Pharmacology June 2019

1 A 75-year-old man with gastrointestinal stromal tumour and bone metastasis presented with bone pain. He also had a medical history of hypertension and chronic kidney disease (plasma urea: 16.9 mmol/L; plasma creatinine: 315 µmol/L; estimated GFR: 24 ml/minute per 1.73 m²). The pain control was not satisfactory with simple analgesic paracetamol. Opioid analgesic was considered necessary by his family doctor. His initial analgesic regime was paracetamol 500 mg q.i.d, and morphine sulphate (syrup) 5 mg q4h. He was also on imatinib mesylate for the treatment of gastrointestinal stromal tumor.

a) Discuss the metabolism of codeine and the impact of pharmacokinetics variation of codeine metabolism on pain control and medication safety (4 marks)

b) Discuss the use of morphine in this patients with chronic kidney disease:

(i) The metabolism and elimination of morphine in human body. (2 marks)

(ii) ONE major morphine toxicity and it’s pharmacological mechanism. (2 marks)

(iii) Recommended morphine dosage adjustment in this patient (1 mark)

c) The patient complained of constipation after use of morphine.

(i) List THREE non-pharmacological measures to prevent constipation. (1.5 marks)

(ii) Give ONE drug example for EACH pharmacotherapeutic agent with different mechanism of action: stool softener; osmotic laxative; contact cathartic. (1.5 marks)

(iii) Give ONE drug example for bulk-forming agents and explain why it should be avoided in opioid induced constipation (1 mark)

d) The bone pain was adequately controlled with the morphine sulphate 45 mg per day. Fentanyl dermal patch was switched for pain control.

(i) Discuss the metabolism and elimination of fentanyl in human body. (2 marks)

(ii) What is the appropriate dosage conversion from morphine sulphate to transdermal fentanyl patch in this patient? (1 mark)

(iii) List THREE important advices to the patient about safe use of fentanyl patch. (3 marks)

(iv) What potential drug-drug interaction may occur in this patient on fentanyl therapy? (1 mark)

2 Mr Lee is a 42-year-old Chinese with a history of Crohn’s disease. He experienced disease flair recently upon tapering of budesonide. Therefore, his physician-in -charge decided to prescribe azathioprine to improve the control of his disease. However he was worried about the potential side-effects of azathioprine, in particular myelosuppression.

a) What genetic test can help to predict the risk of myelosuppression associated with azathioprine? (1 mark)

b) Please explain the pathophysiology of myelosuppression associated with azathioprine? (3 marks)

c) How to interpret the results of this genetic test? (6 marks)

d) If the genetic test is not available in your hospital what is the alternative test that can predict the risk of myelosuppression associated with azathioprine? (1 mark)

Mr Lee was diagnosed to have gout arthritis recently. Since he had two attacks in the last six months, his physician-in-charge decided to prescribe allopurinol for him to lower his serum urate level.

e) What is genetic test can be considered for patients before prescribing allopurinol (1 mark)

f) Name TWO adverse drug reactions of allopurinol that can be prevented by this genetic tests (2 marks)

g) If the test is positive what is your recommendation regarding the long-term management of gouty arthritis (2 marks)

h) What precautions should you recommend to Mr Lee if allopurinol is prescribed while he is receiving azathioprine? Please explain. (4 marks)

3 A 65-year-old man entered a pharmacy with a doctor’s prescription. He had been prescribed rosuvastatin 40 mg daily and has ezetimibe 10 mg daily.

a) Regarding rosuvastatin, he wanted to know:

(i) what it was for; (1 mark)

(ii) whether he could take it intermittently; (1 mark)

(iii) the important adverse facts. (2 marks)

b) Regarding ezetimibe, he wanted to know:

(i) what it was for; (1 mark)

(ii) whether he could take it intermittently; (1 mark)

(iii) how it worked. (1 mark)

c) He had painful knees and the pain was worse when he walked downhill. Was this likely to be related to his drugs? (2 marks)

d) He had a heart attack several years ago. His doctor mentioned that if his blood cholesterol was high, he might need injections of a drug to bring down the cholesterol. What is this class of drugs? How do they work? (4 points)

e) Name ONE advantage and ONE disadvantage of these injections. (2 marks)

f) Name THREE lifestyle changes that would help to lower blood cholesterol. (3 marks)

g) He had read about ‘good’ and ‘bad ‘cholesterol in the newspapers. What might he mean by ‘good’ and ‘bad’ cholesterol? (2 marks)

4 A 73-year-old male smoker with moderate to severe chronic obstructive pulmonary disease (COPD) (FEV1 50% predicted) was admitted to A & E Department with an acute exacerbation of COPD for the fifth time this year. He presented to A & E doctor with fever, increased productive cough and shortness of breath. Upon admission to the ward, chest x-ray revealed an infiltrates. From his previous medical record, the doctor noticed the detection of Pseudomonas aeruginosa in his prior exacerbations.

a) Which class of antibiotics is the drug of choice to be given to the patient? Name the antibiotic and state the route of administration. (3 marks)

b) What is the mechanism of action for this antibiotic? (5 marks)

c) List FOUR common adverse effects. (2 marks)

d) Name TWO potential drug-drug interactions associated with this class of antibiotics and explain the mechanism of such drug-drug interaction involved. (4 marks)

e) State the mechanism of resistance which may develop with the antibiotic used? (4 marks)

f) State FOUR reasons for the increase in prevalence of antibiotic resistance over the years. (2 marks)

5 Corticosteroids are used in the suppression of inflammatory and allergic disorders.

a) Discuss the adverse effects of corticosteroids. (10 marks)

b) What are the differences in the potencies of hydrocortisone, prednisolone and dexamethasone? (6 marks)

c) Adrenal suppression can occur with high doses and/or prolonged corticosteroids treatments. How can this complication be prevented and managed? (4 marks)