antihypertensive drugs 1

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  • 1. Antihypertensive DrugsAntihypertensive Drugs Dr. Yahya Ibn Ilias
  • 2. What is hypertention? WHO standard:WHO standard: Hypertension:Hypertension: People whose blood pressure isPeople whose blood pressure is elevated to More than 140/90mmHg requireelevated to More than 140/90mmHg require antihypertensive agents.antihypertensive agents. The diagnosis ofThe diagnosis of hypertensionhypertension is based on repeated,is based on repeated, reproducible measurements of elevated blood pressure.reproducible measurements of elevated blood pressure.
  • 3. U Hv Got HTN !!
  • 4. Normal Systolic Blood Pressure 90140 mmHg Normal Diastolic Blood Pressure 6090 mmHg
  • 5. Etiology of hypertension Classification of hypertension:Classification of hypertension: Essential hypertensionEssential hypertension andand secondary hypertensionsecondary hypertension Essential hypertension:Essential hypertension: Patients with arterial hypertensionPatients with arterial hypertension and no definable cause are said to have Primary, or Essentialand no definable cause are said to have Primary, or Essential hypertension.hypertension. Secondary hypertension:Secondary hypertension: A specific cause of hypertensionA specific cause of hypertension can be established in only 10-15% of patients.can be established in only 10-15% of patients. it is important to consider specific causes in each case,it is important to consider specific causes in each case, some of them are amenable to definitivesome of them are amenable to definitive surgical treatmentsurgical treatment:: Renal artery constrictionRenal artery constriction,, Coarctation of the aortaCoarctation of the aorta,, PheochromocytomaPheochromocytoma The category of hypertension when the cause is unknown. There are probably several different genetic causes. Includes approximately 90% of cases. Also referred to as Idiopathic hypertension. Approximately 20% of all adults in US are affected. Even though the underlying cause usually is not known, hypertension can usually be very effectively treated.
  • 6. Normal Regulation of Blood Pressure :- Arterial blood pressure (BP) is directly proportionate to the product of the blood flow (cardiac output, CO) and the resistance to passage of blood through precapillary arterioles (peripheral vascular resistance, PVR): BP = CO X PVR
  • 7. In both normal and hypertensive individuals, blood pressure is maintained by: Cardiac output and peripheral vascular resistance, exerted at three anatomic sites: Arterioles, postcapillary venules (capacitance vessels), and heart. A fourth site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid.
  • 8. Baroreflexes, mediated by autonomic nerves Act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of hormones from vascular endothelium may also be involved in the regulation of vascular resistance. For example, nitric oxide : dilates and endothelin-1 constricts blood vessels.
  • 9. Therapeutic goals in hypertension To lower the high blood pressure and reduced cardiovascular morbidity and mortality by least intrusive means. For most of the patients: life-long treatment of an asymptomatic disease. Antihypertensive Agents
  • 10. Antihypertensive Agents 6. Sympatholytic Drugs Centrally acting agents(Alpha-2 Agonists) Ganglionic Inhibitors (Mecamylamine) Adrenergic Neural Terminal Inhibitors (reserpine) Adrenergic receptor blockers - Alpha- Blockers - Beta Blockers - Alpha and Beta Blockers 1. Diuretics 2. Calcium Channel Blockers 3. Angiotensin Converting Enzyme Inhibitors 4. Angiotensin Receptor Antagonists 5. Peripheral Vasodilators
  • 11. Classification : Diuretics: thiazide and loop diuretics B-blockers: atenolol, labetalol, metoprolol, propanolol ACE Inhibitors: captopril,enalapril,lisinopril Angiotensin receptor blockers: losartan
  • 12. Ca-channel blockers: amlodipine, nifedipine, diltiazem, verapamil Alpha blockers: prazosin, doxazocin, terazocin Centrally acting Alfa agonist: clonidine, methyldopa Direct Vasodilators: hydralizine, nitroprusside, minoxidil, diazoxide.
  • 13. Renin angiotensin aldosteroneRenin angiotensin aldosterone system, RAASsystem, RAAS Ag AgACE BP Aldosterone Angiotensinogen Renin Decomposition BP BradykininBradykinin
  • 14. A n g i o t e n s i n II Peripheral resistance Renal function Cardiovascular structure Rapid Pressor Response 1. Direct vasoconstriction 2. Enhancement of peripheral noradrenergic neurotransmission 3. Increased central (CNS) sympathetic discharge 4. Release of catecholamines from adrenal medulla 1. Releases aldosterone from adrenal cortex 2. Increases Na+ reabsorption 3. Altered renal hemodynamics: - renal vasoconstriction - increased noradrenergic neurotransmission in kidney - Increased renal sympathetic tone (CNS) Slow Pressor Response Cardiovascular Hypertrophy and Remodeling 1. Non-hemodynamic effects: - Increased expression of proto-oncogenes - Increased production of growth factors - Increased synthesis of extracellular matrix proteins 2. Hemodynamic effects: - Increased afterload (cardiac) - Increased wall tension (vascular)
  • 15. Inhibitors of Angiotensin
  • 16. Mechanism & Sites of Action : Renin release from the kidney cortex is stimulated by reduced renal arterial pressure, sympathetic neural stimulation, and reduced sodium delivery. Renin acts upon angiotensinogen to split off the inactive precursor decapeptide angiotensin I. Angiotensin I is then converted, primarily by Endothelial ACE, to the arterial vasoconstrictor octapeptide angiotensin II ,which is in turn converted in the adrenal gland to angiotensin III.
  • 17. Juxtaglomerular apparatus
  • 18. Angiotensin II has vasoconstrictor and sodium-retaining activity. Angiotensin II and III both stimulate aldosterone release. Two classes of drugs act specifically on the renin-angiotensin system: the ACE inhibitors and the competitive inhibitors of angiotensin at its receptors
  • 19. ACE Inhibitors Antihypertensive Mechanisms
  • 20. Angiotensin-Converting Enzyme (ACE) Inhibitors 1. Captopril ** 2. Enalapril 3. Fosinopril 4. Lisinopril ** 5. Ramipril Benazepril, fosinopril, moexipril, perindopril, quinapril, and trandolapril
  • 21. Captopril Inhibit the converting enzyme angiotensin I to angiotensin II . Inhibit the inactivation of Bradykinin, a potent vasodilator, which works at least in part by stimulating release of nitric oxide and prostacyclin. Hypotensive activity of Captopril results both from an inhibitory action on the renin-angiotensin system and a stimulating action on the kallikrein-kinin system
  • 22. Enalapril Is a prodrug that is converted by deesterification to a converting enzyme inhibitor, Enalaprilat, with effects similar to captopril. Available only for intravenous use, Use : primarily for hypertensive emergencies.
  • 23. Lisinopril is a lysine derivative of enalaprilat. Benazepril, fosinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril are other long-acting members of the class. All are prodrugs, like enalapril, and are converted to the active agents by hydrolysis, primarily in the liver.
  • 24. Angiotensin II inhibitors lower blood pressure principally by decreasing peripheral vascular resistance. Cardiac output and heart rate are not significantly changed. Useful role in treating patients with diabetic nephropathy because they diminish proteinuria and stabilize renal function.
  • 25. Indication of ACE Inhibitors: Hypertension Congestive heart failure (CHF) Left ventricular dysfunction Prevention of nephropathy in diabetes mellitus Following myocardial infarction.

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