Term
What is the pathophysiology of Parkinson's disease?
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Definition
| There is decrease dopamine in the nigrostriatal pathway, leading to an excess of Ach. |
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Term
| What do Dopamine and Ach control? |
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Definition
Dopamine : Initiation of movement
Ach: Termination of movement |
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Term
| What is drug induced Parkinsonism? |
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Definition
| Due to a long term use of a dopamine D2 receptor antagonist. There is an up-regulation of receptors |
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Term
What is MPTP?
when is it used? |
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Definition
destroies all dopaminergic neurons
Drugs given after the administration of this drug to see what drugs can be used in the management of Parkinsonism. |
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Term
| What are the 2 strategies in treating Parkinson disease |
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Definition
1. Increase Dopamine levels
2. Decrease Ach levels |
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Term
| How are dopamine levels increased? |
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Definition
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1.Give dopamine precursors (converted to dopamine in the body)
2.Give drugs which can stimulate dopamine D2 receptors
3.Give drugs which can inhibit the enzymatic degradation of dopamine (block MAO or COMT)
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Term
| Why is dopamine not given in the treatment of Parkinson's disease? |
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Definition
1. It does not cross the BBB
2. Has high amount of peripheral effects |
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Term
What is the precursor of dopamine?
How is it converted in to dopamine?
What is the problem with this method & how is it overcome? |
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Definition
Leva dopa (L-dopa)
It is converted by DOPA-decarboxylase enzyme aka Aromatic L amino acid decarboxylase (AADC) to dopamine,
This enzyme is present in both central and peripheral neurons, thus Carbidopa is given along with L-dopa which blocks the peripheral actions of DOPA-decarboxylase |
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Term
| What is the enzyme that converts L-dopa to Dopamine? |
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Definition
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Term
What is Sinemet?
why is it used? |
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Definition
Combination of L-dopa & Carbidopa
Carbidopa stops the peripheral DOPA-decarboxylase. |
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Term
| What are the ADR's of L- dopa therapy? |
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Definition
GI - D2 stimulation in the brain : sever nausea & vomiting
Cardio - arrythmias, tachycardia & atrial fibrilation
Levadopa induced Dyskinesias (LID)
Behavioural - mesocortical pathway - psychosis, mania, hallucinations (schizophrenia like) |
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Term
| What is the On and Off phenomena? |
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Definition
•Fluctuations in clinical response to levodopa occur with increasing frequency as treatment continues.
IT IS UNRELATED to the timing of the dosage
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Term
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Definition
| Related to dosage... treatment wears off before time to take next dose. |
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Term
| What is contraindicated when taking L-dopa treatment? |
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Definition
Psycotic patients (D2 activation causes more positive patiente)
Angle closure Glucoma (increases IOP)
Vitamin B6 (Pyridoxine) - must not be taken with this as it increases peripheral metabolism of l-dopa |
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Term
Name the D2 receptor agonists
When are they given? |
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Definition
Bromocriptine (partial D2 agonist)
Pramipexole (D2 agonist)
Ropinirole
Add on therapies to L-dopa (when they stop responding to L-dopa alone) prolong the effects of L-dopa |
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Term
When is bromocriptine used?
What is its MOA? |
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Definition
Hyperprolactinemia (DOC)
Partial D2 agonist - prolongs the effects of L-dopa |
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Term
| How is L-dopa metabolised in the periphery & what drugs stop these processes? |
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Definition
L-dopa is converted to Dopamine via DOPA- decarboxylase (AAD) - this is inhibited via Carbidopa
L-dopa is converted to 3-O-MD via COMT - this is inhibited by tolcapone & entacapone |
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Term
| How is L-dopa metabolised in the CNS & what drugs inhibit these processes? |
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Definition
L-dopa is converted to dopamine via DOPA-decarboxylase (AAD).
Dopamine is converted to DOPAC via MAO - B - this is inhibited by selegiline (in small doses) & resagiline
Dopmaine is converted to 3MT via COMT - this is inhibited by Tolcapone |
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Term
Selegilinge & Rasargiline
What is its MOA
When is it used?
What are the ADR's? |
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Definition
Blocks the MAO - B enzyme from breaking down Dopamine in the CNS
Used alongside L-dopa therapy
Cheese reaction as it is an MAO inhibitor, Mood changes (as it has methamphetamine & amphetamine metabolites), insomnia & GI distress |
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Term
Tolcapone & Entacapone
What are their MOA's?
when are they used?
What are their ADR's |
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Definition
In the periphery it inhibits the COMT enzyme from metabolising L-dopa to 3-O-MD
Used along side L-dopa therapy
Tolcapone - hepatic damage |
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Term
Which antiviral drug is used in Parkinson's Disease?
What are the proposed MOA? |
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Definition
| Amantadine - Increased synthesis, release and inhibition of re-uptake of dopamin. |
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Term
| What is the precursor used in the management of Parkinson's disease? |
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Definition
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Term
| What is the D2 receptor agonist used in Parkinsons disease? |
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Definition
Bromocriptine
Ropinirole
Pramiprexole |
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Term
| What are the drugs used to inhibit the Metabolism of L-dopa and Dopamine & what is their MOA? |
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Definition
MAO - B inhibitors - Selegiline & Resagiline (CNS)
COMT inhibitors - Tolcapone & Entacapone (periphery) |
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Term
| What are the drugs used to decrease ACh? |
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Definition
Anticholinergics:
Benztropine
Diphenhydramine
Procyclidine
Trihexyphenidyl |
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Term
| What is used to revers the EPS of antipsychotics & Drug induced parkinsonisim |
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Definition
Benztropine
Diphenhydramine (Benedrill)
Procycladine
Trihexyphenidyl |
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Term
What drugs cause Drug induced parkinsonism?
What is used to treat this? |
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Definition
Cause:Reserpine & Antipsychotics
Treat with anticholinergics:
Benztropine
DIphenhydramine (benedrill)
Procyclindine
Trihexyphenidyl |
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