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PubMed2001

Benefits and risks of self medication.

Self medication is becoming an increasingly important area within healthcare. It moves patients towards greater independence in making decisions about management of minor illnesses, thereby promoting empowerment. Self medication also has advantages for healthcare systems as it facilitates better use of clinical skills, increases access to medication and may contribute to reducing prescribed drug costs associated with publicly funded health programmes. However, self medication is associated with risks such as misdiagnosis, use of excessive drug dosage, prolonged duration of use, drug interactions and polypharmacy. The latter may be particularly problematic in the elderly. Monitoring systems, a partnership between patients, physicians and pharmacists and the provision of education and information to all concerned on safe self medication, are proposed strategies for maximising benefit and minimising risk.

Drug Therapy↗

PubMed2001

Asthma medications and their potential adverse effects in the elderly: recommendations for prescribing.

The incidence of drug-induced adverse effects is likely to increase as a result of advanced age and exposure of elderly patients to polypharmacy. Therefore, pharmacological therapy of asthma and chronic obstructive pulmonary disease (COPD) in the elderly patient can be potentially hazardous. beta(2)-agonists, administered as therapy for asthma and COPD, have recognised systemic sequelae, such as hypokalaemia and chronotropic effects, which may be life-threatening in susceptible patients. Adverse effects such as hypokalaemia can be aggravated by concomitant treatment with other drugs promoting potassium loss including diuretics, corticosteroids and theophyllines. In addition, relatively minor adverse events associated with the administration of beta(2)-agonists, such as tremor and blood pressure changes, may be of significance to the elderly patient leading to impairment in the quality of life. However, long-term treatment with beta(2)-agonists may reduce the incidence of drug-induced adverse effects as a result of beta-receptor subsensitivity. Oral and inhaled corticosteroids have been used for the treatment of acute asthma and COPD in the elderly patient. Long-term treatment with oral corticosteroids can result in serious systemic adverse effects such as suppressed adrenal function, bone loss, skin thinning and cataract formation. In contrast to beta(2)-agonists, oral corticosteroids can upregulate beta(2)-adrenoceptors and thereby potentiate the systemic sequelae of beta(2)-agonists. Hence, oral corticosteroids should be administered with caution for as short a duration as possible. Inhaled corticosteroids appear to be relatively well tolerated when administered at doses below approximately 1000 microg. However, larger doses of inhaled corticosteroids may affect hypothalamic-pituitary-adrenal function and bone turnover. In the case of inhaled corticosteroids, spacer devices, often used in older patients who cannot operate metered dose inhalers, can potentiate the systemic sequelae of both corticosteroids and beta(2)-agonists. The use of theophyllines in the treatment of COPD or chronic asthma is controversial. Theophyllines have a wide adverse effect profile and are prone to drug-drug interactions. The adverse effects may be mild or life threatening and include nausea and vomiting or sinus and supraventricular tachycardias. Therefore, theophyllines should be prescribed with extreme caution to elderly patients with asthma or COPD. In contrast, inhaled anticholinergic drugs such as ipratropium bromide and oxitropium bromide are generally safe in elderly patients and have useful bronchodilator function. Commonly reported adverse effects are an unpleasant taste and dryness of the mouth. When used as first-line therapy, anticholinergic drugs may optimise the bronchodilator effects of low-dose inhaled beta(2)-agonists in patients with chronic airflow obstruction, and hence obviate the need for higher doses.

Adrenal Cortex Hormones↗

PubMed2002

Clinically significant interactions with drugs used in the treatment of tuberculosis.

