PART II-ESSAY QUESTIONS 

1. Pharmaceutical Calculations 

a) In a clinical trial on a new therapeutic for severe acute stroke, the treatment protocol calls for eligible subjects to receive "sinecteplase", an investigational fibrinolytic, 50 units/kg intramuscularly, followed by 80 units/kg infused over 10 hours. 

Subject 64 is a 55-year-old female. Her weight is 220.2 lb and height is 5'3". She is going to receive sinecteplase per the above protocol. 

(i) The investigational product is available in 20000 units per vial in dried powder form, and the reconstitution instructions state "add 3mL of sterile water to obtain a solution of 4000 units/mL". Intramuscular injection volume for sinecteplase must not exceed 1 mL to minimise risk of bleeding. 

For the injection for subject 64, how much sterile water should be added for reconstitution? 

(ii) The remaining reconstituted solution from the above is used to prepare the infusion solution, which should be diluted in normal saline ("NS") and have a concentration between 30 to 40 units/mL. 

What is the volume of reconstituted solution required, and which size of NS IV bag should be used? 

(iii) What is the appropriate infusion rate, in mL/hr? 

(5 marks) 

b) Nicardipine intravenous infusion 5 mg/h is also initiated in subject 64 to decrease 

her blood pressure. Your hospital stocks nicardipine premixed infusion solution of 20 mg/200 mL in isotonic saline. 

(i) What is the initial infusion rate? 

(ii) To achieve optimal blood pressure control, infusion rate of nicardipine is to be titrated up by 2.5 mg/h every 15 minutes up to a maximum of 15 mg/h. Subject 64 presented with persistent hypertension and therefore the infusion rate is titrated up to the maximum in the shortest allowable time. How much nicardipine does subject 64 receive in the first 2 hours?

(2 marks) 

c) On the next day, subject 64 spikes a high fever and sepsis is suspected. (3 marks) 

Vancomycin is prescribed to cover for potential methicillin-resistant Staphylococcus aureus ("MRSA") infection. 

(i) The estimated clearance for vancomycin based on population parameters is CL (mL/min) = 0.689* CrCl + 3.66, in which CrCL is creatinine clearance calculated from the Cockcroft-Gault equation using an appropriate weight. Subject 64's current serum creatinine is 77 μmol/L. What is her estimated vancomycin clearance (L/hr)? 

(ii) What is the expected half-life of vancomycin for this patient? 

Estimated Vd (L) = 0.72* Body weight. 

(iii) The prescribed dose is vancomycin 500 mg IV Q6H. What is the expected 24-hour area under the curve ("AUC") of vancomycin in subject 64? 

d) Subsequently subject 64 deteriorates quickly. She complains of excruciating pain, muscle paralysis and swallowing difficulty. She is found to have severe cerebral edema, therefore HYPERTONIC saline (sodium chloride 3% solution) intravenous infusion is prescribed. You have CONCENTRATED sodium chloride ("NaCl") 23.4% (w/v) solution (30 mL/vial) for injection and normal saline (sodium chloride 0.9% for injection). Molecular weight of NaCl is 58.44 g/mol. 

(i) You are asked to prepare a 500 mL bag of HYPERTONIC saline for infusion, by diluting the CONCENTRATED NaCl solution with normal saline. For the bag, how much CONCENTRATED NaCl solution and normal saline is required respectively, in mL? 

(ii) What is the approximate amount of sodium (in mEq) in the hypertonic saline solution? (Molecular weight of NaCl is 58.44 g/mol) 

(iii) What is the approximate osmolarity (in mOsmol/L) of the hypertonic saline solution? 

(3 marks)

e) Unfortunately, brain imaging reveals massive intracranial haemorrhage in subject 64. She is eventually discharged to hospice and put on palliative care. 

The discharge prescription reads: 

Morphine 30 mg PO Q12H and 20 mg PO Q3H PRN pain for 10 days, dispense 50%. 

Your pharmacy stocks morphine sulfate sustained release ("SR") 10 mg tablets, morphine SR 30 mg tablets, and morphine sulfate 10 mg/5 mL oral syrup. 

(i) How much should subject 64 take for each dose? 

(ii) What is the total amount required for this prescription? 

(2 marks) 

2. P.P. is a 19-year-old adolescent (body weight 65kg) with a medical history of persistent asthma. His current drug profile includes: 

• Fluticasone/Salmeterol 500/50 mcg 1 puff BD; 
• Salbutamol 1-2 puffs Q4-6H PRN for shortness of breath. 

P.P. has had two asthma exacerbations in the past year. PP's most recent pulmonary function testing is as follows: 

• Forced expiratory volume in 1 second ("FEV1") 54% of predicted, 
• Forced vital capacity ("FVC") 78% of predicted;
• FEV1/FVC 0.64 (ref. > 0.7),
• Peak expiratory flow (personal best) 450 L/minute (ref. 400-700 L/minute) 

Over the past 4 weeks, P.P. states that he has been using the salbutamol inhaler twice weekly and waking once per week because of asthma symptoms. However, P.P. has not been hospitalised due to the worsening in symptoms. 

a) Assess the severity level of P.P.'s asthma according to the Global Initiative for Asthma ("GINA") guidelines. Suggest ONE pharmacist intervention on P.P.'s drug regimen. (2 marks) 

b) Upon the modification of P.P.'s regimen, he is still experiencing worsening of asthma symptoms. P.P. is referred to a respiratory physician with the following tests conducted: 

