fluoxetine

50h

fluoxetine T1/2

240h

Norfluoxetine T1/2

Fluoxetine, Paroxetine

CYP2D6 could inhibit

Fluvoxamine

CYP3A4 could inhibit

Relative improvement to other antidepressants (mostly mild)

GIT

○ nausea, vomiting, abdominal cramps, diarrhea

Headache

Sexual dysfunctions (loss of libido, erectile dysfunction…)

Restlessness (akathisia: a movement disorder that makes it hard for you to stay still. It causes an urge to move that you can't control. fidgets.)

Anxiety - an increase in anxiety or agitation during early treatment

Insomnia and fatigue

Serotonin syndrome upon intoxication or drug interaction

Selective Serotonin Reuptake Inhibitors (SSRI) A/E

Venlafaxine, Desvenlafaxine

Duloxetine

Milnacipran

Selective Serotonin - NE Reuptake Inhibitors (SNRI)

Venlafaxine, Desvenlafaxine

(Bicyclic)

Selective Serotonin - NE Reuptake Inhibitors (SNRI)

Duloxetine

(Three ring structure)

Selective Serotonin - NE Reuptake Inhibitors (SNRI)

Milnacipran

(for fibromyalgia: a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.)

Major depression

★ Pain disorders (neuropathies, fibromyalgia)

★ GAD or Generalized anxiety disorder

○ Generalized anxiety disorder (or GAD) is marked by excessive, exaggerated anxiety and worry about everyday life events for no obvious reason. People with symptoms of generalized anxiety disorder tend to always expect disaster and can't stop worrying about health, money,.family, work, or school.

★ Restlessness

★ Fatigue

★ Excessive anxiety

★ Increased muscle ache or soreness

★ Impaired concentration

★ Irritability

★ Difficulty sleeping

★ Stress urinary incontinence

○ Unintentional loss of urine.

○ Stress incontinence happens when physical movement or activity — such as coughing, laughing, sneezing, running or heavy lifting — puts pressure (stress) on your bladder, causing you to leak urine.

★ Vasomotor symptoms of menopause

○ Vasomotor symptoms are those that occur due to the constriction or dilation of blood vessels.They include hot flashes, night sweats, heart palpitations, and changes in blood pressure.

Selective Serotonin - NE Reuptake Inhibitors (SNRI)

Indications

Vasomotor symptoms of menopause

symptoms are those that occur due to the constriction or dilation of blood vessels. They include hot flashes, night sweats, heart palpitations, and changes in blood pressure.

Venlafaxine

Duloxetine

Examples

Selective Serotonin - NE Reuptake Inhibitors (SNRI)

Venlafaxine

○ Pharmacodynamics like in TCA

○ Improved profile of adverse reactions

Very effective, better remission rate than SSRI

Adverse reactions: nausea, vertigo (both frequent and may improve), hypertension, manic reactions

○ Used in depression and depression with anxiety, generalized anxiety disorders, socialphobias, neuropathic pain

Duloxetine

First antidepressant to secure FDA approval for the treatment of pain associated with diabetic neuropathy and fibromyalgia

Tricyclic Antidepressants (TCAs)

Chemical structure: three-ring nucleus→ lipophilic nature, CAN CROSS THE BBB

Tricyclic Antidepressants (TCAs)

Originally developed as antipsychotics (1949), but were found to have no effect in this indication.

★ Blockade of reuptake of monoamine neurotransmitters noradrenaline (NA) and serotonin (5-HT)

★ By competition for binding site of the carrier protein (NET and SERT)

★ Other Action: blockade of H1-receptor, α-receptors, M-receptors

Tricyclic Antidepressants (TCAs)

PRINCIPAL MECHANISM OF ACTION

Desipramine

the active metabolite of imipramine

Nortriptyline

the active metabolite of amitriptyline

★ Depression that is unresponsive to SSRIs and SNRIs

★ Pain conditions

★ Urinary incontinence / Enuresis

★ Insomnia

Tricyclic Antidepressants (TCAs) uses

○ Anticholinergic (atropine-like) due to M-blockade

➢ Dry mouth, blurred vision, constipation, urinary retention (more in amitriptyline, less in imipramine), Palpitations, tachycardia

○ Postural (orthostatic) hypotension or syncope + reflex tachycardia

➢ α-blockade of adrenergic transmission (frequent in elderly)

○ Sedation - H1 -blockade

➢ drowsiness, difficulty in concentration (amitriptyline,)

○ Sexual dysfunction

➢ Loss of libido, impaired erection

ADVERSE EFFECTS

Tricyclic Antidepressants (TCAs)