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D2 occupancy and weight of patient for controlling extrapyramidal symptoms Health Articles | December 12 Wholesale Dont'a Hightower Jersey , 2016



First generation antipsychotics are typically accompanied by extrapyramidal side effects while second and third generation antipsychotics are accompanied by metabolic side effects. In particular, the D2 occupancy has been linked to side effects – a D2 occupancy greater than 85% typically results in extrapyramidal side effects.



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Schizophrenia is a serious illness that results in the expression of positive, negative and cognitive symptoms. Currently, there is no cure for the disease; rather the symptoms are controlled using antipsychotics. Antipsychotics fall into one of three categories: conventional D2 antagonists (first generation), atypical 5HT2AD2 antagonists (second generation), and D2 partial agonists (third generation). Conventional D2 antagonists are typically accompanied by neurological Wholesale James White Jersey , and extrapyramidal side effects. Atypical 5HT2AD2 antagonists are accompanied by metabolic side effects. Aripiprazole is only drug in the third generation antipsychotics category or the D2 partial agonists. It is hypothesized that psychosis is a result of subcortical hyperdopaminergic activity. Further, it has been demonstrated that potency of drug is dependent on the degree of antidopaminergic actions. As such, first generation antipsychotics are D2 dopamine receptor blockersantagonists. Second and third generation antipsychotics have antidopaminergic activity to variable degrees, but also have the ability to bind other receptors such as serotonergic, cholinergic, and adrenergic receptors. In particular Wholesale Tom Brady Jersey , second and third generation antipsychotics have a multi-receptor binding profile; second and third generation antipsychotics have a high 5-HT2AD2 ratio. Currently second and third generation antipsychotics are favoured over first generation antipsychotics due to the adverse side effects associated with first generation drugs, in particular extrapyramidal side effects, and elevated prolactin levels. Further, first generation antipsychotics are useful for controlling positive symptoms, but poorly control the negative and cognitive symptoms of schizophrenia. Second and third generation antipsychotics have the ability to address negative, and cognitive symptoms. In particular Wholesale Rob Gronkowski Jersey , clozapine and quetiapine are associated with no extrapyramidal side effects; however, extrapyramidal side effects have been noted to be present at higher doses of risperidone, and olanzapine.


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In particular, D2 occupancy has been linked to extrapyramidal side effects, avolition, apathy Wholesale Jake Bailey Jersey , and affective flattening. In fact, a 60% to 70% striatal D2 occupancy is required for antipsychotic potency. A D2 occupancy that exceeds 78% (85% max) results in extrapyramidal side effects. Optimal efficacy and minimization of side effects thus occurs between 65-78% D2 occupancy. The latter implies that varying the dosage of the antipsychotic can vary D2 occupancy, and therefore side effects. Second generation antipsychotics at prescribed or clinically administered doses have D2 occupancies that are less than 85%, and as such are not accompanied by extrapyramidal side effects. Risperidone, for instance, at a dose of 2-6 mgday – prescribed dose - results in a D2 occupancy between 59-83% (1). In most cases Wholesale Jarrett Stidham Jersey , a clinically prescribed dose of a chosen antipsychotic is administered to patients without any consideration to the patient’s weight. In this paper, I shall examine the dosage at which a D2 occupancy between 65% and 85% can be achieved, and whether the said dosage is within the optimal prescribed dose for patients when weight of patient is a factor. Given that side effects are a major problem when dealing with antipsychotics, I examined the antipsychotic dose clinically prescribed, the weight of patients, and the safety zone (the area between the 65% and 85% D2 occupancy). The safety zone is the zone generated by plotting the equation y=mx where m is the 65% or 85% D2 occupancy (in mgkg) Wholesale Hjalte Froholdt Jersey , and x is the weight (in kg). The latter would be specific to both the antipsychotic used, and the weight of the patient. The clinically prescribed doses were then used to determine the weight of individuals who can safely use the medication.


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The relationship between weight, and safety zone was examined for a number of antipsychotics, however, it was only found to be relevant for haloperidol (Figure 1). Haloperidol at 7.5 mg has been shown to have a D2 occupancy of 83-92% (1). In theory, this would imply that haloperidol if prescribed can cause extrapyramidal side effects. However Wholesale Yodny Cajuste Jersey , there is one instance during which haloperidol can be used safely. Haloperidol, a first generation antipsychotic, is usually prescribed at 5 to 20 mg per day. Further, the 65% D2 occupancy of haloperidol is 0.05 mgkg. The latter implies that any persons weighing between 100 to 400 kg (220 lb to 881 lb) can be placed on this treatment. The 85% D2 occupancy of haloperidol is approximately 0.1 mgkg. The latter implies that any persons weighing between 50 kg, and 200kg can be placed on this dosage (Figure 1). Given that the optimal D2 occupancy is approximately 70%, one might claim that a number of individuals may be placed on this treatment in the safe zone (without extrapyramidal side effects). In the case of loxapine Wholesale Damien Harris Jersey , olanzapine, risperidone, clozapine, ziprasidone, and thioridazine the prescribed doses have a D2 occupancy that is significantly lower 70% regardless of weight. Thioridazine is a first generation antipsychotic is prescribed at doses between 200-500 mg. The 70% D2 occupancy of thioridazine is above the prescribed dose for all weight classes. In theory, this would imply that at clinical doses Wholesale Chase Winovich Jersey , thioridazine, a first generation antipsychotic, will not cause any extrapyramidal side ef>Insurance Polic. Todd Gurley II Jersey Authentic T. J. Watt Jersey Stefon Diggs Womens Jersey Shaquem Griffin Womens Jersey Saquon Barkley Youth Jersey Royce Freeman Kids Jersey Roquan Smith Kids Jersey Richard Sherman Kids Jersey Patrick Mahomes Chiefs Jersey Nick Foles Eagles Jersey