Global climate change continues to be the subject of international debate, which has included concern about the health impacts of climate change. Attention has also focused on the impact of ‘heat waves’ on morbidity and mortality.

Over 70,000 additional deaths were recorded in 12 European countries over the summer of 2003 during a prolonged heatwave – after this, a number of related papers were published in medical literature, including some that specifically looked at the potential for increased harm from medicine use during the heatwaves.

A number of countries including Australia have since operationalised ‘National Heat Wave Plans.’ In Australia individual states having developed specific information for to help people to manage in heatwaves, including SA Health’s “Extreme Heat – guide to coping and staying healthy in the heat.”

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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.

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.

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.

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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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.

Huntington’s disease (HD) is a rare, inherited neurodegenerative disorder of the central nervous system, caused by an expansion in the trinucleotide CAG in the huntingtin gene.

Clinical features of the disease include involuntary choreiform movements, psychiatric disturbances, dementia, weight loss and circadian rhythm disturbances.

Multiple areas of the brain are affected by neuronal degeneration, with the predominantly affected neurotransmitters being dopamine, glutamate and GABA.

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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.

There is a 40-50% prevalence of dysphagia among elderly people in residential aged care facilities. Age related, or drug-induced xerostomia may be a cause of difficulty swallowing along with medical conditions such as stroke, Parkinson’s disease and motor neurone disease.

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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.

Low molecular weight heparins (LMWH) are commonly used in the prophylaxis and treatment of venous thromboembolic (VTE) diseases. However, there is limited evidence to guide the use of LMWH in patients with advanced liver cirrhosis.

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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.

Aminoglycosides
Aminoglycosides exert a post-antibiotic effect: high peak levels are required to penetrate the bacterial cell wall, where the drug continues to have a bactericidal effect after systemic levels have declined. Monitoring is used to ensure adequacy of dosing, to delay or prevent the onset of nephrotoxicity and reduce the risk of vestibular and auditory ototoxicity.

Initial gentamicin dosing is based on bodyweight to ensure an adequate peak concentration.

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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.

Confusion surrounds the prescribing of antimicrobials in renal impairment; whether to reduce the dose or extend the dosing interval. Suggested dose adjustments in renal impairment for many commonly used antibiotics are provided here, based on tables which can be found in the Therapeutic Guidelines (TG) Antibiotic, 14th edition.

No dose adjustment is required for some agents – these include azithromycin, roxithromycin, ceftriaxone, cefaclor, clindamycin, doxycycline, linezolid, moxifloxacin, phenoxymethylpenicillin, metronidazole among others.

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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.

Melanoma is the fourth most common cancer affecting Australians, accounting for 9.5% of all cancers in this country, with more than 10,300 new cases diagnosed annually. While melanoma is the least common dermatological cancer, it is associated with the highest rates of mortality and accounts for around 75% of all skin cancer related deaths.

Vemurafenib (Zelboraf®) is a targeted new oral therapy for metastatic and unresectable melanomas which carry the BRAF-V600E gene mutation.

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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.

Calciphylaxis or calcific uremic arteriolopathy is a complex syndrome which causes vascular calcification and skin necrosis.

It is characterised by the presence of calcification of the arteries and soft tissues and it causes skin necrosis resulting in ulcer formation. Clinical markers include altered sensations on the skin and mottled skin lesions, plaques and nodules which can lead to painful necrotic ulcers.

Disorders that are most often implicated in the pathogenesis of calciphylaxis include chronic renal failure, obesity, diabetes, hypercalcemia, hyperphosphotaemia, an elevated calciumphosphate product and secondary hyperparathyroidism.

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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.

Exacerbations of chronic obstructive pulmonary disease (COPD) are periods of worsening COPD symptoms, during which patients experience increased dyspnoea, cough and /or sputum production.

Observational studies have shown patients often delay seeking medical advice for up to one week after symptom onset, and delays are associated with worse clinical outcomes and an increased risk of hospitalisation.

Exacerbations become more frequent as COPD progresses, and in patients with severe COPD often result in hospital admission for management of respiratory failure.

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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.

Riluzole is a neuroprotective agent used in the treatment of motor neurone disease.

The precise mechanism of action of riluzole is unclear, however evidence supports a reduction in glutamate-induced excitotoxicity by three mechanisms: noncompetitive blockade of N-methyl-D-aspartate (NMDA) glutamate receptors, inhibition of the release of presynaptic glutamic acid, and inactivation of voltage-dependent sodium channels.

Motor neurone disease (MND) is a neuromuscular disorder that progressively results in widespread muscle weakness, leading to death within 3-4 years of onset.

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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.

Lactose is the carbohydrate naturally found in all kinds of milk, including human milk. It can also be used as an ingredient in some foods and is commonly used as a filler or excipient in pharmaceutical preparations (both tablets and capsules) including prescription, over the counter and complementary medicines. Lactose can also be used in dry-powder inhalations and rarely in liquid preparations. Approximately one in five prescription products contain lactose.

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The term antibiotic resistance refers to the ability of bacteria and other micro-organisms to withstand the effects of an antibiotic to which it was previously sensitive. Consequently, these resistant organisms are not inhibited by antibiotics at the serum/tissue concentrations achievable after normal dosing of the drug. In contrast to other drugs, antibiotics are unique in that the use of these agents in one patient can influence future efficacy – not only in the same patient but also for other patients and potentially a whole population.

The widespread use of antibiotics has exerted selective resistance pressure, and this, coupled with the transfer of microorganisms between people, has led to (often rapid) emergence of antibiotic resistance. Only a low level of native genetic antibiotic resistance exists in micro-organisms, but the abundance and variation in resistance genes in bacteria became established after extensive clinical use of man-made antibiotics in various settings.

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Ophthalmic medications are used for a number of conditions such as glaucoma, infection, allergy and inflammation, often on a chronic basis. Generally the drugs used in this manner have good safety profiles, but they do have the potential to cause significant adverse drug events, and can interact with other systemic medications.

The pharmacokinetic profile associated with ocular drug delivery resembles that of intravenous administration more closely than that of oral administration. Ophthalmic medications pass through the lacrimal sac and have access to the highly vascular nasal mucosa. Drugs are variably absorbed from this site, but importantly they avoid first-pass hepatic metabolism. This can be important for drugs that undergo a high degree first-pass metabolism, such as timolol. One drop of a 0.5% solution of timolol in each eye is approximately equivalent to a 10mg oral dose of the drug.

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A recent incident at one of the campuses of the Southern Adelaide Local Health Network has once again drawn attention to the potential for significant adverse consequences if a medication is administered to a patient via a route other than that which was intended. If a drug intended for oral administration via a nasogastric tube is inadvertently administered via an IV line, this can cause a serious adverse reaction or even death.

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Since this bulletin came out in June the withdrawal was challenged by one of the manufacturers.

Dextropropoxyphene is an opioid analgesic used to treat moderate to severe pain. In addition to expected opioid adverse effects, serious adverse drug reactions including hepatic reactions, hallucinations, abuse, withdrawal symptoms and cardiac conduction abnormalities have been reported with this agent. A change in the patient’s disease state, other medications, or a decrease in kidney function can greatly increase the risk for cardiac effects.

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Apixaban functions as an oral anticoagulant by inhibiting the clotting factor Xa, resulting in decreased levels of thrombin. Apixaban is one of three orally active anticoagulants now available for subsidised supply in Australia through the Pharmaceutical Benefits Scheme, for the prevention of venous thromboembolism after hip or knee replacement. The others alternative agents are rivaroxaban and dabigatran.

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