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CARDIOVASCULAR DRUGS. ANTIHYPERTENSIVE DRUGS ANTIANGINAL DRUGS CONGESTIVE HEART FAILURE DRUGS ANTIARRYTHMIC DRUGS DIURETIC DRUGS NTITHROMBOTICS ANTIHYPERLIPIDEMICS. Anti-hypertensive Drugs. HYPERTENSION IDIOPATHIC (ESSENTIAL OR PRIMARY HYPERTENSION >90% ; 15-40yrs
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CARDIOVASCULARDRUGS • ANTIHYPERTENSIVE DRUGS • ANTIANGINAL DRUGS • CONGESTIVE HEART FAILURE DRUGS • ANTIARRYTHMIC DRUGS • DIURETIC DRUGS • NTITHROMBOTICS • ANTIHYPERLIPIDEMICS
Anti-hypertensive Drugs HYPERTENSION • IDIOPATHIC (ESSENTIAL OR PRIMARY HYPERTENSION • >90% ; 15-40yrs • Genetic inheritance • SECONDARY HYPERTENSION • Renal artery disease, 1° aldosteronism, pheochromocytoma, renal parenchyma dse, glom'it is, toxemia of pregnancy • CNS disorders, estrogen use
ANTIHYPERTENSIVE DRUGS i. DIURETICS II. SYMPATHOPLEGICS BLOCKERS A. ALPHA OR BETA RECEPTORS B. NERVE TERMINALS C GANGLIA D. CNS SYMPATHETIC OUTFLOW
ANTIHYPERTENSIV3S III. VASODILATORS A. OLDER ORAL VASODILATORS B. CALCIUM BLOCKERS C. [ARENTERAL VASODILATORS IV, ANTIOTENSIN ANTAGONISTS A. ACE INHIBITORS B. RECEPTOR BLOCKERS
DIURETICS • Initially T BP & thus CO. Eventually CO returns to normal but is accompanied by a ^ in PVR. • LOOP DIURETICS • THIAZIDES & RELATED DRUGS • POTASSIUM SPARING DIURETICS
LOOP DIURETICS • • FUROSEMIDE (Lasix) • • Inhibits Na+K+2CI+ symporter • • Inhibits reabsorption of Ca+ & Mg+ • • Short 11/2 , PO, IV • • BUMETANIDE • • TORSEMIDE • • ETHACYRINIC ACID • CLINICAL INDICATIONS: • edema, pulmonary edema • Hypercalcemia • Hypertension • ADVERSE EFFECTS • Hypokalemic metabolic alkalosis • Orthostatic hypotension. Allergic rxs Ototoxicity ( ethacrynic acid)
THIAZIDE DIURETICS • HYDROCHLOROTHIAZIDE • inhibits Na+CI+ symporter • INDAPAMIDE Strongest vasodilator effect) • CHLORTHALIDONE • METOLAZONE
THIAZIDES • CLINICAL INDICATIONS • Hypertension / Edema Nephrotic diabetes insipid us Calcium nephrolitiasis • ADVERSE EFFECTS • 4, Na 4, Cl 4, K 4, Ca 4, Mg • 'h Uric Acid, 'f sugar 'h lipids • Allergic rxa, orthostatic hypotension •DRUG TERACTIONS: LITHIUM/ DIGOXIN
POTASSIUM SPARING DIURETICS • SPIRONOLACTONE • Aldosteroine antagonist • Inhibits steroid biosynthesis, antagonist at androgen receptors • AMILORIDE/TRIAMTERENE • Block sodium channels • CLINICAL INDICATIONS • • Edema / Hypertension • • Primary hyperaldosteronism / Hirsutism • • ADVERSEEFFECTS k, metabolic acidosis, for spironolactone: gynecomastia, menstrual irreg • GIT effects: diarrhea, gastritis, GIT bleeding & peptic ulcer • CNS effects: drowsiness, lethargy, ataxia, confusion & headache
PERIPHERAL SYMPATHOLYTICS • Decrease PVR &/or CO • RESERPINE • GLUANETHIDINE • ALPHA 1 ADRENERGIC BLOCKERS • BETA ADRENERGIC BLOCKERS • RESERPINE • Irreversibly binds to storage vesicles in adrenergic neurons ...> s\, uptake & storage of norepinephrine, dopamine & serotonin both centrally & peripherally • USES: hypertension/ Huntington's dse • ADVERSE EFFECTS: sedation, inability to concentrate, dizziness, loss of appetite, nasal congestion, N & V, dryness of mouth, diarrhea • Extra pyramidal effect, depression
Peripheral Sympatholytics • ■ GUANETHEDINE • Enters neurons by norepinephrine reuptake transporter and slowly displace norepi in the synaptic vesicles...> blocks the release of norepi normally produced by nerve stimulations • VASODILATATION (due to deoletion of catecholamines • Not enter CNS • Salt & water retention
