Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacolog y of the drug and therefore potentially avoidable. Frail elderly patients appear to be particularly at risk of ADRs and this group is also likely to be receiving several medicines. The toxicity of some drug combinations may sometimes be synergistic and be greater than the sum of the risks of toxicity of either agent used alone. In order to recognize and to prevent ADRs (including drug interactions), good communication is crucial, and prescribers should develop an effective therapeutic par tnership with the patient and with fellow health professionals. Undergraduate and postgraduate education in evidence-based therapeutics is also vitally important. The use of computer-based decision support systems (CDSS) and electronic prescribing should be encouraged, and when problems do occur, health professionals need to be aware of their professional responsibility to report suspected adverse drug events (ADEs) and ADRs. 'Rational' or 'obligatory' polypharmacy is becoming a legitimate practice as increasing numbers of individuals live longer and the range of available therapeutic options for many medical conditions increases. The clear risk of ADRs in this situation should be considered in the context that dose-related failure of existing therapy to manage the condition adequately may be one of the most important reasons for admission of the elderly to hospital. Thus, age itself should not be used as a reason for withholding adequate doses of effective therapies.

Inflammation in patients defined as frail by Fried’s phenotypic definition may be related to sarcopenia. This study aimed to investigate inflammation in older patients across different frailty criteria. Frailty status was determined in 110 patients aged over 75 years (mean 83.9 years) according to function (dependent, intermediate, independent); Fried (three or more items of exhaustion, weight loss, slow walking speed, low handgrip strength, low physical activity) and Frailty Index (a measure of accumulated deficits). With increasing patient frailty as defined by function and by Fried phenotype, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) increased significantly. Albumin was lowest in the frailest subjects by each definition. The greatest differences were seen between intermediate and dependent groups and between the pre-frail and frail. Adjustment for multiple covariates (age, sex, BMI category, smoking status, number of co-morbidities and number of prescribed medications) did not account for any of the observed differences in levels of inflammatory markers. The Frailty Index correlated significantly with log-transformed CRP (r= 0.221, P < 0.05), log-transformed IL-6 (r= 0.369, P < 0.01), TNF-α (r= 0.379, P < 0.01) and inversely with albumin (r=– 0.545, P < 0.01). This study provides further evidence linking inflammation and frailty in older people, an association that seems consistent across different frailty measures.

The association of age, physical frailty and liver size upon hepatic conjugation reactions was studied using paracetamol as a model drug. Nineteen fit subjects (mean age 26 years), 20 fit subjects (mean age 73 years), and eight frail, hospitalized subjects (mean age 82 years) were recruited. Paracetamol clearance expressed in terms of body weight was significantly lower in the fit elderly than in the fit young subjects, and was lowest in the frail elderly subjects (p less than 0.01). There was no difference in paracetamol clearance expressed per unit volume of liver between the fit young and fit elderly subjects but it was significantly reduced in the frail subjects. Although the partial metabolic clearance to paracetamol sulphate was preserved per unit volume of liver with ageing and frailty, the partial metabolic clearance to paracetamol glucuronide per unit volume of liver was markedly reduced in the frail elderly (p less than 0.01) when compared with the fit subjects. These results show that age-associated changes in paracetamol clearance are attributable to both changes in liver volume and in general health. The findings underline the important influences of the elderly person's physical state upon drug clearance.

No abstract