Clinically significant interactions occurring during antituberculous chemotherapy principally involve rifampicin (rifampin), isoniazid and the fluoroquinolones. Such interactions between the antituberculous drugs and coadministered agents are definitely much more important than among antituberculous drugs themselves. These can be associated with consequences even amounting to therapeutic failure or toxicity. Most of the interactions are pharmacokinetic rather than pharmacodynamic in nature. The cytochrome P450 isoform enzymes are responsible for many interactions (especially those involving rifampicin and isoniazid) during drug biotransformation (metabolism) in the liver and/or intestine. Generally, rifampicin is an enzyme inducer and isoniazid acts as an inhibitor. The agents interacting significantly with rifampicin include anticoagulants, anticonvulsants, anti-infectives, cardiovascular therapeutics, contraceptives, glucocorticoids, immunosuppressants, psychotropics, sulphonylureas and theophyllines. Isoniazid interacts principally with anticonvulsants, theophylline, benzodiapines, paracetamol (acetaminophen) and some food. Fluoroquinolones can have absorption disturbance due to a variety of agents, especially the metal cations. Other important interactions of fluoroquinolones result from their enzyme inhibiting potential or pharmacodynamic mechanisms. Geriatric and immunocompromised patients are particularly at risk of drug interactions during treatment of their tuberculosis. Among the latter, patients who are HIV infected constitute the most important group. This is largely because of the advent of new antiretroviral agents such as the HIV protease inhibitors and the non-nucleoside reverse transcriptase inhibitors in the armamenterium of therapy. Compounding the complexity of drug interactions, underlying medical diseases per se may also contribute to or aggravate the scenario. It is imperative for clinicians to be on the alert when treating tuberculosis in patients with difficult co-morbidity requiring polypharmacy. With advancement of knowledge and expertise, it is hoped that therapeutic drug monitoring as a new paradigm of care can enable better management of these drug interactions.

AIDS-Related Opportunistic Infections↗

PubMed2004

Tolerability profile of metformin/glibenclamide combination tablets (Glucovance): a new treatment for the management of type 2 diabetes mellitus.

It is important to manage blood glucose intensively in patients with type 2 diabetes mellitus in order to reduce the risk of long-term complications. Oral combination therapy that addresses insulin resistance and beta-cell dysfunction is a proven means of improving glycaemic control when monotherapy becomes insufficiently effective. Metformin/glibenclamide (glyburide) combination tablets were developed to provide a means of applying this strategy while minimising polypharmacy. This review examines the tolerability profile of this treatment from four double-blind, randomised clinical trials in a total of 2342 type 2 diabetic patients with hyperglycaemia despite treatment with diet and exercise, a sulphonylurea or metformin. Treatment with combination tablets was associated with markedly superior blood glucose control, at lower doses of metformin and glibenclamide, compared with monotherapies. The incidence of symptoms of hypoglycaemia varied between dosages and trials, though the incidence of severe or biochemically confirmed hypoglycaemia or withdrawals from clinical trials for this reason was consistently low and comparable with glibenclamide alone. No patient required third-party assistance for hypoglycaemia. Significantly fewer diet-failed patients receiving low-dose combination tablets reported gastrointestinal adverse effects compared with metformin alone, with a comparable incidence between metformin and combination tablets in post-monotherapy studies. The incidence of other adverse events, including serious adverse events, was similar for combination tablets and monotherapies. The lower doses of metformin and glibenclamide with the combination tablet approach, and the design of the combination tablets themselves, may underlie the beneficial tolerability profile of this treatment.

Body Weight↗

PubMed2006

Pharmacokinetic drug interaction profiles of proton pump inhibitors.

Proton pump inhibitors are used extensively for the treatment of gastric acid-related disorders because they produce a greater degree and longer duration of gastric acid suppression and, thus, better healing rates, than histamine H(2) receptor antagonists. The need for long-term treatment of these disorders raises the potential for clinically significant drug interactions in patients receiving proton pump inhibitors and other medications. Therefore, it is important to understand the mechanisms for drug interactions in this setting. Proton pump inhibitors can modify the intragastric release of other drugs from their dosage forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole). Proton pump inhibitors also influence drug absorption and metabolism by interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing simvastatin metabolism), thereby affecting both intestinal first-pass metabolism and hepatic clearance. Although interactions based on the change of gastric pH are a group-specific effect and thus may occur with all proton pump inhibitors, individual proton pump inhibitors differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole have been studied most extensively. A number of studies have shown that omeprazole carries a considerable potential for drug interactions, since it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole appears to have lower potential for interactions with other medications. Although the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been less extensively investigated, evidence suggests that lansoprazole and rabeprazole seem to have a weaker potential for interactions than omeprazole. Although only a few drug interactions involving proton pump inhibitors have been shown to be of clinical significance, the potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.

