Parkinson's Disease Treatment

Dr. Maryam Mohammadzadeh Akın

• In Parkinson's disease, there is a progressive loss of dopaminergic
neurons in the substantia nigra pars compacta.

• Dopaminergic activity decreased in the striatum, and increased

cholinergic activity in the basal ganglia.

• Antipsychotic drugs that decrease dopaminergic activity and drugs

that increase cholinergic activity may cause Parkinson-like symptoms.
• Any drug that blocks the action of dopamine (referred to as a
dopamine antagonist) or decreased the mount of Dopamine is likely to
cause parkinsonism. Drugs used to treat schizophrenia and other
psychotic disorders such as behaviour disturbances are possibly the
major cause of drug-induced parkinsonism worldwide.
 Purpose?????
• The goal of treating Parkinson's disease is to decrease what is
increasing, to increase what is decreasing.
• Purpose of medical treatment of Parkinson's disease; To increase the
decreased dopaminergic activity and to decrease the increased cholinergic
activity.

• Because in Parkinson, the amount of acetylcholine increased, the amount of

dopamine decreased.

• Patients with Parkinson's have bradykinesia, which is due to decreased

dopamine.
• In patients with Parkinson's, if the bradykinesia symptom is far ahead, it is
necessary to increase the dopaminergic activity.
 Bradykinesia???
• Bradykinesia means slowness of movement, and it is one of the cardinal
symptoms of Parkinson’s. You must have bradykinesia plus either
tremor or rigidity for a Parkinson’s diagnosis to be considered.
• In Parkinson’s, this slowness happens in different ways:
Reduction of automatic movements (such as blinking or swinging your
arms when you walk)
Difficulty initiating movements (like getting up out of a chair)
General slowness in physical actions
The appearance of abnormal stillness or a decrease in facial expression
• The tremor and hyper salivation in Parkinson's patients are
increased ,because choleric activity is increased. so we have to give
anticholinergic drugs to reduce this symptom in Parkinson’s patients.

• Since dopamine does not pass to the central nervous system, it is not used
in treatment.
 Parkinson's treatment

• They increase dopaminergic activity (D1, D2) in the central nervous system

• They reduce cholinergic activity in the central nervous system.

• Dopaminergic drugs improve all symptoms, especially bradykinesia, in

Parkinson.

• Anticholinergic drugs correct tremor.

 Drugs that increase dopaminergic activity

• Dopamine itself cannot enter the central nervous system, but its
precursor L-dopa or levodopa passes into the central nervous system.
 Drugs that increase dopaminergic activity
• L-dopa (Levodopa)
• L-dopa is a prodrug. that is, it is not active on its own.
• It is the precursor of dopamine in catecalamine synthesis.

• Although dopamine cannot pass from the circulation to the brain, L-dopa passes to the central nervous
system, In the brain, L-dopa is converted to dopamine By dopa decarboxylase then dopamine formed
and stimulates D2 receptors.

• It does not show a direct agonist effect on D2 receptors.(because after converting L-dopa to
Dopamin, Dopamine itself go and effect D2 receptor.

• Taking it on an empty stomach increases its entry into the central nervous system.(L-dopa can already
get into the brain 1-3 percent.)
• When L-dopa is taken orally, it passes from the small intestine into the
blood and from the blood to the brain via a carrier.
 Drugs that increase dopaminergic activity
• L-dopa (Levodopa)

• While it does not stop the progression of Parkinson's disease, it reduces mortality if
started early. One third of patients respond well to treatment, while one third responds
poorly. After about 3-4 years, its effectiveness begins to decrease.

• Since Dopa decarbacsylase enzyme is found in many peripheral structures such as

intestine and liver; L-dopa dopamine conversion also occurs in peripheral structures.

• Dopamine formed in the periphery cannot pass to the brain; It causes side effects such
as nausea, vomiting and hypotension.
 Drugs that increase dopaminergic activity

• L-dopa (Levodopa)

• When L-dopa is administered with drugs such as carbidopa or Benserazide, which

inhibit the Dopa decarboxylase enzyme in the periphery, its effectiveness increases due
to the amount that passes to the central nervous system, and peripheral side effects
decrease because less dopamine will be formed in the periphery.

• Since the amount passing to the central nervous system will increase, central side
effects related to Dopamine increase.
 Pharmacokinetic Properties

• It is used orally and is taken into the blood and brain by means of a carrier. It is
converted to dopamine by Dopa decarboxylase during its passage through the
liver and intestines.
• If used together with pyridoxine, which activates the Dopa decarboxylase
enzyme, its effectiveness decreases. Therefore, it should not be used together
with pyridoxine.
• It is broken down by the MAO and COMT enzymes. When taken with
Entacapone or Tolcapone, which inhibit the COMT enzyme, its passage to the
central nervous system increases.
dopamine
 contraindications:
• in schizophrenia’s patient
• It is not used in patients with glaucoma because it causes mydriasis.
• Those with arrhythmias due to arrhythmia potential
• It is not used in patients with ulcer because it increases gastric acid
secretion.
 Drugs that increase dopaminergic activity
• Carbidopa / Benserazide

• They inhibit the enzyme dopa decarboxylase in the periphery.

• They have no stand-alone effectiveness in the treatment of Parkinson's.
• They increase the effectiveness of L-dopa by decreasing its extracerebral
metabolism.
• Since less dopamine will be formed in the periphery, they reduce peripheral
side effects such as nausea and hypotension, while increasing central side
effects such as delusion, hallucination and confusion due to the increase in
dopamine in the brain.
Dopamine Receptor Agonists Used in Parkinson's Treatment

Ergot derivatives drugs non-ergot drugs

Lizurid Pramipexole

Ropirinol
Pergolid
Rotigotine
Cabergoline
Bromocriptine Apomorphine
Clinical Use of Dopamine Receptor Agonists

• Because they stimulate the dopaminergic receptor; They are used in the treatment of Parkinson's
disease.

• Because they increase dopaminergic activity; They reduce prolactin and growth hormone, and
are useful in the treatment of prolactin-secreting adenoma and acromegaly.

• Because they reduce prolactin; They are used to suppress physiological milk secretion in men
and women.

• They are given with dantrolene in the treatment of neuroleptic malignant syndrome due to
dopamine receptor blockade..
 Side Effects of Dopamine Receptor Agonists

• Nausea, vomiting, and hypotension are common. As a result of

stimulation of D2 receptors in the central nervous system, they
produce a clinical picture similar to hallucination and schizophrenia.
• Bromocriptine causes red painful swelling in the hands and feet
(erythromelalgia).
• They are not used in patients with angina pectoris, myocardial
infarction or psychosis history.