Duloxetine

NET Desipramine Maprotiline. mianserin Amoxapin. doxepine. nortriptyiine, duloxetine... 

Older- tricyclic antidepressants are set in italics. The specificity of action of tricyclic antidepressants (in particular of amitritpyline, imipramine, doxepine, nortriptyline, duloxetine, maprotiline) is limited because at therapeutic levels these drugs also block recqDtors (Hrhistamine, aradrenergic, muscarinic). 

Gobert, A, Rivet, JM, Cistarelli, L, Melon, C and Millan, MJ (1997) Alpha2-adrenergic receptor blockade markedly potentiates duloxetine- and fluoxetine-induced increases in noradrenaline, dopamine and serotonin levels in the frontal cortex of freely moving rats. J. Neurochem. 69 2616-2619. 

As another successful application of Noyori s TsDPEN ligand, Yan et al. reported the synthesis of antidepressant duloxetine, in 2008. Thus, the key step of this synthesis was the asymmetric transfer hydrogenation of 3-(dime-thylamino)-l-(thiophen-2-yl)propan-l-one performed in the presence of (5,5)-TsDPEN Ru(II) complex and a HCO2H TEA mixture as the hydrogen donor. The reaction afforded the corresponding chiral alcohol in both high yield and enantioselectivity, which was further converted in two steps into expected (5)-duloxetine, as shown in Scheme 9.17. 

Bupropion Venlafaxine Duloxetine Trazodone Nefazodone Mirtazapine... 

Several antidepressants, including most of the SSRIs, nefa-zodone, and duloxetine, are known to inhibit various cytochrome P-450 isoenzymes, thereby elevating plasma levels of substrates for those isoenzymes and thus potentially leading to increased adverse effects or toxicity of those drugs. The propensity to cause these drug interactions will vary with the particular antidepressant and the precise isoenzyme9,19,30 (Table 35-6). 

Duloxetine Cymbalta No Capsule 40-60 40-60 Once to twice daily... 

The starting dose is the usual therapeutic dose for most of the SSRIs, duloxetine, and mirtazapine, whereas there is usually need for at least some upward titration of venlafaxine, bupropion,... 

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

The use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

Not altered in advanced age, mild to moderate renal impairment, mild hepatic impairment (Child-Pugh A). Sign, altered in severe renal disease and moderate hepatic impairment (Child-Pugh B) Systemic exposure to duloxetine decreased by V3 in smokers (dose change not recommended) Multiple drug-drug interactions possible with CYP4502D6 and 1A2 substrates/ inhibitors... 

Guay DRP. Duloxetine for management of stress urinary incontinence. Am J Geriatr Pharmacother 2005 3 25-38. 

More recently, an analysis of pooled data from seven safety and efficacy trials of duloxetine did not find any differences in efficacy in depressed Hispanics compared with Whites (Lewis-Fernandez etal, 2006). Unfortunately, the sample size for the Hispanic group was very small in comparison to the White cohort (n = 58 White, n = 748), and most likely underpowered to detect any differences. Also, the Hispanic group included Mexicans and Mexican Americans along with Central and South Americans (percentage breakdown is unknown). 

Lewis-Fernandez, R., Blanco, C., Mallinkcrodt, C. H., Wohlreich, M. M. et al. (2006). Duloxetine in the treatment ofmajor depressive disorder comparisons of safety and efficacy in US Hispanic and majority Caucasian patients. /. Clin. Psychiatry, 67, 1379-90. 

R)-liINAP-RuBr2 can be successfully applied to the enantioselective hydrogenation of /i-kelo esters in the synthesis of (+)-(2R,3 W)-corynomycolic acid 115. ( S )-MeO-BIPHEP-RuBr2 was used in a similar manner in the synthesis of (R)-fluoxetine (116, Prozac ) and (S)-duloxetine (117).648... 

Generalized anxiety Duloxetine Escitalopram Paroxetine Venlafaxine XR Benzodiazepines Buspirone Imipramine Sertraline Hydroxyzine Pregabalin... 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

The serotonin-norepinephrine reuptake inhibitors include venlafaxine and duloxetine. Venlafaxine is an inhibitor of 5-HT and NE reuptake and a weak inhibitor of DA reuptake. Desvenlafaxine (Pristiq) was recently approved by the FDA. The dose is 50 mg once daily. 

Duloxetine MAOIs Potential for hypertensive crisis, serotonin syndrome, delirium... 

Stress Duloxetine0 40-80 mg/day (one or two doses) Even though not FDA approved, duloxetine is first-line therapy most adverse events diminish with time, so support patient during initial period of use. 

Duloxetine, a dual inhibitor of serotonin and norepinephrine reuptake indicated for depression and painful diabetic neuropathy, is expected to become first-line therapy for SUI. Duloxetine is thought to facilitate the bladder-to-sympathetic reflex pathway, increasing urethral and external urethral sphincter muscle tone during the storage phase. 

Six placebo-controlled studies showed that duloxetine reduces incontinent episode frequency and the number of daily micturitions, increases micturition interval, and improves quality-of-life scores. These benefits were statistically significant but clinically modest. 

To avoid drug interactions, clinicians should be careful when administering duloxetine with substrates or inhibitors of cytochrome P450 (CYP450) isoenzymes 2D6 and 1A2. 

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