Parkinson's disease Flashcards
What is Parkinson’s disease?
Parkinson’s disease is a condition that affects the brain. It causes problems like shaking and stiffness that get worse over time.
The main symptoms of Parkinson’s disease are shaking (tremors), slow movements and stiffness.
What is the neuropathology of Parkinson’s disease?
Severe loss of black pigmentation (neuromelanin) due to dopaminergic neuronal loss in substantia nigra (pars compacta).
Degree of loss of black pigmentation correlated with degree of motor impairment.
Clinical features: at >60-80% dopaminergic neurons loss
Other brain areas are affected: e.g locus ceruleus, raphe cortex.
Why is dopamine important?
Parkinson’s disease is caused by a loss of nerve cells in part of the brain called the substantia nigra.
This leads to a reduction in a chemical called dopamine in the brain.
Dopamine plays a vital role in regulating the movement of the body.
What drugs cause drug-induced Parkinsons?
Neuroleptics (antipsychotics). Dopamine depleting drugs. Antiemetics. Calcium-channel blockers. Mood stabilizers. Antidepressants. Antiepileptic drugs.
Important because it is reversible although it may require weeks or months to reverse after drug discontinuation.
What is the process of the synaptic metabolism of dopamine?
The primary one consists of dopamine reuptake into the presynaptic neuron.
In another termination process, two different enzymes metabolize dopamine.
Catechol‐O‐methyltransferase (COMT), mostly an extracellular enzyme, and monoamine oxidase (MAO), mostly an intracellular enzyme, both metabolize dopamine.
What therapies are used for Parkinson’s disease?
Medications.
Surgery.
Complementary and supportive therapies, such as diet, exercise, physical therapy, occupational therapy, and speech therapy.
What is the best medication for Parkinson’s disease?
Levodopa and carbidopa.
Levodopa (also called L-dopa) is the most commonly prescribed medicine for Parkinson’s. It’s also the best at controlling the symptoms of the condition, particularly slow movements and stiff, rigid body parts.
Levodopa works when your brain cells change it into dopamine.
How is DOPA supplement therapy in Parkinson’s disease?
Dopamine (DA) supplementation therapy by l-dopa for Parkinson’s disease (PD) was established around 1970.
The dose of l-dopa can be reduced by the combined administration of inhibitors of peripheral l-amino acid decarboxylase (AADC), catechol O-methyltransferase (COMT), or monoamine oxidase B (MAO B).
What are the therapeutic effects of L-DOPA?
Levodopa can help treat Parkinson’s symptoms because it helps to top up dopamine levels in the brain.
You may experience a big improvement in your symptoms when taking it, especially with stiffness and slowness of movement. Levodopa becomes less effective over time.
What are the effects of DOPA therapy in PD?
Good absorption from gut. Good penetration of BBB. Peak plasma conc 0.5 - 2 h after dose. Short half-life (t½ = 1 - 3 h). Rapid metabolism.
Acute side-effects of DOPA :
Nausea & vomitting.
Postural hypotension.
Delusions / Hallucinations.
What are the adverse effects of L-DOPA?
Mood changes. Depression. Aggressive behavior. Abnormal heart rhythm. Orthostatic hypotension, a form of low blood pressure. Mental status changes. Excessive nausea. Excessive vomiting.
What are the problems associated with chronic
treatment with L-DOPA in PD?
“Wearing-off” effect.
Abnormal involuntary movements (dyskinesia).
Sudden “ON-OFF” transitions in patient mobility.
Disease progression unretarded and even possibly accelerated.
What is amantadine?
Amantadine is an antidyskinetic medicine. It is used to treat Parkinson’s disease.
Side effects:
Dry mouth. Constipation. Nausea. Vomiting. Decreased appetite. Difficulty falling asleep or staying asleep. Abnormal dreams. Headache.
What is selegiline?
Selegiline is in a group of medications called monoamine oxidase type B (MAO-B) inhibitors.
It works by increasing the amount of dopamine in the brain.
The action of selegiline is to inhibit monoamine oxidase (MAO) type B (and other MAOs at higher doses). The proposed mechanism of action is to inhibit the metabolism of dopamine in the CNS.
What do COMT inhibitors do?
The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson’s medications.
By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier.
