ࡱ> q` _bjbjqPqP 4::1$....4.|$BDh0h0h0h0h0h0h0h0mCoCoCoCoCoCoC$Dh`GrCi2h0h022Ch0h0Cu6u6u62h0h0mCu62mCu6u6:u;,;h0\0 Fɬ.4R; 1=<D0BD;.G 5`G;G;Xh0L06u60,1h0h0h0CCk6 h0h0h0BD2222$$$$Hd$$$H$$$ Pharmacology Lecture 8 Antihypertensive Drugs List the rationale for the drug treatment of hypertension. 10-15% of the population is affected by hypertension and the lifetime probability of developing HTN is 90%. HTN, particularly systolic blood pressure, is strongly related to coronary heart disease, heart failure, stroke and peripheral arterial disease. Effective drug treatment lowers blood pressure and reduces the risk for these diseases. List the classes of antihypertensive drugs available in the U.S. Diuretics Osmotic Diuretics, Carbonic Anhydrase Inhibitors, Loop Diuretics, and Thiazide Diuretics. Adrenergic Inhibitors Central Adrenergic Agonists, Alpha Adrenergic Antagonists, Beta Adrenergic Antagonists, and Dopamine Agonist. Vasodilators Angiotensin Converting Enzyme (ACE) Inhibitors, Angiotensin II Receptor Antagonists, and Calcium Channel Antagonists. For the prototype drugs of each class of antihypertensive drugs; describe the following: Mechanism of action, Hemodynamic effects, Adverse drug effects, Drug-drug interactions, Drug-disease interactions. Drug ClassPrototype DrugMechanism of ActionHemodynamic EffectsAdverse Drug EffectsDrug-Drug InteractionsDrug-Disease InteractionsDiuretics (See Diuretic section)Thiozides, Furosemide, Spronol-acetone, TriamtereneNegative salt and water balance, !PGI2 synthesis & action, vasodilatonEarly drop in CO due to !volume Peripheral resistance decreasedFluid and electrolyte imbalance, particularly hypokalemia with thiazides and loop diureticsCentral AgonistsClonidineCentral 2a recptor stimulation! CO, ! systemic vascular resistanceShort life. Missed dose = rebound HTNAlpha AntagonistsPrazosinBlock peripheral 1 adrenoreceptors! systemic vascular resistanceOrthostatic HTN w/1st dose. Give 1st HS.Beta AntagonistsPropranololNon-selective  receptor blockade! Heart rate and contractility, ! systemic vascular resistanceBad dreams, depression Cardio  worsen CHF and occlusive peripheral vascular disease (OPVD) Lungs  bronchospasm May interact w/CCBs or digoxin causing A-V blockAsthma, COPD, severe heart failure, OPVD, high A-V blockMetoprololCardioselective 1 receptor blockadeVasodilators HydralazineRelax vascular smooth muscle ?! systemic vascular resistanceImmuno  lupus like Sx Cardio - ! HR use  blockMinoxidilVasodilation - ! K+ channel hyperpolarize SM! systemic vascular resistanceCardio - ! HR use  block Fluid retention, HypertrichosisNa+ nitro-prussideCauses NO release, relaxes SM! cardiac preload and afterloadHypotension, cyanide and thiocyanate poisoningKidney or liver diseaseACE InhibitorsCaptoprilInhibits ACE - ! angiotensin II, ! bradykinin! systemic vascular resistance and preloadHTN w/1st dose, Cough & angioedema w/! kinin, renal insufficiency, hyperkalemia, proteinureaPregnancyAngiotensin II receptor AntagonistsLosartanBlocks angiotensin II receptor bindingVasodilation w/! preload !afterloadUnkown (no cough)PregnancyCalcium Channel AntagonistsVerapamil, diltiazem, nifedipineBind Ca2+ channels ! Ca2+ for muscle contr-/ij     * + 4 5 E F ] ^ g h ~ ! 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"@BLNPlnBFLN02hjR RRhhkCJaJUh-_hkCJH*aJhQhkCJaJhkCJH*aJhLFhkCJaJhkCJH*aJhkCJaJhhk5CJaJhhkCJaJ?kd$$IfTl֞o/ %$+ B t0+644 lap T0fh $Ifgd hjkd^$$IfTl4֞o/ %$+``` ``B t0+644 lap Tjl $IfgdkdX$$IfTl4֞o/ %$+     B t0+644 lap T J $Ifgd kdR$$IfTl4֞o/ %$+` B t0+644 lap Tb $Ifgdkd8$$IfTl4֞o/ %$+  B t0+644 lap TB~N $IfgdNPkd$$IfTl4֞o/ %$+  B t0+644 lap TPn4 $Ifgdkd$$IfTl֞o/ %$+ B t0+644 lap TN`0 $Ifgd02kd$$IfTl֞o/ %$+ B t0+644 lap T2jR(RRRS $IfgdactionVasodilationConstipation, peripheral edema, worsen CHF, headacheDigoxin,  blockers = A-V blockUnstable angina, MI, HTN?Dopamine AgonistFenoldopamDopamine (DA) 1 agonist! renal blood flow !Na+ excretion Describe the use of drugs in the management of hypertension as recommended in JNC VII report. The following tables describe the recommended drugs for the management of hypertension. The first table gives BP values and their corresponding treatments while the second table gives conditions with compelling indications and the recommended drugs for each condition. BP classificationSystolic BP, mmHgDiastolic BP, mmHgLifestyle ModificationWithout Compelling IndicationWith Compelling IndicationsNormal<120 and<80EncouragePre-Hypertension120-130 or80-89YesNo antihypertensive drug indicatedDrug(s) for the compelling indicationsStage 1 Hypertension140-159 or90-99YesThiazide-type diuretics for most; may condsider ACE inhibitor, -blocker, CCB or combinationDrug(s) for the compelling indications Other antihypertensive drugs diuretics, ACE inhibitor, ARB, -blocker, CCB as needed.Stage 2 Hypertensione"160 ore"100Yes2-Drug combination for most (usually thiazide-type diuretic and ACE inhibitor, or ARB or -blocker or CCB)Drug(s) for the compelling indications Other antihypertensive drugs diuretics, ACE inhibitor, ARB, -blocker, CCB as needed.Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CCB, calcium channel blocker. 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