Anti-Ulcer Agents↗

PubMed1991

Beta-adrenergic function in aging. Basic mechanisms and clinical implications.

Catecholamines have an important endocrine and neuroendocrine role in mediating a variety of autonomic functions. One consequence of normal aging, in particular in the cardiovascular system, is a decline in beta-adrenergic function associated with an alteration in responsiveness to beta-adrenergic therapy. The intrinsic ability for muscle contractility or relaxation is maintained with age and there appears to be an alteration in the process linking the receptor with the contractile or relaxation mechanisms. In rats, beta-adrenergic receptor density decreases with age in adipose tissues and most brain areas, is unchanged in lymphocytes, heart and lung, and increases in the liver. In humans, there are no receptor changes with age in either lymphocytes or brain. In contrast, the number of high-affinity receptors (or coupled receptors) decreases with age in most tissues. In addition, there is a decrease in membrane adenylate cyclase activity or cellular production of cyclic adenosine monophosphate (adenosine 3',5'-cyclic phosphate; cAMP). Plasma noradrenaline (norepinephrine) concentration increases with age. The reduced receptor number in some tissues (down-regulation), the reduced high-affinity receptors and the reduced hormone-stimulated adenylate cyclase activity with age suggests receptor desensitisation to increased plasma noradrenaline concentration. The inability of older animals to desensitise to beta-adrenergic agonists further supports this hypothesis. However, there is an additional post-receptor reduction in catalytic unit activity with age independent of desensitisation. Medications directed at the beta-adrenergic system are commonly used in the elderly. Many of the data on the impact of age on clinical responses are conflicting or unavailable. Concomitant disease, functional status, nutritional state and polypharmacy may play an even greater role than age. However, the available data can be used to guide the selection of therapy, anticipate side effects, and predict potential interactions with other medications and diseases.

Aged↗

PubMedDate not supplied

A critical review of admission and discharge medications in an elderly Australian population.

Medications were examined on admission to and discharge from hospital in an elderly population. Polypharmacy was documented. Patients were discharged on more medications (4:7) than they were taking prior to admission (4.1). This was statistically significant in men (p < 0.001) but not women. Multiple medication changes were undertaken. Admission drug regimens perceived by patient, admitting hospital doctor and general practitioner were also compared. Of 64 patients who were able to name their medications, only 64% described the same list as admitting doctors and only 43% described the same list as general practitioners. Hospital doctor and general practitioner lists were the same in only 37% of cases. Communication between these 3 groups needs to be optimised.

Adult↗

PubMed1995

Anticoagulants in older patients. A safety perspective.

Although anticoagulants are beneficial in the prevention and management of many thromboembolic disorders, they can cause serious bleeding. However, the risk of anticoagulant-related bleeding is not clearly defined for older patients, who are likely to benefit the most from anticoagulant therapy. Older patients may be at increased risk for anticoagulant-related bleeding because of their increased incidence of adverse drug reactions, increased prevalence of comorbidity and polypharmacy and increased vascular and endothelial fragility. Furthermore, the anticoagulant effect of warfarin is increased in older patients. Therefore, it is important to determine whether or not heparin-related and warfarin-related bleeding are more common in older patients. Most studies that have examined age as a risk factor for heparin-related bleeding have found bleeding to be more frequent in older patients: patients 60 years and older were approximately 3 times as likely to develop bleeding during heparin therapy than were younger patients. Studies that have examined age as a risk factor for warfarin-related bleeding have found conflicting results. Seven studies, enrolling a total of 14,388 patients, found that older patients were approximately twice as likely to bleed during warfarin therapy. In contrast, 7 studies, enrolling a total of 2940 patients, found no increase in the frequency of warfarin-related bleeding in older patients. These findings provide a basis for weighing the risks of anticoagulant therapy and for making decisions about the use of anticoagulants in older patients. These findings also indicate the potential value of methods to decrease the frequency of anticoagulant-related bleeding in older patients. Such methods include maintaining the anticoagulant effect within the therapeutic range and recognising other modifiable factors, such as medication use, that may promote bleeding.

