1. A 67-year-old man with coronary heart disease developed chest pain again on the sixth day after a percutaneous cardiac intervention. Redo coronary angiogram revealed stent thrombosis. He had good medication compliance. Suboptimal response to clopidogrel was suspected. He had a past medical history of hypertension, diabetes mellitus, and gastroesophageal reflux disease.

His medications included: metoprolol 25 mg twice daily; metformin 1000 mg twice daily; omeprazole 20 mg once daily; rosuvastatin 20 mg once daily; clopidogrel 75 mg once daily; aspirin 80 mg once daily. 

(a) Describe the mechanism of action and metabolism of clopidogrel. (4 marks)

(b) From the medication list, identify a drug with potential drug-drug interaction that could lead to decreased metabolism of clopidogrel and explain why. (2 marks)

(c) Suggest TWO alternative medications to avoid the drug-drug interaction described in question (b) and explain why. (4 marks)

(d) Explain the impact of genetic variations on the metabolism of clopidogrel and the potential clinical consequences. What is the prevalence of poor metaboliser by genotype (subjects carry 2 no-function alleles in Han Chinese in Hong Kong? (4 marks)

(e) The genotyping testing result suggests that the patient carries 2 genes associated with decreased metabolism of clopidogrel. Name TWO other alternative medications to clopidogrel as dual antiplatelet therapy with aspirin. (2 marks)

(f) Discuss the difference in metabolism between clopidogrel and the other TWO alternative antiplatelet medications you suggested in question (e) and explain why they are more useful in patients with suboptimal responses to clopidogrel. (4 marks)

2. Mrs. Lam is 67 years old and retired. During a recent visit to her family doctor, she presented with moderate to severe allergic rhinitis symptoms, including nasal congestion, sneezing, and itchy, watery eyes. She has had no significant medical history and is rather healthy. Her doctor prescribed nasal spray combination therapy containing azelastine-fluticasone (Dymista®) to relieve her symptoms. 

(a) Regarding azelastine, name the drug class and describe its mechanism of action. State its advantages. (5 marks)

(b) Regarding fluticasone, name the drug class and describe its mechanism of action. State TWO adverse effects. (5 marks)

(c) Later, Mrs. Lam revisited the family doctor and asked for any oral tablet she might take to help reduce symptoms such as nasal congestion, sneezing, and itching in addition to the nasal spray. Her doctor prescribed montelukast (Singulair ®) to her. Name the class of montelukast and describe its mechanism of action. State TWO adverse effects. (5 marks)

(d) As her condition got worse, Mrs. Lam visited an allergic specialist and was given a subcutaneous injection of omalizumab (Xolair®). Name the class of omalizumab and describe its mechanism of action. State TWO adverse effects. (5 marks)

3. A 70- year-old man with difficult-to-control hypertension, ischemic heart disease, and dyslipidemia attended the outpatient clinic for review. He is on losartan 100 mg once daily, metoprolol (controlled release) 100 mg once daily, amlodipine 10 mg once daily, and hydrochlorothiazide 25 mg once daily for blood pressure. His blood pressure was 179/100 mmHg in the clinic, and his heart rate was 49 beats per minute. His renal function was normal. He confirmed good adherence to his medications. Doxazosin was added to his treatment. 

(a) What class of drug does losartan belong to? What is its mechanism of action in blood pressure lowering? What are the common adverse effects of losartan? (4 marks)

(b) What is the mechanism of action of amlodipine? What are the common adverse effects of amlodipine? (3 marks)

(c) Describe common electrolyte abnormalities that are associated with hydrochlorothiazide. (3 marks)

(d) Describe relative and absolute contraindications of beta-blockers. (4 marks)

(e) The patient experiences postural hypotension after initiating doxazosin. How can this problem be avoided? (3 marks)

(f) What other alternative classes of antihypertensives can be considered in this case? (3 marks)

4. A patient with non-Hopkin lymphoma was admitted to the intensive care unit due to shock. Noradrenaline was administered to him. 

(a) What are the pharmacological effects of noradrenaline on the cardiovascular system and its mechanisms of action? (3 marks)

(b) What are the differences between noradrenaline and adrenaline in terms of their pharmacological actions and mechanisms of action? (2 marks)

(c) A combination of cyclophosphamide, doxorubicin (i.e. hydroxydaunorubicin), vincristine (i.e. oncovin), and prednisolone (“CHOP”) is a common chemotherapy regimen for treating non-Hodgkin lymphoma. Explain the mechanism of anticancer action of these FOUR drugs. (5 marks)

(d) CHOP regimen can also be combined with a monoclonal antibody if the lymphoma is of B cell origin. What is this monoclonal antibody, and what is its target of malignant B lymphocytes. (2 marks)

(e) What are the adverse effects of doxorubicin (i.e. hydroxydaunorubicin) on the cardiovascular system? What drug can be used to reduce this adverse effect, and what is its mechanism of action? (3 marks)

(f) What are the adverse effects of cyclophosphamide on the urogenital system? What drug can be used to reduce this adverse effect, and what is its mechanism of action? (3 marks)

(g) Neutropenia may occur during chemotherapy of lymphoma. Levofloxacin and fluconazole may be used for anti-infective prophylaxis. What are their mechanisms of action? (2 marks)

5. Mr. Lee is a 25-year-old male who has the habit of using cannabis. He was brought into the emergency department by his parents, who reported that Mr. Lee is always anxious and hears several voices commenting on his personality. He also believes that his neighbor is secretly planning to kill him. Mr. Lee’s parents said that Mr. Lee is angry because they do not believe him. Mr. Lee was referred to the Psychiatry Unit for a full work-up. He was diagnosed with schizophrenia. 

(a) Name TWO additional positive symptoms and TWO additional negative symptoms of schizophrenia. (4 marks)

(b) How does cannabis use lead to this increased risk of schizophrenia? (1 mark)

(c) A doctor from the Psychiatry Unit asks for your opinion on deciding between prescribing olanzapine and risperidone based on the main adverse effects they may cause. What is your response? (4 marks)

(d) Name FOUR additional potential adverse effects of antipsychotics. (2 marks)

(e) With respect to the adverse effects described in (c) and (d), how could these be explained with respect to the receptors and regions of the brain that the drugs target? (7 marks)

(f) In addition to medication, provide TWO non-pharmacological advice to Mr. Lee for the management of his disorder. (2 marks)