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Biomedical subjects

M V Rudorfer

Publications and source records attributed to M V Rudorfer.

At least 19 recordsLinked to original sources
PubMed1999

Metabolism of tricyclic antidepressants.

1. Despite the considerable advances in the treatments available for mood disorders over the past generation, tricyclic antidepressants (TCAs) remain an important option for the pharmacotherapy of depression. 2. The pharmacokinetics of TCAs are characterized by substantial presystemic first-pass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1 day (up to 3 days for protriptyline). 3. Clearance of tricyclics is dependent primarily on hepatic cytochrome P450 (CYP) oxidative enzymes. Although the activities of some P450 isoenzymes are largely under genetic control, they may be influenced by external factors, such as the concomitant use of other medications or substances. Patient variables, such as ethnicity and age, also affect TCA metabolism. The impact of gender and related reproductive issues is coming under increased scrutiny. 4. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. 5. Renal clearance of the polar metabolites of TCAs is reduced by normal aging, accounting for much of the increased risk of toxicity in older patients. 6. Knowledge of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications.

Antidepressive Agents, Tricyclic↗
PubMed1994

Comparative tolerability profiles of the newer versus older antidepressants.

Although the standard tricyclic antidepressants (TCAs) are generally effective in the treatment of depression, they can cause several troublesome adverse effects. Chief among these are their anticholinergic actions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs include orthostatic hypotension, tachycardia and cardiac conduction slowing. Many TCAs are sedating and promote weight gain. Also problematic is the potential lethality of TCAs in overdose. The continual introduction of a host of new antidepressants over the past 15 years has provided an opportunity to improve the benefit-risk ratio for many patients by reducing medication-related toxicity. Selective serotonin reuptake inhibitors (SSRIs) and amfebutamone (bupropion), among others, are examples of effective antidepressants free of tricyclic-like anticholinergic, cardiovascular, sedating and appetite/weight-increasing effects. However, the new-generation drugs also present adverse effects of their own, including gastrointestinal distress, agitation and drug-drug interactions in the case of the SSRIs, and the risk of seizures or psychosis in amfebutamone recipients. Monoamine oxidase (MAO) inhibitors have also been refined; reversible inhibitors of MAO-type A afford protection against the usually feared hypertensive reaction to indirect sympathomimetic substances. The availability of new-generation antidepressants thus increases the likelihood of clinical response with a reduction in unwanted toxicity.

Antidepressive Agents↗
PubMed1993

Biogenic amines in seasonal affective disorder: effects of light therapy.

Wintertime measures of central and peripheral monoamine neurotransmitter system activity in 17 medication-free depressed patients with seasonal affective disorder (SAD) were compared with those in eight healthy volunteers. Mean cerebrospinal fluid (CSF) concentrations of the principal metabolites of norepinephrine (NE), serotonin, and dopamine did not differ between the two groups, nor did mean basal or orthostatically stimulated plasma NE levels. Patients' pretreatment depression ratings were inversely correlated with resting plasma NE concentrations. Fourteen SAD patients were clear responders to 2 weeks of full-spectrum bright light treatment. Neither the transmitter measures nor their interrelatedness was affected significantly by phototherapy.

Adult↗
PubMed1993

Psychotherapeutic Medications Development Program (PMDP).

The Psychotherapeutic Medications Development Program (PMDP) of the National Institute of Mental Health was established in 1990. The purpose of the PMDP is to improve, enhance, and speed the development of new medications and improve the therapeutic usefulness of existing medications for the treatment of mental illness. The PMDP will fulfill this mission by implementing four initiatives. In the drug discovery and development initiative, the PMDP will aid in the development of promising new drugs. This initiative will also include improving the therapeutic usefulness of existing medications. In the technology transfer initiative, PMDP will improve the technology transfer from academic and government researchers to the pharmaceutical industry; improve the dissemination of information concerning technology transfer opportunities as it pertains to psychotherapeutic medications; and enhance technology transfer by acting as a broker to bring interested parties together. For the third initiative, the PMDP will develop and maintain a capability to clinically evaluate psychotherapeutic medications. The PMDP will also act to facilitate the development and testing of new concepts and models of mental illness. There is a detailed description of the steps that are involved in developing a new chemical entity (NCE) from the conceptual stage to a medication that is approved for the treatment of a particular illness. The pharmaceutical industry estimates that this medication development process costs $238 million.

Humans↗
PubMed1993

Challenges in medication clinical trials.

The keystone of pharmacological therapy is the medication clinical trial. Beyond the straightforward administration of an adequate amount of medication for a sufficient duration of time, attention to a variety of methodologic issues is necessary to ensure a successful study. These include diagnostic and severity criteria for entry into the trial and a host of potentially confounding biological and psychosocial factors. Adequacy of treatment must be insured, aided by continued refinement of plasma drug concentration monitoring and understanding of the role of active metabolites. Outcome measures must be valid and reliable. These principles are being applied to the still-new field of child and adolescent psychopharmacology. Results thus far have indicated the importance of placebo control in young populations. The equivocal efficacy demonstrated to date for pharmacotherapy in controlled antidepressant trials in children and adolescents has limited understanding of dose (or plasma level)/response relationships which could serve to optimize further studies.

Clinical Trials as Topic↗
PubMed1993

Pharmacokinetics of psychotropic drugs in special populations.

Patients treated for psychiatric illness may have a variety of characteristics that alter the pharmacokinetic profiles of psychotropic drugs. Genetic background, age, health status, and personal habits can change the body's ability to absorb, distribute, and metabolize medications. Most psychotropic drugs, with the exception of lithium, are eliminated via biotransformation in the liver rather than renal excretion, and a number of studies have demonstrated distinct phenotypes for hepatic metabolism involving the cytochrome P450 system. "Slow" metabolizers are likely to develop higher plasma concentrations of several different classes of psychotropic drugs, including tricyclic antidepressants. Advancing age reduces renal function but has little effect on hepatic metabolism. Volume of distribution may also be increased in elderly patients because of their greater percentage of adipose tissue. Ethnic background can significantly influence both drug metabolism and the pharmacodynamics of a variety of drugs. Thus, the physician should carefully consider patient characteristics when prescribing psychotropic medications and should engage in therapeutic drug monitoring when there is any doubt about the plasma drug levels that a given dosing regimen will achieve.

Age Factors↗