1) Pharmaceutical Calculations

a) Syrup British Pharmacopeia (“B.P.”) is an 85% w/v solution of sucrose in water. It has a density of 1.313 g/mL, How many mL of water should be used to make 150 mL of Syrup B.P.? (3 marks)

b) 72 mL of water is needed to produce 100 mL of a mixture containing 250 mg of drug X in every 5 mL dose. Calculate the displacement volume for a quantity of powder equivalent to the 250 mg dose of drug X. (3 marks)

c) Calculate the amount of sodium chloride that must be added to the following formulation of nasal drops to make the final solution isotonic.

Ephedrine 0.15g

Water    to 30mL

(A 1% w/v solution of ephedrine hydrochloride depresses the freezing point by 0.169 ºC. A 1% w/v solution of sodium chloride depresses the freezing point by 0.576 ºC.)

(4 marks)

d) Patient is a 50-year-old male, 70 kg, 5 ft 10 with bipolar disorder. He is prescribed lithium carbonate 300 mg tablets 1 tab orally every 8 hours. (3 marks)

(i) How much lithium, in milliequivalence (“mEq”), is the patient consuming each day? (Molecular weight of Li₂CO₃ is 73.891 g/mol)

(ii) The patient’s serum creatinine is currently 80 µmol/L. The clearance of lithium is estimated to be 20 % of CrCL. The bioavailability of lithium carbonate is expected to be 100 %. What is the expected steady state average concentration of lithium, in mmol/L?

(iii) Subsequently, the patient recovers from the episode and continues on maintenance therapy. An appropriately drawn lithium serum concentration reveals 1.0 mmol/L when the patient is on the above regimen. The physician would like a lithium serum concentration between 0.6 to 0.8 mmol/L for the maintenance therapy. Recommend an appropriate dosing regimen, including drug, dose, route and frequency for that target.

e) Intravenous gemcitabine 1 000 mg/m2 was prescribed for a 5 ft 2 in, 112 lbs female with ovarian cancer. (3 marks)

(i) Calculate the dose for this patient.

(ii) Your pharmacy stocks gemcitabine 1 g vials. Each vial is to be reconstituted with 25 mL of preservative-free normal saline (“NS”) to give a reconstitution solution of 38 mg/mL. What is the volume of reconstituted solution needed for the dose?

(iii) Your hospital policy requires that gemcitabine to be diluted with 100 mL NS and infused over 30 minutes. What is the appropriate infusion rate?

f) Patient required oral corticosteroid therapy for acute exacerbation of asthma. She received hydrocortisone 100 mg intravenously every 8 hours for 3 doses, then prednisolone 40 mg orally (“PO”) daily for 7 days. Upon discharge, she is given the following steroid taper prescription with methylprednisolone.

Day 1: 8 mg PO before breakfast, 4 mg after lunch, 4 mg after dinner, and 8 mg at bedtime

Day 2: 4 mg PO before breakfast, 4 mg after lunch, 4 mg after dinner, and 8 mg at bedtime

Day 3. 4 mg PO before breakfast, 4 mg after lunch, 4 mg after dinner, and 4 mg at bedtime

Day 4: 4 mg PO before breakfast, 4 mg after lunch, and 4 mg at bedtime

Day S. 4 mg PO before breakfast, and 4 mg at be‹Itime

Day 6: 4 mg PO before breakfast

Day 7: OFF taper

(i) Your pharmacy stocks methylprednisolone 4 mg tablets. What is the total quantity to be dispensed for this prescription?

(ii) What is the cumulative steroid dose, in hydrocortisone equivalence, for this episode?

(2 marks)

g) Intravenous mannitol is used preoperatively to reduce intraocular pressure. (2 marks)

(i) Your hospital policy states that mannitol should be diluted to a 15% solution before intravenous administration, to reduce risk of precipitation. Mannitol, United States Pharmacopeia (“USP”) is available as 12.5 g / 50 mL solution. What is the volume of sterile water for injection required to dilute 50 inL of the mannitol solution?

