Antihypertensives

Question 1

1. Which of the following statements regarding antihypertensives and their site of action is INCORRECT?

• a. Vasomotor centre – methyldopa
• b. Beta receptors of the heart – propranolol
• c. Alpha receptors of vessels – hydralazine.
• d. Vascular smooth muscle – nitroprusside
• e. Angiotensin receptors of vessels – losartan

Answer 1

c. Alpha receptors of vessels – hydralazine.

Direct smooth muscle relaxation

Question 2

2. Hydralazine

• a. Dilates veins but not arterioles.
• b. Has low first pass metabolism.
• c. Works best as single therapy for hypertension.
• d. In patients with ischaemic heart disease, may provoke angina or ischaemic arrhythmias.
• e. Has a half life of 10-12 hours.

Answer 2

d. In patients with ischaemic heart disease, may provoke angina or ischaemic arrhythmias.

Due to reflex tachycardia and increased contractility

• a. Dilates arterioles but not veins
• b. Has high first pass metabolism - bioavailablilty of 25%
• c. Works best as part of multi-drug therapy for hypertension.
  
  • Tachyphylaxis develops rapidly to single-agent therapy
• e. Has a half life of 2 hours.

Question 3

3. hydralazine

• a. classically has a biphasic response to BP control.
• b. should not be used in eclampsia
• c. causes significant postural hypotension.
• d. predominantly a vasodilator

Answer 3

d. predominantly a vasodilator

Has a bimodal distribution of effect in population as some people are rapid-metabolisers

Does not affect venous tone, thus does not significantly cause postural hypotension

Question 4

4. diazoxide.

• a. can be used in a hypertensive emergency
• b. structurally related to thiazide

Answer 4

Both of them are true

Question 5

5. ACE inhibitors

• a. Can be used in second and third trimesters.
• b. Have been associated with angioedema

Answer 5

b. Have been associated with angioedema

Due to reduced metabolism of bradykinin (also mechanism of causing cough)

Not used in pregnancy as it is teratogenic

Question 6

6. alpha methyl-dopa

• a. can cause a positive Coombs test
• b. is a potent vasoconstrictor

Answer 6

• a. can cause a positive Coombs test
• b. is a potent vasodilator

• Works by agonising central alpha-2 receptors with methyl-NA, working on central vasomotor centres*
• Analogue of L-dopa which follows the same synthetic pathways, but produces methyl-dopamine and methyl-noradrenaline instead*
• Methyl-NA remains an effective agonist of peripheral α-adrenoreceptors*
• Hence it is not a vasodilator*
• Instead the methyl-dopamine and methyl-NA reduce BP by stimulating central α-adrenoreceptors*
• Most CV reflexes remain intact, so there is less postural drop*
• However does cause a reduction in renal vascular resistance (like dopamine)*
• Decr TPR with variable decr HR and CO. Effect in 4-6 hrs, may last 24 hrs*
• Used in pregnancy induced HTN, pre eclampsia*
• PK – max effect 4-6hrs post, action persists after parent drug gone, t1/2 2hrs, bioavail 25%, start 1g/d, no reduction required in renal imp*
• Toxicity – sedation esp at onset of treatment, lactation, 20% at 12 months have a positive coombs test (reversible)*

Question 7

7. prazosin

• a. has a half life of 18 hours.
• b. adversely affects lipid profiles.
• c. produces a reflex bradycardia.
• d. has a first dose hypotensive effect
• e. can increase CO by decreasing preload and leaving afterload unchanged.

Answer 7

• a. has a half life of 3 hrs
• b. Diuretics adversely affects lipid profiles
• c. produces a reflex Tachycardia ​​
  
  • ​Less than non-selective alpha-blockers, which also block pre-synaptic NA receptors -> no negative feedback
• d. has a first dose hypotensive effect
• e. can increase CO by decreasing preload and reducing afterload
  
  • Arterial vasodilation -> less afterload; reduces venous tone -> less preload

Question 8

8. Female patient on ACE inhibitor, which is most likely to impair hypotensive effects?
   * a. Prostaglandin inhibitor (indomethacin)

Answer 8

a. Prostaglandin inhibitor (indomethacin)

ACEi also stop degradation of bradykinin.

Bradykinin causes prostaglandin synthesis, which in turn cause vasodilation.

Inhibiting prostaglandins reduces this vasodilatory effect.

