Antihypertensive_Agents-F

Antihypertensive Agents Dr.mohan amberkar, MD Asst. Prof-Pharmacology Hypertension is defined conventionally as arterial blood pressure ≥ 140/90 Types of Hypertension: •Essential (Primary) Hypertension •Secondary Hypertension BP = CO X PVR Etiologic Classification: Primary or Essential Hypertension (95%) Arterial hypertension with no definable cause .  Due – Multifactorial Genetic inheritance. Psychological stress. Environmental / Dietary factors Secondary Hypertension (5-10%) Renal – GN, Renal artery constriction. Endocrine – Cushing syndrome, OCP, Thyrotoxicosis , Pheochromocytoma, Vascular – Coarctation of Aorta, Neurogenic – Psychogenic, Intracranial pressure, Classification of Blood Pressure Category Normal High Normal Systolic < 130 130 - 139 Diastolic < 85 85 - 89 Hypertension - Stage 1 Stage 2 Stage 3 140 - 159 160 - 179 > 180 90 - 99 100 -109 > 110 Goal Blood Pressure SBP mm Hg  DBP mmHg Most patients Diabetes Chronic Renal Disease < 140 < 130 < 130 < 90 < 80 < 80   Consequences of Hypertension:      Blood Vessels : Atherosclerosis and its complications aneurism, Dissection, Rupture, necrosis. Heart : Hypertensive cardiomyopathy, IHD, MI. Kidney : Benign/Malignant nephrosclerosis. Infarction Eyes: Hypertensive retinopathy Brain: Haemorrhage, infarction, splinter & Lacunar hemorrhages Subarachnoid Haemorrhage: Left ventricular Hypertrophy: Left Ventricular Hypertrophy Cerebral Infarction (Stroke) : Haemorrhagic Necrosis Normal Retina - Fundoscopy Hypertensive Retinopathy:     Grade I – Thickening of arterioles. Grade II – Focal Arteriolar spasms. Vein constriction. Grade III – Hemorrhages (Flame shape), dot-blot and Cotton wool and hard waxy exudates. Grade IV - Papilloedema Blood Pressure = Cardiac Output X Peripheral Resistance Preload Circulating Fluid Volume Renin Angiotensin Aldosterone System Contractility Heart Rate Vasoconstriction Venous Arteriolar Venous Renal Sodium Handling Sympathetic Nervous System Vascular Smooth Muscle Vascular remodeling Afterload a2 Volume Kidneys Renin Ang I Vasomotor center b1 Cardiac Output Heart b1 Preload Ang II Aldosterone BP= CO x TPVR b2 a1 VSMCs Vascular Smooth Muscle Cells Resistance arterioles Capacitance venules TPVR Total Peripheral Vascular Resistance (TPVR) Figure 11-2. Baroreceptor reflex arc. Classification of Antihypertensive agents Diuretics Thiazides – Eg: Hydrochlorthiazide,Chlorthalidone Loop Diuretics– Eg: Frusemide, Torsemide Potassium Sparing – Eg: Spironolactone, Amiloride, Triamterine Angiotensin converting enzyme (ACE) inhibitors Eg: Captopril, Enalapril, Lisinopril, Ramipril. Classification…….. Angiotensin II antagonists– Eg:Losartan, Valsartan, Telmisartan, Candesartan Sympatholytic Agents Alpha Blockers Eg: Prazosin, Doxazosin, Beta Blockers– Eg: Propranolol, Atenolol Centrally acting – Eg: Clonidine, Methyldopa Adrenergic neuron blockers– Eg: Reserpine, Guanethidine Classification…… Vasodilators -Eg: Hydralazine,Nitroprusside Calcium Channel Blockers (CCBs) Dihydropyridines :Eg-Nifedipine, Amlodipine Non-Dihydropyridines –Diltiazem,Verapamil FIRST-LINE ANTI-HYPERTENSIVES SITE OF ACTION OF ANTI-HYPERTENSIVES SITE OF ACTION OF ANTI-HYPERTENSIVES SITE OF ACTION OF ANTI-HYPERTENSIVES Diuretics ++++ ++ + +  Thiazides & thiazides-like diuretics  Aldosterone antagonists  Potassium sparing diuretics  Loop diuretics Afterload a2 Volume Kidneys Renin Ang I Vasomotor center b1 Cardiac Output Heart b1 Preload Ang II Aldosterone BP= CO x TPVR b2 a1 VSMCs Resistance arterioles Capacitance venules TPVR DIURETICS Thiazides diuretics  Initial effects: natriuresis, diuresis, reduced    extracellular & circulating volume Chronic effect: reduction in peripheral vascular resistance (direct vasodilating effect) There is only slight differences in the duration of action but major one in dosage Given once daily Side Effects At low doses thiazides are well tolerated    Hypokalemia, Lipid