A 75 year old man was admitted to hospital for community acquired pneumonia ("CAP") and atrial fibrillation ("AF") with rapid ventricular response. He had a past medical history of hypertension, diabetes mellitus, duodenal ulcer, atrial fibrillation, congestive heart failure, chronic kidney disease [plasma urea: 16.9 mmol/L; plasma creatinine; 315 micromol/L; estimated Glomerular filtration rate ("GFR") by Modification of Diet in Renal Disease ("MDRD") equation: 24 mL/min per 1.73 m2], and chronic tophaceous gout.

His medications included metoprolol 25 mg bd, apixaban 2.5 mg bd, frusemide 40 mg daily, allopurinol 100 mg daily and protaphane HM 18 unit om. Because of CAP and AF with rapid ventricular response, he was treated with intravenous diltiazem infusion. Later, he developed an acute gouty attack in the knees. The clinician prescribed colchicine 0.5 mg bd for management of acute gouty arthritis.

a) Discuss the pharmacology of colchicine: (5 marks)

i) the anti-inflammatory mechanism of action;

ii) metabolism;

iii) toxicities in overdose; and

iv) the American College of Rheumatology's recommendation on the dosage of colchicine for the treatment of acute gouty arthritis.

b) List FOUR potential drug-drug interactions and the mechanisms which may occur in the patient receiving treatment for CAP, AF and acute gouty arthritis with colchicine. (4 marks)

c) Apart from colchicine, what other THREE drug therapies are useful for the treatment of acute gouty arthritis? What are the cautions for these drugs in this patient? (6 marks)

d) Despite allopurinol therapy, the patient still developed recurrent gouty attack. Discuss the (i) mechanism of action; (ii) adverse reactions; and (iii) cautions of pegloticase for management of chronic gouty arthritis. (3 marks)

e) For patient with chronic tophaceous gout, what anti-hypertensive drugs may be associated with an (i) increase; and (ii) decrease of serum uric acid levels, respectively? (2 marks)