PART II-ESSAY QUESTIONS
1. Pharmaceutical Calculations
a) A child weighing 50 pounds requires a dose of 7 mg/kg of drug X. Given that a 5 mL dose is to be given each time, what volume of water must be added when the drug X powder is reconstituted? Instruction on the label indicates that dilution to 120 mL (by adding 95 mL of water) gives 200 mg drug X per 5 mL.
b) An intravenous solution of sodium chloride 0.5% requires to be made isotonic by the addition of dextrose. What weight of dextrose is required in the preparation of 500 mL of the intravenous solution? (A 1% solution of sodium chloride depresses the freezing point of water by 0.576°C. A 1% solution of dextrose depresses the freezing point of water by 0.091°C.)
c) You have 20%, 15% and 5% zinc oxide ointment. In what proportion should they be mixed together in order to make a 10% zinc oxide ointment? All these 3 ointments must be used.
d) Patient MMK is a 56-year-old, 154 pounds and 5 feet 4 inches female. She is starting her first dose of rituximab for Non-Hodgkin's Lymphoma.
(i) The regimen is 375 mg/m2 IV once weekly for 4 doses. Calculate the dose for this patient.
(ii) Rituximab is available in 100mg/10mL and 500mg/50mL single-dose vials. You are going to procure the medication for her entire rituximab regimen. How many vials do you need to order for this patient?
(iii) The instruction for the first infusion is as follows:
“Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr. "
What is the minimum infusion time for her first infusion, assuming she does not have any infusion toxicity?
(e) Subsequently, patient MMK from part (d) presents with urinary tract infection. (3 marks)
Her latest serum creatinine is 105 μmol/L. The physician prescribed gentamicin 420 mg IV Q24H infused over 1 hour.
(i) Gentamicin volume of distribution is estimated to be 0.25 L/kg, and clearance is expected to 100% of creatinine clearance. What is the expected half-life of gentamicin in this patient?
(ii) Your pharmacy stocks gentamicin 80 mg/2 mL vials. Your hospital policy states that extended-interval aminoglycosides should be diluted in 100 mL normal saline ("NS"). What is the appropriate infusion rate?
(iii) Therapeutic drug monitoring of extended-interval aminoglycoside typically involves taking a single blood level in the middle of the dosing interval. What is the expected steady state concentration at 12 hours after start of infusion?
f) After receiving the gentamicin as in part (e), patient MMK develops mild hypokalemia and the doctor orders potassium chloride ("KCI") 8 mmol to be added to 500 mL of Dextrose 5% + NaCl 0.45% (“D5-1⁄2NS”), and to be infused as a continuous infusion.
(i) The KCl is available in 14.9% concentrated solution. What is the volume required to prepare the infusion solution (molecular weight of KCl is 74.5 g/mol)?
(ii) What is the approximate concentration of potassium (in mEq/L) in the infusion solution?
(iii) What is the approximate osmolarity (in mOsmol/L) of the infusion solution?
g) Eventually patient MMK in part (f) is discharged home with an oral antibiotic. Because she suffers painful mouth sore after her chemotherapy, she requests to have oral solution instead of solid dosage forms.
(i) The doctor orders co-trimoxazole 960 mg PO BD for 3 days. Your pharmacy stocks co-trimoxazole 480 mg oral tablets and 240 mg/5 mL oral suspension in 60 mL bottles. What is the total quantity to be dispensed for this prescription?
2. H.T. is a 55-year-old man in the status of post neurosurgery secondary to head trauma sustained from a motor vehicle crash. H.T. is intubated and sedated but has spiked multiple fevers (maximum temperature, 39°C) over the past 24 hours. There is no change in oxygen requirements and laboratory test values are stable with normal renal function. Blood and urine culture and sensitivity results are pending.
a) Dr. Fernando, a medical officer of the night shift, made an enquiry on the concern of possible central nervous system ("CNS") bacterial source for empirical antibiotic coverage.
(i) Suggest TWO common pathogens the empirical treatment should cover.
