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The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
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Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can...
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Related Experiment Video

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Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
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Published on: November 27, 2016

Selective serotonin reuptake inhibitor exposure.

Kevin T Fitzgerald1, Alvin C Bronstein

  • 1VCA Alameda East Veterinary Hospital, Denver, CO, USA. kfitzgerald@aevh.com

Topics in Companion Animal Medicine
|June 26, 2013
PubMed
Summary

Selective serotonin reuptake inhibitors (SSRIs) are effective antidepressants with fewer side effects. While SSRI overdose can cause serotonin syndrome, they remain relatively safe with an excellent prognosis in animals.

Area of Science:

  • Veterinary Pharmacology
  • Clinical Toxicology

Background:

  • Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed antidepressants.
  • They are effective for major depression and other conditions, with a favorable side effect profile compared to older antidepressants.
  • SSRIs are also used in veterinary medicine, for example, fluoxetine for canine separation anxiety.

Purpose of the Study:

  • To review the clinical signs, diagnosis, and treatment of SSRI toxicosis in animals.
  • To highlight the relative safety of SSRIs even in overdose situations.

Main Methods:

  • Review of clinical signs associated with SSRI overdose.
  • Discussion of diagnostic approaches, including history and clinical presentation.
  • Outline of treatment goals for SSRI intoxication.

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Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome

Published on: September 23, 2015

Main Results:

  • SSRI overdose can lead to serotonin syndrome, characterized by symptoms like ataxia, tremors, rigidity, hyperthermia, diarrhea, and seizures.
  • Diagnosis relies on history and clinical signs, as no specific test exists.
  • Treatment focuses on supportive care, preventing absorption, managing CNS effects, controlling hyperthermia, and seizure control.

Conclusions:

  • Despite potential for serotonin syndrome, SSRIs demonstrate relative safety in overdose compared to other antidepressants.
  • The prognosis for animals treated for SSRI toxicosis is excellent, with no reported deaths in one large retrospective study.
  • Differential diagnoses for suspected SSRI poisoning should include other serotonergic agents.