elevation Glucose intolerance Hyperuricemia & Hypercalcemia Thiazides diuretics  YES: (useful in)     No: (avoid in) Patients with NIDDM Patients with hyperlipidemia Patients with gout Sexually active males GFR < 30ml/min    Elderly patients African Americans Patient with mild or incipient heart failure When cost is crucial When salt intake is high Combined with other first line drugs      Loop Diuretics Weaker antihypertensive than thiazides Short acting – 4-6Hrs Indicated in hypertension; Hypertension with CCF 2. Fluid retention with vasodilators Diuretics as Antihypertensives 1. Less expensive 2. Once daily dosing 3. No fluid retention or postural hypotension 1. Potassium-Sparing Diuretics Spironolactone - Antagonizes Aldosterone Side Effects: Hyperkalemia, gynecomastia Amiloride Side Effects: Hyperkalemia, GI disturbances Role in HTN: In combination with other diuretics - Prevent or correct hypokalemia + Synergistic action ACE Inhibitors ( … pril) Captopril Enalapril Lisinopril Benazepril Fosinopril Quinapril Ramipril Spirapril Moexipril Perindopril Trandolapril Angiotensin Converting Enzyme (ACE) Inhibitors Mechanism of Action: ANGIOTENSINOGEN Renin ANGIOTENSIN – I ACE-I ACE ANGIOTENSIN – II Vasoconstriction Aldosterone * (Na+ & H2O retention) ACE-Inh Angiotensinogen Renin Angiotensin I Vasoconstriction Cell growth Na+/H2o retention ACE Cough angioedema Bradykinin Angiotensin II AT1 AT2 Aldosterone Inactive fragments Na+/H2o retention Actions of Angiotensin II Site of Action Myocyte, Cardiocyte Fibroblast stimulation Sympathetic Nerve Endings Vasoconstriction Glomeruli Cellular Effect Consequence IP3 and Ca++ increase Constriction Protein kinase C Expression of protooncogenes; cell growth Enhanced NE release Enhanced Efferent arteriolar Promotes constriction microalbuminuria Enlarges glomerular pores Proteinuria Renin inhibition Relief of raised intraglomerular pressure Juxtaglomerular Apparatus Adrenal Cortex Synthesis of Aldosterone Increased sodium retention and kaliuresis An giote ns in Peripheral resistance Renal function II Cardiovascular structure 1. Direct vasoconstriction 2. Enhancement of peripheral noradrenergic neurotransmission 3. Increased central (CNS) sympathetic discharge 4. Release of catecholamines from adrenal medulla Rapid Pressor Response 1. Non-hemodynamic effects: - Increased expression 1. Increases Na+ reabsorption of proto-oncogenes 2. Releases aldosterone from adrenal cortex - Increased production of growth factors 3. Altered renal hemodynamics: - Increased synthesis of - renal vasoconstriction extracellular matrix - increased noradrenergic proteins neurotransmission in kidney - Increased renal sympathetic 2. Hemodynamic effects: - Increased afterload tone (CNS) (cardiac) - Increased wall tension (vascular) Slow Pressor Response Cardiovascular Hypertrophy and Remodeling Afterload a2 Volume Kidneys Renin Ang I Vasomotor center b1 Cardiac Output Heart b1 Preload Ang II Aldosterone BP= CO x TPVR b2 a1 VSMCs Resistance arterioles Capacitance venules TPVR ACE Inhibitors ACE Inhibitors -Antihypertensive Mechanisms  Inhibition of circulating RAS  Inhibition of tissue and vascular RAS  Decreased formation of endothelin from endothelium  Increased formation of bradykinin and vasodilatory prostaglandins  Decreased sodium retention (decreased aldosterone secretion, and/or increased renal blood flow) ACEIs : Prevention of Nephropathy INTRAGLOMERULAR PRESSURE Arterial pressure Afferent arteriole Bowman’s capsule + Angiotensin II + 20 mmHg ++ Angiotensin II Efferent arteriole excess glomerular pressure hyperfiltration microalbuminuria ACE Inhibitors: ( … pril)  Side effects  Cough  Hypotension  Hyperkalemia  Angioedema  Renal Insufficiency  Fetal injury (2nd & 3rd trimesters)  “High-dose Captopril” Adverse effects  ( Neutropenia, Impaired taste, Proteinuria ) ACE Inhibitors ( … pril)  YES: (useful in)  Younger patients  Post MI LV