ITEMS IN AFP WITH MESH TERM:
ABSTRACT: Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.
ABSTRACT: Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. Genetic variability (polymorphism) in these enzymes may influence a patient's response to commonly prescribed drug classes, including beta blockers and antidepressants. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes. Knowledge of the most important drugs metabolized by cytochrome P450 enzymes, as well as the most potent inhibiting and inducing drugs, can help minimize the possibility of adverse drug reactions and interactions. Although genotype tests can determine if a patient has a specific enzyme polymorphism, it has not been determined if routine use of these tests will improve outcomes.
Genetic Factors In Drug Metabolism - Article
ABSTRACT: Patients vary widely in their response to drugs. Having an understanding of the pharmacokinetic and pharmacodynamic properties of various medications is importantwhen assessing ethnic differences in drug response. Genetic factors can account for 20 to 95 percent of patient variability. Genetic polymorphisms for many drug-metabolizing enzymes and drug targets (e.g., receptors) have been identified. Although currently limited to a few pathways, pharmacogenetic testing may enable physicians to understand why patients react differently to various drugs and to make better decisions about therapy. Ultimately, this understanding may shift the medical paradigm to highly individualized therapeutic regimens.
ABSTRACT: Chronic kidney disease affects renal drug elimination and other pharmacokinetic processes involved in drug disposition (e.g., absorption, drug distribution, nonrenal clearance [metabolism]). Drug dosing errors are common in patients with renal impairment and can cause adverse effects and poor outcomes. Dosages of drugs cleared renally should be adjusted according to creatinine clearance or glomerular filtration rate and should be calculated using online or electronic calculators. Recommended methods for maintenance dosing adjustments are dose reductions, lengthening the dosing interval, or both. Physicians should be familiar with commonly used medications that require dosage adjustments. Resources are available to assist in dosing decisions for patients with chronic kidney disease.
ABSTRACT: Family physicians commonly care for patients with serious mental illness. Patients with psychotic and bipolar disorders have more comorbid medical conditions and higher mortality rates than patients without serious mental illness. Many medications prescribed for serious mental illness have significant metabolic and cardiovascular adverse effects. Patients treated with second-generation antipsychotics should receive preventive counseling and treatment for obesity, hyperglycemia, diabetes, and hyperlipidemia. First- and second-generation antipsychotics have been associated with QT prolongation. Many common medications can interact with antipsychotics, increasing the risk of cardiac arrhythmias and sudden death. Drug interactions can also lead to increased adverse effects, increased or decreased drug levels, toxicity, or treatment failure. Physicians should carefully consider the risks and benefits of second-generation antipsychotic medications, and patient care should be coordinated between primary care physicians and mental health professionals to prevent serious adverse effects.
ABSTRACT: Subopitmal glycemic control in hospitalized patients with type 2 (non-insulin-dependent) diabetes mellitus can have adverse consequences, including increased neurologic ischemia, delayed wound healing and an increased infection rate. Poor glycemic control can also affect the outcome of the primary illness. If possible, hospitalized diabetic patients should continue their previous antihyperglycemic treatment regimen. Decreased physical activity and the stress of illness often lead to hyperglycemia in hospitalized patients with type 2 diabetes. When indicated, insulin is given either as a supplement to usual therapy or as a temporary substitute. The overall benefit of the traditional sliding-scale insulin regimen has been questioned. Insulin supplementation given according to an algorithm may be a logical alternative. Any antihyperglycemic regimen should be administered and monitored in a manner coincident with the intake of food or other sources of calories. Factors that can alter glycemic control acutely, including specific medical conditions and medications, should be identified and anticipated.
ABSTRACT: The primary goal of antiretroviral therapy for human immunodeficiency virus (HIV) infection is suppression of viral replication. Evidence indicates that the optimal way to achieve this goal is by initiating combination therapy with two or more antiretroviral agents. The agents now licensed in the United States for use in combination therapy include five nucleoside analog reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine and lamivudine), two nonnucleoside reverse transcriptase inhibitors (delavirdine and nevirapine) and four protease inhibitors (saquinavir, ritonavir, indinavir and nelfinavir). Current recommendations suggest that antiretroviral therapy be considered in any patient with a viral load higher than 5,000 to 20,000 copies per mL, regardless of the CD4+ count. Selection of the combination regimen must take into account the patient's prior history of antiretroviral use, the side effects of these agents and drug-drug interactions that occur among these agents and with other drugs as well. Because of the potential for viral resistance, nonnucleoside reverse transcriptase inhibitors and protease inhibitors should only be used in combination therapy. Antiretroviral agents are rapidly being developed and approved, so physicians must make increasingly complex treatment decisions about medications with which they may be unfamiliar.
Aminoglycosides: A Practical Review - Article
ABSTRACT: Aminoglycosides are potent bactericidal antibiotics that act by creating fissures in the outer membrane of the bacterial cell. They are particularly active against aerobic, gram-negative bacteria and act synergistically against certain gram-positive organisms. Gentamicin is the most commonly used aminoglycoside, but amikacin may be particularly effective against resistant organisms. Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis, especially against endocarditis. Resistance is rare but increasing in frequency. Avoiding prolonged use, volume depletion and concomitant administration of other potentially nephrotoxic agents decreases the risk of toxicity. Single daily dosing of aminoglycosides is possible because of their rapid concentration-dependent killing and post-antibiotic effect and has the potential for decreased toxicity. Single daily dosing of aminoglycosides appears to be safe, efficacious and cost effective. In certain clinical situations, such as patients with endocarditis or pediatric patients, traditional multiple dosing is still usually recommended.
ABSTRACT: A growing number of Americans are using herbal products for preventive and therapeutic purposes. The manufacturers of these products are not required to submit proof of safety and efficacy to the U.S. Food and Drug Administration before marketing. For this reason, the adverse effects and drug interactions associated with herbal remedies are largely unknown. Ginkgo biloba extract, advertised as improving cognitive functioning, has been reported to cause spontaneous bleeding, and it may interact with anticoagulants and antiplatelet agents. St. John's wort, promoted as a treatment for depression, may have monoamine oxidase-inhibiting effects or may cause increased levels of serotonin, dopamine and norepinephrine. Although St. John's wort probably does not interact with foods that contain tyramine, it should not be used with prescription antidepressants. Ephedrine-containing herbal products have been associated with adverse cardiovascular events, seizures and even death. Ginseng, widely used for its purported physical and mental effects, is generally well tolerated, but it has been implicated as a cause of decreased response to warfarin. Physicians must be alert for adverse effects and drug interactions associated with herbal remedies, and they should ask all patients about the use of these products.
Mirtazapine: A Newer Antidepressant - Article
ABSTRACT: Mirtazapine is a newer antidepressant that exhibits both noradrenergic and serotonergic activity. It is at least as effective as the older antidepressants for treating mild to severe depression. Sedation is the most common side effect. Although agranulocytosis is the most serious side effect, it is rare (approximately one in 1,000) and usually reversible when the medication is stopped. Mirtazapine is relatively safe in overdose. Many clinicians consider mirtazapine a second-line or even third-line antidepressant to be used when older antidepressants are not tolerated or are ineffective. Physicians who are concerned about the risks of elevated lipid levels and agranulocytosis may choose to reserve mirtazapine as a third-line choice. It is particularly useful in patients who experience sexual side effects from other antidepressants. Mirtazapine is also a good choice in depressed patients with significant anxiety or insomnia. Although mirtazapine has been used successfully in Europe for a number of years, its place in the care of patients with depression in the United States has not yet been established.