Age Factors↗

PubMed1996

Selective inhibitors of cyclooxygenase-2. Potential in elderly patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used as anti-inflammatory and analgesic agents in the elderly, as well as for their anti-thrombotic properties. In the future, NSAIDs may be more widely used in this sector of the population for the prevention of colon cancer. However, the elderly demonstrate a particularly high incidence of adverse reactions to this class of compounds. The factors responsible for this differential toxicity involve age-related pharmacokinetic, pharmacodynamic and physiological factors, as well as coincident disease states and polypharmacy. Selective inhibitors of cyclooxygenase-2 form a novel class of anti-inflammatory drugs that, in animal studies, exhibit significantly fewer adverse effects on the gastrointestinal tract than standard NSAIDs. If this proves to be the case in humans, these novel agents may be useful for the treatment of inflammation and pain as well as in colorectal cancer prevention, but they will not have utility as antithrombotic agents.

Aged↗

PubMed1997

Drug therapy for obesity in the elderly.

The prevalence of obesity is increasing rapidly in the US and other developed countries. Even though the percentage of older individuals is increasing worldwide, obesity has only recently become a recognised problem in this population. Obesity occurs when energy intake chronically exceeds energy expenditure. Moreover, advancing age is associated with an inability to couple energy intake with energy expenditure. Obesity contributes to many adverse health outcomes, including non-insulin-dependent (type II) diabetes mellitus, as well as to an increase in both cardiovascular and all-cause mortality. Only recently has the medical community begun to accept obesity as a disease with a multifactorial pathogenesis that requires systematic lifestyle changes and pharmacological treatment. Several groups of drugs are available for the pharmacotherapy of obesity; anorectic medications (e.g. fenfluramine, dexfenfluramine); substances affecting energy expenditure and body composition [e.g. chromium (chromium picolinate), ephedrine, anabolic steroids, beta 3-adrenoceptor agonists]; and drugs affecting the absorption of nutrients (e.g. orlistat). To date, few drugs have produced and sustained a significant bodyweight loss. However, some drugs induce a significant short term reduction in bodyweight compared with placebo. Moreover, there is a paucity of information regarding the effectiveness of these drugs in the treatment of obesity in the elderly. Furthermore, it is even debated whether obesity should be treated with drug intervention in the elderly. Clinicians prescribing medications for obesity treatment in the elderly need to carefully consider the benefit: risk ratio, given the high prevalence of polypharmacy in elderly patients. Furthermore, physiological changes that occur with aging may affect the pharmacokinetics of administered drugs and need to be taken into consideration.

Aged↗

PubMed1997

Systemic adverse effects of topical ophthalmic agents. Implications for older patients.