dysfunction  Pt. with heart failure  Diabetic patients  Non-diabetic nephropathy  Metabolic disorders (hyperlipidemia, gout)  No: (avoid in)  Renal artery stenosis  Fluid-depleted patients  Pregnancy Ang II Receptor Blockers (...sartans) Losartan Valsartan Irbesartan Candesartan Eprosartan Tasosartan Telmisartan Angiotensin II Antagonists (ARBs) Mechanism of Action: ANGIOTENSINOGEN Renin ANGIOTENSIN – I ACE ARBs Vasoconstriction ANGIOTENSIN – II Aldosterone * (Na+ & H2O retention) Angiotensin Converting Enzyme Kininogens Kallikrein Renin Angiotensinogen Bradykinin ACEIs Inactive Peptides Angiotensin I ACEIs ACE Angiotensin II BK receptors AT-1 receptors Afterload a2 Volume Kidneys Renin Ang I Vasomotor center b1 Cardiac Output Heart b1 Preload Ang II Ang II Aldosterone BP= CO x TPVR b2 a1 VSMCs Resistance arterioles Capacitance venules Ang II TPVR Ang II Receptor Blockers Ang II Receptor Blockers (...sartans)  Sartans are selective and competitive antagonists of angiotensin II type 1 (AT1) receptors and do not inhibit AT2 receptors  The physiological function of angiotensin II is mediated by AT1 receptors (vasoconstriction, catecholamine release, aldosterone synthesis, and renal sodium and water retention)  Blockade of AT1 receptors increases plasma levels of Angiotensin I, Angiotensin II, and PRA Ang II Receptor Blockers (...sartans)  Side effects  Dizziness  Angioedema has been reported rarely  Hyperkalemia, comparable with that seen in   patients treated with ACEIs Risk of fetal injury and death; should not be used during the 2nd and 3rd trimester of pregnancy Risk of symptomatic hypotension in hypovolemic patients • Except for the absence of cough, Yes (useful in) and No (avoid in) same as for ACE inhibitors Calcium Channel Blockers (CCBs)  Dihydropyridines- Nifedipine, Amlodipine, Felodipine, Isradipine, Nicardipine, Nisoldipine  Non-Dihydropyridines- Diltiazem, Verapamil Afterload a2 Volume Kidneys Renin Ang I Vasomotor center b1 Cardiac Output Heart b1 AV Preload Ang II Aldosterone BP= CO x TPVR Ca++ Resistance arterioles Capacitance venules L-type Ca++ channels TPVR Calcium Channel Blockers CCBs….. Mechanisms and Sites of Action Block transmembrane entry of calcium into arteriolar smooth muscle cells and cardiac myocytes thus inhibiting excitationcontraction Negative Inotropic and Produce Vasorelaxation Chronotropic Effects at Arterioles L-type Ca++ channels Reduce Peripheral Resistance Nifed>Dilti+Verap Verap+Dilti>Nifed CCBs….. Pharmacologic Effects of CCBs Effect Peripheral Vasodilation Heart Rate Cardiac Contractility SA / AV Nodal Conduction Coronary Blood Flow Verapamil Diltiazem Dihydropyridines ↑ ↓↓ ↓↓ ↑ ↓ ↓ ↑↑ ↑ 0/↓ 0 ↓ ↑ ↓ ↑ ↑↑ Calcium Channel Blockers Nifedipine - relatively selective vasodilator & less cardiac depression, short acting. Side Effects: Reflex tachycardia, headache, peripheral edema, flushing Amlodipine –Preferred Long acting, Less reflex tachycardia, high bioavailabilty, less diurnal fluctuation. Calcium Channel Blockers Side effects  Facial Flushing  Headaches  Non-pitting ankle edema  Constipation CCBs  YES: (useful in)  Elderly patients  pregnant hypertensives  Patients with peripheral vascular disease  Patients with cerebrovascular disease  No: (avoid in)  Patients with heart failure  Patients with heart block  Patients receiving b-blockers  Short-acting dihydropiridines:  Patients with angina pectoris  Asthma/COPD Pts.  