• Immunoglobulin E (“IgE”) 2290 IU/mL, (ref 0-100 IU/mL)
• fractional exhaled nitric oxide ("FeNO") 55 ppb, (ref. <25 ppb)
• blood eosinophil count 190 cells/mm3. (ref. 30-350 cells/mm3) 

P.P.'s is subsequently diagnosed with severe eosinophilic asthma with phenotype of Type 2 airway inflammation after 3 months. List at least TWO biologic therapies of different drug classes or mechanism of action, specifying BOTH drug class and drug name, which can be used as an add-on therapy in P.P.'s asthma. (4 marks) 

c) P.P.'s case medical officer has prescribed Reslizumab IV 19 5 mg every 4 weeks, but you just realised that it is not yet registered and available in Hong Kong. Suggest TWO alternate treatment options to P.P.'s case medical officer under this situation. (2 marks) 

d) P.P.'s case medical officer made a final decision to prescribe Mepolizumab SC 100 mg every 4 week which is a registered drug item in Hong Kong. Suggest the treatment duration of Mepolizumab IV for P.P. before the assessment of clinical response. (1 mark) 

e) P.P.'s case medical officer has made a drug information enquiry to Pharmacy regarding the treatment response to Mepolizumab. List at least TWO factors which may predict good asthma response to Mepolizumab. (3 marks) 

f) After a year, you assessed that P.P. has achieved good asthma response to Mepolizumab therapy. Other than inhaler technique and drug compliance, suggest any future treatment plan for P.P.'s severe asthma treatment. (3 marks) 

3. Antibody-drug conjugates ("ADCs") are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. They are like a precision guided "biological missile" with the ability to destroy the cancer cells accurately, improving the therapeutic window and reducing the off-targeted side effects. 

a) Please draw a schematic to illustrate the major components of an ADC drug and their functions (5 marks) 

b) Please list out THREE different types of therapeutic monoclonal antibodies used for ADCs and comment on their level of immunogenicity. (4 marks) 

c) Please describe the mechanisms of action of an ADC drug. (4 marks) 

d) Please comment on how the side effects of an ADC drug arise. (2 marks) 

4. AYYH is a 42-year-old male with type 2 diabetes and chronic kidney disease (“CKD") for follow-up today. His home blood pressure ranges from 140-160/80-90 mmHg, heart rate 70-80 beats per minute. His latest glycated haemoglobin A1c ("HbA1c") is 6.5% (target set by doctor: < 7%), estimated glomerular filtration rate ("eGFR") 55 mL/min/1.73m2 (ref. > 60 mL/min/1.73m2) and a urine albumin-to-creatinine ratio ("UACR") of 24 mg/mmol (ref. <1 mg/mmol). He is currently taking metformin 500 mg BD and gliclazide 80 mg BD for his diabetes. 

a) Using the cause, GFR category, and albuminuria category ("CGA"), what is his current stage of CKD? (1 mark) 

b) AYYH reads on the internet saying metformin is not suitable for patients with impaired renal function. How would you respond? (2 marks) 

c) Devise a treatment plan, with monitoring parameters, to optimise his diabetic control, CKD progression and/or blood pressure. (4 marks) 

d) Three months later, AYYH presents at your pharmacy counter requesting to purchase paracetamol. He explains that he tested positive for COVID-19 four days ago using a rapid antigen test ("RAT"). He reports feeling tired and nauseous. 

Upon further questioning, AYYH reveals that his fluid and food intake have been reduced over the past few days, and his urine output has been noticeably less than usual. He is currently taking enalapril 10 mg daily (increased from 5 mg daily last week), empagliflozin 10 mg daily, gliclazide 80 mg BD, and metformin 500 mg BD. 

You suspect that AYYH is experiencing acute kidney injury ("AKI"). What are the potential causes of AKI? (2 marks) 

e) Describe the appropriate course of action for a community pharmacist in this situation. (2 marks) 

f) Your pharmacy is recently collaborating with the Hospital Authority to manage patients with chronic diseases. Devise a comprehensive sick-day management plan for AYYH to minimise the risk of similar events occurring in the future. 

(4 marks) 

5. A 64-year-old female diagnosed with B-cell lymphoma is to start on combination chemotherapy with rituximab. Besides the lymphoma, the only medical condition the patient has is osteoporosis. Her pre-treatment lab values and Hepatitis B serology testing results are below: 

WBC: 5.1 × 109 cells/L (ref. 4.5 - 11 × 109/L) 

Hgb: 11.2 g/dL (ref. 12.1-15.1 g/dL) 

Creatinine clearance: 40 mL/min (ref. > 60 mL/min) 

Alanine transaminease ("ALT"): 35 IU/L (ref. 10-40 IU/L) 

Hepatitis B surface antigen ("HBsAg"): (-) 

Hepatitis B surface antibody (“Anti-HBs"): (-) 

Hepatitis B core antibody (“Anti-HBc"): (+) 

a) Please describe to the patient her Hepatitis B serology results and any suggestions you may have regarding her Hepatitis B status. (6 marks) 

b) The oncologist is also prescribing tenofovir for this patient along with her cancer treatment. Please state the rationale for doing this. 

(5 marks) 

c) For the tenofovir prescription, please indicate whether the tenofovir alafenamide ("TAF") or the tenofovir disoproxil ("TDF") form is more suitable for this patient, and why. (4 marks) 

END OF PAPER