Topical ophthalmic medications are widely prescribed by growing numbers of eye-care professionals. Increasingly, these agents are being prescribed by optometrists and ophthalmic-trained nurses in addition to ophthalmologists and general practitioners. As the number and variety of topical agents on the market rises, and as the number of clinicians involved in prescribing those agents increases; the risk of systemic adverse effects will also increase. Thus, professionals involved in the care of these patients must be aware of the risks associated with these drugs in order to minimise the likelihood of complications. Moreover, inadequate training may result in the clinician failing to associate a topical medication with a systemic condition, allowing an adverse effect to pass unrecognised. It is therefore in the interest of the ophthalmic and pharmaceutical communities to improve awareness of the potential dangers intrinsic in the use of topical eye medications. It is the elderly population who are at greatest risk of experiencing systemic adverse effects of topical agents. Chronic ophthalmic diseases, and hence long term ophthalmic drop treatments, are more prevalent among older people. Such individuals are also likely to have other medical conditions (e.g. cardiac, respiratory or neurological disease) that may be induced or exacerbated by topical ophthalmic agents. Moreover, polypharmacy is common in elderly people, and this is associated with an increased risk of drug interactions.

Administration, Topical↗

PubMed1998

Depression in Parkinson's disease. Pharmacological characteristics and treatment.

Parkinson's disease (PD) is a common neurological illness and various degrees of depression frequently complicate its course. Risk factors for developing depression with PD include right-sided hemiparkinsonism, akinesia, increased severity of disability, anxiety and psychosis. Onset of parkinsonism at a younger age, female gender and the use of levodopa are arguable risk factors. Depression may be difficult to diagnose in patients with PD because the signs of the 2 disorders overlap. In addition, patients with atypical PD more commonly have depression than patients with classical PD presentations. Antidepressant response to antiparkinsonian treatment has been limited. Enhancement of catecholamine levels in the CNS by selegiline (deprenyl), a monoamine oxidase (MAO) type B inhibitor, has shown potential antidepressant as well as neuroprotective effects. Other MAO inhibitors have shown antidepressant efficacy in animal models but have not been well tolerated by patients with PD. A catechol-O-methyltransferase (COMT) inhibitor combined with an MAO inhibitor might synergistically maximise the levels of catecholamines in the CNS. Antidepressant medications used in patients without PD include tricyclic antidepressants (TCAs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), but only TCAs have been carefully studied for their antidepressant effects in PD. Electroconvulsive therapy has proven efficacy as antidepressant therapy in patients with PD, and transcranial magnetic stimulation has provided temporary relief of depression under experimental conditions. Adverse effects of polypharmacy in the attempted treatment of depression in patients with PD are common in the elderly. A 'serotonin syndrome' has occurred frequently enough to preclude the coadministration of selegiline with SSRIs or TCAs, and multiple interactions between antiparkinsonian and antidepressant medications further complicate treatment strategies in patients with PD. An algorithmic approach to the pharmacological treatment of depression is described in this article.

Aged↗

PubMed1998

Streptogramins and their potential role in geriatric medicine.

Despite advances in antimicrobial chemotherapy over recent decades, morbidity and mortality secondary to infection continues to rise. In addition, the incidence of infection caused by resistant organisms has also increased. Concurrently, the elderly are living longer than prior generations, often with disabling chronic diseases. The more debilitated of the geriatric population are at greater risk for infection, and more likely to acquire or develop antimicrobial resistant organisms. Gram-positive organisms are a source of resistance and commonly cause infection in older patients. Whereas resistance is a concern in all patients, in the elderly this is magnified by limitations in treatment options because of differences in pharmacokinetics and tolerance as compared with younger counterparts. Pharmacokinetic differences include changes in drug distribution and may arise as a result of diminished end organ function. Age-related decreases in renal function often impact on commonly prescribed antimicrobials. In addition, the elderly are more susceptible to drug-drug interactions because polypharmacy is common in this patient population. Streptogramins may offer a useful alternative in the treatment of infections in the elderly due to their coverage of organisms commonly causing infections in this population and because of their favourable pharmacokinetic profiles. While published experience is limited, streptogramins are not appreciably eliminated by the kidney and, therefore, they are less subject to age-related changes in renal elimination. What is required is multi-dose pharmacokinetic analysis of streptogramins in geriatric populations and subset analysis of patient use data on file. The following will provide the reader with the most recently presented data on streptogramin use and their potential. While focusing on potential use in the elderly, we have cited data and issues which we believe will be relevant in the geriatric population.

