UNIT 2: ANTIHYPERTENSIVE DRUGS UNIT INSTRUCTIONAL OUTCOMES: At the end of this unit, the student should be able to, Differentiate the types of hypertension Explain short and long term control of blood pressure List the classes of drugs used to treat hypertension and their mechanism of action Recall vital information about the drugs used in hypertension. Apply pharmacological knowledge gained in the clinical scenario.

HYPERTENSION- BASICS Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

ANTI-HYPERTENSIVES Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

ACE INHIBITORS CONTRAINDICATED IN PREGNANCY Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

Angiotensin Antagonists Losartan and Valsartan are examples CONTRAINDICATED IN PREGNANCY Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

BETA ADRENERGIC BLOCKERS Beta-1 blockade in cardio myocyte blocks tachycardia,hypertension and force of contraction of heart. Beta-2 blockade in lungs causes bronchoconstriction, poor peripheral circulation. Selective beta-1 blockers are preferred in patients with respiratory troubles as the non selective blockers alters both heart and lungs. Example for selective beta-1 blockers and non selective blockers are atenelol,metaprolol and propranolol respectively.

MOA and ADR of beta blockers Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

CALCIUM CHANNEL BLOCKERS Contraindicated in patients with CHF Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

CALCIUM CHANNEL BLOCKERS Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

3. All diuretics reduce BP by lowering blood 1. Apart from Thiazide diuretics,Loop diuretics and Spiranolactone also employed in treatment of hypertension. 2. Indapamide is the only thiazide diuretic which can be used in HTN patients with Diabetes Mellitus. 3. All diuretics reduce BP by lowering blood volume which eventually decrease cardiac output. Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

ALPHA ADRENERGIC ANTAGONISTS Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

CENTRALLY ACTING ANTIHYPERTENSIVES Both drugs are used to treat mild to moderate hypertension. Positive coomb’s test and rebound hypertension are the respective ADR of methyl dopa and clonidine respectively. Guanafacine has same ADR and MOA as that of clonidine

HYPERTENSIVE EMERGENCY Hypertensive emergency is a rare, but life-threatening situation in which the diastolic blood pressure is either over 150 mm Hg (with systolic blood pressure greater than 210 mm Hg) in a healthy person or 130 mm Hg in an individual with preexisting complications, such as encephalopathy, cerebral hemorrhage, left ventricular failure, or aortic stenosis.

HYPERTENSIVE EMERGENCY Sodiumnitroprusside,Diazoxide and Labetalol are used in hypertensive emergency. Sodiumnitroprusside is the doc but cyanide toxicity is produced during its metabolism which is treated with an enzyme called Rhodanase Diazoxide is used in patients with coronary insufficiency. Labetelol is also used to treat hypertensive emergency but carries the risk of being nonselective beta blocker.

JNC-8 Guidelines Beta blockers are no longer considered as first line drugs as they increase mortality. Thiazides diuretics, ACEIs, ARBs and CCBs are first line drugs. Rest of the drugs are called later line drugs as B.P should be controlled by 1st line drugs/ in combination. ACEIs and ARBs should not be given to simultaneously to a person. Irrespective of ethnic background ARBs and ACEIs should be used as 1st choice drugs in CKD patients. For African patients without CKD, Thiazides and CCBs should be preferred.

HYPERTENSION- Summary Therapeutic goals: 1)Reduce volume overload 2)Reduce sympathetic outflow 3)Block adrenergic receptors of the heart 4)Dilate blood vessels James Olson, Clinical Pharmacology Made Ridiculously Simple, Second Edition, MedMaster Series