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Parkinson’s disease

Parkinson’s disease

?Introduction:
Parkinson’s disease is a long-lasting disease result from disorder of motor system in the central nervous system, it has very slow progression and it starts with a symptom that appear over the time in its early stage such as difficulty with walking, rigidity and shaking. Whereas, in it is late stages a symptom like Dementia is very common.

Physiology:
the anatomical faction of the basal ganglia including the neostriatum, the subthalamic nucleus and the substantia nigra with its pars reticulata and pars compacta and the external and internal pallidal segments. They all participate in segregated loops that involve specific thalamic and cortical areas. The parallel circuits are divided into ‘motor’, ‘associative’ and ‘limbic’ loops, then the information is transferred to the basal ganglia output nuclei depending on the function of the cortical area involved. via specific areas of the cerebral cortex or thalamus received from striatum and the subthalamic nucleus glutamatergic afferents. The projections between the striatum and internal pallidal segments / substantia nigra are divided into two separate pathways, the direct which its about the (monosynaptic) connection, and an indirect projection, through the intercalated external pallidal segments and the subthalamic nucleus.

Pathophysiology:
Parkinson disease result from deficits in the motor loop of the basal ganglia, the abnormal neuronal behavior results from multiple disturbance in neurons, which will lead to increased firing, correlated activity, an augmented synchrony, bursting, and a tendency towards loss of specificity in their receptive fields. As a result, signs and symptoms such as, bradykinesia, akinesia, losing of normal postural reflexes and hypokinetic will appear. One of the initial symptoms is firing out of control this happens due to a deficiency in the striatum the nerve cells. With time the disease will start to progress causing more damage to the other areas of the brain and nervous system as well, which will lead to more movement disorder. With time moving on and after progressing the morphological changes corticostriatal transmission for example can be significantly changed after dopamine loss in the basal ganglia, and the reduction of the density of dendritic spines on MSNs.

Pharmacological treatment:
Although Parkinson disease can’t be treated, it’s still can be managed or controlled via different methods. Starting with the antiparkinson medication levodopa, once the levodopa become less effective dopamine agonists can be used. Over the time as the disease progressing and neurons losing continue, these medications become no longer beneficial to the patient as it is starting to produce complication side result in involuntary writhing movements. The symptoms can also be improved through diet and some exercises. Eventually it might require surgical involvement, such as replacing the microelectrodes for deep brain stimulation.

Calcification of Parkinson disease drugs:
1- Levodopa
The mechanism of action of levodopa is metabolic precursor of dopamine it can cross the blood-brain barrier, and then it starts to convert into dopamine in the brain. After administration of levodopa it will temporary reduce the motor symptoms of Parkinson disease.

Side effects:
Levodopa might cause unwanted effect such as twisting, and uncontrolled repetitive movements of the tongue, face, lips, arms, or legs and less common side effect for example, chest pain, Bladder pain, bloody urine, and lack of appetite.

2- COMT inhibitors

By inhibiting the Catechol-O-methyltransferase activity, which degrade dopamine, COMT inhibitors does not contain levodopa therefore it has to be taken with it to make it lest longer.
Examples: Tolcapone, Entacapone

Side effects:
1- dyskinesias
2- diarrhea
3-vivid dreams
4- liver toxicity.

3-Dopamine agonists:
They and Levodopa have kind of similar effect. But the dopamine agonists bind to receptors in dopamine, unlike levodopa. Whereas the main use of dopamine agonists nowadays is to delay the complications of Levodopa.

Side effects:
Most common side effects are Euphoria, Weight loss, Dizziness, Drowsiness, and Lightheadedness.