Question 9

9. With respect to angiotensin converting enzyme (ACE) inhibitors:

• a. Decreased levels of bradykinin are associated with their use.
• b. They cause reflex tachcardia
• c. There is a strong correlation between plasma renin activity and antihypertensive response
• d. Concomitant use of NSAIDs may decrease the hypotensive effects
• e. Most ACE inhibitors are cleared by hepatic metabolism.

Answer 9

d. Concomitant use of NSAIDs may decrease the hypotensive effects

By reducing prostaglandin synthesis

(Prostaglandins cause vasodilation)

• a. Increased levels of bradykinin are associated with their use.
• b. They do not cause reflex tachcardia
• c. There is a strong correlation between plasma renin activity and antihypertensive response???
• e. Most ACE inhibitors are cleared by renal metabolism.

Question 10

10. Which of the following is selective for arteriolar dilation only?

• a. Glyceryl trinitrate
• b. Nifedipine
• c. Prazosin
• d. Hydralazine
• e. Clonidine

Answer 10

d. Hydralazine

Others all cause venous dilation too

Question 11

11. With regard to sodium nitroprusside, which is not true?

• a. It dilates both arterial and venous vessels
• b. Toxicity can be managed with sodium thiosulfate and hydroxycobalamin
• c. It is rapidly metabolized by the liver to cyanide and to thiocyanate
• d. It acts by activating guanylyl cyclase
• e. Its effects disappear within 1 to 10 minutes of discontinuing an infusion

Answer 11

c. It is rapidly metabolized by the liver to cyanide and to thiocyanate

(thycyanate takes several days to accumulate)

• b. Toxicity can be managed with sodium thiosulfate and hydroxycobalamin - cyanide toxicity
• d. It acts by activating guanylyl cyclase (same as GTN) -> increased cGMP -> smooth muscle relaxation (vascular only)
• e. Its effects disappear within 1 to 10 minutes of discontinuing an infusion - hence needs an IV infusion to administer

Question 12

12. Regarding methyl-dopa, which is NOT true?

• a. It undergoes extensive metabolism by GIT mucosa resulting in low bioavailability
• b. It is metabolized to alpha-methylnoradrenaline in order to be active
• c. Its antihypertensive effect results primarily from peripheral action
• d. Long use is associated with a positive Coombs test and haemolytic anaemia
• e. Common side effects are sedation and impaired concentration

Answer 12

c. Its antihypertensive effect results primarily from central action

On alpha-2 adrenoreceptors in the vasomotor centre

Greater action than the alpha-1 agonism peripherally which causes vasoconstriction

Question 13

13. Regarding antihypertensive medication

• a. Thiazide diuretics are the drugs of choice in cases of moderate to severe hypertension
• b. Losartan inhibits synthesis of angiotensin II
• c. Clonidine causes a brief rise in blood pressure followed by prolonged hypotension
• d. Propranolol does not prevent reflex tachycardia
• e. Bioavailability of captopril may increase if taken with food

Answer 13

c. Clonidine causes a brief rise in blood pressure followed by prolonged hypotension

Presumably due to the peripheral alpha agonism taking effect before the central effects

• b. Losartan antagonises angiotensin II receptors peripherally
• d. Propranolol does prevent reflex tachycardia - hence its utility in treating dissection
• e. Bioavailability of captopril may decrease?? if taken with food
  
  • All ACEi except captopril are prodrugs which require liver metabolism to activate

Question 14

14. The adverse effects of captopril include

• a. Hypokalaemia.
• b. Hypoglycaemia
• c. Increased cholesterol
• d. Polycythaemia
• e. Dry cough

Answer 14

e. Dry cough
* Can cause hyperkalaemia*
* Diuretics increase cholesterol*

Question 15

15. Hydralazine

• a. May provoke angina through reflex sympathetic stimulation
• b. Exerts its effect through arteriolar and venous dilation.
• c. Decreases heart rate.
• d. Has high oral bioavailability.
• e. Tachyphylaxis precludes intravenous use

Answer 15

• a. May provoke angina through reflex sympathetic stimulation
• b. Exerts its effect through arteriolar only dilation.
• c. increases heart rate.
• d. Has low (25%) oral bioavailability.
• e. Tachyphylaxis precludes intravenous use - it doesn’t.

Question 16

16. Inhibition of angiotensin converting enzyme results in which of the following?

• a. A decrease in vascular tone
• b. Inhibition of aldosterone release
• c. Increase in plasma renin activity
• d. All of the above
• e. None of the above

Answer 16

d. All of the above

Question 17

17. Indications for an ACEI include all of the following EXCEPT:

• a. Hypertension
• b. Heart failure.
• c. Diabetic nephropathy.
• d. Post myocardial infarct.
• e. Angioedema

Answer 17

• a. Hypertension
• b. Heart failure.
  
