ANTIHYPERTENSIVES

1. ANTIHYPERTENSIVES • DIURETICS • ADRENERGIC ANTAGONISTS • DRUGS AFFECTING RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM • CALCIUM CHANNEL ANTAGONISTS • CENTRALLY ACTING • GANGLION BLOCKADE • ADRENERGIC NEURON BLOCKADE

2. DIURETICS • THIAZIDES – USEFUL IN HYPERTENSION. HAVE BEEN SHOWN TO REDUCE INCIDENCE OF STROKE • LOOP DIURETICS – HAVE HYPOTENSIVE EFFECTS BUT NOT GENERALLY USED FOR HYPERTENSION. MAIN USES- HEART FAILURE AND RENAL FAILURE • POTASSIUM SPARING

3. THIAZIDES • BENDROFLUAZIDE, CHLORTIAZIDE AND METOLAZONE • ACT ON DCT BY INHIBITING REABSORPTION OF Na AND Cl, THERREFORE INCREASING Na , Cl AND WATER EXCRETION • MAXIMAL EFFECT AT LOWER DOSES

4. EFFECTS OF THIAZIDES • REDUCE PLASMA VOLUME, SVR AND BP • REDUCE RBF AND CAN REDUCE GFR • BIOCHEMICAL IMBALANCE THROUGH ACTIONS ON KIDNEY – HYPOKALAEMIC HYPOCHLORAEMIC ALKALOSIS. ALSO HYPONATAREMIA, HYPOMAGNAESAEMIA AND HYPERCALACEMIA • COMPETITIVELY INHIBITS EXCRETION OF URIC ACID – CAN PREDISPOSE TO GOUT • DECREASED GLYCOGENESIS AND INSULIN SECRETION CAN INCREASE BLOOD SUGAR LEVELS ESP. IN DIABETICS • ALSO INCREASE TG AND CHOLESTEROL LEVELS • BLOOD DYSCRASIAS, RASH, PHOTOSENSITIVITY

5. POTASSIUM SPARING DIURETICS • USED IN COMBINATION WITH THIAZIDES TO PREVENT HYPOKALAEMIA • SPIRONOLACTONE – ACTS AS A COMPETITIVE ALDOSTERONE ANTAGONIST • S.E GYNAECOMASTIA, HYPERKALAEMIA AND HYPONATRAEMIA • AMILORIDE – ACTS BY BLOCKING Na/ K EXCHANGE IN DCT – DIURESIS AND REDUCED K EXCRETION

6. ADRENERGIC BLOCKERS • BETA BLOCKERS • ALPHA BLOCKERS • MIXED ALPA AND BETA ANTAGONISTS

7. BETA - BLOCKERS • SHOWN TO IMPROVE PROGNOSIS • HAVE VARYING DEGREES OF CARDIOSELECTIVITY ie BETA 1. ATENOLOL, ESMOLOL AND METOPROLOL MOST CARDIOSELECTIVE • SOME ALSO HAVE INTRINSIC SYMPATHOMIMETIC ACTIVITY ie ARE PARIAL AGONISTS • HAVE CLASS 2 ANTI-ARRHYTHMIC PROPERTIES TOO • CI IN ASTHMA, HEART FAILURE AND PVD

8. EFFECTS OF B- BLOCKERS • NGATIVE INOTROPIC AND CHRONOTROPIC EFFECTS. • BRADYCARDIA LENGTHENS CORONARY PERFUSION TIME AND DECREASED CONTRACTILITY REDUCES OXYGEN DEMAND. WITH POOR LV FUNCTION CAN CAUSE FAILURE • LOWER BP BY LOWERING HR AND CO • ALSO INHIBIT RENIN ANGIOTENSIN SYSTEM

9. OTHER EFFECTS • BETA 2 BLOCKADE LEADS TO BRONCHOCONSTRICTION • NON-SELECTIVE B BLOCKADE OBTUNDS NORMAL BLOOD SUGAR RESPONSE TO EXERCISE • CONVERSELY INCREASES RESTING GUCOSE LEVEL IN DIABETICS • MAY ALSO INCREASE TG AND DECREASE HDL • MORE LIPID SOLUBLE CAUSE CNS EFFECTS - DEPRESSION, FATIGUE , PARANOIA AND HALLUCINATIONS • INCREASE IOP, DRY MOUTH, GI UPSET.

