CARDIOVASCULAR DRUGS ANTIHYPERTENSIVE DRUGS ANTIANGINAL DRUGS CONGESTIVE HEART

CARDIOVASCULAR DRUGS • ANTIHYPERTENSIVE DRUGS • ANTIANGINAL DRUGS • CONGESTIVE HEART FAILURE DRUGS • ANTIARRYTHMIC DRUGS • DIURETIC DRUGS • NTITHROMBOTICS • ANTIHYPERLIPIDEMICS Page 1 of 39

Anti-hypertensive Drugs HYPERTENSION • IDIOPATHIC (ESSENTIAL HYPERTENSION • >90% ; 15 -40 yrs • Genetic inheritance OR PRIMARY • SECONDARY HYPERTENSION • Renal artery disease, 1° aldosteronism, pheochromocytoma, renal parenchyma dse, glom'it is, toxemia of pregnancy • CNS disorders, estrogen use Page 2 of 39

ANTIHYPERTENSIVE DRUGS i. DIURETICS II. SYMPATHOPLEGICS BLOCKERS A. ALPHA OR BETA RECEPTORS B. NERVE TERMINALS C GANGLIA D. CNS SYMPATHETIC OUTFLOW Page 3 of 39

ANTIHYPERTENSIV 3 S III. A. B. C. IV, A. B. VASODILATORS OLDER ORAL VASODILATORS CALCIUM BLOCKERS [ARENTERAL VASODILATORS ANTIOTENSIN ANTAGONISTS ACE INHIBITORS RECEPTOR BLOCKERS Page 4 of 39

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 Page 5 of 39

LOOP DIURETICS • FUROSEMIDE (Lasix) • Inhibits Na+K+2 CI+ 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) Page 6 of 39

THIAZIDE DIURETICS • HYDROCHLOROTHIAZIDE • inhibits Na+CI+ symporter • INDAPAMIDE Strongest vasodilator effect) • CHLORTHALIDONE • METOLAZONE Page 7 of 39

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 Page 8 of 39

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 Page 9 of 39

• 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 Page 10 of 39

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 Page 11 of 39

GUANETHIDINE • USES: Severe Hypertension • ADVERSE EFFECTS • Orthostatic hypotension, impotence • Diarrhea • Bradycardia, weakness • Peripheral edema • C l : pheochromocytoma Page 12 of 39

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 Page 13 of 39

Alpha Adrenergic Blockers • CLINICAL USES • HYPERTENSION • BENIGN PROSTATIC HYPERPLASIC ADVERSE EFFECTS • First Dose Phenomena • Dizziness / Headache • lassiture Page 14 of 39

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 Page 15 of 39

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 Page 16 of 39

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 Page 17 of 39

CENTRAL SYMPATHOLYTICS Decrease PVR by inhibiting sympathetic outflow centrally • METHYLDOPA • CLONIDINE Page 18 of 39

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 Page 19 of 39

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 Page 20 of 39

Vasodilators Mechanism of Action of Vasodilators MECHANISM EXAMPLES Release of nitric oxide from drug or Nltroprusside endothelium Hydralazine Nlmoxidil Hyperpolarization of vascular smooth muscle thru opening of K Diazepoxide channels Reduction of Calcium Influx Verapa„o; . Diltiazem Nifedipine Fenoldopam Activation of dopamine receptors Page 21 of 39

DIRECT VASODILATORS • Directly vasodilating arterioles • HYDRALAZINE • MONOXIDIL • HYDRALAZINE ( APROESOLINE) • Arteriolar smooth muscle , „> 4/ PVR renal blood flow < 8 h r s ; I V , PO, IM • USES: hypertension, CHF • Adverse Effects: headache, nausea, diarrhea, hypotension, palpitation, tachycardia, angina Lupus like syndrome, edema Page 22 of 39

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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 Page 24 of 39

ANGIOTENSIN CONVERTING ENZYMES INHIBITOR (acei) PVR by level pf vaspcpmtroctomg angiotensin II blood volume by, aldosterone secretion • CAPTOPRIL • LISINOPRIL • ENALAPRIL Page 25 of 39

CAPTOPRIL (capoten) I. Reversibly inhibits angiotensin converging enzyme ( Kinase III) preventing the conversion of angiotensin I into the vasocontrictor angiotension. II. AT II levels ' aldosterone. Na & H 20 retention III. AT II levels. . renin release & the formation of AT ACEI. . bradykinin. . > PG synthesis (vasodilators) Page 26 of 39

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 Page 27 of 39

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 & H 20 retention • Also renin release & the formation of angintensin 1 Possess uricosuric effects Page 28 of 39

LOSARTAN USE: HYPERTENSION • ADVERSE EFFECTS: • Headache • Hypotension • Hyperkalemia • Contraindications: pregnancy, fetal exposure » >hypotension, renal failure, anuria, skull hyperplasia, death Page 29 of 39

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 Page 30 of 39

NIFEDIPINE Calcium influx. . . > Relaxation of arterial smooth muscle & 4/ PVR > reflex 1 s in sympathetic tone which may mask th (-) inotropic effect Less effect on SA node, automaticity & AV nodal conduction USES: HYPERTENSION/ ANGINA ADVERSE EFFECTS: headache, dizziness, peripheral edema, tachycardia, flushing nausea, fatigue, constipation, hypotension Page 31 of 39

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 Page 32 of 39

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 Page 33 of 39

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 Page 34 of 39

SODIUM NITROPRUSSIDE • Nitric Oxidec. GMP. . . >4/ Ca ions in arteriolar & venous vessels causing vasodilatation. . >4/ preload & afaterload • USES: hypertensive emergencies, CHF • Adverse Effects: hypotension, arrhythmias • Cyanide toxicity, thiocycnate poisoning Page 35 of 39

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 Page 36 of 39

LABETALOL • MIXED ADRENERGIC ANTAGONIST • WITH INTRINSIC SYMPATHOMIMETIC ACTIVITY • USES: Hypertensive emergencies • HYPERTENSION • ADVERSE EFFECTS: • orthostatic hypotension, dizziness Page 37 of 39

CLINICAL USES OF ANTIHYPERTENSIVE DRUGS A. B. C. D. STEPPED CARE MONOTHERAPY AGE & ETHNICITY MALIGNANT HYPERTENSION Page 38 of 39

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