Appropriate use of psychotropic drugs in nursing homes

The Omnibus Budget Reconciliation Act (OBRA) of 1987 limited the use of psychotropic medications in residents of long-term care facilities. Updates of OBRA guidelines have liberalized some dosing restrictions, but documentation of necessity and periodic trials of medication withdrawal are still emphasized. Antidepressant drugs are typically underutilized in nursing homes. Tricyclic antidepressants have many side effects and thus are not preferred medications in elderly patients. Anxiety and insomnia are common problems in the institutionalized elderly. If behavioral measures are not successful, antidepressant medications with shorter half-lives may avoid drug accumulation, which can lead to excessive sedation, cognitive impairment and an increased risk for falls. In the elderly, antipsychotic medications can cause serious side effects, such as extrapyramidal symptoms and tardive dyskinesia. Newer antipsychotic drugs are less often associated with these side effects, but they should be used only for specific diagnoses and when behavioral and environmental measures are unsuccessful.     

Alcohol effects in the elderly

Alcohol is a potent drug and must be included in the medication history of the patient. The physician must be alert to the possibility of alcohol abuse by the elderly, in whom typical clues may not be present. Alcohol has a greater dose-related effect in elderly persons because of their decreased total body water, which leads to persistently higher blood alcohol levels. Alcohol causes unique kinds of brain damage, a fact that may aggravate the clinical symptoms of dementia such as Alzheimer's disease, but there is no convincing proof of premature aging because of alcohol abuse. Alcohol potentiates the sedating effects of many drugs acting on the CNS. This is especially serious in elderly patients, and they should be cautioned concerning the use of alcohol and drugs.     

Substance abuse and the hospitalized elderly

Health care professionals frequently fail to recognize and address the misuse and abuse of alcohol and drugs in the elderly. Estimates of alcohol abuse in the older adult population range from 4% to 20% in the community dwelling elderly and up to approximately 25% among hospitalized older adults (Adams & Cox, 1995; Adams & Kinney, 1995; Beresford et al., 1990). In addition, the present population of older adults consumes 2-3 times more psychoactive medications than younger age groups (Sheahan et al., 1995). The effects of alcohol and substance abuse in older adults are influenced by physical, developmental, and psychosocial changes that occur with aging. Identification of alcohol and substance abuse presents a challenge for health care providers as older adults often present with atypical symptoms. Accurate diagnosis allows for the initiation of interventions for both immediate and long-term treatment.     

Alcohol and gene interactions.

Alcohol use produces both desirable and undesirable effects, ranging from short-term euphoria and reduction in cardiovascular risk, to violence, accidents, dependence and liver disease. Outcomes are affected by the amount of alcohol used (which is itself affected by genetic variation) and also by the drinker's genes. Genetic effects have been most clearly demonstrated for alcohol dependence, and several of the genes for which variation leads to increased dependence risk have been identified. These include genes for enzymes involved in alcohol metabolism (alcohol dehydrogenase and aldehyde dehydrogenase), and genes for receptors affected by alcohol (particularly gamma-aminobutyric acid receptors). Many other gene/dependence associations have been reported but not fully substantiated. Genetic effects on phenotypes other than alcohol dependence are less well understood, and need to be clarified before a full picture of gene-alcohol interactions can be achieved.     

Pharmacokinetic interactions between acute alcohol ingestion and single doses of benzodiazepines, and tricyclic and tetracyclic antidepressants – an update

Recent reports of interactions between alcohol and benzodiazepines, tricyclic and tetracyclic antidepressants during their acute concomitant use are reviewed. Acute ingestion of alcohol (ethanol) with tranquilizers or hypnotics is responsible for several pharmacokinetic interactions that can have significant clinical implications. In general, metabolism of these drugs is delayed when combined with alcohol but some reports have suggested otherwise. The amount of alcohol consumed, the presence or absence of liver disease, and differences in the dosage and administration of these drugs may account for the observed discrepancies.
In recent years, the cytochrome P450 (P450 or CYP) isoenzyme that catalyses the metabolism of these drugs has also been identified. However, since changes in the pharmacogenetic metabolism of benzodiazepines and tricyclic and tetracyclic antidepressants are mainly governed by CYP2C19 and CYP2D6, caution is needed when used together with alcohol.     

