L33. Drugs used in neurological disorders I →↑↓

Question 1

Mechanism, Contraindication, S/E of Dopamine Precurosr Levo-dopa (L-Dopa)

Answer 1

High Therapetuic index

Mechanism
Readily transported into the CNS and →converted to dopamine in the brain by DOPA decarboxylase

Well absorbed from the GI tract
Extremely short half-life

Contraindication with given L-dopa

Nonselective MAO inhibitors (e.g. phenelzine)
→Resulting in excess dopamine in the periphery, which could lead to a life-
threatening hypertensive crisis

Pyridoxine (Vitamin B6)
→Increasing peripheral breakdown of L-dopa

Antipsychotics
Blocking dopamine receptors and causing parkinsonian-like symptoms

Adverse (side) Effects
Due to the conversion of L-dopa to dopamine in the periphery
→Nausea
→ Vomiting
→ Arrhythmias
→ Postural (orthostatic) hypotension: on standing or sitting up

Due to overstimulation of central dopamine receptors
Dyskinesia: presence of involuntary movements
→ Hallucination
→ Restlessness
→ Confusion

Question 2

Mechanism, Contraindication, S/E of Carbidopa

Answer 2

peripheral DOPA decarboxylase inhibitor

Administered with L-dopa (L-dopa + carbidopa in 4:1 ratio known
as SINEMET®)
→ To reduce the metabolism of L-dopa in the periphery
→To increase the availability of dopamine to the CNS

Question 3

Mechanism, Contraindication, S/E of Benserazide

Answer 3

peripheral DOPA decarboxylase inhibitor

Administered with L-dopa (L-dopa + benzerazide in 4:1 ratio
known as MADOPAR®)
→ To reduce the metabolism of L-dopa in the periphery
→ To increase the availability of dopamine to the CNS

Question 4

Mechanism, Contraindication, S/E of Bromocriptine

Answer 4

Dopamine receptor agonists

MOA
An ergot derivative
→ Acts as a dopamine receptor agonist at D2-like receptors

In conjunction with L-dopa / carbidopa
→To relieve rigidity and tremor
→Minimal effects on bradykinesia

Side (adverse) effects
→Hallucination and delirium
→Nausea and vomiting
→Cardiac arrhythmia, postural hypotension
→Erythromelalgia: a condition characterized by red, painful, and
swollen feet or hands

Question 5

Mechanism, Contraindication, S/E of Pergolide

Answer 5

MOA
An ergot derivative
→Acts as a dopamine receptor agonist at both D1-like and D2-like receptors

→ In combination with L-dopa / carbidopa and anticholinergic drugs

Side (adverse) effects
→Hallucination
→Confusion
→Postural hypotension
→Urinary tract infection

Question 6

Mechanism, Contraindication, S/E of of Pramipexole and Ropinirole

Answer 6

First-line therapy in young patient

MOA
Non-ergot dopamine receptor agonists at D2-like receptors
Added on to L-dopa / carbidopa treatment in patients with advanced Parkinson’s disease

side (adverse) effects
→Dyskinesia
→Dizziness
→Insomnia or somnolence (drowsiness)
→Postural hypotension

Question 7

Mechanism, Contraindication, S/E of of Rotigotine

Answer 7

MOA
→Non-ergot dopamine D2-like receptor agonist at clinical doses
→Transdermal patches when used in the treatment of Parkinson’s disease

Side (adverse) effects
→Application site reactions including hypersensitivity reactions or skin
problems such as redness, rashes, itching, irritation, burning
sensations etc.
→Dizziness
→Headache
→Nausea

Question 8

Mechanism, Contraindication, S/E of Selective Monoamine Oxidase B (MAO-
B) Inhibitors

Answer 8

(Selegiline and Rasagiline)
MOA
→by inhibiting the enzyme MAO-B in the brain that metabolizes or breakdown brain dopamine
→Decrease the metabolism of dopamine in the periphery and brain
→ Increase dopamine levels
→ Enhance the effects of L-dopa / carbidopa or L-dopa / benserazide

Side (adverse) effects:
→a threat of hypertensive crisis in high dosages
→nausea
→headache
→abdominal pain
→dry mouth

Question 9

Mechanism, Contraindication, S/E of
Catechol-O-methyl Transferase (COMT)
Inhibitors

Answer 9

Entacapone Tolcapone
Mechanism of action:
by blocking COMT for the peripheral conversion of levodopa (L-dopa) to 3-O-methyldopa

Adverse (side) effects
→Dyskinesia
→Hallucination
→Postural hypotension
→Diarrhea
→Sleep disorders
→Hepatic necrosis (for tolcapone only)

Question 10

Mechanism, Contraindication, S/E of 
 Dopamine Facilitator (Amantadine)

Answer 10

→To enhance the release of dopamine from surviving nigral neurons
→ To inhibit the reuptake of dopamine at synapses
→ More effective than anticholinergic agents in improving bradykinesia and rigidity when used along with L-dopa /
carbidopa or L-dopa / benserazide

Adverse (side) effects
→Restlessness, agitation, confusion
→Postural hypotension
→Peripheral edema
→Skin rash

Question 11

Mechanism, Contraindication, S/E of

Central Anticholinergic Agents

Answer 11

Benztropine, benzhexol and biperidine

MoA
→To reduce cholinergic output of the striatum by blocking the receptors
→To reduce primary symptoms such as tremor, rigidity, and akinesia (NOT bradykinesia) as well as secondary symptom such as drooling

Side (adverse) effects
→Sedation
→ Urinary retention
→ Dry mouth
→ Constipation
→ Mental confusion

Question 12

Choices of treatment for PD

Answer 12

→L-dopa + carbidopa (SINEMET)

→ L-dopa + benzerazide (MADOPAR) is the best treatment for elderly initially diagnosed with PD

→Addition of a COMT inhibitor or a MAO-B inhibitor to L-dopa / carbidopa can reduce motor fluctuations in patients with
advanced disease

→Anticholinergics can be useful addition to L-dopa / carbidopa
for control of tremor

→ Apomorphine should be available for rescue use in patients
with “off” episodes

Question 13

Treatment for Huntington’s Disease

Answer 13

Medications for movement disorder
→ Tetrabenazine – “dopamine-depleting” to suppress the involuntary jerking
and writhing movement (chorea)
→ Antipsychotic drugs
→ → Haloperidol and risperidone (newer) – using side effect of this class of drugs to
suppress movements

Medications for psychiatric disorder
→ Antidepressants
→ → Fluoxetine (SSRI) – to treat depression
→ Mood-stabilizing drugs
→ → Carbamazepine – to treat irritability

Question 14

Mechanism, Contraindication, S/E of

Acetylcholinesterase inhibitors

Answer 14

Galantamine Rivastigmine Donepezil

To increase the amount of acetylcholine (ACh) available by preventing its breakdown within the synaptic cleft

Side (adverse) effects
─ Nausea, vomiting
─ Diarrhea
─ Abdominal cramps
─ Anorexia (appetite and weight loss)
─ Agitation
─ Dizziness
─ Urine incontinence

Question 15

Mechanism, Contraindication, S/E of

NMDA receptor antagonists (uncompetitive)

Answer 15

Memantine
MoA
─An uncompetitive NMDA receptor antagonist (Block open channel )
─To improve cognitive ability by protecting CNS neurons
from the excitotoxic effects of glutamate

Adverse (side) effects
─Headache
─Dizziness
─Confusion
─Constipation