Download PHARMACOTHERAPY OF HYPERTENSION

PHARMACOTHERAPY OF
HYPERTENSION
Dr. R. Jamuna Rani MD,
Professor & HOD,
Department of Pharmacology
INTRODUCTION
Hypertension is a common disorder if not
effectively treated results in coronary
thrombosis, stroke, retinopathy and renal
failure
Blood pressure is intimately related to
kidneys – renovascular hypertension.
Sympathetic over activity, renin
angiotensin, aldosterone system and
endothelium derived autocoids play a
major role in the development of
hypertension
NON PHARMACOLOGICAL LINE
OF TREATMENT
Reduction of body weight.
Sodium restriction 5gms/day.
Potassium therapy.
Physical exercise.
Relaxation exercise (meditation and yoga).
Avoid smoking and alcohol.
AVOID CURRY, HURRY AND WORRY.
HISTORY
Before 1950 veratrum and sodium thiocyanate
were used.
1950 – Ganglion blocker, reserpine and
hydralazine
1960 – 1970 – Guanethidine, Beta blockers,
Alpha blockers, Alpha methyldopa, clonidine and
diuretics
1980 – 1990 – ACE inhibitors and calcium
channel blockers
1992 – Angiotensin1 receptor antagonist
ACE INHIBITORS
Captopril, Enalapril, Lisinopril, Ramipril,
Benazepril, perindopril
Does not affect the quality of life.
First line drug in the treatment of hypertension
Safe in asthma, diabetes mellitus and peripheral
vascular diseases
Renal blood flow is well maintained
Prevent left ventricular remodeling, vascular
hypertrophy and secondary hyperaldosteronism
MECHANISM OF ACTION
Angiotensin I
ACE inhibitors
ACE
Angiotensin
converting
enzyme
Angiotensin II
ADVERSE EFFECTS
Brassy cough, Angiooedema
Hypotension
Hyperkalemia
Acute renal failure
Fetopathic potential
Proteinuria
Loss of taste (dysgeusia)
Neutropenia – Common in collagen
vascular disease or renal parenchymal
disease
DRUG INTERACTIONS
Antacids reduce the bioavailability of ACE
inhibitors
NSAIDs reduce anti hypertensive effect of
ACE inhibitors
K+ sparing diuretics and K+ supplement
exacerbate ACE inhibitor induced
hyperkalemia
(Contd…)
ACE inhibitors increase plasma levels of
digoxin and lithium (dosage adjustment is
necessary)
Increase hypersensitivity reactions to
allopurinol.
Contraindications: Bilateral renal artery
stenosis and pregnancy
USES
Hypertension
Left ventricular dysfunction
Acute myocardial infarction
Patient who are at high risk of
cardiovascular events
Chronic renal failure
Scleroderma renal crisis
ANGIOTENSIN ANTAGONIST
Losartan potassium, Irbesartan, candesartan,
valsartan
Angiotensin II receptor antagonist; losartan block
the AT1 receptors competitively and the
metabolite E3174 irreversibly inhibits AT1
receptor
Brassy cough is less common
Adverse effects, contraindications and drug
interaction are similar to ACE inhibitors
USES
All angiotensin II receptor antagonist are
approved for the treatment of hypertension
Irbesartan and losartan are approved for
diabetic retinopathy
Valsartan is approved for heart failure
Losartan is approved for stroke
prophylaxis and cirrhosis with portal
hypertension
CALCIUM CHANNEL
BLOCKERS
Nifedipine, amlodipine, felodipine
They block voltage sensitive L – type
calcium channels
Side effects: Headache, hypotension,
reflex tachycardia and ankle oedema
Uses: Idiopathic systolic hypertension ,
cyclosporine induced hypertension, and in
pregnancy – discontinue before labour.
BETA BLOCKERS
Propranolol, timolol, atenolol, acebutalol and
metaprolol
First line drug in hypertension
Less effective in elderly patients
Side effects: Bradycardia, cause rebound
hypertension on sudden withdrawal
Fatigue sleep disturbances and depression
Propranolol mask the hypoglycemic symptoms
produced by insulin and oral hypoglycemic
agents
C/I: Bronchial Asthma
ALPHA BLOCKERS
Phentolamine, phenoxybenzamine,
prazosin, terazosin and doxazosin
Side effects: Hypotension, tachycardia,
nasal stuffiness, diarrhoea, miosis and
impotence
Uses: Hypertension with benign
enlargement of prostate
Pheochromocytoma
ALPHA & BETA BLOCKERS
Labetalol
Carvedilol – also has antioxidant action
Uses: hypertensive emergency, idiopathic
dilated cardiomyopathy
ALPHA METHYL DOPA
Drug of choice for hypertension in pregnancy
Activate alpha2 receptors (presynaptic) and
decrease norephinephrine release
Side effects: Sedation, hypotension,
hypersensitivity, nasal stuffiness, weight gain
Produce positive coomb’s test
Tricyclic antidepressants reverse its effect
Dose: 250mg – 500mg b.d
CLONIDINE
Alpha2 agonist used in moderate
hypertension.
Sudden withdrawal cause rebound
hypertension
CPZ and TCA abolish antihypertensive
action of clonidine
Dose: 100mcg b.d
THIAZIDES
Chlorthalidone, hydrochlorothiazide
Used in mild hypertension and effective in
elderly patients
It potentiate the action of all
antihypertensive drugs except calcium
channel blockers
Side effects: Hypokalemia, hyponatremia,
hypomagnesemia, hyperglycemia,
hypercalcemia and hyperuricemia
VASODILATORS
Hydralazine – useful in pregnancy
Minoxidil – Alopecia (male type baldness)
Diazoxide – In operable insulinomas
Sodium nitropruside
Balanced vasodilator, produce vasodilatation by
activating glutathione and release NO used in
hypertensive emergency produce controlled
hypotension if it is administered continuously release
cyanide and latter converted to thiocyanate and cause
psychosis. Also cause palpitation, lactic acidosis,
vomiting & pain abdomen.
NEW DRUGS
Ambrisentan and Bosentan – endothelin
receptor antagonist used in pulmonary
hypertension
Fenoldopam – (I.V infusion) selective D1
receptor agonist for short term
management of severe hypertension
Moxonidine – Alpha2 agonist produce less
sedation
Aliskiren – Renin inhibitors