Drugs for Parkinson's Disease

Question 1

1. Akinesia

2. Bradykinesia

Answer 1

1. Difficulty initiating movement

2. Slowness of movement

Question 2

3 general ways to treat Parkinsons

Answer 2

1. Drugs that increase DA levels in the brain
2. DA receptor agonists
3. Acetylcholine Antagonists

Question 3

Drugs that increase DA levels

Answer 3

Levodopa (L-DOPA)
Precursor of DA
Can cross the BBB (unlike DA) and is taken up by neurons in the substantia nigra (where it is converted to DA by DDC)
Adverse effects: nausea, orthostatic hypotension, cardiac arrhythmias - due to increase catecholamines in peripheral tissues

Question 4

Dopa decarboxylase Inhibitor

Answer 4

Ex: Carbidopa
Analog of L-DOPA
Inhibits conversion of L-DOPA to DA in peripheral tissue
Does NOT cross the BBB
Need combo with L-DOPA

Question 5

Catechol-O-methyltransferase (COMT) inhibitors

Answer 5

Ex: Entacapone, tolcapone
Block conversion of L-DOPA to 3-OMD which may compete for CNS uptake
Used in combo with L-DOPA
Inhibits activity of COMT
Maximizes the bioavailability of L-DOPA to go into brain

Question 6

Selegiline

Answer 6

Irreversible inhibitor of MAO-B in the striatum
Striatal MAO-B metabolizes DA
Inhibits oxidation of DA to DOPAC (increase DA levels in striatum

Question 7

Dopamine Receptor Agonists

Answer 7

Directly activate DA receptors (bromocriptine, pramipexole)
Can be used in combo with L-DOPA/carbidopa
Act at post synaptic DA receptors
Activation of specific DA receptors may limit adverse effects of these drugs

Question 8

Antimuscarinic Drugs

Answer 8

Block striatal muscarinic receptors (benztropine)
Not as effective as L-DOPA/carbidopa treatment
Efficient in control of tremors
Often used in combo therapy
Alleviate extrapyramidal effects caused by older anti-psychotic drugs

Question 9

Amantadine

3 proposed mechanisms

Answer 9

Often used with L-DOPA/carbidopa therapy
Also an anti-viral drug
Used in patients who dont respond well to L-DOPA
Proposed mechanisms of action: Inhibits DA re-uptake, facilitate pre-synaptic DA release, antagonise NMDA receptors

Question 10

Bromocriptinie and pramipexole

Answer 10

DA agonists

Question 11

Selegiline

Answer 11

MAO inhibitors

Question 12

Entacapone, tolcapone

Answer 12

COMT inhibitors

Question 13

Benztropine

Answer 13

Muscarinic Antagonists