Antihypertensives Flashcards
1
Q
- 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
A
c. Alpha receptors of vessels – hydralazine.
Direct smooth muscle relaxation
2
Q
- 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.
A
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.
3
Q
- 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
A
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
4
Q
- diazoxide.
- a. can be used in a hypertensive emergency
- b. structurally related to thiazide
A
Both of them are true
5
Q
- ACE inhibitors
- a. Can be used in second and third trimesters.
- b. Have been associated with angioedema
A
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
6
Q
- alpha methyl-dopa
- a. can cause a positive Coombs test
- b. is a potent vasoconstrictor
A
- 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)*
7
Q
- 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.
A
- 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
8
Q
- Female patient on ACE inhibitor, which is most likely to impair hypotensive effects?
* a. Prostaglandin inhibitor (indomethacin)
A
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.
9
Q
- 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.
A
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.
10
Q
- Which of the following is selective for arteriolar dilation only?
- a. Glyceryl trinitrate
- b. Nifedipine
- c. Prazosin
- d. Hydralazine
- e. Clonidine
A
d. Hydralazine
Others all cause venous dilation too
11
Q
- 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
A
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
12
Q
- 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
A
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
13
Q
- 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
A
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
14
Q
- The adverse effects of captopril include
- a. Hypokalaemia.
- b. Hypoglycaemia
- c. Increased cholesterol
- d. Polycythaemia
- e. Dry cough
A
e. Dry cough
* Can cause hyperkalaemia*
* Diuretics increase cholesterol*
15
Q
- 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
A
- 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.
16
Q
- 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
A
d. All of the above
18
Q
- 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
A
a. Inhibit increased aldosterone release
- Cause Hyperkalaemia*
- ACEi inhibit bradykinin breakdown but ARB do not*
20
Q
- 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.
A
- 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.
