Duloxetine-antidepressent drug and its pharmacology

DESCRIPTION:

 Duloxetine (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) is a drug which primarily targets major depressive disorder (MDD), generalized anxiety disorder (GAD), pain related to diabetic peripheral neuropathy and in some countries stress urinary incontinence (SUI). It is manufactured and marketed by Eli Lilly and Company.

 Duloxetine has not yet been FDA approved for stress urinary incontinence or for fibromyalgia.

 Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Duloxetine is a systemic drug therapy which affects the body as a whole. Known also under the code name LY248686, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE- and 5-HT transporter sites. It is a less potent inhibitor of dopamine reuptake.

PHARMACODYNAMICS:

Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and primarily targets major depressive disorders (MDD) and stress urinary incontinence (SUI). Duloxetine is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes). Known also as LY248686, it is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake, possessing comparable affinities in binding to NE and 5-HT transport sites. Interestingly, its behavior contrasts to most other dual-reuptake inhibitors. Furthermore, duloxentine lacks affinity for monoamine receptors within the central nervous system.

PHARMACOKINETICS: 

  Absorption: Orally administered duloxetine hydrochloride is well absorbed.

  Volume of distribution -1640 L.

  Protein Binding: Protein binding is greater than 90%.

 Metabolism:  The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP2D6 and CYP1A2 catalyze the oxidation of the naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. The major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine.

Route of elimination: Excreted in urine. 70% in urine and 20% in faeces

Half life: 12 hours. 

SIDE EFFECTS:

  1.Tremors.

  2.convulsions.

  3.Reduced activity.

  4.Slow pupillary response.

  5.Intermittent tremors.

  6.Rigidity. 

DRUG INTERACTIONS:

  1. Acebutalol + Duloxetine = Increase the orthostatic hypotensive activities of Duloxetine.

  2. Acetazolamine + Duloxetine = Increase the orthostatic hypotensive activities of Duloxetine.

  3. Acetophenazine + Duloxetine = Risk or severity of adverse effects can be increased.    

  4. Abirateron + Duloxetine = Serum concentration of Duloxetine can be increased.

  5.  Triptans + Duloxetine =  Increased risk for serotonin syndrome.

CONTRAINDICATIONS:

 1.Hypersensitivity.

 2.MAOIs. 

 3. CNS .

THERAPEUTIC USES:

 1.Antidepressant.

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no-458,462.464