Sam, a 58-year old male, has been treated with extended release lithium carbonate for the management of bipolar depression for the past 23 years. He has presented to the Emergency Department after experiencing increasingly frequent and severe episodes of dizziness and tremors over the past three days. On presentation, he is found to have a blood pressure of 86/43, and an irregular heart rate of approximately 41bpm. A panel of blood tests are ordered as a component of Sam’s initial diagnosis, the results of which are all normal, except for an estimated glomerular filtration rate (eGFR) of 15mL/min. The clinician concludes that Sam’s symptoms are most likely the result of an adverse drug reaction resulting from his use of lithium carbonate.

Question:

Discuss the factors that are likely to have contributed to Sam’s presentation. (Hint: consider the consequences of long-term lithium use and the mechanism of lithium clearance) (300 words; 3 marks)

Inter-Individual Variability

As a new targeted anti-cancer drug ‘FCIC-15’ enters Phase III clinical trials, it is determined that the drug requires hepatic activation in order to elicit a therapeutic effect. Further studies identify that the sole enzyme involved in the activation of this drug is CYP2C19.

Question:

a) Select ONE specific factor (from the categories environmental, genetic or physiological) that may contribute to inter-individual variability in the activation of ‘FCIC-15’, and explain the potential consequences of this variability in terms of treatment response and tolerability. (200 words; 3 marks)
b) Briefly discuss how this variability may be controlled for in clinical practice. (100 words; 1 mark)