DULOXETINE… 4 BIRDS ONE STONE?

Duloxetine four birds with one stone?

In medical school we learn about diseases in isolation, but in clinical practice many patients concomitantly have two or more conditions or diseases for example ….. Olders is the rule rather than the exception.

Often we do not like to think of comorbidity, as it makes more difficult our diagnostic and therapeutic approach.

A better understanding of comorbidity can help in obtaining optimal results for our patients.

Comorbidities that occur more often than expected based on chance can point to pathophysiological factors common to both conditions, which have so far remained unknown; a practical level, comorbidities offer the potential to treat various conditions with a drug and therefore to minimize the number of pills a patient has to take a day, a factor that should not be underestimated when it comes to improving adherence to treatment; Therefore in this context the effects of noradrenaline uptake inhibitor / serotonin (Cymbalta) gives us four treatment options:

Stress urinary incontinence (SUI).

Major depressive disorder (MDD)

Neuropathic pain due to diabetic neuropathy (NPDP).

Fibromyalgia

The mechanism of action of duloxetine is inhibition of the new carrier protein that noradrenaline and serotonin transport in neurons thus increasing concentrations acutely both transmitters in the synaptic cleft and thereby provides a greater and more prolonged receptor stimulation for both transmitters.

Serotonin acts on ionotropic (ligand-gated ion channels) and 13 subtypes of metabotropic receptors (G-protein coupled receptors) whereas noradrenaline acts nine subtypes of G coupled protein receptors.

The demonstrated efficacy of duloxetine; versus placebo in the treatment of SUI, TDM and neuropathic pain suggests that such stimulation of the receptor improves the diseases.

The specific contributions of noradrenaline and serotonin and also each of its receptor subtypes desired and adverse effects of the drug in the various indications in still largely unclear.

Moreover, some of the effects of duloxetine, such as nausea, apparently occur as a direct consequence of increased acutely transmitter exposure while others, for example, the anti-depressive effect, only produced after several weeks and probably refer to side effects such as down-regulation of certain types of receptors phenomena.

While it remains tempting to speculate that the IUE, MDD and diabetic peripheral neuropathic pain share at least some pathophysiological aspects, the large number of receptors that are activated following administration of duloxetine leaves it open to interpretation whether any of these are attributed to the condition.

Emerging epidemiological data on the comorbidity of IUE, MDD and / or fibromyalgia and diabetic neuropathic pain are promising.

Lq duloxetine efficacy against three different conditions may have practical value, namely, by allowing the treatment of two or even three of them with a drug.

From the viewpoint of side effects, the duloxetine is generally a safe drug. While side effects are uncommon, like other drugs with a mechanism of molecular action, most are rather unpleasant and harmful transient or persistent.

In an indication of the IUE regime specific dose adjustment can help limit side effects; while it is likely that this also applies to the other two directions, there is no specific data.

All the known side effects of duloxetine seem to address the molecular mechanism of action, with the most common, nausea, probably related to the inhibition of serotonin uptake and stimulation of serotonin 5-HT3receptors gastrointestinal. Interestingly, a polymorphism in the gene encoding this receptor was recently reported to predict the occurrence of nausea during treatment with inhibitors of serotonin reuptake, but has to be confirmed by the use of duloxetine.

In the same vein, particularly physicians who are not psychiatrists should check whether other inhibitors of amine uptake have been prescribed by other doctors, and it is possible that their side effects may be additive.

The concept of multiple comorbid conditions be susceptible to treatment with a single drug is attractive from a theoretical and a practical point of view.

Meanwhile, practical use of up to four treatment with a drug comorbidities possible duloxetine

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