7 Drugs used to treat hypertension

Question 1

Drugs used to treat hypertension

Answer 1

Diuretics Vasodilators
[calcium antagonists a1-blockers, angiotensin antagonists]
b-blockers ACE inhibitors

Question 2

Hypertension

Answer 2

Blood pressure • hypertension
= pressure in arteries
= blood pressure above normal level
• antihypertensives lower blood pressure

Question 3

Why treat hypertension?

Answer 3

Hypertension is very common, • > 50% of elderly
• major risk factor for stroke
• Major risk factor for ischaemic heart disease
– E.g. angina, myocardial infarction

Question 4

Why treat hypertension?

Answer 4

Drug treatment of hypertension
– saves lives
– prevents unnecessary morbidity

Question 5

Benefits of drug treatment

Answer 5

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

Question 6

Decision to treat hypertension

Answer 6

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

Question 7

Pharmacological principles in the treatment of hypertension

Answer 7

BP = CO x TPR
Reduce cardiac output by reducing: heart rate stroke volume
plasma volume Reduce total peripheral resistance by dilating arterioles

Question 8

The Ideal antihypertensive drug

Answer 8

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

Question 9

Antihypertensive drugs

Answer 9

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

Question 10

Diuretics

Answer 10

Act on the kidney to increase diuresis

Question 11

Actions of diuretics

Answer 11

increase Na+ excretion
– reduce salt re-absorption from glomerular filtrate
• water loss follows
• reduce plasma volume • reduce cardiac output

Question 12

Nephron

Answer 12

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

Question 13

Thiazides

Answer 13

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

Question 14

Examples of thiazides

Answer 14

Derived from benzothiadiazine. – chlorothiazide
– hydrochlorothiazide
– bendrofluazide
• Thiazide like structure – chlorthalidone
– metolazone.

Question 15

Adverse effects of thiazides

Answer 15

more frequent urination but
• high safety
• low profile of side effects

Question 16

Loop diuretics

Answer 16

very potent diuretics
• no more effective than thiazides at reducing BP
• reserved for use in patients with renal insufficiency, resistant hypertension or heart failure

Question 17

Vasodilator Drugs

Answer 17

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

Question 18

Vasodilator Action

Answer 18

actdirectlyonthesmoothmusclecellsofarteries and arterioles
• lowertheintracellularcalciumconcentration
• causemusclecellrelaxation
• resultsinvasodilation

Question 19

Calcium Antagonists

Answer 19

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

Question 20

Adverse effects of calcium antagonists

Answer 20

All
– flushing
– ankle oedema
• diltiazem
– cardiac depression
– interaction with b-blockers

Question 21

a-blockers

Answer 21

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

Question 22

Adverse effects of a1-blockers

Answer 22

postural hypotension
– dizziness, light headedness
possible severe hypotension after first dose but
generally well tolerated

Question 23

b-blockers

Answer 23

Atenolol

metoprolol

Question 24

b-blockers

Answer 24

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

Question 25

Adverse effects of b-blockers

Answer 25

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

Question 26

ACE Inhibitors

Answer 26

aptopril – 2x daily dose
• enalapril – single daily dose
• lisinopril – lysine analogue of enalapril
• ramipril –

Question 27

Renin angiotensin system

Answer 27

aldosterone
angiotensinogen
renin

Angiotensin I Angiotensin II
ACE inhibitor
vasoconstriction


Question 28

ACE inhibitor actions

Answer 28

prevent conversion of angiotensin I to angiotensin II
– potent vasoconstrictor
– stimulates aldosterone secretion
• which inhibits salt and H2O excretion
• cause vasodilation
• reduce plasma volume

Question 29

Adverse effects of ACE inhibitors

Answer 29

dry cough
• hypotension initially, especially if given with a diuretic
• these effects usually wear off with time

Question 30

Angiotensin II receptor antagonists

Answer 30

osartan
• candesartan
• eprosartan
• valsartan
• Block the action of angiotensin II at its receptors
– competes for binding to AT receptors

Question 31

Use of AT II receptor antagonists

Answer 31

n combination with ACE inhibitor
– improved mortality and morbidity vs. ACEI alone
• alternative to ACE inhibitor in intolerant patients

Question 32

Choice of drug:

Answer 32

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

Question 33

Summary

Answer 33

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