Farnesyltransferase inhibitors in Hutchinson-Gilford progeria – RGH Pharmacy E-Bulletin

Interaction

Farnesyltransferase inhibitors (FTIs) are a new class of biologically active agents originally developed as potential anticancer drugs, and are currently unavailable in Australia.

FTIs inhibit the enzyme farnesyltransferase, preventing the farnesylation and hence activation of a wide range of target proteins, including Ras (which is mutated in 30 % of all human cancers), ultimately resulting in cell growth arrest. In preclinical models, farnesyl transferase inhibitors showed great potency as a novel anti-cancer agent; yet in clinical studies, the early potential of FTIs were not realised.

This was attributed to several reasons: the molecular pharmacology and biology of FTIs had not yet been fully elucidated, an escape mechanism for the inhibition by FTIs was discovered (known as geranylgeranylation) and a well-defined proof of the concept of clinical studies was lacking.

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A joint initiative of the Patient Services Section and the Drug and Therapeutics Information Service of the Pharmacy Department, Repatriation General Hospital, Daw Park, South Australia. The RGH Pharmacy E-Bulletin is distributed in electronic format on a weekly basis, and aims to present concise, factual information on issues of current interest in therapeutics, drug safety and cost-effective use of medications.
Editor: Assoc. Prof. Chris Alderman, University of South Australia – Director of Pharmacy, RGH © Pharmacy Department, Repatriation General Hospital, Daw Park, South Australia 5041.

Factors influencing clozapine plasma concentrations – RGH Pharmacy E-Bulletin

Interaction

The use of therapeutic drug monitoring for clozapine is indicated in various situations, including poor compliance, inadequate response to treatment, presence of significant adverse effects, the presence of specific disease states (especially hepatic disease) and where there may be drug interactions.

In clinical practice, the dose of clozapine is usually adjusted to provide plasma concentrations of 350 – 600micrograms per litre. However some patients may respond to lower concentrations, or conversely may experience limiting adverse effects despite concentrations in the recommended range.

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A joint initiative of the Patient Services Section and the Drug and Therapeutics Information Service of the Pharmacy Department, Repatriation General Hospital, Daw Park, South Australia. The RGH Pharmacy E-Bulletin is distributed in electronic format on a weekly basis, and aims to present concise, factual information on issues of current interest in therapeutics, drug safety and cost-effective use of medications.
Editor: Assoc. Prof. Chris Alderman, University of South Australia – Director of Pharmacy, RGH © Pharmacy Department, Repatriation General Hospital, Daw Park, South Australia 5041.

Rasagiline – RGH Pharmacy E-Bulletin

Interaction

The treatment of Parkinson’s disease often requires the use of multiple agents to achieve optimal symptom control with minimal side effects.

The mainstay of treatment is levodopa, however the development of movement disorders occurs with long term treatment. In younger patients, therefore, it may be preferable to reserve levodopa for use later in the course of disease progression. Also, in patients taking long term levodopa, additional therapies may help to reduce motor fluctuations.

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Duration of dual-antiplatelet therapy after coronary stenting – RGH Pharmacy E-Bulletin

Interaction

Acute coronary syndrome (ACS) encompasses the spectrum of unstable angina and myocardial infarction, with or without ST elevation.

Percutaneous coronary intervention (PCI) including coronary stenting is often performed in this context. Both ACS and PCI are associated with high levels of platelet activation, and thus dual-antiplatelet therapy with aspirin and clopidogrel is essential after coronary stent implantation to reduce the risk of thrombosis.

A longer duration of dual-antiplatelet therapies is often required after implantation of drug-eluting stents due to delayed endothelialisation, but the optimal duration of dual antiplatelet therapies and the associated risk-benefit ratio is not well defined.

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A joint initiative of the Patient Services Section and the Drug and Therapeutics Information Service of the Pharmacy Department, Repatriation General Hospital, Daw Park, South Australia. The RGH Pharmacy E-Bulletin is distributed in electronic format on a weekly basis, and aims to present concise, factual information on issues of current interest in therapeutics, drug safety and cost-effective use of medications.
Editor: Assoc. Prof. Chris Alderman, University of South Australia – Director of Pharmacy, RGH © Pharmacy Department, Repatriation General Hospital, Daw Park, South Australia 5041.

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