Aged↗

PubMed1999

Treatment of amyotrophic lateral sclerosis.

Survival of patients with amyotrophic lateral sclerosis (ALS) is improving. Timely and more frequent implementation of bimodal passive airway pressure (BIPAP) and percutaneous endoscopically placed gastrostomy (PEG) may be the major factors impacting on longer survival. However, several drugs recently subjected to rigorous clinical trials have demonstrated significant results or encouraging trends. ALS is a complex disease in which aging neurons are subjected to a variety of susceptibility genes, most of which remain to be discovered, that interact with equally unrecognised environmental factors. This makes it unlikely that a single therapeutic agent will be of value. The thrust must be on polypharmacy. The 'cocktail' that will eventually be of greatest benefit has yet to be formulated. It might contain glutamate N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists, antioxidants or a combination of trophic factors and neuroprotective agents. This statement is made with the understanding that the aetiopathogenesis of ALS is far from clear. Drug delivery is a problem and better delivery systems are needed. The efficacy of some of the medications that presently only induce modest benefit may be improved by liposomal packaging, use of a patch or inhalation delivery or intraventricular pump reservoirs. There is a great need to develop an early marker of ALS and sensitive reproducible measures of disease progression. This will curtail the present need for large, lengthy and very expensive clinical trials. The new millennium will see the advent of targeted therapy using viral vectors which can deliver replacement genes, trophic factors and other drugs to degenerating neurons; transplantation of neural progenitor cells which can become mature functioning neurons; anti-apoptotic agents which will allow neurons to survive longer; and mechanisms that can protect the telomerase maintenance system which is so crucial in the immortalisation of cells.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Differential kinetics of phenytoin in elderly patients.

The elderly have a relatively high risk of developing adverse drug reactions. Phenytoin continues to be a preferred drug for treating generalised tonic-clonic seizures in the elderly and simple partial seizures that generalise. Phenytoin is eliminated almost entirely by hepatic oxidation. The principle enzymes responsible are cytochrome P450 (CYP)2C9 and CYP2C19. CYP2C9 is saturated by therapeutic doses of phenytoin, and at steady state both enzymes are probably operant in most people. The nonlinear pharmacokinetics of phenytoin make it a difficult drug for which to establish safe and effective administration regimens. An important area of inquiry is whether the differential disposition kinetics of phenytoin in the elderly render its administration an even more difficult challenge. Moreover, since the elderly are generally subject to more polypharmacy than younger adults, are they, as a result, subject to either more frequent or more severe drug interactions with phenytoin than younger adults? In order to examine these issues we were interested in learning the extent to which old age might affect the plasma protein binding of phenytoin, its hepatic metabolism and, ultimately, its pharmacokinetic profile. With regard to the latter we looked carefully at the methods that have been used to characterise the disposition kinetics of phenytoin in general, and in the elderly, in particular. There are many conflicting findings with regard to the effect of age on the disposition kinetics of phenytoin. However, the strategies used for estimating kinetic parameters for phenytoin [viz the maximum rate of metabolism/elimination (Vmax) and the Michaelis-Menton constant (Km)] exhibit deficiencies that could account for some of the disparate findings. Certainly, more careful prospective studies focusing on the effects of age on phenytoin disposition kinetics are warranted. However, in light of the information currently available, no special attention need be paid to the initiation of phenytoin administration in elderly patients who are taking multiple anticonvulsants. On the other hand, for the elderly receiving phenytoin monotherapy, the initiation of phenytoin administration should occur at lower doses than would be customary for younger adults, and phenytoin blood concentrations should be appropriately monitored in order to evaluate individual Vmax and Km values for informed dosage adjustments.

Age Factors↗

PubMed2000

Optimising management of patients with advanced heart failure: the importance of preventing progression.

