ANTIHYPERTENSIVES

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ANTIHYPERTENSIVES

1. DIURETICS
2. ADRENERGIC ANTAGONISTS
3. DRUGS AFFECTING RENIN-ANGIOTENSIN-ALDOSTERONE
   SYSTEM
4. CALCIUM CHANNEL ANTAGONISTS
5. CENTRALLY ACTING
6. GANGLION BLOCKADE
7. ADRENERGIC NEURON BLOCKADE

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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

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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

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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

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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

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ADRENERGIC BLOCKERS

• BETA BLOCKERS
• ALPHA BLOCKERS
• MIXED ALPA AND BETA ANTAGONISTS

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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

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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

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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.

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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

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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.

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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

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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

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Ca CHANNEL BLOCKERS
BP HR Av node Conduction time Myocardial contractility Vaso- dilatation
VERAPAMIL reduced reduced Incresed reduced
NIFEDIPINE reduced same same same
DILTIAZEM reduced reduced Increased reduced
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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)

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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

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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

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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