Parkinsons Flashcards
(44 cards)
What are the symptoms of Parkinsons?
The main symptoms of Parkinson’s disease affect physical movement:
tremor – shaking, which usually begins in the hand or arm and is more likely to occur when the limb is relaxed and resting
slowness of movement (bradykinesia) – physical movements are much slower than normal, which can make everyday tasks difficult and result in a distinctive slow, shuffling walk with very small steps
muscle stiffness (rigidity) – stiffness and tension in the muscles, which can make it difficult to move around and make facial expressions, and can result in painful muscle cramps (dystonia)
These main symptoms are sometimes referred to by doctors as parkinsonism.
What is Parkinsons caused by? When do symptoms begin to occur?
Parkinson’s disease is caused by a loss of nerve cells in the part of the brain called the substantia nigra.
Nerve cells in this part of the brain are responsible for producing a chemical called dopamine.
Dopamine acts as a messenger between the parts of the brain and nervous system that help control and co-ordinate body movements.
If these nerve cells die or become damaged, the amount of dopamine in the brain is reduced.
This means the part of the brain controlling movement cannot work as well as normal, causing movements to become slow and abnormal.
The loss of nerve cells is a slow process. The symptoms of Parkinson’s disease usually only start to develop when around 50% of the nerve cell activity in the substantia nigra have been lost.
What drugs are used to relieve symptoms of parkinsons?
Medication can be used to improve the main symptoms of Parkinson’s disease, such as shaking (tremors) and movement problems.
Three main types of medication are commonly used:
levodopa
dopamine agonists
monoamine oxidase-B inhibitors
How does Levodopa work? How is it taken? What is levodopa taken with?
Levodopa is absorbed by the nerve cells in your brain and turned into the chemical dopamine, which is used to transmit messages between the parts of the brain and nerves that control movement.
Increasing the levels of dopamine using levodopa usually improves movement problems.
It’s usually taken as a tablet or liquid, and is often combined with other medication, such as benserazide (DOPA decsraboxylase inhibitor) or carbidopa (decarboxylase inhibitor)
These medications stop the levodopa being broken down in the bloodstream before it has a chance to get to the brain.
They also reduce the side effects of levodopa, which include:
feeling and being sick
tiredness
dizziness
Disadvantage of levodopa?
Long-term use of levodopa is also linked to problems such as uncontrollable, jerky muscle movements (dyskinesias) and “on-off” effects, where the person rapidly switches between being able to move (on) and being immobile (off).
dyskinesia It can look like fidgeting, writhing, wriggling, head bobbing or body swaying. Rapid jerking movements or slow muscle spasms
What are dopamine agonists? Give an example?
Dopamine agonists act as a substitute for dopamine in the brain and have a similar but milder effect compared with levodopa. They can often be given less frequently than levodopa.
They’re often taken as a tablet, but are also available as a skin patch (rotigotine).
What does the substantia nigra produce? What does that product do?
The substantia nigra (part of brain) Dopamine, Dopamine acts as a messenger between the parts of the brain and nervous system that help control and co-ordinate body movements.
If these nerve cells die or become damaged, the amount of dopamine in the brain is reduced.
This means the part of the brain controlling movement cannot work as well as normal, causing movements to become slow and abnormal.
What are the three main dopaminergic pathways?
Motor Control (Nigrostriatal Pathway)
Behaviour/Emotion (Mesocortical Pathway)
Endocrine/Secretion (Tuberohyophyseal Neurons)
What does drug treatment do to patients with parkinsons?
Aims to treat symptoms not the cause of the neurodegeneration
Improve quality of life for patient
Minimize deterioration
Minimize side effects
What are the roles of Dopaminergic drugs?
Increase levels of DOPAMINE in the striatum
Deliver a precursor of dopamine
Prevent degradation of dopamine at the neurones
Stimulate dopamine receptors (D2 and D3)
Mainstay of treatment of PD (particularly levodopa)
Improve bradykinesia and rigidity, less effective at controlling tremor
How is levodopa converted into dopamine?
Dopamine is unable to cross the BBB, therfore Levodopa is a precursor to dopamine that passes the blood-brain barrier and is mainly taken up by the dopaminergic neurons that convert L-DOPA to dopamine by the aromatic amino-acid DOPA decarboxylase enzyme in the blood and increase their dopamine production and storage.
Carboxylates
What does DOPA stand for?
DihyrOxyPhenylAlanine: DOPA
Advantaged of Levodopa?
Improvement in initiating and stopping movements
Smoother, faster, more controlled movement
Speech
Tremor alleviated to a lesser degree
Improvement in ~70% of patients
Some dopa decarboxylase in remaining striatal neurones
What are the side effects of Levodopa?
Nausea and vomiting (CNS, area postrema)
Postural hypotension and cardiac arrhythmia (kidney and autonomic)
Dyskinesia (CNS)
Psychiatric disturbances (CNS)
Colours urine (reddish)
GI bleeding
How do COMT inhibitors work and what are they?
COMT is an enzyme that break down neurotransmitters (chemical messengers) like dopamine. COMT inhibitors block the action of COMT enzyme. Levodopa therapy provides the precursor to dopamine which is used to make dopamine. Adding a COMT inhibitor slows the breakdown of levodopa in the body allowing more of it to get into the brain increasing its effects to increase dopamine levels.
entacapone and tolcapone
Examples of COMT inhibitors?
Comtan® (entacapone)
Tasmar® (tolcapone)
Ongentys® (opicapone)
Drugs used along with carbidopa-levodopa therapy.
What other inhibitor should COMT inhibitors not be used along with?
COMT inhibitors and non-selective MAO-B (monoamine oxidase-B) inhibitors should not be taken at the same time.
What and where is dopamine broken down into?
Dopamine is broken down in liver and excreted in the urine as homovanillic acid.
What is the degradation mechanism of the conversion of dopamine to homovanillic acid?
Dopamine is transported by a dopamine transporter, monoamine oxidase catalyses the reaction from Dopamine to DOPAC (dihydroxyphenylacetic acid). DOPAC is converted to homovanillic acid by COMT ( catechol-O-methyl-transferase). All occurs in the brain
OR
Dopamine catalysed by COMT to 3- Methoxytryramine (3-MT). 3-MT is then catalysed by Monoamin oxidase (MAO) Aldehyde dehydrogenase to form HVA homovanillic acid.
What drugs are used for Primary or Idiopathic Parkinson’s disease?
ALL drugs are used.
What drugs are used for secondary or drug-induced parkinsonism?
ONLY antimuscarinics are used.
What happens when drug therapy is used?
INCREASING dopaminergic activity and reducing the relative cholinergic overactivity. Both approaches aim to restore balance in basal ganglia.
What anti-muscarinic drugs are used in Parkinsons disease? adv and disadv
Orphenadrine, Trihexyphenidyl (benzhexol), Benztropine, Procyclidine (kemadrin)
Moderate effect in most patients
Less effective than levodopa
Reduce tremor,but no effect on the slowness of movements
Treatment of drug-induced parkinsonian symptoms
What are the anti- muscarinic side effects? Which patients need extra caution when taking anti muscurinics?
MORE SYMPATHETIC ACTIVITY because antimuscarinics medications work by blocking muscarinic receptors from the action of acetylcholine, the chief chemical messenger controlling parasympathetic functions.
Peripheral- dry mouth, blurred vision, constipation, urine retention, worsening of glaucoma
Central - confusion,hallucinations, excitement, euphoria and insomnia
To be used with caution in patients with cardiovascular disease, untreated urinary retention, glaucoma and gastro-intestinal obstruction