Unstable angina  Recent MI Centrally Acting Sympatholytic agents  Clonidine  Methyldopa  Old drugs:  Guanfacine  Guanabenz Central a2–Agonists Diminished CNS Sympathetic Outflow Activation of Pre-synaptic Alpha-2 Receptors Reduces NE Release at Synapse Alpha-2 Agonist Rostral Ventrolateral Medulla Post-synaptic Effector Pre-synaptic Neuron Alpha-1 Receptor Beta Receptor Alpha-2 Receptor NE Centrally Acting Sympatholytic agents… Methyldopa: Mechanism of Action: Converted to α-Methylnorepinephrine Acts as an α2 agonist-Brain Inhibit adrenergic neuronal outflow from the brainstem Methyldopa…. PK: Duration of action is usually about 24 hrs Adverse Effects: Sedation, depression, dryness of the mouth, hyperprolactinemia, Hepatotoxicity Therapeutic Uses:    Not used as the initial drug in monotherapy. Effective when given with diuretic Reserved for treating hypertension in pregnancy Clonidine, Guanabenz & Guanfacine Mechanism of action: Stimulate α2A-adrenergic receptors present mainly prejunctionally in Vasomotor centre Results in reduction in sympathetic outflow - CNS Pharmacological EffectsLower BP by an effect on both CO & PVR. Have either no effect on plasma lipids or produce a slight reduction of total cholesterol, LDL-cholesterol & triglycerides Clonidine exhibits therapeutic window phenomenon – 0.2 to 2.0ng/ml Adverse Effects Sedation, depression, dryness of the mouth, Impotence, salt & water retention Uses: A/E limits its use as first choice Moderate hypertension, HTN in Pregnancy Alpha-1 - Adrenergic Receptors Blockers •Prazosin •Terazosin •Doxazosin •Tamsulosin – BPH Old drugs Alpha-1 + Alpha 2 Blockers •Phenoxybenzamine •Phentolamine SYMPATHOLYTIC AGENTS α-Blockers- α1-blockers preferred MOA: S/E: Postural hypotension, reflex tachycardia, Retention of salt & water Therapeutic Uses:   Mild-to-moderate hypertension Diuretics & β-blockers – synergistic Reduce total cholesterol, LDL-c & triglycerides. Alpha-1 – Blockers…..  Side effects:      First dose hypotension Dizziness, lethargy, fatigue Palpitation, syncope Peripheral edema Incontinence Beta Blockers ( …lol)  Beta-Non-Selective        Propranolol Nadolol Carteolol* Timolol Pindolol* Sotalol Penbutol*  Beta-Selective       Acebutolol * Atenolol Betaxolol Bisoprolol Esmolol Metoprolol  Beta-1,2 & Alpha 1Selective  Labetalol , Carvedilol * - ISA Beta Blockers ( Mechanisms of Action … lol) Negative Chronotropic & Inotropic Effects - Reduction in CO - Reduction in PVR - Effects on presynaptic b2 receptors - Inhibition of Renin Release Attenuation of pressor response to catecholamines (stress, exercise) ? CNS effects SYMPATHOLYTIC AGENTS…… β-blockers: MOA: Blockade of β adrenergic receptors + Reduces renin secretion - cause fall in angiotensin II levels + Central action A/E & C/I: Therapeutic Uses:  Used in all grades of hypertension No postural hypotension, salt & water retention, low incidence of S/E, Less expensive, once daily dosing. Peripheral Vasodilators  Hydralazine  Minoxidil  Diazoxide Sodium Nitroprusside Arteriolar + Venous Arteriolar Afterload a2 Volume Kidneys Renin Ang I Vasomotor center b1 Cardiac Output Heart b1 Preload b2 a1 Ang II Aldosterone BP= CO x TPVR NO → cGMP → Ca++ Capacitance venules Resistance arterioles TPVR Peripheral Vasodilators Activators of NO/guanylate cyclase pathway a1 – Adrenoreceptor antagonists Doxazosin Prazosin Hydralazine ? Nitroprusside Nitroglycerin NO Ca2+ - channel blockers Dihydropiridines Verapamil Diltiazem Ca2+ VSMCs Ang II receptor antagonists Losartan K+ K+ - channels activators Minoxidile Diazoxide Peripheral Vasodilators Peripheral Vasodilators  Hydralazine   Arteriolar vasodilation by mechanism not well-defined (NO ?) Minoxidil  Arteriolar vasodilation by activation of ATP-modulated potassium channels resulting in hyperpolarization of arteriolar VSMCs  Second-third line of drugs for hypertension  Induce reflex tachycardia, fluid and sodium retention  Have be combined with first-line antihypertensive drugs Peripheral Vasodilators Hydralazine:  In slow acetilators, “lupus-like” syndrome (arthralgia,  myalgia, skin rashes, and fever). For patients with CHF, pre-eclampsia Minoxidil:  ”Last choice” for treatment of hypertension  Minoxidil: Headache, sweating, and hirsutism,  Topical minoxidil used for correction of baldness. Vasodilators….. Minoxidil – Prodrug, K+ opener, powerful vasodilator Acts similar to hydralazine Side Effects: = Hydralazine+ Hypertrichosis Nitroprusside: Rapid onset (30sec), short duration of action (25mins); dilates both arterioles & veins; decreases both CO & PVR Nitroprusside: Mechanism of Action Sodium Nitroprusside Endothelial cells Vascular SM Hypertension and Diabetes Treatment: • • Early treatment to prevent cardiovascular disease and minimize progression of renal and retinal disease. The benefits of tight blood pressure control in diabetics may be as great or greater than benefits of strict glycemic control. Initial therapy should include non-pharmacological methods. ACE Inhibitors, ARBs, CCBs, • • Nitroprusside…. Adverse Effects: Palpitation, nervousness, vomiting, lactic acidosis, pain abdomen. Rebound hypertension may occur after abrupt cessation of short-term nitroprusside infusions Uses:    Hypertensive emergencies In refractory CCF To induce controlled hypotension during anesthesia Autonomic Ganglionic Inhibitors Mechanisms and Sites of Action Inhibit neurotransmission in autonomic ganglia by competing with acetylcholine for ganglionic cholinergic receptor sites. Reduced peripheral resistance and venous return Autonomic Ganglionic Inhibitor Post-ganglionic Neuron Pre-ganglionic Neuron Acetylcholine Ganglionic ACh Receptor Combination Drugs in Hypertension  ACE Inhibitor + Diuretic  Ang II Receptor Antagonist + Diuretic  Beta-Blocker + Diuretic  ACE Inhibitor + CCB  Alpha-1 Blocker + Diuretic  Alpha-2 Agonist + Diuretic Combination therapy- HTN Drugs which increase plasma renin – D, VD CCBs, ACE-I Drugs which decrease plasma renin – BB, Cl, Methyldopa All sympatholytics (except β-Blocker) + VD Diuretics as they fluid retention Hydralazine & DHPs Tachycardia is counteracted Β-blockers ACE-I + ARBs Synergistic Diuretics Antihypertensives in Pregnancy Safe Hydralazine Methyldopa DHPs CardioselectiveB-blockers Clonidine Prazosin Unsafe Diuretics ACE-I ARBs Non-selectiveB blockers Nitroprusside Antihypertensive Drugs for Hypertensive Crisis  Hypertensive Emergency: Severe elevation in blood pressure in the presence of acute or ongoing end-organ damage.  Hypertensive Urgency: Severe elevation of blood pressure in the absence of target-organ involvement Asthma COPD and Hypertension • Beta-blockers (i) increase bronchial obstruction, (ii) increase in airways reactivity, and (iii) inhibit the bronchodilatatory effects of beta agonist Cardioselective, beta-blockers none should be considered safe.Even topical administration for the treatment of glaucoma may led to asthmatic exacerbations. ACE inhibitors are not contraindicated and may be used; very rarely worsen airflow obstruction; produce persistent dry cough and are not first line drug for hypertensive patients with asthma or COPD. • • Asthma, COPD and Hypertension Calcium channel blockers (CCB) are preferred for treatment of hypertension in astma & COPD. May be combined with diuretics Short-acting CCB (niphedipine) should not be used because they increase CV risk. Only long-acting CCB or slow-release niphedipine formulation should be used. Asthma, COPD and Hypertension • Diuretics: can be effectively used but there is an increased risk of hypokalemia (inhaled b-2 agonist drive potassium into cell and orally administered corticosteroids mildly increase urinary potassium excretion). • • Only low dose (12.5-25 mg) of thiaizides to be used. In patients with COPD and chronic hypercapnia, diuretics-induced metabolic alkalosis may suppress the ventilatory drive and exacerbates the hypoxia. Ischemic Heart Disease and Hypertension  IHD is the most common form of target-organ damage associated with hypertension. Beta blockers and long acting Ca++ channel blockers are the first choice in HTN patient with stable angina pectoris.   HTN patients with unstable angina or MI should be treated with beta blocker or ACE inhibitor. In patients with post-myocardial infarction, ACE inhibitors, beta blockers and aldosterone antagonists; all reduce progression of left ventricular dysfunction and mortality.  