(ii) List TWO antibiotics in combination as empirical treatment for H.T. (Note: antibiotic dosages are not required)
b) In addition, Dr. Fernando was concerned about the antibiotic penetration into the CNS for the empirical treatment of suspected meningitis. (6 marks)
(i) List THREE drug characteristics which determine the antibiotic penetration into CNS (i.e. Cerebrospinal fluid ("CSF") concentration).
(ii) Explain how each drug characteristic influences the antibiotic penetration into CNS.
c) On the day of intensive care unit (“ICU”) admission, you performed medication reconciliation on H.T.'s drug profile and revealed that H.T. is receiving adalimumab SC injection for rheumatoid arthritis.
(i) Explain the rationale in reviewing the bacteria coverage for H.T.'s empirical treatment.
(ii) What is the additional bacteria coverage to be considered?
(iii) Suggest an antibiotic to be added to the empirical treatment for H.T.
d) Given H.T.'s decline in mental status on day 2 of ICU admission, Dr. Fernando asked if adjuvant corticosteroid would be indicated for H.T.
(i) Give ONE benefit of adjuvant corticosteroid use in suspected bacterial meningitis.
(ii) Suggest the corticosteroid and the route of administration for use in H.T.
3. The Atrigel® system is a sustained-release drug delivery platform that delivers a wide spectrum of drugs over a few days to several months with a single injection. Atrigel® consists of biodegradable polymers dissolved in biocompatible carriers. When the liquid product is injected into the subcutaneous space through a small gauge needle, water in the tissue fluids causes the polymer to precipitate and trap the drug in a solid implant. A number of marketed products based on this technology include Atridox® and Atrisorb (Doxycycline hyclate), Eligard (Leuprolide acetate), Sandostatin® (Octreotide acetate), and Sublocade® (Buprenorphine extended-release) etc.
a) Explain how the sustain-release of incorporated drug can be achieved. (5 marks)
b) Drug delivered by the Atrigel system can last for a few days to several months. Please list out THREE factors that can affect the release rate and provide brief explanation. (6 marks)
c) Please comment on the ADVANTAGE and DISADVANTAGE of Atrigel® drug delivery system. (4 marks)
4. JCC is a 49-year-old male patient who has been taking the below medications for at least a year. His medical history is significant for hypertension, insomnia and anxiety disorder.
Losartan 100 mg daily
Amlodipine 5 mg daily
Vortioxetine 20 mg at bedtime
Diazepam 5 mg TDS
Melatonin 2 mg at bedtime
Mirtazapine 45 mg at bedtime
Zolpidem 10 mg at bedtime PRN
a) Despite the drug treatment for insomnia, JCC complains that he often has problems of waking too early and waking a few times at night. Describe any pharmacological modifications to his current medications that can improve his sleep. (6 marks)
b) Lemborexant belongs to the class of dual orexin receptor antagonists and is available in Hong Kong. Discuss why it may be more suitable for JCC when compared to his current regimen. (6 marks)
c) Suggest an initial dose of Lemborexant and provide TWO important counselling points to JCC. (3 marks) .
5. YSK is an 81-year-old female admitted for acute exacerbation of COPD. She has been admitted multiple times for the same condition in the past 12 months. YSK's past medical history is also significant of peptic ulcer (resolved one year ago), tuberculosis, and adrenal insufficiency on hydrocortisone. During day 3 of this hospitalization, YSK complained of epigastric pain and vomited twice. Endoscopy revealed a bleeding ulcer in the gastric antrum.
a) Please identify all the potential risk factors in YSK for this upper gastrointestinal ("GI") bleeding. (4 marks)
b) What is your recommendation for the pharmacological management of acute GI bleeding? Please provide specific regimens and state the purpose of each of the management strategies. (6 marks)
c) YSK eventually stabilized and is discharged home with her usual medications and oral pantoprazole. What are the possible side effects with long-term proton-pump inhibitor use? (5 marks)
END OF PAPER