(ii) Calculate the theoretical osmolarity of the 15 % mannitol solution. (Molecular weight of mannitol is 182 g/mol)

2) P.E. is a 54-year-old female recently diagnosed with rheumatoid arthritis. P.E. had received drug treatment of methotrexate (“MTX”) and leflunomide but failed to achieve remission within 6 months of disease-modifying antirheumatic drugs (“DMARDs”) therapy. P.E.’s case medical officer is considering to prescribe biologic or targeted synthetic disease-modifying antirheumatic drugs (“bDMARDs” or “tsDMARDs”) for her.

a) Describe any TWO types of bDMARDs for the treatment of rheumatoid arthritis. List ONE example of drug agent for EACH type of bDMARDs and the route of administration. (3 marks)

b) Describe the screening laboratory tests required for P.E. before the initiation of bDMARDs. (2 marks) 

c) Describe ONE type of tsDMARD for the treatment of rheumatoid arthritis. List ONE example of drug agent for this type of tsDMARD and its route of administration. (2 marks)

d) P.E.’s case medical officer enquired about the United States Food and Drug Administration (“USFDA”)’s warning on the use of tsDMARD. Describe in detail on your reply to P.E.’s case medical officer. (3 marks)

e) Describe the treatment options for P.E. if eventually, she does not respond adequately to the drug therapy of MTX plus bDMARD or tsDMARD. (5 marks)

3) SANCUSO transdermal patch is indicated in adults for the prevention of nausea and vomiting caused by chemotherapy. It contains granisetron as the active ingredient. The patch is usually applied 24 to 48 hours before chemotherapy begins and should be left in place for at least 24 hours after chemotherapy, but should not be worn continuously for longer than a total of 7 days.

a) Explain why the patch should be applied 24 to 46 hours before chemotherapy. (2 marks)

b) Explain why the patch should be applied to a specific location (outer part of the upper arm or abdomen) and why it has to be applied on intact healthy skin. (3 marks)

c) How would you counsel patients if they enquire whether the patch can be cut into pieces and what would you do if the patch is detached during the treatment? (4 marks)

d) Granisetron is also available in oral tablet form and solution form for injection/infusion. Compare these routes of administration for granisetron. (6 marks)

4) Mr C.D. was admitted to hospital for ischaemic stroke of moderate severity 5 hours after the onset of his symptoms. Selected information from the medical chart is as follows.

a) The treating team asked for your opinion in starting dual antiplatelets (both short term and long term) for Mr C.D. given his history of TIA and now episode of ischaemic stroke despite of being on aspirin. Provide your advice with explanation. (5 marks)

b) What statin benefit group does Mr C.D. belong to? Would you suggest any changes to Mr C.D.’s current statin? Please provide rationale to support your recommendation. (4 marks)

c) What is statin intolerance? If Mr C.D. is intolerant to statins, please identify an alternative cholesterol-lowering drug and describe the mechanism of action for this drug. (4 marks)

d) During this admission, the doctor would like to improve patient’s diabetes control and help him lose some weight. Name the drug that is indicated for both weight loss and diabetic control and the proposed mechanism of this drug in weight loss. (2 marks)

5) L.C.M. is a 61-year-old female with newly diagnosed Stage IV non-small cell lung cancer (“NSCLC”). The oncologist would like to start her on the first-line regimen containing carboplatin, paclitaxel, bevacizumab, and atezolizumab. L.C.M.’s past medical history is also significant of type 2 diabetes, hypertension, and chronic kidney disease.

a) Please advise on the necessary lab monitoring and physical assessment required before starting on bevacizumab therapy. (5 marks)

b) L.C.M. was given a granisetron patch to be applied the day before chemotherapy. On the day of chemotherapy, she tells you that she has just put the patch on that same morning. What is your recommendation to the patient and doctor? What other pre-medications needs to be given to L.C.M. before starting her chemotherapy regimen? (4 marks)

c) 8 weeks after the start of anti-cancer therapy, L.C.M reports nausea, severe diarrhea, along with abdominal pain. Upon further assessment, the symptoms are suggestive of non-infective colitis. What is likely the causative agent and how would you manage these symptoms? (6 marks)