37. Answer: D
Minoxidil is metabolised to an active sulfate metabolite, which antagonises the effect of ATP on KATP channels. The cell is thus hyperpolarised, which deactivates voltage‐dependant calcium channels. The net effect of this action is smooth muscle relaxation. Undesirable side effects of KATP channel blockade include hirsutism and marked salt and water retention. Therefore, minoxidil is usually co‐administered with a loop diuretic.
38. Answer: C
Sacubitril (through its active metabolite sacubitilat) inhibits neprolysin, which in turn increases circulating levels of natriuretic peptides, thus decreasing extracellular volume through induction of renal sodium excretion. In combination with valsartan, sacubitril shows efficacy in treating symptomatic patients with heart failure with reduced ejection fraction. Neprolysin is involved in the degradation of other peptides including bradykinin which elicited adverse effects of renal failure, angioedema, and hyperkalaemia in the randomised controlled trial.
39. Answer: B
Moxonidine antagonises the central control of sympathetically mediated vasoconstriction by stimulating the imidazoline (I1) receptor present in the brainstem, which in turn decreases central catecholamine synthesis. Moxonidine and clonidine act at α2 receptors as well, however moxonidine has much higher affinity for the I1 receptor.
40. Answer: E
Captopril is the archetypal ACE inhibitor that decreases the production of angiotensin II by competitively adhering to the binding site for angiotensin I on ACE. ACE is a membrane bound enzyme predominantly present on vascular endothelium which is most extensively, but not exclusively, expressed in the lung. Angiotensin I undergoes conformational change when interacting with ACE to produce angiotensin II. Angiotensin II has multiple effects which increase blood pressure including proximal tubular absorption of sodium, increased secretion of aldosterone, increased noradrenaline release, and growth of cardiac and vascular cells. ACE is also involved in the degradation of bradykinin, consequently angioedema is a well‐known side effect.
41. Answer: G
Some drugs induce relaxation of vascular smooth muscle by increasing cellular concentration of either cyclic adenosine monophosphate (cAMP) or cyclic guanine monophosphate (cGMP). Nitrates are reduced to nitric oxide by a variety of mechanisms. Nitric oxide activates guanylyl cyclase, which in turn increases cGMP production from guanosine triphosphate, which stimulates dephosphorylation of myosin, leading to vasodilation.
42. Answer: A
Beta receptor blockers decrease blood pressure by two main mechanisms. The first is by decreasing cardiac output by blockade of cardiac β1‐receptors, the second is by blocking renal β1‐receptors, resulting in decreased renin secretion.
43. Answer: F
Hydralazine is an arterial and arteriolar vasodilator that directly causes a fall in systemic vascular resistance by interfering with inositol triphosphate's effects on the sarcoplasmic reticulum, which decreases calcium release, resulting in less smooth muscle contraction. The fall in blood pressure is usually accompanied by reflex tachycardia and increased cardiac output. Hydralazine causes drug‐induced lupus, which can limit its use in the medium to long term.
Rang H, Ritter J, Flower R, et al. Rang and Dale's pharmacology. 9th ed. Edinburgh: Elsevier; 2019.
https://www.elsevierhealth.com.au/rang‐dales‐pharmacology‐9780702074486.html
44. Answer: E
All of the signs suggest pulmonary hypertension, pointing to Eisenmenger's syndrome, which may be found in older adults who have had a reversal of shunt from right‐to‐left before open‐heart surgery is available. It is the most advanced form of pulmonary arterial hypertension due to elevated pulmonary vascular resistance causing right‐to‐left intracardiac shunt or great artery shunting, leading to systemic arterial desaturation.
45. Answer: G
Tetralogy of Fallot is associated with a combination of four clinical features:
1 VSD
2 Right ventricular outflow obstruction
3 Overriding aorta
4 Right ventricular hypertrophy
Although the long‐term survival has improved for patients with repaired tetralogy of Fallot, residual haemodynamic and electrophysiological sequalae are common in adults. These groups of patients may have symptoms of arrythmias, heart failure, exercise intolerance, and death in early adulthood. Implantable cardioverter–defibrillators (ICDs) as a primary intervention should be considered in patients who meet standard qualifying criteria (i.e. LV ejection fraction ≤35% with NYHA class II or III symptoms).
46. Answer: D
The most common site for coarctation (CoA) is just distal to the origin of the left subclavian artery. An ECG may show signs of systolic overload, including left ventricular hypertrophy.
Sometimes the diagnosis can be easily missed if the lower limb blood pressure is not routinely measured. The long‐term complications of CoA are generally related to chronic upper body systemic hypertension. Complications in patients with repaired CoA include recoarctation of the aorta, aneurysm, pseudoaneurysm, and dissection; thus, patients will require ongoing monitoring after operation. CoA is also known to be associated with Turner's syndrome.
47. Answer: A
There are two common types of ASD in adults: ostium secundum (most common) and ostium primum. These patients characteristically exhibit a left‐to‐right intracardiac shunt which may lead to right heart enlargement and, in a minority of the patients, pulmonary arterial hypertension (PAH). ECG findings may demonstrate right‐axis deviation, right bundle branch block pattern, right ventricular hypertrophy from systolic overload and CXR findings may show an enlarged right atrium and ventricle, increased pulmonary vasculature, a dilated main pulmonary artery, and a small aortic knob. Almost all ASDs need to be closed surgically or, if the patient is suitable, with a percutaneous closure device when a pulmonary‐to‐systemic blood flow (shunt) ratio (Qp/Qs) >1.5:1. It is important to evaluate severe PAH prior to operation since closure of ASDs is contraindicated in this group of patients.
ASD due to ostium primum is caused by an endocardial cushion defect adjacent to the atrioventricular valves. In addition to the aforementioned signs in patients with ostium secundum, there is also associated mitral regurgitation, tricuspid regurgitation or VSD. ECG findings should show left‐axis deviation, right bundle branch block and sometimes a prolonged PR interval. The condition is associated with Down's syndrome and Holt‐Oram syndrome.
48. Answer: B
VSD in adults are usually small or large with Eisermenger's syndrome. Small restrictive defects may be monitored conservatively without the need for operation. ECG and CXR findings may demonstrate left ventricular hypertrophy. Closure of the VSD is indicated when the left‐to‐right shunt is moderate to large when the pulmonary‐to‐systemic flow is >1.5 to 1. Eisermenger's syndrome and severe PAH are contraindications to operative intervention due to significantly increased surgical risks. VSD is associated with Down syndrome.