Antihypertensive drugs 1 - vasodilators RAS, B-blockers

Question 1

hydralazine is a vasodilator anti-hypertensive drug that is rarely used. list the two side effect this drug causes when used as monotherapy

Answer 1

1) Tachycardia

2) Fluid retention

Question 2

1) minoxidil is a vasodilator reserved for the treatment of severe hypertension resistant to other drugs. what are the side effects of this drug? (3)
2) how can these side effects be reduced?
3) why is this drug not suitable for females?

Answer 2

1) Increased cardiac output, tachycardia, fluid retention
2) Addition of a B-blocker and diuretic (furosemide)
3) Hypertrichosis- abnormal hair growth

Question 3

list 3 centrally acting antihypertensive drugs

Answer 3

1) Methyldopa
2) Clonidine HCL
3) Moxonidine

Question 4

what can sudden withdrawal of clonidine HCL cause?

Answer 4

Severe rebound hypertension

Question 5

1) how do adrenergic neurone blocking drugs work?

2) why are these drugs seldom used nowadays?

Answer 5

1) Prevent the release of noradrenaline from post ganglionic adrenergic neurones . (Noradrenaline increases heart rate, BP ect)
2) May cause postural hypotension

Question 6

list 3 alpha-adrenoceptor blocking drugs

Answer 6

1) Prazosin (rarely causes tachycardia)
2) Doxazosin
3) Terazosin

Question 7

1) what should be checked before starting ACE inhibitors?

2) what should be monitored in those taking ACEi?

Answer 7

1) Renal function and electrolytes (also when increasing dose)
2) Monitor for hyperkalaemia : potassium-sparing diuretics and supplements should be stopped before (but low dose spironolactone may be beneficial in heart failure)

Question 8

what can taking ACEi and NSAIDs increase the risk of ?

Answer 8

Renal damage

Question 9

1) what effect can taking ACEi in volume depleted patients cause?
2) how can this be prevented?
3) how would ACEi be administered to patients taking diuretics to prevent rapid falls in BP?

Answer 9

1) Very rapid fall in BP
2) Initiate treatment with low dose
3) Diuretic dose may need to be reduced or diuretic discontinued at least 24h beforehand

Question 10

why do ARB’s not cause a dry cough?

Answer 10

They do not inhibit the breakdown of bradykinin and other kinins unlike ACEi. ( useful in patients who have to discontinue ACEi due to dry cough)

Question 11

1) why is concomitant use of drugs affecting the rennin-angiotensin system not recommended?
2) which patients are most at risk of these SE?

Answer 11

1) Use of ACEi + ARB not recommended due to risk of hyperkalaemia, hypotension and renal impairment
2) Patients with diabetic nephropathy as they are at higher risk of developing hyperkalaemia

Question 12

1) how can the side effects of methyldopa be reduced?

2) what are the monitoring requirements for this drug?

Answer 12

1) Keep daily dose below 1g

2) Monitor blood counts and liver function before and at intervals during first 6-12w or if unexplained fever occurs

Question 13

With regards to B-Blockers, what does intrinsic sympathomimetic activity measure?
what are the benefits of using B-Blockers with intrinsic sympathomimetic activity?

Answer 13

1) Capacity of beta blockers to stimulate as well as to block adrenergic receptors
2) cause less bradycardia and may also cause less coldness of extremities (e.g. oxprenolol, pindolol)

Question 14

1) list the 4 most water soluble B-blockers

2) water soluble B-blockers are less likely to enter the brain, what is the benefit of this?

Answer 14

1) Atenolol, nadolol, sotalol and celiprolol
2) Less likely to cause sleep disturbance and nightmares
(→ water soluble B-Blockers also are present in breast milk in greater amounts than other B-Blockers)

Question 15

1) how should water soluble B-blockers be dosed in renal impairment?
2) how should B-blockers be dosed in hepatic impairment?

Answer 15

1) Dose reduction is often necessary, as they are excreted by the kidneys
2) Generally require dose reduction in significant hepatic failure

Question 16

why should B-blockers be avoided in patients with a history of asthma

Answer 16

Can precipitate Bronchospasm. This is mediated through bockade of β2-adrenoreceptor in the airways
→ B-blockers are usually safe in COPD

Question 17

If there is no alternative and asthma is well controlled, a cardioselective B-blocker can be used at a low dose in patients with respiratory disease. List the cardioselective B-blockers (4)

Answer 17

The following have less of an effect on B₂ receptors: 
1) Atenolol 
2) Bisoprolol 
3) metoprolol 
4) nevibolol 
→ (Acebutolol lesser extent)

Question 18

list the main side effects associated with B-blockers (6)

Answer 18

1) Fatigue
2) Coldness of extremities
3) Sleep disturbance with nightmares (less in water soluble)
4) Headache
5) GI disturbance (nausea)
6) Impotence in men

Question 19

Discuss the use of B-blockers in diabetes and why they might not be suitable.

Answer 19

1) Can affect carbohydrate metabolism causing hypo/hyperglycemia
2) Can also mask symptoms e.g. tachycardia
3) Not C/I in diabetes but cardioselective preferred although avoid completely in those with frequent hypo episodes
4) B-blockers + thiazides should be avoided in diabetics or those at risk of diabetes

Question 20

B-blockers are effective for reducing BP but they are not the preferred drug for routine initial treatment of uncomplicated hypertension. Explain why

Answer 20

Other anti-hypertensives are usually more effective for reducing incidence of stroke, MI and cardiovascular mortality, especially in elderly

Question 21

1) outline the MOA of B-Blockers in improving prognosis in heart failure
2) outline the MOA of B-Blockers in AF
3) outline the MOA of B-Blockers in hypertension

Answer 21

1) Via β1 receptor, B-Blockers reduce the force of contraction and speed of conduction in the heart. This relieves myocardial ischemia by reducing cardiac work and oxygen demand and increasing myocardial profusion
2) Slow ventricular rate in AF by prolonging the refractory period of the AV node
3) In hypertension through a variety of means, one way involves reducing renin secretion from the kidneys, since this is mediated by β1 receptors

Question 22

list 2 non-selective B-blockers

Answer 22

1) Propranolol

2) Carvedilol

Question 23

how should B-blockers be initiated in patients with heart failure?

Answer 23

Start at very low dose and increase slowly as they may impair cardiac function

Question 24

which patients should B-Blockers be completely avoided in?

Answer 24

Those with haemodynamic instability

→ also contraindicated in heart block

Question 25

what are the important interactions to be aware of with regards to B-blockers?

Answer 25

Do not use with non-dihydropyridine CCB’s (verapamil, diltiazem) unless directed by specialist. This combination may cause heart failure, bradycardia or even asystole

Question 26

why should abrupt withdrawal of B-blockers be avoided?

Answer 26

Abrupt withdrawal especially in those with ischemic heart disease can cause a rebound worsening of myocardial ischaemia

Question 27

what should dosage adjustments in those receiving treatment with B-blockers be based on?

Answer 27

Best guide to dosage adjustment is patients symptoms and heart rate. In ischemic heart disease aim for heart rate of around 55-60 BPM

Question 28

Excessive bradycardia can occur when B-Blockers are administered by intravenous injection. Explain how this can be countered

Answer 28

With intravenous injection of atropine sulfate

Question 29

list the side effects that therapeutic overdoses of B-blockers cause

Answer 29

1) Lightheadedness
2) Dizziness
3) Syncope due to bradycardia and hypotension

Question 30

what is the maximum dose of Bisoprolol in hepatic impairment?

Answer 30

Max 10mg OD in severe hepatic impairment (normal max dose 20mg OD)