#Parkinsonism#sinemet#dopamine#levodopa#carbidopa#bradykinesia#ropinirole#cabergoline#pergolide#pramipexole#entacapone#onoffeffect#selegiline
a term that refers to the symptoms of Parkinson’s disease.
as well as the Parkinson-like symptoms, that may be seen with the use of antipsychotics drugs.

Parkinsonism is characterized by a resting tremor, slow initiation of movements (bradykinesia), and muscle
rigidity.

Typically, a patient with parkinsonism will present with.

A shuffling shuffling and unsteady gait.

the upper part of the body is bent forward.

A blank ‘mask-like’ and emotionless expression.

Speech impairment and inability to perform purposeful movement or skilled tasks.

Parkinson’s disease is caused by a progressive degeneration of the dopaminergic neurons, of the substantia nigra.

which project via the nigrostriatal pathway to the corpus striatum.

The reduction in the inhibitory dopaminergic activity of the nigrostriatal pathway.

results in unopposed cholinergic neuron hyperactivity from the corpus striatum.
which contributes to the pathological features of parkinsonism.

Since there is no cure for parkinsonism, the aim of pharmacological therapy is to provide symptomatic relief.

The treatment of parkinsonism is based on correcting
the imbalance between the dopaminergic,
and cholinergic systems at the basal ganglia.

Two major groups of drugs are used.

First the drugs that increase dopaminergic activity between the substantia nigra and the corpus striatum.

And second group is anticholinergic drugs that inhibit
striatal cholinergic activity.

Let’s start with Drugs that increase dopaminergic activity.

Dopamine itself is cannot be used to supplement dopamine deficiency caused due to degeneration of the dopaminergic neurons.

because dopamine can not to cross the blood–brain barrier if administered by systemic routes.

Levodopa

Levodopa or L-dopa a precursors of dopamine is used as frontline in parkinsonism.

Levodopa can cross the blood–brain barrier and then converted into dopamine by an enzyme dopa decarboxylase.

This causes replenishment of the dopamine content of the corpus striatum.

The adverse effects of L-dopa.

The adverse effects of L-dopa are caused due to extensive peripheral metabolism of L-dopa to dopamine.

adverse effects include.
Nausea and vomiting.


Next category of drug is Decarboxylase inhibitor

Carbidopa is an example of L-amino acid decarboxylase inhibitor.

In the presence of carbidopa, less levodopa is decarboxylated by dopa decarboxylase to Dopamine in the periphery.

therefore, the therapeutic dose of levodopa can be reduced by up to 80%, substantially minimizing nausea and vomiting and adverse cardiovascular effects.


End of dose deterioration and the on-off effect.

Although L-dopa and carbidopa restores dopamine levels in the short term, therapy has no effect on the underlying degenerative disease process.

As progressive neuronal degeneration continues, the capacity of the corpus striatum to convert L-dopa to dopamine diminishes.

This affects the majority of patients within 5 years and manifests itself as ‘end of dose deterioration’ that is a shortening of duration of each dose of L-dopa

the ‘on-off effect’ means rapid fluctuations in clinical state, varying from increased mobility and a general improvement to increased rigidity and hypokinesia.

The on off effect occurs suddenly and for short periods from a few minutes to a few hours, tending to worsen with length of treatment.

The next category of drug is Dopamine agonists

The dopamine agonists include bromocriptine, ropinirole, cabergoline, pergolide, pramipexole, lisuride and apomorphine.

The Bromocriptine, ropinirole, cabergoline, pergolide, pramipexole, lisuride and apomorphine are dopamine agonists selective for the D2 receptor.

The Dopamine agonists are used in combination with L-dopa in an attempt to reduce the late adverse effects

of L-dopa therapy that is ‘end of dose deterioration’ and ‘on-off effect’ or when L-dopa alone does not adequately control the symptoms.

The adverse effects of dopamine agonists are similar to those of L-dopa that is nausea, postural hypotension, psychiatric symptoms.

but they tend to be more common and more severe. Apomorphine produces profound nausea and vomiting.

Currently bromocriptine is the most used of the dopamine agonists in the treatment of Parkinson’s disease

Drugs stimulating release of dopamine
Amantadine
Amantadine is an antiviral drug.
Amantadine Facilitation the neuronal release of dopamine and inhibit reuptake of dopamine into nerves.
It also has additional muscarinic blocking actions.

Amantadine is useful in the early stages of parkinsonism or as an adjunct to levodopa therapy.

Adverse effects Amantadine includes headache, insomnia, confusion, hallucinations, and peripheral edema.

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