Pharmacokinetics of Tricyclic Antidepressants (TCA)
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Questions and Answers

Which of the following SSRI's is not affected by food in terms of its absorption?

  • Fluoxetine
  • Citalapram (correct)
  • Sertraline
  • Paroxetine

    • What is the primary mechanism by which SSRI's interact with other drugs?

  • Enzyme induction
  • Receptor antagonism
  • Receptor activation
  • Enzyme inhibition (correct)

    • Which of the following is a potential side effect of SSRI's due to their anticholinergic actions?

  • Dry mouth (correct)
  • Hyponatremia
  • Headache
  • Insomnia

    • What is the difference between Citalapram and Escitalapram in terms of their composition?

    <p>Citalapram is a mixture of two stereo-isomers, while Escitalapram is a single isomer</p> Signup and view all the answers

    Which of the following SSRI's has the highest protein binding percentage?

    <p>Paroxetine</p> Signup and view all the answers

    What is the potential consequence of SSRI's inhibiting hepatic cytochrome p450 isoenzymes?

    <p>Decreased metabolism of other drugs</p> Signup and view all the answers

    Which of the following is a potential interaction between SSRI's and Tricyclic Antidepressants (TCA's)?

    <p>Increased anticholinergic actions</p> Signup and view all the answers

    What is the primary mechanism by which enzyme inhibitors affect the levels of TCAs in the body?

    <p>They inhibit the enzyme responsible for breaking down TCAs</p> Signup and view all the answers

    Which of the following side effects of TCAs is most closely related to their anticholinergic properties?

    <p>Urinary retention</p> Signup and view all the answers

    Which of the following is a common side effect of SSRI's that can be mistaken for a symptom of depression?

    <p>Loss of libido</p> Signup and view all the answers

    What is the recommended course of action when switching from a MAOI to a TCA?

    <p>Wait for 1-2 weeks before starting the TCA</p> Signup and view all the answers

    What is the effect of alcohol on the side effects of TCAs?

    <p>It potentiates the drowsy effect of TCAs</p> Signup and view all the answers

    Which of the following is a characteristic of the pharmacokinetics of TCAs?

    <p>They are strongly protein bound</p> Signup and view all the answers

    What is the effect of enzyme inducers on the levels of TCAs in the body?

    <p>They decrease the levels of TCAs</p> Signup and view all the answers

    What is the therapeutic effect of TCAs typically seen in?

    <p>Within 2-4 weeks</p> Signup and view all the answers

    Which of the following is a potential interaction between TCAs and clonidine?

    <p>Increased antihypertensive effects</p> Signup and view all the answers

    What is a significant difference between venlafaxine and desvenlafaxine in terms of metabolism?

    <p>Venlafaxine relies on CYP2D6 for conversion to desvenlafaxine</p> Signup and view all the answers

    What is a common side effect of tricyclic antidepressants (TCA's) that can be reduced with slow titration?

    <p>Anticholinergic effects</p> Signup and view all the answers

    Which of the following serotonin modulators is associated with weight gain and sexual dysfunction?

    <p>Imipramine</p> Signup and view all the answers

    What is the primary mechanism of action of tricyclic antidepressants (TCA's)?

    <p>Blocking the uptake of NE, 5HT, and dopamine into the nerve terminal</p> Signup and view all the answers

    What is the primary treatment for serotonin syndrome?

    <p>Anti-seizures, muscle relaxants, and 5HT blockers</p> Signup and view all the answers

    What is a common side effect of SNRI's, such as venlafaxine?

    <p>Nausea and dry mouth</p> Signup and view all the answers

    What is the primary difference between secondary and tertiary amines in tricyclic antidepressants?

    <p>Side effect profile</p> Signup and view all the answers

    What is the primary concern when prescribing venlafaxine, especially at higher doses?

