The clinical pharmacist improves pharmacotherapy in hospital patients: Medication reviews - Metformin toxicity - Binding interactions

This thesis describes, in three different parts, how the clinical pharmacist can contribute in improving pharmacotherapy of hospital patients.

Firstly, the clinical value of pharmacist-led medication reviews was assessed in (pre)dialysis patients and older patients with cancer. We concluded that pharmacist-led medication reviews are a suitable instrument to identify drug related problems and inappropriate prescribing in order to improve medication management in these complex hospital patients.

Secondly, the management of metformin associated lactic acidosis (MALA), a rare but serious adverse effect of a frequently used drug for diabetes mellitus type 2, was studied.
The incidence of MALA is 5 to16 times higher than reported in literature. When managing lactic acidosis in the emergency department the diagnosis MALA should be considered in patients with a creatinine concentration ≥ 256 umol/l and lactate concentration ≥ 8.4 mmol/l. Severity of lactic acidosis and renal impairment are the main indications for initiating extracorporeal treatment, which may be lifesaving in treating MALA.

Finally, several potential new drug binding interactions were studied with sevelamer and polystyrene sulfonate, drugs that are often used by chronic kidney disease patients.
Fourteen and 23 potentially new binding interactions with sevelamer and polystyrene sulfonate were established based on an in silico – in vitro approach, which have to be confirmed in vivo. The binding interaction, amitriptyline with polystyrene sulfonate, was studied in healthy volunteers. The exposure of amitriptyline was decreased with 75% when amitriptyline was simultaneously ingested with polystyrene sulfonate compared to intake of amitriptyline alone, necessitating staggered dosing between drugs.