is the role of a "reversal" agent and how do they work? ++ Intended to curb effect of paralytics (neostigmine, edrophonium) act by blocking acetylcholinesterase, leaving more acetylcholine to overcome original competing drug +++ Used preoperatively (antimuscarinic) to reduce salivary, tracheobronchial, and pharyngeal secretions: ++ Glycopyrrolate, atropine +++ List the inhaled agents: ++ Nitrous oxide halothane, enflurane, isoflurane, sevoflurane +++ What is minimal alveolar concentration (MAC)? ++ Lowest degree of drug concentration causing 50% of patients to not respond to noxious stimuli. High MAC is less potent. Low MAC is highly lipid soluble (think brain tissue) and highly potent +++ What is the mechanism of action of most local anesthetics? ++ Blocks sodium channel ATPase increasing threshold for action potential. (Note: general maximum dose of lidocaine is 7 mg/kg if using with epinephrine, 4.5 mg/kg if using preparation without epinephrine