?THE SILENT KILLER

ANTI-HYPERTENSIVES - I

DR PADMAVATHI S

ASSOCIATE PROFESSOR, MGMCRI

JNC - 8

CLASSIFICATION

A CE inhibitors & Angiotensin Receptor Blockers A drenergic Blockers Beta blockers, alpla blockers , β + α blockers C alcium channel blockers – NIFEDIPINE C entral sympatholytics D iuretics – thiazide diuretics

high ceiling diureticsK+ sparing diuretics

D irect renin inhibitors – ALISKIREN V asodilators

CALCIUM CHANNEL BLOCKERS - MECHANISM • Blocks L – type calcium channels• Smooth muscle relaxation

markedly relax arterioles more than veins• Negative effects

-ve chronotropic-ve inotropic-ve dromotropic

CCBS - ADVANTAGES • Onset of action is quick• No impairment of physical work capacity• No sedation or other CNS effects• NOT contraindicated – asthma, angina, PVD patients• Do not impair renal perfusion• Do not affect male sexual function• No deleterious effect on lipid, uric acid level & electrolyte

imbalance

CCB - DISADVANTAGES

• Verapamil & diltiazem – negative inotropic & dromotropic effect

worsen CHF & conduction defects

• Worsen GE reflux

• Accentuate bladder voiding difficulty

CCBS

•Elderly with HT – prevent stroke & HT /diabetic nephropathy

•USED IN PREGNANCY•Cyclosporine induced HT - In renal transplant

recipients

DIURETICS

•ThiazidesHydrochlorothiazideChlorthalidoneIndapamide

MECHANISM AS ANTIHYPERTENSIVE

• Initial diuresis – reduce plasma & ECF volume• Compensatory mechanisms – CO restored• Slow reduction in t.p.r – maintain fall in BP• Due to indirect effect persisting Na+ & volume deficit• Develops gradually 2-4 weeks• No effect on capacitance vessels & sympathetic system• Potentiate all anti-hypertensives EXCEPT DHPs

ADVANTAGES OF THIAZIDES

• Once a day dosing• No fluid retention / tolerance• No postural hypotension• Effective in isolated systolic HT• Lessened risk of hip fracture• Low cost

CURRENT STATUS OF THIAZIDES

• 1st choice – elderly with essential hypertension • Combination with K+ sparing diuretics• LOW DOSE thiazide

risk of hypokalemia is lessless prone to arrhythmiano significant effect on glucose/ lipid & uricacid

levelsreduce % of fatal MI & stroke

HIGH CEILING DIURETICS – FUROSEMIDE / FRUSEMIDE

• Weaker antihypertensive than thiazides• Due to short duration of action• Adverse effects – electrolyte imbalance, weakness etc.,• Indication - chronic renal failure

- coexisting refractory CHF- resistance to combination regimens containing

a thiazide or marked fluid retention due to use of vasodilators

ANGIOTENSIN CONVERTING ENZYME INHIBITORS

• 1st choice – for all grades of essential & reno-vascular HT• Low dose & well tolerated• SUPRA- ADDITIVE synergism with diuretics• More suitable

DIABETES, NEPHROPATHY, LV HYPERTROPHY, CHF, ANGINA, POST MI• Major drawback - dry persistent cough

ANGIOTENSIN RECEPTOR BLOCKERS

• NO – dry cough angioedema urticaria taste disturbances

• Equally effective as ACE inhibitors• Replacement – for patients not tolerating ACE inhibitors

CENTRAL SYMPATHOLYTICS

•Clonidine•Methyldopa

CLONIDINE - MECHANISM

• Partial agonist alpha 2 receptors ( α 2A )• Decrease sympathetic outflow, plasma NA declines• Fall in BP & bradycardia• Also ACTIVATES IMIDAZOLINE receptors • Therapeutic window phenomenon

ADVERSE EFFECTS - CLONIDINE

• Sedation, mental depression, sleep disturbances, constipation• Impotence• Salt & water retention, bradycardia• Postural hypotension

• hypertension – withdrawal or missed doses

Sudden removal of central sympathetic inhibition supersensitivity of Adr recptors

OTHER USES OF CLONIDINE

• Opioid withdrawal• Alcohol withdrawal & smoking cessation• Analgesic effect – substitute morphine• Attenuates vasomotor symptoms of menopausal

syndrome• Control diarrhea due to diabetic neuropathy

METHYLDOPA

• Precursor of dopamine & NA Converted to α methyl NA• Acts on central alpha 2 Receptors Reduce sympathetic outflow• AE similar to clonidine• Positive Coombs test• Rebound hypertension less • Hypertension during pregnancy