7 Drugs used to treat hypertension Flashcards
Drugs used to treat hypertension
Diuretics Vasodilators
[calcium antagonists a1-blockers, angiotensin antagonists]
b-blockers ACE inhibitors
Hypertension
Blood pressure • hypertension
= pressure in arteries
= 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
Why treat hypertension?
Drug treatment of hypertension
– saves lives
– prevents unnecessary morbidity
Benefits of drug treatment
cases prevented after 5 years treatment (%) Stroke Mortality 40 Morbidity 35 Combined 37
Coronary Heart Disease (CHD)
Mortality 26
Morbidity 15
Combined 20
CV events
Mortality 30
Decision to treat hypertension
ustained 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
Diuretics
Act on the kidney to increase diuresis
Actions of diuretics
increase Na+ excretion
– reduce salt re-absorption from glomerular filtrate
• water loss follows
• reduce plasma volume • reduce cardiac output
Nephron
the functional unit of the kidney
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 main type for essential hypertension
– a1-blockers
– angiotensin antagonists
– potassium channel activators – sodium nitroprusside
– hydralazine
Vasodilator Action
actdirectlyonthesmoothmusclecellsofarteries and arterioles
• lowertheintracellularcalciumconcentration
• causemusclecellrelaxation
• resultsinvasodilation
Calcium Antagonists
Block Ca2+ entry through voltage-operated calcium channels in arterial smooth muscle cells
• Dihydropyridines -
• nifedipine
• amlodipine - • nicardipine -
• Benzothiazepine - • diltiazem
highly selective for smooth muscle but affect most smooth muscle
longer acting (once daily dose) some selectivity for cerebral & coronary arteries
also block calcium channels in conducting tissue of the heart
slows heart rate
potentiates b-blocker action
Adverse effects of calcium antagonists
All – flushing – ankle oedema • diltiazem – cardiac depression – interaction with b-blockers
a-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 a1-blockers
postural hypotension
– dizziness, light headedness
possible severe hypotension after first dose but
generally well tolerated
b-blockers
Atenolol
metoprolol
b-blockers
bind to and block b1-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 b-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
aptopril – 2x daily dose
• enalapril – single daily dose
• lisinopril – lysine analogue of enalapril
• ramipril –
Renin angiotensin system
aldosterone
angiotensinogen
renin
Angiotensin I Angiotensin II
ACE inhibitor
vasoconstriction

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
osartan • candesartan • eprosartan • valsartan • Block the action of angiotensin II at its receptors – competes for binding to AT receptors
Use of AT II receptor antagonists
n combination with ACE inhibitor
– improved mortality and morbidity vs. ACEI alone
• alternative to ACE inhibitor in intolerant patients
Choice of drug:
as suggested by pharmacology
1. thiazide
– effective, safe history and few side effects
2. if thiazide ineffective
– add ACE inhibitor or calcium antagonist
3. until recently b-blockers were first line choice, but
– less effective at reducing risk of stroke
– More side effects
Summary
Many different groups of antihypertensive drug with different mechanisms of action
• Cause of hypertension directs choice
• Preferred drugs for essential hypertension – ACE inhibitors, calcium antagonists, thiazides
• Other drugs used in special circumstances
– e.g. b-blocker for catecholamine-secreting tumour
Choice of drug: NICE guidelines