Stress, ethanol, and neuroactive steroids

Neurosteroids play a crucial role in stress, alcohol dependence and withdrawal, and other physiological and pharmacological actions by potentiating or inhibiting neurotransmitter action. This review article focuses on data showing that the interaction among stress, ethanol, and neuroactive steroids may result in plastic molecular and functional changes of GABAergic inhibitory neurotransmission. The molecular mechanisms by which stress-ethanol-neuroactive steroids interactions can produce plastic changes in GABA(A) receptors have been studied using different experimental models in vivo and in vitro in order to provide useful evidence and new insights into the mechanisms through which acute and chronic ethanol and stress exposure modulate the activity of GABAergic synapses. We show detailed data on a) the effect of acute and chronic stress on peripheral and brain neurosteroid levels and GABA(A) receptor gene expression and function; b) ethanol-stimulated brain steroidogenesis; c) plasticity of GABA(A) receptor after acute and chronic ethanol exposure. The implications of these new mechanistic insights to our understanding of the effects of ethanol during stress are also discussed. The understanding of these neurochemical and molecular mechanisms may shed new light on the physiopathology of diseases, such as anxiety, in which GABAergic transmission plays a pivotal role. These data may also lead to the need for new anxiolytic, hypnotic and anticonvulsant selective drugs devoid of side effects.     

Laboratory testing in ethanol,methanol, ethylene glycol,and isopropanol toxicities

Toxicity from ethanol, methanol, ethylene glycol, and isopropyl alcohol varies widely, and appropriate use of the available laboratory tests can aid in timely and specific treatment. Available testing includes direct measurements of serum levels of these alcohols; however, these levels often are not available rapidly enough for clinical decision making. This article discusses the indications and methods for both direct and indirect testing for ethanol, methanol, ethylene glycol, and isopropanol toxicity. Also discussed are the costs, availability, and turn-around times for these tests.     

Cyclooxygenase-2-selective inhibitors in the management of acute and perioperative pain

Postsurgical pain is often undertreated. Opioids are frequently used in perioperative analgesia, but concern about side effects can result in administration of an inadequate dose for pain relief. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used increasingly for postoperative analgesia. The use of balanced analgesia-a combination of opioids, NSAIDs, and local anesthesia utilizing agents from other classes (eg, ketamine, clonidine)-improves the efficacy of pain relief and decreases risk of side effects. While lacking some of the troublesome side effects of opioids, nonselective NSAIDs may cause bleeding as a result of their inhibitory effects on COX-1. For this reason, COX-2-selective inhibitors (coxibs) are attractive opioid-sparing analgesic options in the perioperative setting. Factors in addition to side effects such as time to onset of action, duration of action, maximum pain relief, use of rescue medication, and other factors relevant to a given pain model are important in determining overall analgesic efficacy. Clinical studies show that COX-2-selective inhibitors are effective for the treatment of preoperative and postoperative pain and reduce postsurgical requirements for opioids. This evidence supports a role for COX-2-derived prostaglandins as key mediators of nociceptive pain and peripheral sensitization (hyperalgesia). Pain management in the perioperative setting and the role of COX-2-selective inhibitors in acute and postoperative pain are reviewed here.     

Alcohol and the gastrointestinal tract

The effects of acute and chronic ethanol ingestion on esophageal motility and the potential complications of these alterations are reviewed. Injury to the gastric mucosa and the small intestine and alterations in intestinal absorption can also result from alcohol abuse.     

Medication use in the elderly patient: Focus on the perioperative/perianesthesia setting

As the population ages, the use of multiple medications also increases. Polypharmacy (taking multiple drugs at a time) presents concerns to the perianesthesia nurse who is caring for the geriatric patient. The pharmacokinetics and pharmacodynamics of drugs are often altered in older adult patients. Adverse drug reactions and drug interactions occur more often in geriatric patients than in younger patients. For these reasons, the benefits and risks of multiple medications and the administration of certain types of drugs must be carefully considered in the elderly patient. The selection of any medication should be individually based on the benefits and risks. Adverse drug reactions play a significant role in hospitalization for the general population, and the elderly are more susceptible to these. These drug reactions often contribute to significant morbidity as well as mortality. Medications need to be considered carefully in the older adult patient, but perhaps more so in the perioperative/perianesthesia period. Drug interactions are diverse. The type of anesthesia may influence the patient's outcome, depending on the medications the patient is currently taking. The patient's response to the stress of surgery is also affected by individual medical conditions as well as medications the patient is currently receiving Polypharmacy, inappropriate medications, adverse drug reactions, drug-disease issues, and drug interactions in the geriatric population are concerns in the perioperative/perianesthesia setting.     

Obstetric and neonatal effects of drugs of abuse

With an increase in illicit drug use in North America, more fetuses are exposed to cocaine, cannabinoids, alcohol, cigarettes, and opioids. Whereas the adverse fetal effects of some agents have been established (for example, ethanol), those of other compounds are still controversial (for example, cocaine, THC). Two important trends may hamper our understanding of the potential reproductive risks of recreational drugs: 1. The clustering of many other risk factors in the same women. 2. A tendency to publish studies showing adverse reproductive fetal effects while discouraging reports of no effects by drugs and chemicals. Although short-term research has addressed some of the immediate postnatal physical and behavioral performance of these babies, much more work is needed to address the difficult questions of long-term neurobehavioral outcome in babies exposed to recreational drug abuse in utero.     