Heart failure is a highly complex, progressive and deadly disease. When incorrectly treated, it results in irreversible structural damage to the myocardium and resists any conventional treatment. This stage has been arbitrarily termed refractory heart failure. However, with timely and sufficiently applied neurohumoral antagonists, progression can be prevented, or at least delayed. In contrast, as soon as heart failure has become moderate or severe due to advanced left ventricular dysfunction, polypharmacy is the rule. Physicians should make every effort to maintain or reconsider optimal neurohumoral antagonist therapy in such patients, even if symptomatic improvement from these agents may be slow. Proper use of diuretics is essential not only for symptom relief but also to achieve full benefit from angiotensin converting enzyme inhibitors and beta-blockers. Digitalis may be particularly indicated in severe heart failure, irrespective of rhythm. Adjunctive regimens can be helpful in specific patients, but evidence of their salutary effects to prolong life is lacking. In the decompensated state, tailoring intravenous therapy to haemodynamic goals followed by (re-)institution of optimal oral therapy is an option. Only if these strategies fail is heart transplantation justified. While waiting for a donor, patients have been bridged with various intravenous agents, most often inotropes, but symptom relief is associated with risk of increased mortality due to these drugs. New hope emerges from drugs interfering with endothelin and the cytokines, and from research into increasing contractility with calcium sensitising agents. Even though these developments follow established routes, they may enable a more effective approach to prevent worsening heart failure in every single patient.

Cardiovascular Agents↗

PubMed2000

Differential pharmacokinetics of digoxin in elderly patients.

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.

Absorption↗

PubMed2000

Choice and use of newer anticonvulsant drugs in older patients.

Epilepsy is common in the elderly. The incidence of epilepsy is age-dependent, with a peak during the first year of life and higher incidence in those older than 75 years. Cerebrovascular disease is a common cause of epilepsy in the elderly. Drug treatment of the elderly is a challenge because of pharmacokinetic changes with aging, including impaired drug protein binding or displacement of drug from protein binding sites, potentially causing drug toxicity as a result of increased free drug concentrations. With aging, hepatic mass and blood flow decline along with renal function. Established anticonvulsant drugs have adverse effects and drug interactions that can make treating the elderly difficult. Newly available anticonvulsants cause fewer drug-drug interactions and less toxicity. Gabapentin is not metabolised, is not bound to protein, and has a favourable adverse effect profile and thus may be useful in the treatment of elderly patients. Lamotrigine reduced seizures between 20 and 30% in trials. Dose response was between 300mg per day and 500mg per day. This drug was well tolerated in open-label trials. Rash occurred in younger patients. Oxcarbazepine is rapidly absorbed and is converted to a monohydroxy derivative. Use with hepatic enzyme-inducing drugs necessitates an increase in dose. This drug may be substituted for carbamazepine. Hyponatraemia has been reported and monitoring is suggested. Topiramate blocks voltage-dependent sustained repetitive firing and has an effect on the gamma-aminobutyric acid (GABA) receptors. It affects glutamate responses and inhibits carbonic anhydrase. Topiramate has a dose response pattern up to 400mg per day. Cognitive effects limits its use in some patients. Nephrolithiasis has occurred with this drug. Tiagabine blocks GABA transporter proteins. Clearance is rapid and metabolism complete. Hepatic dysfunction prolongs clearance. The use of tiagabine has not been reported in the elderly. Zonisamide is rapidly absorbed and protein binding is 50%. Plasma half-life is 55 hours but is reduced to about 30 hours by hepatic enzyme-inducing drugs. Responder rate is 45%. Adverse effects include drowsiness, altered thinking and nephrolithiasis. Treatment of the elderly requires obligatory polypharmacy with potential drug interactions. Changes in body physiology alter absorption, binding, metabolism and elimination of drugs. Concomitant illness and sensitivity to drug effects narrow the therapeutic range and complicate pharmacokinetics in elderly patients. Newer anticonvulsant drugs have advantages that may outweigh risks and have therapeutic profiles that may aid in the treatment of this special population of patients.

Aged↗