    <p>Hypertension</p> Signup and view all the answers

    Study Notes

    Pharmacokinetics of TCA's

    • TCA's are rapidly and well absorbed after oral dosing, may undergo first-pass metabolism
    • Lipophilic and strongly protein-bound (90-95%)
    • Metabolized in the liver, peak plasma levels reached in 2-6 hours
    • Half-life (t ½) is generally long, ranging from 12-44 hours (average 24 hours)
    • Therapeutic effect is seen in 2-4 weeks

    Side Effects of TCA's

    • Anti-muscarinic/anticholinergic effects:
      • Dry mouth
      • Blurred vision and disturbance of accommodation
      • Increased intraocular pressure
      • Constipation
      • Urinary retention
    • These effects are worst with amitriptyline and weaker with desipramine
    • Other side effects:
      • Postural hypotension
      • Tachycardia
      • Confusion
      • Fatigue, sedation, drowsiness, and lassitude
      • Agitation, sweating, and weight gain

    Drug Interactions with TCA's

    • Enzyme inhibitors (e.g. fluoxetine, cimetidine, erythromycin, verapamil) increase TCA levels
    • Enzyme inducers (e.g. CZB, phenytoin, barbiturates) decrease TCA levels
    • Management: decrease dose of TCA's until enzyme inhibitor is removed, or increase dose of TCA's in the presence of enzyme inducers
    • Other interactions:
      • Alcohol potentiates TCA's drowsy effect
      • Clonidine increases antihypertensive effects
      • IV NE/EP increases pressor pressure response 2-4 fold
      • MOAI's may cause hypertensive crisis, avoid large doses, and monitor patient with combination therapy

    Pharmacokinetics of SSRI's

    • Citalopram:
      • Not affected by food
      • Metabolized in the liver
      • 80% protein bound
    • Escitalopram:
      • Not affected by food
      • Metabolized in the liver
      • 56% protein bound
    • Fluoxetine:
      • Not affected by food
      • Metabolized in the liver to active and less active metabolites
      • 94.5% protein bound
    • Paroxetine:
      • Not affected by food
      • Extensively metabolized in the liver
      • 95% protein bound
    • Sertraline:
      • Peak absorption delayed with food
      • Metabolized in the liver
      • 98% protein bound

    Citalopram vs Escitalopram

    • Citalopram is a mixture of two stereo-isomers: R-citalopram and S-citalopram
    • Escitalopram contains only one isomer, S-citalopram
    • Equivalent dose of escitalopram is approximately half of that of citalopram
    • Dosing range of escitalopram is 10-20 mg/day, and the dosing range for citalopram is 20-40 mg/day

    Common Side Effects of SSRI's

    • Insomnia
    • Loss of libido/failure to orgasm
    • Increased aggression and occasional violence
    • Dry mouth
    • Headache and abnormal dream
    • Extrapyramidal symptoms (akathisia, dyskinesia, dystonia)
    • Hyponatremia
    • May precipitate mania and hypomania

    Drug Interactions - SSRI's

    • Many SSRI's are enzyme inhibitors
    • Inhibit hepatic cytochrome P450 isoenzymes, leading to increased activity of other drugs
    • Effects of other enzyme inhibitors:
      • Large volume of distribution
      • Side effects are similar to SSRI's, including nausea and dry mouth
      • Increased BP, nausea/vomiting/diarrhea with venlafaxine

    Venlafaxine vs Desvenlafaxine

    • Venlafaxine relies on CYP2D6 for conversion to desvenlafaxine
    • Desvenlafaxine has no significant metabolism by CYP2D6 at recommended doses
    • Both venlafaxine and desvenlafaxine have limited clinically significant drug interactions
    • The most striking difference between the two products is cost
    • Hypertension is an important side effect to bear in mind when prescribing venlafaxine

    Precaution

    • Concurrent use with other antidepressants, e.g. MAOI's, can result in serotonin syndrome
    • Excess of NA and 5HT, causing tremors, hyperthermia, muscle rigidity, CV collapse, and CNS stimulation, inducing seizures
    • Treatment: anti-seizures, muscle relaxants, 5HT blockers (e.g. cyproheptadine)

    New Serotonergic Agents

    • Levomilnacipran (Fetzima): SNRI
    • Vortioxetine (Trintellix): serotonin modulator - SSRI
    • Vilazodone (Viibryd): SSRI - not associated with weight gain and sexual dysfunction

    Tricyclic Anti-depressants (TCA's)

    • Secondary Amines:
      • Despramine
      • Nortriptyline
      • Protriptyline
    • Tertiary Amines:
      • Imipramine (150-300mg/day)
      • Amitriptyline (150-300mg/d)
      • Trimipramine
      • Doxepin

    Mechanism of Action of TCA's

    • TCA's block the uptake of NE, 5HT, and dopamine into the nerve pre-synaptic nerve ending
    • The net result is the potentiating of the neurotransmitters' action at the post-synaptic receptor

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    Description

    Learn about the pharmacokinetics of Tricyclic Antidepressants (TCA), including their absorption, metabolism, protein binding, and side effects.

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