L10 - Hypertension II Flashcards
Why are Ca channel blockers different to Ca antagonists?
Ca channel blocker drugs
- Affect the channels through which Ca travels
- They are directly acting vasodilators – unlike things that target angiotensin II
What are the main clinical indications of Ca channel blockers?
Hypertension
Ischaemic heart disease – angina
Some of them have rate limiting properties - Diltiazem and erapamil
- Angina occurs when heart rate is increased and oxygen demand on the heart is increased
Tachycardia
What are the examples of Ca channel blockers?
Amlodipine Nifedipine Lacidipine Felodipine Diltiazem Verapamil
What are amlodipine, nifedipine, lacidipine and felodipine used to treat?
Hypertension
Amlodipine – relatively long - Needed as hypertension is normally asymptomatic
Nifedipine – short acting – have formulated so it is only slowly released
What are diltiazem and verapamil used to treat?
Ischaemic heart disease
Arrhythmia
What are the 3 groups of L-type Ca channel blockers?
Dihydropyridines: nifedipine, amlodipine, felodipine, lacidipine
Phenylalkylamines: verapamil
Benzothiazepines: diltiazem
What do dihydropyridines do?
Preferentially affect VSMCs – where the issue with peripheral resistance is
Peripheral arterial vasodilators
What do phenylalkylamines do?
Main effects on the heart
Negatively chronotropic, negatively inotropic – reduces heart rate and force of contraction
What do benzothiazepines do?
Intermediate heart/peripheral vascular effects
What adverse effects do Ca channel blockers have due to peripheral vasodilation?
Flushing
Headache
Ankle oedema – opened up peripheral vessels to allow more leaching of fluid from circulation – then gravity acts
Palpitations – body thinks the BP is trying to fall so compensated by increasing heart rate
- It is called inappropriate reflex tachycardia
These effects are more common in women
What adverse effects do Ca channel blockers have due to negatively chronotropic effects?
Bradycardia
Atrioventricular block
Mainly verapamil/diltiazem
What adverse effects do Ca channel blockers have due to negatively inotropic effects ?
Worsening of cardiac failure
- Failing heart relies on Ca to cause contraction
Mainly verapamil
Amlodipine – is safe to use for hypertension and heart failure
What adverse effect does verapamil cause?
Constipation
What receptor does noradrenaline act through?
Vasodilator that acts through alpha-1 receptors
What are 4 examples of alpha-1 adrenoceptor blockers?
Doxazosin
Indoramin
Terazosin
Prazosin
What are the adverse effects of alpha-1 adrenoceptor blockers?
Postural hypotension - if patients stand up they may feel faint
Also used in benign prostatic hypertrophy – more likely to be on them for this reason
- Will always impact prostate and BP –> side effects
What are 3 examples of centrally acting drugs?
Moxonidine
Methyldopa
Clonidine
What does moxonidine do?
Imidazoline type 1 receptor agonist
Cause reduction in sympathetic outflow from CNS –> lower BP
What does methyldopa do?
Activates pre-synaptic alpha 2 receptors to decrease noradrenaline release
Competitive inhibitor of DOPA decarboxylase
- Converts DOPA to dopamine
- Tyrosine –> DOPA –> dopamine –> noradrenaline –> adrenaline
Can be used in pregnancy
What does clonidine do?
Activates pre-synaptic alpha 2 receptors to decrease noradrenaline release
- More specific than methyldopa
Tends to lower BP too much
What is an example of a direct renin inhibitor?
Aliskiren - blocks renin from converting angiotensinogen to angiotensin I
What are the adverse effects of direct renin inhibitors?
Hyperkalaemia Dizziness Arthralgia Diarrhoea Caution with other renin-angiotensin-aldosterone system inhibitors Concomitant use not recommended
Why do direct renin inhibitors cause hyperkalaemia?
Drugs reduce amount of aldosterone produced
Aldosterone controls K excretion
Why do you have to be careful not to use direct renin inhibitors with other renin-angiotensin-aldosterone system inhibitors?
Adverse effects outweigh benefits
The one combination that works is
- Heart failure – ACE inhibitor and aldosterone antagonist
What are the 5 treatment steps for hypertension - NICE guidance
- Determine age and race
- Over 55 or Afro-Caribbean - use either Ca chan
Under 55 - use ACE inhibitor or ARB - If step 2 doesn’t work - combine ACE inhibitor/ARB with Ca channel blocer
- If step 3 doesn’t work combine with thiazide like diuretic
- If step 4 doesn’t work - spironolactone, higher thiazide like diuretic dose, alpha blocker or beta blocker
Why do you use different treatments depending on age or race?
Differences due to renin
- Some patients have low renin hypertension – old and Afro-Caribbean
- Some patients have normal/high renin hypertension – young
If we block renin-angiotensin-aldosterone
- More likely to work in people whose hypertension is being driven by renin – younger people
What % of patient need 2 drugs to control hypertension properly?
40-50%
Why is it sometimes better two give two different drugs as treatment?
Safer to give two drugs at lower doses, that work in different ways synergistically than high doses of one drug
If you give a calcium channel blocker – the effects of these drugs to either reduce Na and water or vasodilate can activate the renin-angiotensin system and sympathetic nervous system
- Can then give a second drug to block this activated response
What do you do if a patient has resistant hypertension?
Try other drugs
- If patient asthmatic – can’t use beta-blocker
- If patient old – maybe avoid alpha blocker
Have to consider secondary causes - underlying cause driving high BP
- E.g. adrenal steroid secreting tumour
- Then have to treat this at the source
If still not working – maybe patient is not taking the medication