Side effects of antipsychotic drugs. Avoiding and minimizing their impact in elderly patients

Antipsychotic drugs are very useful in treatment of psychosis and severe agitation in the elderly. Their use for other behavioral problems is contraindicated. Antipsychotics have many potential side effects (e.g., sedation, cardiovascular effects, anticholinergic effects, incontinence, reduced appetite, such motor disturbances as drug-induced parkinsonism, akathisia, dystonia, TD). Prevention, by using the minimum dose and duration of treatment possible, is the key to managing motor side effects. If prevention fails, drug-induced parkinsonism and dystonia may improve with use of anticholinergics, and akathisia may improve with use of benzodiazepines or low-dose propranolol. There is no proven treatment for TD, which is most likely to be observed during dose reduction or after discontinuation of antipsychotic drugs. Compared with older agents, newer antipsychotic drugs are less likely to cause parkinsonism, akathisia, and dystonia and may cause TD less often. More research is needed to clarify use of the new drugs in the elderly.     

Sudden severe perioral swelling in an adolescent boy

Methanol and ethylene glycol (EG) poisonings share many characteristics, both clinically and biochemically. Both alcohols are metabolized via alcohol dehydrogenase (ADH) to their toxic metabolites. The treatment traditionally consists of alkali to combat metabolic acidosis, ethanol to inhibit production of toxic metabolites and hemodialysis to remove the alcohols and their toxic metabolites. Though ethanol is an effective and available antimetabolite for these intoxications, its use is labor intensive and hampered by dosage problems, a relatively rapid elimination (especially during hemodialysis), and side effects like significant CNS-denression in these often critically ill Patients.     

Selective prescribing of spasmolytics

BACKGROUND: Daily clinical practice often differs largely from the clinical trial setting, so extrapolation of outcomes from trial data, such as safety, effectiveness, and economic outcomes, can be deceptive. Prescribers may intend to treat a selected group of patients with new drugs; this practice could result in significant bias in assessing outcomes of these agents during their use in daily clinical practice. OBJECTIVE: To evaluate what type of patient received tolterodine compared with the spasmolytic drugs previously marketed (oxybutynin, flavoxate, emepronium). DESIGN: An observational, follow-up study. SETTING: Eighteen collaborating community pharmacies. PATIENTS: Aged > or = 18 years, noninstitutionalized; initial therapy with tolterodine, oxybutynin, flavoxate, or emepronium. RESULTS: Tolterodine was often used as a second-line and even as a third-line treatment, and was prescribed to a "polluted" population in terms of concomitant psychotropic medication. Tolterodine users were 7.5 times more likely to have received another spasmolytic drug (RR 7.5, 95% CI 4.8 to 11.9). In addition, these patients more frequently used antiparkinsonian drugs (RR 4.1, 95% CI 1.6 to 10.4) as well as antipsychotic drugs (RR 2.9, 95% CI 1.4 to 6.2). There was a small difference in concomitant use of antidepressants and benzodiazepines between patients receiving tolterodine versus those taking other spasmolytic drugs. CONCLUSIONS: Tolterodine is prescribed for a population differing from that receiving previously marketed spasmolytic drugs. Selective prescribing should recognized when evaluating new drugs in daily clinical practice. Policy makers, such as pharmacy and therapeutics committees, should consider this aspect in their formulary decisions since selective prescribing can lead to unjustified conclusions about a drug's therapeutic effects (e.g., efficacy, safety, cost-effectiveness).     

Anorexia and weight loss in the elderly. Causes range from loose dentures to debilitating illness

Differentiating between anorexia (loss of appetite) and weight loss (documented loss of pounds) can be difficult, but the same causes and treatments apply to both. Gastrointestinal and metabolic disorders, cardiopulmonary disease, the presence of a neoplasm or infection, and use of certain drugs are possible medical causes. Inadequate nutritional intake can result from the inability to obtain and prepare foods, dietary restrictions, intolerance to certain foods, and poor oral and dental health. Social factors that can greatly reduce an elderly person's interest in food include loneliness, depression, isolation, and self-consciousness because of hearing and visual impairments. Some problems, such as alcohol abuse or inappropriate use of certain medications, may be revealed only with difficulty, and some of the problems mentioned may overlap. Although the physician may find assessment of anorexia or weight loss in the elderly a challenge, it usually responds well to corrective measures.     