Heart Failure and Hypertension  ACE inhibitors and beta blockers are recommended for HTN patients with asymptomatic ventricular dysfunction In HTN patients with symptomatic ventricular dysfunction (NYHA III and IV) in addition to ACE inhibitors and beta blockers, treatment with diuretics, Ang II receptor antagonists and aldosterone antagonists. In hypertensive HF patient, if volume depleted, ACE inhibitors may induce hypotension and acute renal failure. Beta blockers may induce initial/transient worsening of HF.   HYPERTENSIVE EMERGENCIES & URGENCIES Hypertensive emergency, also called hypertensive crisis, is severe HTN with acute end-organ damage BP control within min –hrs within hours Hypertensive urgency is a condition where rise in BP is a potential risk but has not yet caused acute endorgan damage. BP control over several days to weeks. HYPERTENSIVE EMERGENCIES & URGENCIES Management:  Sodium Nitroprusside –-0.25 to 1.5 µg/kg per min - as a controlled, continuous i.v infusion & patient  must be closely monitored Diazoxide- 50 -100 mg / 5-10 min; lowers BP within 30 sec; accurate infusion pumps -not available & close monitoring of BP is not feasible.  Hydralazine-10 -20mg IM/ slow IV; acts within 20min Management……  Esmolol- 50–100 µg/kg per min IV infusion; acts within 1–2 min & action lasts for 10–20 min Frusemide- 40-80 mg IV given along with any of above drug if there is volume overload like LVF, Pulmonary or Cerebral edema  Selection of Antihypertensive Drug Alpha Blocker a2 - agonists Dr. Rx Ganglionic Rational blockers Vasodilators Drug of choice Ca++ Antagonist Selection of Antihypertensive Drug 1 Level of blood pressure + 2 Presence of other risk factors for CVD & target organ damage + 3 Coexisting diseases Antihypertensive Therapy Blood Pressure Classification JNC 7 Normal SBP mm Hg DBP mmHg  <120 & <80  Prehypertensive Stage 1 Hypertension 120-139 140-159 or or 80-89 90-99   Stage 2 Hypertension > 160 or > 100 Algorithm for JNC 7 Treatment of Hypertension Initial Drug Choices “Excellent clinical trial outcome data prove that lowering BP with several classes of drug, including ACE inhibitors, angiotensin receptors blockers (ARBs),”beta-blickers”, calcium channel blockers (CCBs) and thiazide-type diuretics will reduce the complications of hypertension.” Algorithm for Treatment of Hypertension Initial Drug Choices JNC 7 Stage 1 Hypertension 140-159 / 90-99 mmHg Without Compelling Indication Thiazide-like diuretics for most, ACEI, ARB, BB or CCB May consider combination Algorithm for Treatment of Hypertension Initial Drug Choices JNC 7 Stage 2 Hypertension >160 / > 100 mmHg Without Compelling Indication 2-drug combination for most Usually thiazide-like diuretic plus ACEI, or ARB, or BB or CCB Hypertension in Elderly  Pharmacological treatment: - Lower initial doses (1/2 dose than in younger patients) - The reduction in BP should be gradual - Greater caution in patients with co-existing diseases or orthostatic hypotension.  Choice of therapy: - Thiazide diuretic (hydrochlorothiazide, HCTZ 12. 5mmg) - STOP-Hypertension trial: ACE inhibitors, long-acting calcium antagonist and beta- blockers may provide the same protection as diuretics. Hypertension in Elderly  Choice of therapy: special considerations  A diuretic should be used for heart failure or edema  A beta-blocker should be used for patient with coronary heart disease, tachyarrhythmias or migraine  An ACE inhibitors in patients with heart failure  Calcium antagonist should be used in patients with angina pectoris,and peripheral vascular disease  Alpha-blocker in patient with benign prostatic hyperplasia Thiazides…. In elderly patients > 65 yrs, - initial drug of choice - Reasons;    High level of efficacy in the clinical trials Relatively less side effects, Low-renin status in elderly- predicts a good response to diuretic therapy.