antihypertensive agents emel songu-mize, phd 568-2240emize@lsuhsc.edu

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  • Slide 1
  • Antihypertensive Agents Emel Songu-Mize, PhD 568-2240emize@lsuhsc.edu
  • Slide 2
  • Lecture Outline Hypertension Hypertension Definition, classification Definition, classification Prevalence Prevalence Complications Complications Contributing factors Contributing factors Update on VII th report of the JNC Update on VII th report of the JNC Drugs that lower blood pressure Drugs that lower blood pressure
  • Slide 3
  • Blood Pressure Classification Blood Pressure Classification Classification SBP ( mmHg )DBP ( mmHg ) ______________________________________________________ Normal 160 or >100 Stage 2 Hypertension >160 or >100_____________________________________________
  • Slide 4
  • Essential Hypertension In 9095% of cases the cause isn't known = ESSENTIAL HYPERTENSION Symptomatic treatment, i.e. reduce blood pressure. No real cure yet.
  • Slide 5
  • Identifiable Causes of Secondary Hypertension Sleep apnea Drug-induced or related causes Chronic kidney disease Primary aldosteronism Renovascular disease Chronic steroid therapy and Cushings syndrome Pheochromocytoma Coarctation of the aorta Thyroid or parathyroid disease
  • Slide 6
  • Prevalence High in this country: 50% of adults, 60% of whites, 71% of African Americans, 61% Mexican Americans over the age of 60 High in this country: 50% of adults, 60% of whites, 71% of African Americans, 61% Mexican Americans over the age of 60 More prevalent in men than in women More prevalent in men than in women Highest prevalence in elderly African-American females Highest prevalence in elderly African-American females
  • Slide 7
  • Complications Cardiovascular system Cardiovascular system CNS CNS Renal system Renal system Retinal damage Retinal damage
  • Slide 8
  • Target Organ Damage Heart Left ventricular hypertrophy Coronary artery disease Myocardial infarcts Heart failure Brain Stroke or transient ischemic attacks Chronic kidney disease, kidney failure Retinopathy
  • Slide 9
  • Contributing Factors Obesity Obesity Stress Stress Lack of exercise Lack of exercise Diet (excess dietary salt) Diet (excess dietary salt) Alcohol intake Alcohol intake Cigarette smoking Cigarette smoking
  • Slide 10
  • National Heart Lung Blood Institute National High Blood Pressure Education Program The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7, 2003) http://www.nhlbi.nih.gov/guidelines/hypertension /index.htm
  • Slide 11
  • Why Guidelines for Hypertension? 50 million people with hypertension in USA 10 years ago 1:4 overall (Currently 31 %), half of people > age 60 Only 1 in 2 on drug treatment to lower BP Only 1 in 4 age 18-74 controlled to
  • Slide 12
  • Slide 13
  • New BP Goals 1.0 g/24 hours
  • Slide 14
  • Highlights of Current Guidelines JNC, WHO/ISH, BHS, Canada, and More New aggressive treatment strategies based on a patients medical profile Treat to goal and hit the target, not to be satisfied with less
  • Slide 15
  • Treatment Overview Goals of therapy Lifestyle modification Pharmacologic treatment Algorithm for treatment of hypertension Classification and management of BP for adults Follow-up and monitoring
  • Slide 16
  • Lifestyle Modifications Reduce weight to normal BMI (
  • Slide 17
  • DASH Diet Dietary Approaches to Stop Hypertension Emphasizes: Fruits, vegetables, low fat dairy foods, and reduced sodium intake Includes whole grains, poultry, fish, nuts Reduced amounts of red meat, sugar, total and saturated fat, and cholesterol Sacks FM et al: NEJM 344;3-10, 2001
  • Slide 18
  • Algorithm for Treatment of Hypertension Not at Goal Blood Pressure (160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Without Compelling Indications Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.
