Week 7 - Hypertension Treatments Flashcards
Why treat hypertension?
- major risk factor for stroke
- major risk factor for ischaemic heart disease - e.g. angina, MI
When is hypertension treated?
-sustained systolic BP of >160mmHg
OR
-sustained diastolic BP of >100mmHg
If known CV disease, diabetes or organ damage:
-sustained systolic 140-159mmHg
OR
-sustained diastolic BP of 90-99mmHg
What are the types of anti hypertensive drugs?
Diuretics
Vasodilators (calcium antagonists, a1-blockers, angiotensin antagonists)
B-blockers
ACE inhibitors
How is BP calculated?
BP = CO (cardiac output) X TPR (total peripheral resistance)
How can cardiac output be reduced?
- HR
- stroke volume
- plasma volume
How can total peripheral resistance be reduced?
-dilating arterioles
What do diuretics do?
- reduce plasma volume then gradually TPR
- act on the kidney to increase diuresis
What do vasodilators do?
Directly lower TPR
What do B-blockers do?
Reduce cardiac output and kidney renin secretion
What do ACE inhibitors do?
Inhibit endogenous vasoconstrictor production
What do a-blockers do?
Reduce TPR by inhibiting noradrenaline action
What do angiotensin antagonists do?
Reduce TPR by inhibiting angiotensin action
What are the actions of diuretics?
- increase Na+ excretion (reduce salt reabsorption from glomerular filtrate)
- water loss follows
- reduce plasma volume
- reduce cardiac output
What are the types of diuretics?
- thiazide diuretics
- loop diuretics
Describe thiazide diuretics
- 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
- potentiate effects of other antihypertensives
- increase renin release (may counteract effects on BP)
What is the mechanism of action of thiazide diuretics?
Inhibit Na+, Cl- co-transport in distal tubule
Name some examples of thiazide diuretics
Derived from benzothiadiazine:
- chlorothiazide
- hydrochlorothiazide
- bendrofluazide
Thiazide like structure:
- chlorthalidone
- metolazone
What are the side effects of thiazides?
-more frequent urination
but
-high safety
-low profile of side effects
Describe 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
Name the different types of vasodilator drugs
Calcium antagonists (main type)
A1-blockers Angiotensin antagonists (both used but less often)
Potassium channel activators
Sodium nitroprusside
Hydralazine (others used in special circumstances)
What is the action of vasodilators?
- act directly on the smooth muscle cells of arteries and arterioles
- lower the intracellular calcium concentration
- cause muscle cell relaxation
- results in vasodilation
Name some caccium channel antagonists
Dihydropyridines
- amlodipine
- nicardipine
- nifedipine
Benzothiazepine
-diltiazem
-verapamil
What are calcium channel antagonists mechanism of action?
Block Ca2+ entry through voltage-operated calcium channels in arterial smooth muscle cells - vasodilation
Describe how Dihydropyridines act
-highly selective for smooth muscle but affect most smooth muscle
- nifedipine
- amlodipine - longer acting (once daily dose)
- nicardipine - some selectively for cerebral and coronary arteries
Describe how benzothiazepines act
- also block calcium channels in the conducting tissue of the heart
- diltiazem - slows heart rate, potentiate a B-blocker action
What are the side effects of calcium antagonists?
All:
- flushing
- ankle oedema
Diltiazem:
- cardiac depression
- interaction with B-blockers
What is the mechanism of action of a1-blockers?
- drugs used for hypertension are selective blockers of a1-adrenoceptors
- prevent vasoconstrictor action of endogenous noradrenaline
Name some examples of alpha receptor antagonists/a1-blockers
- doxazosin - once daily
- terazosin - once daily
- prazosin - shorter acting, 3X daily
What are the adverse effects of a1-blockers
-postural hypertension (dizziness, light headedness)
-possible severe hypotension after first dose
but
-generally well tolerated
Name some examples of B-blockers
- atenolol
- metoprolol
What is the mechanism of action of B-blockers?
- bind to and block B1-adrenoreceptors in the heart (sino atrial node and ventricular muscle)
- block action of noradrenaline released from sympathetic nerves and circulating adrenaline
What is the initial effect of B-blockers?
- reduce rate and force of heart beat
- decrease cardiac output
What is the effect of bB-blockers after continued treatment?
- CO returns to normal but BP remains low
- TPR reset at lower level
What are the adverse effects of B-blockers?
Common:
- cold hands
- fatigue
Less common but serious:
- can provoke asthma attack in asthmatic
- heart failure
- conduction block in heart
Also:
-may affect blood lipids
Name some examples of ACE inhibitors
Angiotensin-converting enzyme inhibitors
- captopril - 2x daily dose
- enalapril -single daily dose
- lisinopril - lysine analogue of enalapril
- ramipril
What system do ACE inhibitors have an effect on?
Renin angiotensin system
Angiotensinogen–> (renin helps convert to) angiotensin I –> (angiotensin converting enzyme (ACE helps convert to)) angiotensin II –> vasoconstriction
What is the mechanism of action of ACE inhibitors?
-prevent conversion of angiotensin I to angiotensin II (potent vasoconstrictor, stimulates aldosterone secretion - which inhibits salt and H2O excretion)
- causes vasodilation
- reduces plasma volume
What are the adverse effects of ACE inhibitors?
- dry cough
- hypotension initially, especially if given with a diuretic
- these effects usually wear off with time
Name some angiotensin II receptor antagonists
- losartan
- candesartan
- eprosartan
- valsartan
What is the mechanism of action of angiotensin II receptor antagonists?
- block the action of angiotensin II (vasoconstriction) at its receptors
- competes for binding to AT receptors
- so vasodilation
How and when are angiotensin II receptor antagonists used?
- in combination with an ACE inhibitor (improved mortality and morbidity vs. ACE inhibitor alone)
- alternative to ACE inhibitor in intolerant patients
How are antihypertensive drugs chosen for patients?
- Thiazide diuretic
- 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 now:
- less effective at reducing risk of stroke
- more side effects
What is hypertension?
Blood pressure is above normal level
