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Antihypertensive Drugs

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ANTIHYPERTENSIVE AGENTS - PowerPoint PPT Presentation

ANTIHYPERTENSIVE AGENTS

Describe the impact and mechanisms involved in essential ... drugs: hydralazine, diazoxide, sodium nitroprusside, minoxidil, enalapril, lisinopril, losartan ... – powerpoint ppt presentation.

• Philip J. Kadowitz, Ph.D.
• Describe the impact and mechanisms involved in essential hypertension.
• Explain actions of major classes of antihypertensive drugs.
• Describe the use of drugs in the treatment of essential hypertension and of a hypertensive emergency or crisis.
• Drugs hydralazine, diazoxide, sodium nitroprusside, minoxidil, enalapril, lisinopril, losartan
• a. Thiazide diuretics important for antihypertensive therapy
• ? do not exert their effect simply by lowering plasma volume
• ? plasma volume returns to pre-treatment levels, but antihypertensive effect persists
• ? alter arteriolar tone
• b. Potassium-sparing diuretics spironolactone, eplerenone, amiloride, triamterene.
• c. Loop diuretics (e.g., furosemide) used for edema reduction decrease plasma volume thereby lowering pressure. Use with low GFR.
• Clonidine (Catapress) acts direclty on alpha-2 receptors in vasomotor center
• Methyldopa (Aldomet - metabolized in CNS to ?-methyl norepinephrine, which acts on ?2-receptors in vasomotor center
• 3. Adrenergic receptor-blocking agents
• a. ?-blockers propranolol, metoprolol, atenolol, etc., act on the heart to decrease heart rate and stroke volume also more slowly to reduce TPR
• b. ? -blockers
• Prazosin (Minipress) blocks ? 1 receptors, thereby permitting norepinephrine to act on ? 2 receptors and inhibit release
• Non-selective ? -blockers rarely used, due to reflex tachycardia (phentolamine)
• Reserpine depletes adarenergic terminals
• Guanethidine reserpine-like and bretylium-like effects of guanethidine deplete adrenergic terminals of norepinephrine and inhibit transmitter release, thereby reducing sympathetic tone to vessels and heart
• MAO inhibitors (e.g., tranylcypromine, phenelzine, pargyline ) not used
• 5. Direct vasodilators
• a. Arteriolar
• Hydralazine always used with ?-blocker due to reflex tachycardia and with a diuretic
• Diazoxide chemically related to thiazide diuretics used in hypertensive crisis
• Minoxidil used in hypertensive patients refractory to other agents grows hair
• Nitroprusside (Nipride) - used only i.v. in hypertensive crisis can titrate blood pressure to desired level with infusion (rapid onset, rapid termination of action)
• 6. Calcium entry blockers
• L-type calcium channel blockers
• 7. Renin-angiotensin inhibitors
• a. ACE inhibitors
• ? peptidyl dipeptidase (converting enzyme) inhibitors
• ? inhibit formation of angiotensin II (active) from angiotensin I (inactive)
• ? inhibit breakdown of bradykinin
• ? effective orally
• ? cause coughing in up to 25 of patients
• ? short-acting
• ? not a prodrug
• ? prodrug long-acting
• b. Angiotensin receptor antagonists ARBS effective orally, do not alter bradykinin levels
• Candesartan
• ? Diuretics
• ? Beta-blockers
• ? Calcium entry blockers
• ? ACE inhibitors
• ? Allhat trial
• ? JNC 7 and 8

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Antihypertensive drugs

Mar 21, 2019

370 likes | 1.57k Views

Antihypertensive drugs. BACKGROUND. NBP 120-90/90-60mmHg, Affecting factors: Volume of blood, Cardiac Output, resistance of Arterioles HBP SBP>140/ DBP>90 mmHg Morbidity 30% CLASSES OF HYPERTENISON Essential hypertension Secondary hypertension. CLASSES OF DRUGS. DRUGS Targets

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• hypertension
• cardiac output
• mild hypertension
• secondary hypertension
• positive feedback na
• na na ca ca

Presentation Transcript

BACKGROUND • NBP 120-90/90-60mmHg, • Affecting factors: Volume of blood, Cardiac Output, resistance of Arterioles • HBP SBP>140/ DBP>90 mmHg • Morbidity 30% • CLASSES OF HYPERTENISON • Essential hypertension • Secondary hypertension

CLASSES OF DRUGS • DRUGSTargets • Diuretics • Agents act on ANS. • Direct Vasodilators • CCB • RAS blockers (ACEI, AT1B) • Blood Volume • Cardiac Output • Resistance of Vessel • Arterioles • RAS • Neuroregulation

Diuretics • Agents Furosemide (Lasix) thiazides • Mechanism • Blood Volume • Na Na Ca Ca • Na PGE2, Kinin • reactivity to vaso-excitor material(NA)

Diuretics • Clinic uses • Alone: Mild hypertension • United: Mediate & serious • ADR • K Na • CE TG LDL • Renin activity

RAS blockers • ACEI(…pril) • Captopril • Mechanism • Angiotensin Renin AI ACE AII • Bradykinin NO,EDHF Vasoconstriction Aldosterone Proliferation

Renin angiotensin aldosterone system, RAAS AgⅠ BP↑ AgⅡ ACE aldosterone ↑ renin 降解产物 心室重构 血管重构 缓激肽 血管紧 张素原 BP↓

RAS blockers • Clinic uses: hypertension & CHF • ADR • Hypotension • Dry Cough • Hyperkalaemia • Antagonists of AT1 • Losartan • AII: AT1-R, AT2-R

ANS Blockers • Antagonists of β-R • Propranolol,Metoprolol, atenolol • Mechanism • Heart Rate Cardiac Output • Rinin, positive feedback-NA • Clinic uses • Mild-mediate hypertension • ADR constriction

ANS Blockers • sympathetic nerve inhibitor 1.Central hypotensive drugs:clonidine 2.Ganglion blockers:mecamylamine 3.Drugs affecting NA stores or release • Reserpine; Quanethidine 4. Adrenoceptor blokers • Antagonists of α-R:Prazosin, Urapidil • Antagonists of α, β –R:Labetalol

Calcium antagonists • Target at vascular smooth muscle • nifedipine • amlodipine • tetrandrine

Direct Vasodilators • Sodium nitroprusside • Mechanism • NO • Pharmacokinetics(P.K.) • P.E. • Directly on a. & v. • Clinic uses Serious hypertension • ADR : hypotension, thiocyanate toxicity ivgtt only Rapid onset(<2min) Cease in 5 min

Direct Vasodilators • Potassium Channel Openers • Pinacidil • Mechanism • K hyperpolarization • Ca • Clinic use mild-midiate hypertention • ADR edema

Review & questions • Classes of antihypertensive • Agents & main mechanisms of each. • Serious hypertension use ____ first. • Common ADR of them is ____. • Mild hypertension use ___ first, if no use, add ___ /-------.

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