Drugs used for Neurodegenerative disorders . Nootropic drugs

Question 1

Name the Drugs used for parkinson’s disease

Answer 1

Levodopa

DOPA decarboxylase inhibitor
Carbidopa

COMT inhibitor
Entacapone
Tolcapone

MAOi B
Selegiline

D receptor agonists
Ropinirole
Pramipexole

Endogenous Dopamine enhancement
Amantadine

Antimuscarinic Drugs
Trihexyphenidyl
​Benztropine

Question 2

Levodopa metabolism

Answer 2

L-DOPA → Dopamine in periphery + CNS

Levodopa can cross BBB
Dopamine can’t cross BBB

Question 3

side effects of Levodopa

Answer 3

-levodopa can cause GI distress
(due to peripheral conversion into dopamine)

• levodopa can cause cardiac arrhythmias
  (due to peripheral conversion into dopamine)

-levodopa can cause orthostatic hypotension
(due to peripheral conversion into dopamine)

• levodopa can cause neuropsychiatric symptoms e.g. anxiety, agitation, insomnia, confusion, hallucination (due to excess dopamine in the CNS)
• chronic levodopa therapy can cause response fluctuations (wearing-off reaction, on-off phenomenon) and dyskinesias

-chronic levodopa therapy can cause a wearing-off reaction
(akinesia and dyskinesia re-emerge at the end of each dose)

-chronic levodopa therapy can cause an on-off phenomenon
(periods of akinesia alternate with periods of improved mobility, not related to dose)

-the therapeutic window of levodopa therapy narrows as Parkinson’s progresses

(unpredictable response to therapy) (“watch”)

• chronic levodopa therapy can cause dyskinesias (choreoathetosis of the face and distal extremities)
• levodopa is contraindicated in psychotic patients

Question 4

Carbidopa

Answer 4

• carbidopa (peripheral DOPA decarboxylase inhibitor)
• carbidopa increases the bioavailability of levodopa (prevents peripheral conversion into dopamine)
• carbidopa decreases peripheral side effects of levodopa therapy

(but exacerbates neuropsychiatric side effects)

Question 5

Entacapone
Tolcapone

Answer 5

• (COMT) converts dopamine to (3-MT) in the CNS
• tolcapone (a peripheral and central COMT inhibitor) increases the bioavailability of levodopa
• entacapone (a peripheral COMT inhibitor) increases the bioavailability of levodopa
• tolcapone (a peripheral and _central C_OMT inhibitor) increases dopamine levels in CNS
• tolcapone can cause hepatic failure

Question 6

Selegiline

Answer 6

• monoamine oxidase B (MAO-B) selectively metabolizes dopamine
• selegiline -a selective MAO-B inhibitor increases dopamine levels in the CNS

Question 7

Ropinirole
(“rope in a role”)

Pramipexole
(“big pex”)

Answer 7

Ropinirole (D2 dopamine receptor agonists)

is an important initial treatment of Parkinson’s
(“Rope in a roll”):

Pramipexole (D3 dopamine receptor agonist)

is an important initial treatment of Parkinson’s
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• dopamine receptor agonists
  (e. g. ropinirole, pramipexole) treat restless leg syndrome (RLS)

• dopamine receptor agonists (e.g. ropinirole) may enhance impulse control disorders
  (e. g. gambling, shopping, hypersexuality)

Question 8

Amantadine

Answer 8

• amantadine enhances the effect of endogenous dopamine
  (by increasing its synthesis/release and inhibiting its uptake)
• amantadine can treat some motor symptoms of Parkinson’s

Question 9

Trihexyphenidyl
Benztropine

Answer 9

-Trihexyphenidyl and Benztropine
(antimuscarinic agents used to treat parkinsonism)

-trihexyphenidyl and benztropine (antimuscarinic agents) improve tremor and rigidity of Parkinson’s with no effect on bradykinesia