10. OTHER ADRENOCEPTOR ANTAGONISTS • DOXAZOSIN/PRAZOSIN – CAUSES POSTSYNAPTIC ALPHA1 BLOCKADE RESULTING IN VASODILTATION AND REDUCED BP • LABETALOL- ALPHA 1 AND NONSELECTIVE B-BLOCKER CAUSES VASODILATATION AND DROP IN BP WITHOUT REFLEX TACHYCARDIA. USED ORALLY IN PREGNANCY. USED IV IN HYPERTENSIVE CRISES AND TO CONTROL HIGH BP INTRA-OP

11. DRUGS ACTING ON RENIN-ANGIOTENSIN SYSTEM • ACE INHIBITORS – ESP. USEFUL IN HYPERTENSIVE DIABETICS WHERE THEY SLOW DISESASE PROGRESSION AND IN LVF WHERE THEY IMPROVE SURVIVAL • THEY INHIBIT CONVERSION IN LUNG OF ANGIOTENSIN 1 TO ANGIOTENSIN2 BY ANGIOTENSIN CONVERTING ENZYME • ANGIOTENSIN 2 IS A POTENT VASOCONSTRICTOR, IT CAUSES SNS ACTIVATION, IT INCRESASES THIRST AND CAUSES SECRETION OF ADH & ACTH. • ANGIOTENSIN 2 ALSO CAUSES ALDOSTERONE RELEASE AND INHIBITS RELEASE OF RENIN.

12. EFFECTS OF ACE INHIBITORS • REDUCE SVR ASND BP • CAN DECREASE RENAL PERFUSION LEADING TO RENAL FAILURE. CI IN RENOVASCILAR DISESE. • COUGH DUE TO INCREASED LEVELS OF BRADYKININS NORMALLY BROKEN DOWN BY ACE • ANGIOTENSIN 2 ANTAGONISTS EG LOSARAN COMPETITIVELY BLACK AT BINDING SITES – EFECTS SIMILAR TO ACE INHIBITORS BUT WITHOUT THE COUGH

13. CALCIUM CHANNEL BLOCKERS • 3 CLASSES- USEFUL IN HYPERTENSION AND IHD • PHENYALKYLAMINES EG VERAPAMIL • DIHYDROPYRIDINES EG NIFRDIPINE, AMLODIPINE • BENZOTHIAZEPINES EG DITIAZEM • ALL ACT BY BLOCKING L TYPE CA CHANNELS WHICH ARE WIDESPREAD IN CVS. HAVE VARIABLE AFFINITY FOR L-CHANNELS IN MYOCARDIUM, NODAL AND VASCULATURE RESULTING IN VARIABLE EFFECTS • SE- HEADACHE, FLUSHING AND PALPITAIONS

14. Ca CHANNEL BLOCKERS

15. CENTRALLY ACTING ANTIHYPERTENSIVES • METHYLDOPA – CROSSES BBB WHERE IT IS DECARBOXYLATED TO ALPHA- METHYL-NORADRENALINE WHICH IS A POTENT ALPHA2 AND LIMITED ALPHA I AGONIST. • STIMULATION OF PRESYNAPTIC ALPHA 2 RECEPTORS IN CNS CAUSES NEGATIVE FEEDBACK LOOP FOR FURTHER RELEASE OF NORADRENALINE AND DECREASE IN CENTRALLY MEDIATED SYMPATHETIC TONE • USED PARTICULARLY IN HYPETENSION ASSOC. WITH PREGNANCY • ALSO CLONIDINE ( ALSO HAS ANALGESIC EFFECTS AUGMENTING ENDOGENOUS OPIOID RELEASE AND MODULATING SPINAL NOCICEPTIVE PATHWAYS)

16. ADRENERGIC NEURON BLOCKADE • GUANETHIDINE- INTERFERES WITH RELEASE OF NORADRENALINE FROM ADRENERGIC NEURONS LEADING TO HYPOTENSION. • SE – DIARRHOEA AND IMPOTENCE AND FLUID RETENTION • OTHER USE IS IN IV REGIONAL BLOCKS FOR CHRONIC PAIN

17. GANGLION BLOCKADE • THIS GROUP OF DRUGS COMPETITIVELY ANTAGONIZES NICOTINIC RECEPTORS IN AUTONOMIC GANGLIA AND ADRENAL CORTEX. DO NOT BLOCK NICOTINIC RECEPTORS AT NMJ. • TRIMETAPHAN –QUATERNARY AMMONIUM COMPOUND WHICH CAUSES GANGLION BLOCKADE, HAS DIRECT VASODILTATOR EFFECT AND RELEASES HISTAMINE. CAUSES RAPID HYPOTENSION. • SE- ANTICHOLINERGIC EFECTS-DRY MOUTH ETC, HISTAMINE RELEASE CAN CAUSE BRONCHOSPASM • PROLONGS EFFECTS OF DEPOALRIZING AND NON-DEPOLARIZING MUSCLE RELAXANTS

18. MISCELLANEOUS • HYDRALAZINE- EXACT MECHANISM IS UNCLEARBUT IT INVOLVES ACTIVATION OF GUANYLATE CYLCASE AND INCREASED INTRACELLULAR CGMP AND REDUCED INTRACELLULAR CALCIUM - VASODILATATION • SE BLOOD DYSCRASIAS, LUPUS LIKE SYNDOME,FLUID RETENTION, PERIPHERAL NEUROPATHY • USED IN ACUTE HYPERTENSION ASSOC. WITH PRE-ECLAMPSIA