GUANETHIDINE • USES: Severe Hypertension • ADVERSE EFFECTS • Orthostatic hypotension, impotence • Diarrhea • Bradycardia, weakness • Peripheral edema • Cl: pheochromocytoma
Alpha Adrenergic Blockers • DOXAZOSIN (cardiac) • PRAZOSIN (minipress) • TERAZOSIN (Mytrin) • Antagonist at both arterioles & veins...> ^ PVR & venous return to the heart • ↓cardiac preload & after load with minimal effects on CO & HR • Relax smooth muscle in the bladder neck & prostate 4/ plasma lipid & LDL & HDL
Alpha Adrenergic Blockers • CLINICAL USES • • HYPERTENSION • • BENIGN PROSTATIC HYPERPLASIC • ADVERSE EFFECTS • First Dose Phenomena • Dizziness / Headache • lassiture
BETA ADRENERGIC BLOCKER * PROPRANOLOL (inderal) • > non selective * Antianginal effect: negative isotropic & chronotropic effects...>4^myocardial oxygen demand • Antiarrythmic (class III) Antihypertensive effects ^ CO ^sympathetic outflow to peripheral vasculature..> 4^ PVR..> inhibition of rennin relase by the kidney
PROPRANOLOL • USES : • Angina: stable • Arrhythmias Myocardial infarction Hypertrophic cardiomegaly, • Hyperthyroidism, pheochromocytoma Migraine prophylaxis, stage fright ADVERSE EFFECTS: mpotence bronchoconstriction, Arrythmias, CHF or angina (abrupt withdrawal) CNS: drowsiness, insomnia, fatique Hypoglycemia,, lipidemia, claudicating of peripheral vessels
METOPROLOL • Selective beta one • Antianginal effect Antiarrythmic effects • Antihypertensive effects USES: hypertension, angina, arrhythmias, Ml ADVERSE EFFECTS: bradycardia, sedation, fatique, bronchospasm, hypoglycemia, hyperlipidemia congestive heart failure
CENTRAL SYMPATHOLYTICS Decrease PVR by inhibiting sympathetic outflow centrally • METHYLDOPA • CLONIDINE
METHYLDOPA (Aldomet) • Prodrug ...> methyl norepinephrine which activates alpha adrenergic receptors to inhibits sympathetic outflow • Antihypertensive effect mediated by a N|/ PVR and ^ CO • Renal blood flow maintained • USE: hypertensive • Adverse effects: edema, drowsiness, dry mouth, hepatotoxicity, + Coombs test
CLONIDINE • Stimulates alpha two receptors..> inhibits sympathetic outflow • Antihypertensive effect: ^ PVT ^ CO • Duration < 8 hrs. PO, IV, transversal patch • USE: hypertension • ADVERSE EFFECTS: Drowsiness, itching & redness of skin, dizziness, constipation, reduced libido, rebound hypertension
Mechanism of Action of Vasodilators Vasodilators
DIRECT VASODILATORS • Directly vasodilating arterioles • HYDRALAZINE • MONOXIDIL • HYDRALAZINE ( APROESOLINE) • Arteriolar smooth muscle ,„> 4/ PVR renal blood flow <8hrs;IV, PO, IM • USES: hypertension, CHF • Adverse Effects: headache, nausea, diarrhea, hypotension, palpitation, tachycardia, angina Lupus like syndrome, edema
DIRECT VASODILATORS MINOXIDIL • Arteriolar smooth muscle vasodilator • Increases K efflux by opening K channels ...> hyper polarization...> relaxation of smooth muscle • Vasodilatation...> 4^ PVR More potent than hydralozine • USE : hypertension • alopecia androgenetica • Adverse Effects: edema, reflex tachycardia, flushing, hypertrichosis
ANGIOTENSIN CONVERTING ENZYMES INHIBITOR (acei) PVR by level pf vaspcpmtroctomg angiotensin II blood volume by, aldosterone secretion • CAPTOPRIL • LISINOPRIL • ENALAPRIL
CAPTOPRIL (capoten) Reversibly inhibits angiotensin converging enzyme ( Kinase III) preventing the conversion of angiotensin I into the vasocontrictor angiotension. AT II levels ' aldosteroneNa & H20 retention AT II levels.. renin release & the formation of AT ACEI.. bradykinin ..> PG synthesis (vasodilators)
