A/34. Drugs used for treatment of neurodegenerative disorders. Nootropic drugs

Question 1

Drugs need to know in this topic

Answer 1

Levodopa/Carbidopa

Ropinirle

Pramipexole

Selegiline

Entacapone

Amantadine

Procyclidine

Memantine

Rivastigmine

Piracetam

Question 2

Levodopa(L-DOPA)/Carbidopa

Answer 2

• *Mechanism of action:**
  1. Dopamine precursor, enters the brain via L-amino acid transporter (LAT)
  2. Converted to dopamine by the enzyme dopa decarboxylase → increased dopamine activity in the brain (bradykinesia ↓)
  3. Levodopa is given with the drug Carbidopa → acts as a peripheral dopa decarboxylase inhibitor (does not cross the blood-brain-barrier)

Oral

1. Parkinson disease

Side effects:
1. GI distress – nausea, vomiting, anorexia
2. Dyskinesia (‘on/off phenomenon’)
3. Hypotension, arrhythmias (peripheral effects of DA)
4. Psychosis, agitation, anxiety, delusion, hallucinations (central effects
od dopamine, regardless of the peripheral effects of carbidopa)

Question 3

Selegiline

Answer 3

MAO inhibitors

• *Mechanism of action:**
  1. Selective MAO-B inhibitor → decreased metabolism of dopamine → increased dopamine activity in the brain (bradykinesia ↓)
  2. No tyramine interaction (no ‘cheese effect’) as seen with non-selective MAO inhibitors

Oral

Hepatic metabolism to form desmethylselegiline (neuroprotective) and amphetamine
(psychostimulant)

1. Parkinson disease – monotherapy (early disease) or
   adjunct to levodopa/carbidopa (advanced disease)

• *Side effects:**
  1. Dyskinesia
  2. Psychosis
  3. Hypotension
  4. Insomnia
  5. Serotonin syndrome when used with SSRI’s

Question 4

Entacapone

Answer 4

COMT inhibitors
Mechanism of action:
1. Catechol-O-methyl-transferase converts levodopa to 3-O-methyldopa (3-OMD)
2. 3-OMD acts as a partial agonist (antagonist in the presence of a full agonist) and competes with levodopa for transport and activity
3. Inhibition of COMT enhances levodopa uptake and efficacy
4. In the CNS, inhibition of COMT enhances dopamine activity

Oral

1. Parkinson disease (adjunct to levodopa/carbidopa)

• *Side effects:**
  1. Related to increased levels of L-dopa
  2. Sleep disorders
  3. Hepatotoxicity (tolcapone)

Question 5

Ropinirole

Pramipexole

Answer 5

Dopamine agonists

Oral

1. Parkinson disease – monotherapy (early disease) or adjunct to
   levodopa/carbidopa (advanced disease)
2. Pramipexole is a potential anti-oxidant
   Side effects:
3. Dyskinesia
4. Psychosis, hallucination
5. Anorexia, nausea

Question 6

Amantadine

Answer 6

• *Mechanism of action:**
  1. Antiviral medication, weak to moderate anti-parkinsonism effect
  2. Potentiate endogenous dopaminergic function by influencing the synthesis, release, or reuptake of dopamine
  3. Muscarinic blockade
  4. NMDA receptor blockade

Oral

1. Parkinson disease (adjunct to levodopa/carbidopa)
   * *Side effects:**
2. Livedo reticularis (specific dermatological presentation)

Question 7

Procyclidine

Answer 7

1. Muscarinic blockade → decrease the excitatory activity of cholinergic neurons in the striatum
2. Improves tremor and rigidity, no effect to bradykinesia
3. Oral
4. Parkinson disease (not recommended as monotherapy at early
   disease)
5. Drug-induced extra-pyramidal symptoms
   Side effects: (‘atropine-like effects’)
6. Dry mouth
7. Urinary retention
8. Constipation
9. Hyperthermia
10. Sinus tachycardia
11. Mydriasis
12. Blurred vision
13. Toxicity (‘3 C’s’) → cardiotoxicity, convulsions, coma
    Contraindications:
14. Glaucoma
15. Prostatic hyperplasia