anti hypertensive drugs Flashcards
Hypertension
Blood pressure = pressure in arteries • hypertension = blood pressure above normal level • antihypertensives lower blood pressure
Why treat hypertension?
• Hypertension is very common, • > 50% of elderly • major risk factor for stroke • Major risk factor for ischaemic heart disease – E.g. angina, myocardial infarction • Drug treatment of hypertension – saves lives – prevents unnecessary morbidity
Decision to treat hypertension
sustained systolic BP ≥ 160 mm Hg or sustained diastolic BP ≥ 100 mm Hg. If known CV disease, diabetes or organ damage sustained systolic 140-159 mm Hg and/or diastolic BP 90-99 mm Hg
Pharmacological principles in the
treatment of hypertension
BP = CO x TPR
Reduce cardiac output by reducing: heart rate
stroke volume
plasma volume
Reduce total peripheral resistance by dilating arterioles
The Ideal antihypertensive drug
should:
• reduce blood pressure
• show predictable dose-effect relationship
• have an acceptable profile of side effects
• reduce incidence of hypertensive complications
(e.g. CHD, stroke)
• provide 24 hour control
– BP highest in the morning
• be effective as once daily tablet
– improves compliance
– long half life in plasma
Antihypertensive drugs
diuretics Reduce plasma volume then gradually TPR
vasodilators Directly lower TPR
b-blockers Reduce cardiac output & kidney renin secretion
ACE inhibitors Inhibit endogenous vasoconstrictor production
a-blockers Reduce TPR by inhibiting noradrenaline action
angiotensin antag Reduce TPR by inhibiting angiotensin action
Actions of diuretics
• increase Na+ excretion – reduce salt re-absorption from glomerular filtrate • water loss follows • reduce plasma volume • reduce cardiac output
Thiazides
• moderately potent diuretics
• reduce systolic and diastolic pressure
• widely used antihypertensive, suitable for most
patients
• inhibit Na+
,Cl- co-transport in distal tubule
• additional vasodilator action
– mechanism not known
• potentiate effects of other antihypertensives
• increase renin release
– may counteract effects on blood pressure
Examples of thiazides
• Derived from benzothiadiazine. – chlorothiazide – hydrochlorothiazide – bendrofluazide • Thiazide like structure – chlorthalidone – metolazone.
Adverse effects of thiazides
• more frequent urination
but
• high safety
• low profile of side effects
Loop diuretics
very potent diuretics • no more effective than thiazides at reducing BP • reserved for use in patients with renal insufficiency, resistant hypertension or heart failure
Vasodilator Drugs
A range of drugs with different mechanisms of action – calcium antagonists – alpha1-blockers – angiotensin antagonists – potassium channel activators – sodium nitroprusside – hydralazine
Vasodilator Action
• act directly on the smooth muscle cells of arteries
and arterioles
• lower the intracellular calcium concentration
• cause muscle cell relaxation
• results in vasodilation
Calcium Antagonists
• Block Ca2+ entry through voltage-operated calcium channels in
arterial smooth muscle cells
• Dihydropyridines - highly selective for smooth muscle
but affect most smooth muscle
• nifedipine
• amlodipine - longer acting (once daily dose)
• nicardipine - some selectivity for cerebral &
coronary arteries
• Benzothiazepine - also block calcium channels in conducting
tissue of the heart
• diltiazem slows heart rate
potentiates b-blocker action
Adverse effects of
calcium antagonists
• All – flushing – ankle oedema • diltiazem – cardiac depression – interaction with b-blockers
