TCA antidepressants, tetracyclic and unicyclic, and MAOIs Flashcards

1
Q

What is are the two main hypotheses about depression.

A

Amine hypothesis and the neurogenesis hypothesis

  • The amine hypothesis of mood postulates that brain amines, particularly norepinephrine (NE) and serotonin (5-HT), are neurotransmitters in pathways that function in the expression of mood, and a functional decrease of these transmitters results in depression.
  • Based on studies showing that many drugs capable of alleviating symptoms of major depressive disorders
    enhance the actions of the central nervous system (CNS) neurotransmitters 5-HT and NE.

Difficulties with this hypothesis include the facts that
(1) postmortem studies of patients do not reveal decreases in the brain levels of NE or 5-HT;
(2) although antidepressant drugs may cause changes in brain amine activity
within hours, clinical response requires weeks;
(3) most antidepressants ultimately cause a downregulation of amine receptors;
(4) bupropion has minimal effects on brain NE or 5-HT;
(5) Brain-derived neurotrophic factor (BDNF) is depressed in the brains of depressed patients.

Neurogenesis hypothesis
Depression is a result from impaired hippocampal neurogenesis. Explains the lag time.

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2
Q

List the TCA antidepressants

A

Imipramine
Desipramine

Amitriptyline
Nortriptyline

Clomipramine
Trimipramine

Doxepin

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3
Q

List the tetracyclic antidepressants

A

Maprotiline

Amoxapine

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4
Q

What is the unicyclic AD

A

Buproprion

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5
Q

What are the active metabolites of Imipramine and AMitryptyline

A

Impiramine –> Desipramine

Amitryptyline –> Nortriptyline.

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6
Q

Actions of the TCAs

A

Main: inhibit NET and SERT

also:
anti-adrenergic alpha’s
anti-histamine
anti-muscarinic

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7
Q

Actions of the Tetracyclic ADs

A

same, but Amoxapine also blocks D2 receptors.

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8
Q

Which has the strongest anticholinergic actions?

Which has the least?

A

Amitryptyline

The secondary amines have the least

Desipramine
Nortryptyline

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9
Q

What are the SEs of the TCAs

A

General SEs:

  • sedation
  • antimuscarinic
  • orthostatic hypotension
  • possible refractory hypotension
  • Sexual dysfunction, decreased libido
  • anorgasmia
  • Impotence
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10
Q

Treatment for TCA overdose

A

Sodium Bicarbonate i.v.

Increases pH, which decreases TCA ionization and inhibits its Na+ channel binding.

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11
Q

What are the indications for TCAs

A

1st line for neuropathic or chronic pain syndromes

2nd line for SSRI/SNRI resistant:

  • Major depressive disorder
  • Panic disorder
  • Phobias

Clomipramine 2nd line for SSRI resistant O.C.D.

Amitriptyline 2nd line for migraine prophylaxis.

Doxepine at low doses - H1 inhibition for insomnia.

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12
Q

Indications for the tetracyclic ADs

A

Maprotiline -
same as the secondary amine TCAs, disipramine and nortriptyline

Amoxapine -
Also inhibits D2 and 5HT2, sometimes used off label as an atypical antipsychotic, otherwise classified as a regular TCA.

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13
Q

Bupropions mechanism and indications

A

Inhibits NET and DAT.
Mild inhibition of nicotinic receptors

does not have ANY effect on serotonin receptors

Indications:

1) Antidepressant for people that couldn’t tolerate SSRI/SNRI side effects
- Bupropion has no sexual effects or weight gain

2) Quitting Smoking

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14
Q

Buproprion SEs and contraindications

A

Can increase seizure risk

Contraindicated in anyone with any history of seizures

Also contraindicated in any patients with history of eating disorders, bc these are associated with seizures as well.

No other SEs, its used because it LACKS sexual or weight gain.

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15
Q

List the NON-selective MAO-Is

A

Tranylcypromine

Phenelezine

Isocarboxazid

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16
Q

Is Tranylcypromine reversible or irreversible

A

All the non-selective MAOIs are Irreversible.

17
Q

What are the MAO-B selective inhibitors

are they reversible or irreversible?

A

Selegeline
Rasageline
Safinamide.

They are all Irreversible.

18
Q

What is the reversible MAO inhibitor?

Is it selective?

A

Moclobeminde

Non-selective and reversible.

19
Q

Indications of the non-selective MAOIs

A

third line for MDD,
suggested to be more effective in atypical depression
- mdd with hyperphagia, hypersomnia, leaden paralysis.

third line for panic disorder and phobias.

Tranylcypromine
Phenelezine
Isocarboxazid

20
Q

Indications for the MAO-B inhibitors

A

Selegeline and Rasageline are used in parkinson’s to increase DA in the brain.

21
Q

SEs of MAOis

A

DELAYED Orthostatic hypotension, after 2-3 weeks, unclear why.

CNS excitation
Insomnia, hypomania, agitation
Convulsions

Weight loss or gain

Sexual dysfunction –> highest rates of this of all antideps

Serotonin syndrome, especially when given with SSRIs, absolutely contraindicated

Tryamine cheese reaction.
Hypertensive crisis, arrhythmias, strokes, AMI.