Leva DOPA (L-DOPA)

Question 1

What is L-Dopa a precursor too?

Answer 1

Dopamine (does not cross the Blood Brain barrier)

1-3% of L-Dopa crosses the BBB (due to extra cerebral metabolism)

Question 2

What converts L-DOPA to DA?

Answer 2

DOPA decarboxylase

Turns L-DOPA int aDA immediately peripharrly, only a small amount is transported unchanged across the BBB

Question 3

What is an adverse effect of L-DOPA?

Answer 3

takes large amounts for theurapuedic affects, this causes nausea in patients

Question 4

What is COMT?

Answer 4

Converts L- DOPA to 3-OMD
3-OMD is a poor response to LDOPA
Inhibition of DDC induces compensatory increase in COMT

Question 5

What are DOPA Decarboxylase (DDC) Inhibitors and how are they used in the treatment with L DOPA?

Answer 5

Carbidopa- does not cross the BBB
inhibits L DOPA to DA in the periphery
cause an increase the L DOPA side effects

Question 6

What are the COMT inhibitors?

Answer 6

ENTACAPONE & TOLCAPONE)

Question 7

What are adverse side effects of COMT?

Answer 7

increased plasma L-DOPA
dyskinesias, nausea, confusion
diarrhea, abdominal pain, orthostatic hypotension, sleep disorders, orange urine discoloration (Entacapone)
Tolcapone – potentially hepatotoxic

Question 8

What is the mechanism of L-DOPA?

Answer 8

Restore Synaptic DA Levels (activates the postsynaptic D2 receptors)-inhibits movement by the indirect pathway

Activates D1 receptors- facilitate movement by the direct pathway

Question 9

What are the therapeutic effects of L DOPA?

Answer 9

Best results 1st few years of treatment
Over time, L-DOPA therapy becomes less effective:
(Progressive loss of nigral dopaminergic neurons
Downregulation of striatal D1/D2 receptors
Some patients require reduced L-DOPA to prevent side effects)

Question 10

What are the adverse effects of L DOPA?

Answer 10

Dyskinesis-80% of patients on long-term levodopa therapy (>5 yrs)-occurs more frequently in younger patients

On/Off effect - fluctuations in clinical response to L-DOPA
Off” = marked akinesia
“On” = improved mobility but marked dyskinesia

Question 11

How can the on and off effects of L-DOPA be smoothed out?

Answer 11

Fluctuations can be “smoothed out” by incorporating a dopamine receptor agonist into pharmacotherapy
Pramipexole (activates D2 and D3 receptors)
Ropinirole (activates D2 and D3 receptors)
Apomorphine (activates D2 receptors)

Question 12

What are th ACUTE side effects of L DOPA and what are they related to?

Answer 12

Nausea
Anorexia – treated with peripherally-acting
dopamine antagonist (i.e., Domperidone).
Hypotension – particularly in patients on
anti-hypertensive drugs

Other common side effects:
Confusion
Insomnia
Nightmares
Schizophrenic-like syndrome – 
    delusions and hallucinations due to 
    elevated CNS concentrations of DA