Parkinson’s Disease

general information

  1. Dopamine-receptor agonists

The most prominent features of parkinsonism are

  1. Monoamine oxidase (MAO-B) inhibitors

Parkinson disease is a neurodegenerative diseases
characterized by the progressive loss of dopaminergic
neurons in the basal ganglia system

It generally affects the elderly

the causes of Parkinson disease are of
unknown origin

Genetic factors do not play a dominant role in the etiology of
Parkinson disease,

Tremors ,Rigidity, Bradykinesia,The absence of facial expression, Inability to swallow leads to drooling,Orthostatic hypotension,Cognitive dysfunction

  1. Levodopa (L-DOPA)

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effects “wear off

is a metabolic precursor of
dopamine, which is actively transported into the
CNS and is converted to dopamine in the brain

in new patients, the therapeutic response to
levodopa is consistent

is rapidly absorbed from the small intestine

The main metabolic products being 3-methoxy-4-hydroxyphenyl

Levodopa with Carbidopa can greatly enhance the effect of Ledodopa in CNC

– the older ergot derivatives dopamine agonists: bromocriptine and pergolide
– the newer nonergot drugs: pramipexole, ropinirole, apomorphine and
rotigotine which has less side effect and they show the same effect

They have durations of action longer than levodopa

they do
not require enzymatic conversion to an active metabolite

🚩Bromocriptine

a derivative of the vasoconstrictive alkaloid,
ergotamine, is a dopamine-receptor agonist

The usual daily dose of bromocriptine varies between 7.5 and 30
mg.

should not be given to patients with psychiatric illness, a history of myocardial infarction, peripheral vascular disease, peptic ulcer

Apomorphine 🚩 is used in severe and advanced stages of the disease
as an injectable dopamine agonist

Rotigotine 🚩 is available as a once-daily transdermal patch, which is
used in the treatment of the signs and symptoms of early stage
Parkinson disease

selectively inhibits MAO Type B

Selegiline will decrease the metabolism of dopamine, thus leads to
increase dopamine levels in the brain and enhances the actions of levodopa when these drugs are
administered together

Rasagiline, an irreversible and selective inhibitor of brain
monoamine oxidase Type B, has five times the potency of
selegiline.

  1. Catechol-O-methyltransferase inhibitors

Normally, the methylation of levodopa by COMT to 3-O-methyldopa is a
minor pathway for levodopa metabolism.

Inhibition of COMT by Entacapone leads
to decreased plasma concentrations of 3-O-methyldopa, increased
central uptake of levodopa, and greater concentrations of brain dopamine

Oral absorption occurs
readily and is not influenced by food and extensively bound to plasma albumin with limited volumes of distribution.

  1. Anticholinergic agents

are much less efficacious than levodopa
and play only an adjuvant role in antiparkinsonism therapy

25 Amantadine

has several effects on a number of neurotransmitters
implicated in causing parkinsonism, including increasing the release
of dopamine, blockading cholinergic receptors, and inhibiting the Nmethyl-D-aspartate
(NMDA) type of glutamate receptors.

was antiviral drug amantadine

It is less efficacious than levodopa, and tolerance develops more
readily