-1-Dental Pharmacology, Spring 2011Review Document for Exam 4, April 28, 2011ANTI-ATHEROSCLEROTIC DRUGS Atherosclerosis - LDL in blood penetrates into the subendothelium and becomesoxidized. Oxidized LDL causes transendothelial migration ofmonocytes/macrophages which in turn ingest oxidized LDL to formfoam cells in fatty streaks. Further proliferation of smooth musclecells and deposition of extracellular matrix results in atheroscleroticplaque formation. - affects large and medium sized arteries - elevated LDL and TG levels are associated with increased risk- HDL levels are inversely related to risk Regulation of cholesterol and triglyceride (TG) metabolism: 1. Exogenous pathway: Chylomicrons (CM) are degraded by lipoprotein lipase Uptake of TG by adipose tissue and muscle Transport of CM remnants to liver 2. Endogenous pathway: Liver synthesize and secrete VLDL VLDL is degraded by lipoprotein lipase to form IDL and LDLUptake of IDL and LDL by LDL receptor-mediatedendocytosis 3. Reverse transport of cholesterol: As cells die, cholesterol is released andtrapped in HDL Cholesterol in HDL is esteriftedby LCAT and transferred to VLDL, which thenis metabolized to IDL and LDL 4. De Novo Cholesterol Synthesis: Liver is the major site of cholesterol synthesis HMG-CoA reductase is the rate limiting enzyme 5. Enterohepatic Circulation: Bile salt is synthesized by the liver, releasedinto the intestine and recycled Therapeutic strategy - identify patients at risks - modify diet and lifestyle- pharmacologic therapy Drug Therapy Bile salt sequestrants- anion exchange resins binding negatively charged bile acids - increased cholesterol conversion to bile acid - increased cholesterol synthesis and LDL receptors in liver-2-- increased LDL uptake and decreased serum LDL and cholesterol levels - increased HDL/LDL ratio Niacin (nicotinic acid) - inhibits a hormone-sensitive lipase involved in lipolysis in adipose tissue - decreased free fatty acid available to the liver for TG synthesis - decreased production and release of VLDL by the liver - decreased serum levels of VLDL, LDL and TG - decreased HDL clearance - increased HDL/LDL ratio Statins - HMG-CoA reductase inhibitors - cells express more LDL receptors - decreased cholesterol and VLDL production and release by the liver - decreased HDL clearance - increased HDL/LDL ratio Fibrates- stimulate lipoprotein lipase - increased VLDL clearance - reduced serum levels of TG and LDL - decreased HDL clearance - increased HDL/LDL ratio Probucol- inhibits LDL oxidation and uptake by foam cells- small reduction in serum LDL; greater reduction in serum HDL- useful in combination therapy, not proven useful in single-drug therapy Drugs for Gastrointestinal DisordersLearn the mechanisms of action and general uses of drugs that affect GI motility:Pro-emetic agentsAnti-emetic agentsProkinetic agentsAntidiarrheal agentsLaxatives and catharticsLearn the mechanisms of action and uses of drugs that affect gastric acidity:AntacidsH2 receptor antagonistsProton pump inhibitorsProstaglandins and protective agentsUnderstand in a general way the therapeutic strategies for Peptic Ulcer Disease,Gastroesophageal Reflux Disease, and Inflammatory Bowel Disease-3-Insulin and oral hypoglycemic (antidiabetic) drugs1. Be able to describe the various types of Diabetes Mellitus, what is different abouteach type that affects therapeutic intervention?2. Be able to define the normal profile of glucose and insulin levels in normal anddiabetic patients.3. Define the types of insulin therapies available to Type I diabetics. What is therationale behind the choice of single or mixed insulin therapy and subcutaneous pumps.What formulations of insulin are used and why?4. Define the mechanism of action of insulin.5. Be able to define the major differences between hypoglycemic versusantihyperglycemic drugs. What are the major advantages/disadvantages of each class.6. Be able to discuss the different types of hypoglycemic drugs and their mechanismsof action.7. Be able to discuss the different types of antihyperglycemic drugs and theirmechanisms of action.Antiseizure Drugs Know what a seizure is, its potential causes and how it relates to epilepsy. Know how seizures are classified (i.e., simple partial vs. complex partial vs. tonic clonic,etc. - see table in handout) Know the general principles of antiseizure drug therapy Know the identified mechanisms by which antiseizure drugs work. Know the drugs of choice for the various types of seizures, their mechanism of actionand major side effects. What are the 4 major types of drug interactions seen with antiseizure drugs?GENERAL ANESTHETICSDefinitions: partial pressure, MAC, blood/gas partition coefficient, oil/gas partitioncoefficientWhat determines anesthetic potency?What are the 4 potential targets for the action of general anesthetics?How do blood/gas solubility, ventilation rate and cardiac output affect equilibration ofanesthetics (rate of induction of anesthesia)?What is the mechanism of the “concentration effect” and the related “second gas-4-effect”?What factors determine the rate of anesthetic equilibration into different tissues?What is the route of elimination of general anesthetics and how is recovery fromanesthesia affected by the blood/gas partition coefficient, ventilation rate and cardiacoutput?What are the common pharmacological effects of inhalational anesthetics?Know the major differences between the inhalational anesthetics (e.g., which ismost/least potent, induction/recovery rate, etc.- see table p. 14 of handout; don't needto memorize numbers).What are the major uses of the various intravenous anesthetic agents discussed andtheir major advantages and disadvantages?OPIOID ANALGESIC DRUGS1. Know about mechanism of nociception (physiology)Dorsal horn of the spinal cord – gate control mechanism2. Know about classification of opioid analgesic drugsStrong agonists – morphine, meperidine, methadone, heroin, fentanylModerate agonists – propoxyphene, codeineMixed agonists-antagonists – pentazocine, nalbuphine, buprenorphineAntagonist – naloxone, naltrexone3. Know about endogenous opioid peptidesEnkepalins, endorphins, dynorphins, endomorphins4. Know about opioid receptors and the mechanism of actionMu (m), Kappa (k), Delta (d). All G-protein coupled receptors. Increase K+ efflux(hyperpolarization) and reduce voltage-gated Ca2+ entry.5. Know about the sites of opioid receptor