  • Slide 19
  • Renal function Blood volume Venous tone Venous return Heart rate Nervous control Muscular responsiveness Myocardial contractility Stroke volume Cardiac output CNS factors Renin release Angiontensin II formation Intrinsic vascular responsiveness Peripheral resistance Nervous control Renal function Mean arterial pressure Factors that Govern the Mean Arterial Pressure
  • Slide 20
  • Mean Arterial Pressure MAP = CO MAP = CO CO = HR X SV CO = HR X SV SNS Blood volume SNS Blood volume Heart contactility Venous tone Heart contactility Venous tone X PVR X PVR myogenic tone vascular responsivenes nervous control vasoactive metabolites endothelial factors circulating hormones
  • Slide 21
  • Antihypertensive Drugs Classification Diuretics Diuretics Agents affecting adrenergic function Agents affecting adrenergic function Vasodilators Vasodilators Agents affecting Renin Angiotensin System (RAS) Agents affecting Renin Angiotensin System (RAS)
  • Slide 22
  • Diuretics Used as initial therapy alone or in combination with drugs from other groups Adverse effects: renin secretion due to volume and Na depletion Thiazides: chlorothiazide, hydrochorothiazide Thiazides: chlorothiazide, hydrochorothiazide Loop Diuretics: furosemide, bumetanide, ethacrynic acid Loop Diuretics: furosemide, bumetanide, ethacrynic acid Potassium sparing diuretics: spironolactone, triamterene, amiloride Potassium sparing diuretics: spironolactone, triamterene, amiloride
  • Slide 23
  • About Diuretics Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): Diuretics have been virtually unsurpassed in preventing the cardiovascular complications of hypertension. Diuretics enhance the antihypertensive efficacy of multidrug regimens, can be useful in achieving BP control, and are more affordable than other anti- hypertensive agents. Despite these findings, diuretics remain under- utilized.
  • Slide 24
  • Agents that affect adrenergic function a)Agents that prevent adrenergic transmission (reserpine, guanethedine, guanadrel) b)Selective alpha-1 adrenergic receptor blockers (prazosin, terazosin, doxazosin) c)Beta-adrenergic blocking agents (propranolol and others) d)Agents that act on the CNS (methyldopa, clonidine, guanabenz, guanfacine)
  • Slide 25
  • a) Agents that prevent adrenergic transmission: Reserpine (Serpasil) Mechanism: depletes neurotransmitters (NE, DA, 5HT) in the storage vesicle of the central and peripheral nerve endings Mechanism: depletes neurotransmitters (NE, DA, 5HT) in the storage vesicle of the central and peripheral nerve endings Main effects: depress SNS function centrally and peripherally decreased HR, contractility and PVR Main effects: depress SNS function centrally and peripherally decreased HR, contractility and PVR Adverse effects: depression, insomnia, nightmares, ulcers, diarrhea, abdominal cramping, nasal stuffinessorthostatic hypotension, dry mouth,impotence Adverse effects: depression, insomnia, nightmares, ulcers, diarrhea, abdominal cramping, nasal stuffiness, orthostatic hypotension, dry mouth, impotence Pharmacokinetics: onset is slow and full effect is seen in weeks Pharmacokinetics: onset is slow and full effect is seen in weeks Use: infrequently Use: infrequently
  • Slide 26
  • Mechanism: Depletes the nerve ending of NE in the periphery Main effects: decrease in PVR and decrease in HR decrease in BP Adverse effects: Orthostatic hypotension, Na + and water retention. Other side-effects similar to reserpine except the CNS effects Pharmacokinetics: Poorly absorbed from the G.I. Onset slow (1-2 weeks). Metabolites excreted in urine Use: Not used anymore because of severe side effects a) Agents that prevent adrenergic transmission: Guanethedine (Ismelin)
  • Slide 27
  • Mechanism and main effects Similar to guanethidine Adverse effects are less than gunethidine: less orthostatic hypotension, less diarrhea, less effect on sexual function. Pharmacokinetics: better absorption, rapid onset, shorter duration of action than guanethidine a) Agents that prevent adrenergic transmission: Guanadrel (Hylorel)
  • Slide 28
  • b) Selective alpha-1 adrenergic receptor blockers (prazosin- Minipres, terazosin- Hytrin, doxazosin- Cardura ) They favorably influence plasma lipid profile, and do not interfere with glucose metabolism. Mechanism: block 1 receptors in vasculature Main effects: decreased PVR decrease BP Adverse effects: 1 st dose phenomenon, fluid retention, dizziness, headache Pharmacokinetics: t 1/2 = 4.5, 12, 20, respectively Use: used in stage 1 and stage 2 HT in combination with a diuretic and a -blocker
  • Slide 29
  • c) Beta-adrenergic blocking agents (see table) Classification Nonselective (1 st generation) Nonselective (1 st generation) Cardioselective ( -1 selective, 2 nd generation ) Cardioselective ( -1 selective, 2 nd generation ) blockers with intrinsic sympathomimetic activity (ISA) blockers with intrinsic sympathomimetic activity (ISA) With additional CV actions (3 rd generation) With additional CV actions (3 rd generation) P