Impact of renal aging on drug therapy

Elderly patients (age ≥ 65 years old) use up to 30% of all commonly prescribed medication, and they suffer more their adverse effects than the general population. In order to minimize this risk, physicians should avoid polypharmacy, dangerous pharmacological interactions and take into account pharmacodynamic and senile pharmacokinetic changes before prescribing any medication to the elderly. The present review article originally describes how renal physiology changes secondary to aging such as dysautonomia, glomerular filtration rate reduction, tubular back-filtration, sodium, calcium and magnesium loss, potassium retention, altered dilution-concentration capability, tubular frailty, genetics, internal milieu and body composition are senile changes that when combined predispose elderly people to suffer from pharmacological adverse effects. Knowledge of these physiological modifications associated with aging and their impact on the pharmacology of particular drugs may help to optimize drug use and to avoid complications in this age group.     

Continued importance of diuretics and beta-adrenergic blockers in the management of hypertension

The use of thiazide diuretics as one of the preferred antihypertensive medications has stood the test of time. Since the introduction of orally effective agents in 1957 to 1958, these drugs have continued to prove their usefulness. Numerous clinical trials have confirmed that these medications are as or more effective in reducing blood pressure and cardiovascular events than any of the other effective antihypertensive agents. Although some metabolic changes may occur with higher dosages of these medications, they seem to be of limited clinical significance. In addition to being well tolerated and effective. thiazide-type diuretics are less expensive than other agents. This should be considered in view of the fact that quality of care is not compromised when the less expensive medication is used. beta-Blockers should also be considered as a major drug class in the management of hypertensive patients. There are few studies directly comparing these drugs with other agents. Although some data suggest that they are less effective in reducing CHD events in the elderly, there are numerous situations where beta-blockers are clearly indicated. Combination therapy with a beta-blocker and diuretic has been shown to be highly effective in reducing cardiovascular events in both diabetic and nondiabetic patients.     

Non-pharmacological means to prevent fractures among older adults

Bone fractures affecting elderly people are a true public health burden, because they represent one of the most important causes of long-standing pain, functional impairment, disability, and death among this population. Compromised bone strength (osteoporosis) and falling, alone, or more frequently in combination, are the two independent and immediate risk factors of elderly people's fractures through which all the other, more distant risk factors, such as aging, inactivity, poor nutrition, smoking, use of alcohol, diseases, medications, functional impairments, and disabilities, operate. Of these two, falling, not osteoporosis, is the strongest single risk factor for a fracture. The most usual occurrence resulting in a fracture of an older adult is a 'simple' fall from standing height or less. Although in general terms this type of trauma is mild or moderate only (compared with, for example, motor vehicle collisions), to the specific injury site these traumas are high-impact injuries often creating forces clearly exceeding the breaking strength of the bone. Therefore, fractures affecting elderly people should be called 'fall-induced high-impact injuries' instead of the commonly used, partly misleading terms of osteoporotic fractures or minimal-trauma fractures. Prevention of elderly people's fractures consists of prevention of osteoporosis and of falling, and prevention of fractures using injury-site protection. Concerning osteoporosis, maximizing peak bone mass and preventing bone loss by regular exercise, calcium, and vitamin D, and, treatment of established osteoporosis with bone-specific drugs, have a strong scientific basis. In fall prevention, regular strength and balance training, reducing psychotropic medication, and diet supplementation with vitamin D and calcium have been shown to be effective. The multifaceted risk factor-assessing and modifying interventions have also been successful in preventing falls among the older adults by simultaneously affecting many of the risk factors of falling. Finally, concerning injury-site protection, padded strong-shield hip protectors whose effectiveness is scientifically proven seem to be a promising option in preventing hip fractures.     

Fomepizole in the treatment of ethylene glycol poisoning

The management of ethylene glycol poisoning is reviewed, with a focus on the use of the new antidote fomepizole. Ethylene glycol is a widely used industrial agent that is also easily obtained commercially, usually as radiator antifreeze. Ingestion of as little as 30 to 60 mL can result in death or serious permanent disability. Traditional management of poisoning includes the use of ethanol, with or without hemodialysis. Activated charcoal is not indicated, and gastric lavage may be beneficial only in the first hour after ingestion. Cofactors such as pyridoxine and thiamine may be beneficial in patients deficient in these vitamins. A new antidote, fomepizole, has recently been approved for use in Canada. Like ethanol, it is a competitive inhibitor of alcohol dehydrogenase. Potential benefits of fomepizole include its ease of administration and lack of serious adverse effects. Fomepizole may be recommended over ethanol in situations in which avoidance of ethanol-induced side effects is imperative or when ethanol is not readily available. Further studies are required to verify its comparative efficacy and cost-effectiveness compared to ethanol.