mechanisms
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I am not sure if I have to post question on the board in a multiple choice format or simply ask my question, so forgive me.
I am confused how drugs which prevent parkison disease have a side effect of Dyskinesia. Aren't the drugs being given to prevent Bradykinesia, muscle rigidity and resting tremor.
I was confused because it makes sense to see dyskinesea when we use drugs for Antipsychotics where we are trying to block the dopamine activity. But then how do we see the same side effect with drugs that increase dopamine.
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| new_n_lost
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The most widely accepted mechanism by which antipsychotics cause NMS is that of dopamine D2 receptor antagonism. In this widely accepted model, central D2 receptor blockade in the hypothalamus, nigrostriatal pathways, and spinal cord leads to increased muscle rigidity and tremor via extrapyramidal pathways. Hypothalamic D2 receptor blockade results in an elevated temperature set point and impairment of heat-dissipating mechanisms. Peripherally, antipsychotics lead to increased calcium release from the sarcoplasmic reticulum, resulting in increased contractility, which can contribute to hyperthermia, rigidity, and muscle cell breakdown.
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| new_n_lost
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Beyond these direct effects, D2 receptor blockade might cause NMS by removing tonic inhibition from the sympathetic nervous system. The resulting sympathoadrenal hyperactivity and dysregulation leads to autonomic dysfunction. This model suggests that patients with baseline high levels of sympathoadrenal activity might be at increased risk.
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| new_n_lost
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Tardive dyskinesias (TDs) are involuntary movements of the tongue, lips, face, trunk, and extremities that occur in patients treated with long-term dopaminergic antagonist medications. Although they are associated with the use of neuroleptics, TDs apparently existed before the development of neuroleptics. People with schizophrenia appear especially vulnerable to developing TDs after exposure to conventional neuroleptics, anticholinergics, toxins, substances of abuse, and other agents. TDs are most common in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who have been treated with antipsychotic medication for long periods, but TDs occasionally occur in other patients as well.
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| new_n_lost
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Its the Super sensitivity of the Dopamine REceptors which has been postualted.
Striatal dopamine receptor supersensitivity may be responsible.
Chronic dopamine blockade may result in up-regulation of dopamine receptor responsiveness.
TD is hypothesized to result from compensatory supersensitivity of dopamine receptors following chronic blockade. Long-term blockade of dopamine D2 receptors in the basal ganglia by dopamine D2 antagonists (eg, neuroleptics) may produce TD.
When dopamine D2-receptor blockade is reduced (even slightly), an exaggerated response of the postsynaptic dopamine D2-receptor (even to low concentrations of dopamine) may result.
Striatal disinhibition of the thalamocortical pathway from imbalance of D1 and D2 receptors may be involved.
Neurodegeneration secondary to lipid peroxidation or excitotoxic mechanisms may be responsible.
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| mechanisms
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Yes, this explains well why we see Tardive Dyskinesia in Antipsychotics, essentially due to blockade of dopamine receptors.
But why do we se Dyskinesia (not tardive dyskinesia) in patients that are taking levodopa, or tolcapone, or bromocriptine.
The supersensitivity of the dopamine receptors in patients with parkinson causes Dyskinesia?
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| new_n_lost
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FORUM RULES-- Those who believe in telekinesis, raise my hand. I get enough exercise just by pushing my luck --P4U World.." The pure and simple truth is rarely pure and never simple."
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