CAPTOPRIL • USES: • Hypertension • Congestive heart failure • Scleroderma renal crsisi • Diabetic nephropathy • ADVERSE EFFECTS: • dry cough, headache, fatique, hypotension, skin rash, dyspepsia, hyperkalemia, proteinuria • Acute renal failure
ANGIOTENSIN II RECEPTOR ANTAGONISTS • LOSARTAN • Inhibits the vasocontrictor & aldosterone secreting effects of angiotensin II • Converted to a 5 carboxylic acid metabolite AT II levels,,, > aldosterone levels,,,> Na & H20 retention • Also renin release & the formation of angintensin 1 Possess uricosuric effects
LOSARTAN USE: HYPERTENSION •ADVERSE EFFECTS: • Headache • Hypotension • Hyperkalemia • Contraindications: pregnancy, fetal exposure »>hypotension, renal failure, anuria, skull hyperplasia, death
CALCIUM CHANNEL BLOCKERS • CALCIUM INFLUX IN VASCULAR SMOOTH MUSCLE &/OR CARDIAC MUSCLE Effect on vascular smooth muscle • Nifedipine > diltiazem > Verapamil Effect on cardiac muscle • Verapamil > Diltiazem > Nifedipine
NIFEDIPINE Calcium influx...> Relaxation of arterial smooth muscle & 4/ PVR > reflex 1s in sympathetic tone which may mask th (-) inotropic effect Less effect on SA node on SA node, automaticity & AV nodal conduction USES: HYPERTENSION/ ANGINA ADVERSE EFFECTS: headache, dizziness, peripheral edema, tachycardia, flushing nausea, fatigue, constipation, hypotension
DILTIAZEM • Binds cardiac L type calcium channels SA node automaticity & AV nodal conduction with some (-) inotropic effect on the heart mild vasodilator effects on blood vessels • USES: Hypertension, Angina, supraventricular arrhythmias • Adverse Effects: rash, hypotension, CHF, dizziness, flushing, headache
VERAPAMIL • • MOA same as diltiazem • • Exhibits mild vasodilators effects on arterioles • USES: • Hypertension, Angina • supraventricular arrhythmias • Hypertrophic cardiomyopathy • ADVERSE EFFECTS: • Rash, bradycardiak CHF, hypertension, peripheral edema, constipation, dizziness, fatigue, headache
HYPERTENSIVE EMERGENCIES • I. DIAZOXIDE: • Activates ATP sensitive K+ channels causing hyper polarization of arterioles smooth muscle cells,. > arteriolar vasodilatation • Stimulates reflex sympathetic tone...> T CO, HR, contractility • USES: Hypertensive Emergencies • Adverse effects: edema, tachycardia, hyperglycemia
SODIUM NITROPRUSSIDE • Nitric OxidecGMP...>4/ Ca ions in arteriolar & venous vessels causing vasodilatation..>4/ preload & afaterload • USES: hypertensive emergencies, CHF • Adverse Effects: hypotension, arrhythmias • Cyanide toxicity, thiocycnate poisoning
TRIMETHAPHAN • Ganglionic glocking agent which competitively antagonizes postsynaptic acetylcholine receptors • 4/ both arterial BP & the upslope of the arterial pressure wave in the aorta • Direct peripheral vasodilatation & release of histamines • USES: hypertensive emergencies • ADVERSE EFFECTS: orthostatic hypotension, constipation, urinary retention, blurred vision, dry mouth, impotency
LABETALOL • MIXED ADRENERGIC ANTAGONIST • WITH INTRINSIC SYMPATHOMIMETIC ACTIVITY • USES: Hypertensive emergencies • HYPERTENSION • ADVERSE EFFECTS: • orthostatic hypotension, dizziness
CLINICAL USES OF ANTIHYPERTENSIVE DRUGS A. STEPPED CARE B. MONOTHERAPY C. AGE & ETHNICITY D. MALIGNANT HYPERTENSION
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