Question

1. Myocardial infarction

You attend an emergency call to the home of Robert, a 63 year old male with a documented history of compensated congestive heart failure (CHF), who you diagnose is currently suffering a myocardial infarction. You prepare to administer GTN to Robert in the form of a sublingual spray. GTN is a potent vasodilator that works by (Choose...increasing guanylate cyclase mediated degradation of cGMP, decreasing guanylate cyclase mediated production of cGMP, decreasing guanylate cyclase mediated degradation of cGMP, increasing guanylate cyclase mediated production of cGMP) in vascular endothelial smooth muscle. Prior to administering GTN, you ensure Robert has (Choose...an adequate systolic blood pressure, a palpable JVP, an adequate diastolic blood pressure, a shockable heart rhythm) and ask if he has taken any erectile dysfunction medication in the last 24hrs, to which Robert responds “the only medication he has taken in the last 24hrs is his regular Aspalgin”. On this basis you (Choose...administer double the dose of GTN to Robert, administer GTN and monitor Roberts haemodynamics, do not administer GTN to Robert, administer GTN and monitor Roberts respiratory rate) because (Choose...Aspalgin is a phosphdiesterase 5 inhibitor, Aspalgin will inhibit the metabolic activation of GTN, GTN will reduce Roberts blood pressure, GTN will reduce Roberts respiratory drive) , which may cause Robert to (Choose...retain CO2 leading to respiratory failure, experience a drug interaction resulting in therapeutic failure of GTN, become hemodynamically unstable and decompensate, experience a drug interaction resulting in uncontrolled hypotension) .

2. Calculation

Following a short stay in hospital, Robert is discharged with a number of new medications including an anti-platelet drug called prasugrel. It is common to use dual anti-platelet therapy for at least 6 months following a myocardial infarction in order to reduce the risk of a second myocardial infarction. For many years a combination of aspirin and clopidogrel has been used for this purpose. However, the use of a newer anti-platelet drug prasugrel in place of clopidogrel is now being considered.

Over 12 months, it is expected that prasugrel will cost $670 more per person treated than clopidogrel. It is estimated that if prasugrel is used a person will have 13.325 QALYs on average, whereas if clopidogrel is used a person will have 13.300 QALYs on average. QALYs are a measure of life expectancy that has been adjusted for quality of life.

What is the incremental cost-effectiveness ratio of prasugrel? (i.e. cost per QALY)

3. Short Answer

Ipilimumab is a new targeted therapy for metastatic melanoma and is also being considered for addition to Robert's hospital's formulary. It has been estimated that the incremental cost-effectiveness of ipilimumab is $100,000 per QALY.

If there is only enough funding to add either prasugrel or ipilimumab to the formulary, which would you choose solely on the basis of cost-effectiveness? Explain your reasoning (maximum of 100 words).

Answer 1

ANSWER 1 :-

1. GTN is a potent vasodilator that works by increasing guanylate cyclase mediated production of cGMP. Hence, option 'D' is the most appropriate answer. GTN (Nitroglycerin) is a potent agent that acts on the endothelial lining of the blood vessels by mediating guanylate cyclase mediated production of cGMP enhacncing the production of nitric oxide (NO) which helps in dilation of the blood vessels thereby reducing the blood vessels.

The most appropriate answer is option 'D'.

2. Prior to administration of GTN, you ensure Robert has an adequate systolic blood pressure. This is because the drug mainly acts by reducing the systolic blood pressure and if it falls below the level of 90mmHg, there occurs a problem in which filling of the heart with blood becomes difficult and hence monioring the systolic blood pressure before and after the procedure is important and hence option 'A' is the most appropriate answer. JVP (Jugular Venous pressure) palpations may be associated with the venous blood entering the heart and does not give any idea regarding the pressure regulation process or more specifically blood pressure upon which the drug has more effect. Diastolic blood pressure also shows changes but are acute and not much important as systolic pressure deals mainly with the contractile activity of the heart and thus can help to derive heart related condition like congestive heart failure. Shockable heart rhyth also called as Ventricular tachycardia or Fibrillation deals with either generation of more irregular beats or no beating sensation which is not co-related to the changes mediated by the drug.

The most appropriate answer is option 'A'.

3. On this basis, you do not administer GTN to Robert (Option 'C' is appropriate) because Aspalgin is a Phosphodieaterase 5 inhibitor (Option 'A' is appropriate) which may cause Robert to become Hemodynamically unstable and decompensate (Option 'C' is appropriate answer).

Basically, GTN is a drug which can work in association with the drug Aspalgin. Aspalgin is a phosphodiesterase inhibitor involved in elevating the levels of cGMP and thus if the drug is given along with GTN, can lead to to more decline in blood pressure levels (systolic pressure) and can lead to hemodynamic unstability in which the blood pressure falls upto 90 mmHg which may lead to irregularities in blood supply and thus can lead to failure of other organs or in short worsen the process.

The appropriate answers are option 'C', option 'A' and option 'C'.

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