Dept .

Pharmacology and Toxicology COVAS,Parbhani

Hypertension is the leading cause of cardiovascular disease and mortality Proper medication will control most cases of hypertension

Most people have essential hypertension where the exact cause is not known Increased sympathetic activity and sodium overload increase blood pressure (BP) Renal disease and increased reninangiotensin- aldosterone activity raise BP and cause sodium and fluid retention Smoking, body overweight, and increased sodium consumption contribute to hypertension

Diuretics Sympatholytic drugs Vasodilator drugs Calcium antagonist drugs Angiotensin-converting enzyme inhibitor and angiotensin receptor blocking drugs

Diuretics increase sodium excretion and relax arterial blood vessels (vasodilation) Thiazides are preferred in patients with adequate renal function Organic acid diuretics (loop diuretics) are used in patients with reduced renal function Diuretics can be used alone or in combination with other antihypertensive drugs Excessive loss of fluid, sodium, and potassium are common adverse effects

 Diuretics are drugs that increase renal excretion of water, sodium & other electrolytes, thereby increasing urine formation & output Used in the management of heart failure, renal & hepatic disease, hypertension, ophthalmic surgery

 Thiazide diuretics:

Decrease reabsorption of Na, water, Cl & bicarbonate in the distal convoluted tubule Hydrocholorothiazide 25-100 mg daily or BD po Indapamide (Natrilix) 2.5 mg/1.5mg(S.R.) daily po

 Inhibit Na & Cl reabsorption in the ascending loop of Henle Frusemide 1-2 mg in dogs Bumetanide (Burinex) 0.5-2 mg daily po
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 Act directly on the distal tubule to decrease the exchange of Na for K Amiloride : 5-20 mg daily po Triamterene: 100-300 mg daily in divided dose po Spironolactone Block the Na-retaining effects of aldosterone in the distal tubule 25-200 mg daily po

 Thiazide & related diuretics are available in numerous fixed-dose combination with non-diuretic antihypertensive agents & with K-sparing diuretics. This can increase patient compliance & prevent K imbalances: Dyazide (Hydrochlorothiazide 25mg+Triamterene 50mg) Moduretic (Hydrochlorothiazide 50mg+Amiloride 5mg) Hyzaar (Losartan 50mg+Hydrochlorothiazide 12.5mg)

Alpha blockers lower BP by vasodilation Beta blockers lower BP by decreasing heart rate and cardiac output Centrally acting sympatholytic drugs decrease the activity of the cardiovascular centers in the medulla oblongata

Receptor Subtype Alpha 1,2

Tissue Vascular smooth muscle Heart

Effects Contraction

Beta 1

Inc. Heart Rate Inc. Force of Contraction

Beta 2

Smooth muscle

Relaxation

Prazosin Terazosin Phenoxybenzamine

 Block beta-1 receptors in the heart Hence:

Reduce heart rate Reduce force of contraction Reduced velocity impulse conduction through the AV node

Propranolol Metoprolol

Labetalol is a mixed antagonist

Hypertension
Angina pectoris Arrhythmias Myocardial Infarction Heart Failure

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Adverse Effects

Nursing Alert
Check blood

Bradycardia Hypotension Brochospasms GI disturbances Heart failure Fatigue

pressure & pulse frequently, especially when dosage is being increased

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Vasodilators decrease the muscular tone and contractile function of blood vessels Hydralazine and minoxidil are potent vasodilators that must be used with diuretics and sympathetic blocking drugs Minoxidil causes hirsutism and is sold topically for treatment of baldness

Block the influx of calcium into the heart and arterial blood vessels Verapamil and diltiazem act on both the heart and blood vessels to lower BP Nifedipine and other calcium blockers lower BP only by vasodilation Calcium antagonists are also used to treat angina pectoris and cardiac arrhythmias

 Drugs that prevent calcium ions from

entering cells. Have the greatest effect on the heart and blood vessels. Widely used to treat hypertension and cardiac dysrhythmias

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 Hypotension, dizziness, weakness, peripheral edema, headache, heart failure, pulmonary edema, nausea, constipation Bradycardia (Verpamil, Diltiazem) Tachycardia (Nifedipdine & other dihydropyridines)

ACEIs inhibit the formation of angiotensin which is a potent vasoconstrictor ACEIs decrease the release of aldosterone which retains sodium and water These drugs produce a low incidence of adverse effects and do not interfere with mental activity or renal function

These drugs block angiotensin receptors on blood vessels and adrenal cortex Like the ACEIs, these drugs produce vasodilation and decrease the activity of aldosterone The angiotensin receptor blockers generally produce a lower incidence of adverse effects than the ACEIs

There are 2 families of drugs:

Angiotensin-converting enzyme (ACE) inhibitors Block the enzyme (ACE) that normally converts angiotensin I to the potent vasoconstrictor angiotensin II Decrease vasoconstriction & decrease aldosterone production, reducing retention of Na and water
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 Used to treat hypertension, heart failure, myocardial infarction, and nephropathy Enalapril 10-40mg/day in 1 or 2 doses Lisinopril 10-40mg once daily Perindopril 2-8mg daily Ramipril 1.25-10mg once daily Side Effects: Can produce serious first-dose hypotension Cough, due to accumulation of bradykinin Hyperkalaemia, due to inhibition of aldosterone release 27

 Angiotensin II receptor blockers (ARBs) Compete with angiotensin II for tissue binding sites & prevent angiotensin II from combining with its receptors in body tissues Used for hypertension, may be used as an alternative to ACE inhibitors in the management of heart failure and diabetic nephropathy. Irbesartan 150-300mg once daily Losartan 25-100mg once daily Valsartan 80-160mg once daily

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 Hypotension Less likely to cause cough and hyperkalaemia than ACE inhibitors

Severe hypertension is a medical emergency that can lead to stroke and sudden death Immediate parenteral administration of antihypertensive drugs can avoid severe complications and irreversible damage Diazoxide and nitroprusside are potent vasodilators used in hypertensive crisis

Veterinary Pharmacoloy and Toxicology -B.K.ROY

Essentials of Veterinary pharmacology and therapeutics - H S Sandhu

Thank you