However, the significance of this property is not fully clear. Fluoxetine also functions as a channel blocker of anoctamin 1, a calcium-activated chloride channel. A number of other ion channels, including nicotinic acetylcholine receptors and 5-HT3 receptors, are also known to be inhibited at similar concentrations.Fluoxetine has been shown to inhibit acid sphingomyelinase, a key regulator of ceramide levels which derives ceramide from sphingomyelin. Mechanism of action
Fluoxetine elicits antidepressant effect by inhibiting serotonin reuptake in the synapse by binding to the reuptake pump on the neuronal membrane to increase serotonin availability and enhance neurotransmission. Over time, this leads to a downregulation of pre-synaptic 5-HT1A receptors, which is associated with an improvement in passive stress tolerance, and delayed downstream increase in expression of brain-derived neurotrophic factor, which may contribute to a reduction in negative affective biases. Norfluoxetine and desmethylfluoxetine are metabolites of fluoxetine and also act as serotonin reuptake inhibitors, increasing the duration of action of the drug. Pharmacokinetics
The bioavailability of fluoxetine is relatively high (72%), and peak plasma concentrations are reached in 6–8 hours. It is highly bound to plasma proteins, mostly albumin and α1-glycoprotein. Fluoxetine is metabolized in the liver by isoenzymes of the cytochrome P450 system, including CYP2D6. The role of CYP2D6 in the metabolism of fluoxetine may be clinically important, as there is great genetic variability in the function of this enzyme among people. CYP2D6 is responsible for converting fluoxetine to its only active metabolite, norfluoxetine.
Halo nevus (also known as "Leukoderma acquisitum centrifugum," "Perinevoid vitiligo," and "Sutton nevus": 689 ) is a mole that is surrounded by a depigmented ring or halo. Presentation
Halo nevi are also known as Suttons nevi, or leukoderma acquisitum centrifugum. Halo nevi are named such because they are a mole (nevus) that is surrounded by an area of depigmentation that resembles a halo. Halo nevi are associated with vitiligo. Sometimes the pale (hypopigmented) areas will spontaneously regress, and pigment returns. Causes
The formation of a halo surrounding a nevi is believed to occur when certain white blood cells called CD8+ T lymphocytes destroy the pigment-producing cells of the skin (melanocytes). The cause for the attack is unknown. Diagnosis
Treatment
As halo nevi are only of cosmetic significance, no treatment is required, and patients will be asymptomatic. Although halo nevi are harmless, it is important to monitor the lesion on regular basis. Watch out for any changes in appearance of existing or new halo nevi. If there is any change in appearance or is associated with pain, itch, and infection, a doctor should be consulted immediately to exclude the possibility of melanoma. Epidemiology
Halo nevi are estimated to be present in approximately 1% of the general population, and are found to be more prevalent in people with vitiligo, malignant melanoma, or Turner syndrome. All races and sexes are equally susceptible to this disease, although a familial tendency has been reported. The average age of onset is in a persons teenage years. See also
Nevus
List of cutaneous conditions

References


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