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Comprehensive Guide to Antihypertensive Drugs and Diuretics

This guide provides in-depth information on different classes of antihypertensive drugs and diuretics, their mechanisms of action, clinical indications, and potential adverse effects. Learn about loop diuretics, thiazides, potassium-sparing diuretics, as well as peripheral sympatholytics like reserpine and guanethidine. Understand how alpha and beta adrenergic blockers work and their clinical applications. Explore the uses and side effects of common medications such as propranolol and metoprolol. Enhance your knowledge of managing hypertension effectively with this comprehensive resource.

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Comprehensive Guide to Antihypertensive Drugs and Diuretics

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  1. CARDIOVASCULARDRUGS • ANTIHYPERTENSIVE DRUGS • ANTIANGINAL DRUGS • CONGESTIVE HEART FAILURE DRUGS • ANTIARRYTHMIC DRUGS • DIURETIC DRUGS • NTITHROMBOTICS • ANTIHYPERLIPIDEMICS

  2. 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

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

  4. ANTIHYPERTENSIV3S III. VASODILATORS A. OLDER ORAL VASODILATORS B. CALCIUM BLOCKERS C. [ARENTERAL VASODILATORS IV, ANTIOTENSIN ANTAGONISTS A. ACE INHIBITORS B. RECEPTOR BLOCKERS

  5. 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

  6. 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)

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

  8. 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

  9. 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

  10. 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

  11. 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

  12. GUANETHIDINE • USES: Severe Hypertension • ADVERSE EFFECTS • Orthostatic hypotension, impotence • Diarrhea • Bradycardia, weakness • Peripheral edema • Cl: pheochromocytoma

  13. 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

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

  15. 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

  16. 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

  17. 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

  18. CENTRAL SYMPATHOLYTICS Decrease PVR by inhibiting sympathetic outflow centrally • METHYLDOPA • CLONIDINE

  19. 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

  20. 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

  21. Mechanism of Action of Vasodilators Vasodilators

  22. 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

  23. 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

  24. ANGIOTENSIN CONVERTING ENZYMES INHIBITOR (acei) PVR by level pf vaspcpmtroctomg angiotensin II blood volume by, aldosterone secretion • CAPTOPRIL • LISINOPRIL • ENALAPRIL

  25. 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)

  26. 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

  27. 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

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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. LABETALOL • MIXED ADRENERGIC ANTAGONIST • WITH INTRINSIC SYMPATHOMIMETIC ACTIVITY • USES: Hypertensive emergencies • HYPERTENSION • ADVERSE EFFECTS: • orthostatic hypotension, dizziness

  37. CLINICAL USES OF ANTIHYPERTENSIVE DRUGS A. STEPPED CARE B. MONOTHERAPY C. AGE & ETHNICITY D. MALIGNANT HYPERTENSION

  38. THANK YOU

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