  • Mortality benefit if LV EF < 40%. LV remodelling
• c. Diabetic nephropathy.
  
  • Renal protective
• d. Post myocardial infarct.
  
  • Improved LVEF at 1 year, plus mortality benefit for anterior MI
• e. Angioedema - this is a side-effect, mediated by increased bradykinin levels -> increased prostaglandin -> vasodilation + leakiness

Question 18

18. AT2 receptor antagonists have which of the following actions?

• a. Inhibit increased aldosterone release
• b. Reduce K+ plasma concentration.
• c. Reduce Na+ plasma concentration
• d. Inhibit bradykinin breakdown
• e. Inhibit H+ secretion

Answer 18

a. Inhibit increased aldosterone release

• Cause Hyperkalaemia*
• ACEi inhibit bradykinin breakdown but ARB do not*

Question 19

19. Sodium nitroprusside

• a. Increases cGMP by release of nitric oxide
• b. Decreases vascular resistance but increases blood pressure.
• c. Is a complex of calcium and cyanide groups.
• d. Is predominantly an arterodilator.
• e. Has its onset of action in 10-15 minutes.

Answer 19

• a. Increases cGMP by release of nitric oxide
  
  • ​Same as GTN
• b. Decreases vascular resistance and hence decreases blood pressure.
• c. Is a complex of i**ron and cyanide groups
• d. Is an arterodilator and Venodilator as well
• e. Has its onset of action in <10min as its duration of effect is 1-10min after stopping infusion

Question 20

20. ACE inhibitors

• a. Cause a concomitant reduction in bradykinin.
• b. Directly inhibit angiotensin receptors.
• c. Work predominantly by venodilation.
• d. Can cause angioneurotic oedema
• e. Are only available intravenously.

Answer 20

• a. Cause a concomitant increase in bradykinin.
• b. Inhibit ACE from converting Angiotensin 1->2
• c. Work predominantly by vasodilation
• d. Can cause angioneurotic oedema
• e. Are only available intravenously.
  
  • Obviously are available orally, if you thought this, give up your career now.

Question 21

21. Regarding diazoxide, which of the following is INCORRECT?.

• a. Is used to treat severe hypertension
• b. Acts by direct smooth muscle relaxation
• c. Causes salt and water retention.
• d. Was a favourite medication of Michael J. Foxes which lead to him getting Parkinsons and ending the Back to the Future franchise
• e. is a thiazide derivative

Answer 21

Trick question. Did not come with a wrong answer so I made one up. It was d.

Pharmacodynamics – opens K channel –> hyperpolarises/stabilises membrane potential so prevents vascular smooth muscle from contracting –> reflex tachycardia and increased CO.

It is used in hypertensive emergencies and so is used in severe hypertension

It causes salt and water retention, so despite being structually-related to thiazides, it has a paradoxical effect.

Question 22

22. Hydralazine

• a. Causes an abrupt but transient fall in blood pressure
• b. Displays a biphasic blood pressure response

Answer 22

a. Causes an abrupt but transient fall in blood pressure

Has a bimodal population effect as some people are rapid metabolisers.

Question 23

23. Losartan differs from enalapril in:

• a. Its selective action on angiotensin type 1 receptors
• b. Its enhanced effect on bradykinin metabolism.
• c. Its prolonged half life.
• d. Its higher incidence of drug related angioedema.
• e. Its increased incidence of cough.

Answer 23

a. Its selective action on angiotensin type 1 receptors

• b. Its lack of effect on bradykinin metabolism.
• c. Its reduced half life.
  
  • Half-life is 2 hrs (has an active metabolite whose half-life is 4 hrs)
  • Enalapril 11 hours. Should get this answer without knowing that.
• d. Its reduced incidence of drug related angioedema.
• e. Its reduced incidence of cough.

Question 24

24. All of the following anti-hypertensives act directly on vascular smooth muscle EXCEPT:

• a. Felodipine
• b. Nitroprusside
• c. Indapamide.
• d. Prazosin
• e. Hydralazine

Answer 24

c. Indapamide.

A diuretic

• a. Felodipine - CCB
• b. Nitroprusside - NO -> increased cGMP ->SM relaxation
• d. Prazosin - selective alpha-1 inhibition
• e. Hydralazine - directly acts on arterioles