L10 - Hypertension II

Question 1

Why are Ca channel blockers different to Ca antagonists?

Answer 1

Ca channel blocker drugs

• Affect the channels through which Ca travels
• They are directly acting vasodilators – unlike things that target angiotensin II

Question 2

What are the main clinical indications of Ca channel blockers?

Answer 2

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

Question 3

What are the examples of Ca channel blockers?

Answer 3

Amlodipine 
Nifedipine 
Lacidipine 
Felodipine 
Diltiazem 
Verapamil

Question 4

What are amlodipine, nifedipine, lacidipine and felodipine used to treat?

Answer 4

Hypertension

Amlodipine – relatively long - Needed as hypertension is normally asymptomatic
Nifedipine – short acting – have formulated so it is only slowly released

Question 5

What are diltiazem and verapamil used to treat?

Answer 5

Ischaemic heart disease

Arrhythmia

Question 6

What are the 3 groups of L-type Ca channel blockers?

Answer 6

Dihydropyridines: nifedipine, amlodipine, felodipine, lacidipine
Phenylalkylamines: verapamil
Benzothiazepines: diltiazem

Question 7

What do dihydropyridines do?

Answer 7

Preferentially affect VSMCs – where the issue with peripheral resistance is
Peripheral arterial vasodilators

Question 8

What do phenylalkylamines do?

Answer 8

Main effects on the heart

Negatively chronotropic, negatively inotropic – reduces heart rate and force of contraction

Question 9

What do benzothiazepines do?

Answer 9

Intermediate heart/peripheral vascular effects

Question 10

What adverse effects do Ca channel blockers have due to peripheral vasodilation?

Answer 10

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

Question 11

What adverse effects do Ca channel blockers have due to negatively chronotropic effects?

Answer 11

Bradycardia
Atrioventricular block
Mainly verapamil/diltiazem

Question 12

What adverse effects do Ca channel blockers have due to negatively inotropic effects ?

Answer 12

Worsening of cardiac failure
- Failing heart relies on Ca to cause contraction
Mainly verapamil
Amlodipine – is safe to use for hypertension and heart failure

Question 13

What adverse effect does verapamil cause?

Answer 13

Constipation

Question 14

What receptor does noradrenaline act through?

Answer 14

Vasodilator that acts through alpha-1 receptors

Question 15

What are 4 examples of alpha-1 adrenoceptor blockers?

Answer 15

Doxazosin
Indoramin
Terazosin
Prazosin

Question 16

What are the adverse effects of alpha-1 adrenoceptor blockers?

Answer 16

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

Question 17

What are 3 examples of centrally acting drugs?

Answer 17

Moxonidine
Methyldopa
Clonidine

Question 18

What does moxonidine do?

Answer 18

Imidazoline type 1 receptor agonist

Cause reduction in sympathetic outflow from CNS –> lower BP

Question 19

What does methyldopa do?

Answer 19

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

Question 20

What does clonidine do?

Answer 20

Activates pre-synaptic alpha 2 receptors to decrease noradrenaline release
- More specific than methyldopa
Tends to lower BP too much

Question 21

What is an example of a direct renin inhibitor?

Answer 21

Aliskiren - blocks renin from converting angiotensinogen to angiotensin I

Question 22

What are the adverse effects of direct renin inhibitors?

Answer 22

Hyperkalaemia
Dizziness
Arthralgia
Diarrhoea
Caution with other renin-angiotensin-aldosterone system inhibitors
Concomitant use not recommended

Question 23

Why do direct renin inhibitors cause hyperkalaemia?

Answer 23

Drugs reduce amount of aldosterone produced

Aldosterone controls K excretion

Question 24

Why do you have to be careful not to use direct renin inhibitors with other renin-angiotensin-aldosterone system inhibitors?

Answer 24

Adverse effects outweigh benefits
The one combination that works is
- Heart failure – ACE inhibitor and aldosterone antagonist

Question 25

What are the 5 treatment steps for hypertension - NICE guidance

Answer 25

1. Determine age and race 2. Over 55 or Afro-Caribbean - use either Ca chan Under 55 - use ACE inhibitor or ARB 3. If step 2 doesn't work - combine ACE inhibitor/ARB with Ca channel blocer 4. If step 3 doesn't work combine with thiazide like diuretic 5. If step 4 doesn't work - spironolactone, higher thiazide like diuretic dose, alpha blocker or beta blocker

Question 26

Why do you use different treatments depending on age or race?

Answer 26

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

Question 27

What % of patient need 2 drugs to control hypertension properly?

Answer 27

40-50%

Question 28

Why is it sometimes better two give two different drugs as treatment?

Answer 28

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

Question 29

What do you do if a patient has resistant hypertension?

Answer 29

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