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
alpha-blockers
drugs used for hypertension are selective blockers of a1 -adrenoceptors • prevent vasoconstrictor action of endogenous noradrenaline • examples – doxazosin: once daily – terazosin: once daily – prazosin: shorter acting, 3x daily
Adverse effects of alpha1-blockers
• postural hypotension – dizziness, light headedness • possible severe hypotension after first dose but • generally well tolerated
beta-blockers
- Atenolol
* metoprolol
beta-blockers
• bind to and block beta1
-adrenoceptors in the heart
– sino atrial node + ventricular muscle
• block action of noradrenaline released from
sympathetic nerves and circulating adrenaline
• initial effect
– reduce rate and force of heart beat
– decrease cardiac output
• after continued treatment
– CO returns to normal but BP remains low
• TPR “reset” at lower level
Adverse effects of beta-blockers
• common side effects – cold hands – fatigue • less common but serious – can provoke asthma attack in asthmatic – heart failure – conduction block in heart • Also – may affect blood lipids
ACE Inhibitors
- captopril – 2x daily dose
- enalapril – single daily dose
- lisinopril – lysine analogue of enalapril
- ramipril –
ACE inhibitor actions
prevent conversion of angiotensin I to angiotensin II – potent vasoconstrictor – stimulates aldosterone secretion • which inhibits salt and H2O excretion • cause vasodilation • reduce plasma volume
Adverse effects of ACE inhibitors
dry cough
• hypotension initially, especially if given
with a diuretic
• these effects usually wear off with time
Angiotensin II receptor antagonists
• losartan • candesartan • eprosartan • valsartan • Block the action of angiotensin II at its receptors – competes for binding to AT receptors
Use of AT II receptor antagonists
in combination with ACE inhibitor
– improved mortality and morbidity vs. ACEI
alone
• alternative to ACE inhibitor in intolerant
patients
Choice of drug
- thiazide
– effective, safe history and few side effects - if thiazide ineffective
– add ACE inhibitor or calcium antagonist - until recently b-blockers were first line
choice, but
– less effective at reducing risk of stroke
– More side effects
