Drugs of Neurodegenerative Disorders

Question 1

Levodopa

Answer 1

L-DOPA. Parkinson’s. Increases DA synthesis.
Precursor of DA, can cross BBB. Oral, rapidly absorbed by GI. Only 1-3% of L-DOPA reaches brain. Rest is metabolized peripherally by aromatic l-amino acid decarboxylase.
“wearing-off” effect after 3-5 years.
SE: Peripheral - (conversion to NE) nausea, vomiting, anorexia, arrhythmias, orthostatic hypotension. CNS - visual & auditory hallucinations, abnormal involuntary movements (dyskinesia). Psych changes.

Question 2

Levodopa/Carbidopa

Answer 2

Parkinson’s. Increases DA synthesis.
Medication of choice for symptomatic Tx of parkinson’s disease, esp. at advanced stage.
Carbidopa is a l-amino acid decarboxylase inhibitor, blocking peripheral metabolism of L-DOPA. Increases L-DOPA availability in brain.
Reduces the dose of L-DOPA by 4-5 fold (& SE)

Question 3

Entacapone/Levodopa/Carbidopa

Answer 3

Parkinson’s. Increases DA synthesis.
Entacapone inhibits catechol-O-methyltransferase, further decreasing metabolism of L-DOPA in the periphery, increasing brain availability.

Question 4

Selegiline

Answer 4

Parkinson’s. Decreases DA catabolism.
Inhibits Monoamine Oxidase Type B (MAO-B) & decreases production of the byproduct H2O2 (neurotoxic free radical)
MAO-B metabolizes Dopa.
Adjunct with Levodopa - little effect seen when alone.
AE: metabolized to amphetamine & methamphetamine (insomnia)

Question 5

Rasagiline

Answer 5

Parkinson’s. Decreases DA catabolism.
Selective inhibitor of brain MAO-B. More potent than Selegiline.
MAO-B metabolizes Dopa.
Does not metabolize to amphetamine or methamphetamine.

Question 6

Bromocriptine

Answer 6

Parkinson’s. Dopamine receptor agonist.
D2 agonist, D1 partial agonist
Effective as mono therapy early in disease or adjunct to L-DOPA in later stages.
AE: Arrhythmias, postural hypotension, depression, confusion, hallucinations, sleepiness, nausea, vomiting. CI in patients with Heart or Mental problems.

Question 7

Ropinirole

Answer 7

Parkinson’s. Dopamine receptor agonist.
D2 & D3 agonist.
Effective as mono therapy early in disease or adjunct to L-DOPA in later stages.
AE: Arrhythmias, postural hypotension, depression, confusion, hallucinations, sleepiness, nausea, vomiting. CI in patients with Heart or Mental problems.

Question 8

Pramipexole

Answer 8

Parkinson’s. Dopamine receptor agonist.
D2 & D3 agonist.
Effective as mono therapy early in disease or adjunct to L-DOPA in later stages.
AE: Arrhythmias, postural hypotension, depression, confusion, hallucinations, sleepiness, nausea, vomiting. CI in patients with Heart or Mental problems.

Question 9

Apomorphine

Answer 9

Parkinson’s. DA receptor agonist.
Acute treatment of patients with advanced disease for ‘off’ periods (marked bradykinesia, immobility)
SubQ injection (NOT IV - risk of thrombus & PE)
SE: N/V, arrhythmias, postural hypotension, hallucinations, pronounced sleep.

Question 10

Benztropine

Answer 10

Parkinson’s. Muscarinic Antagonist.
Used alleviate Tremor and Rigidity (not bradykinesia) as a mono therapy or adjunct. Block effect of increased firing of striatal cholinergic interneurons.
SE: blurred vision, dry mouth, urinary retention, constipation, glaucoma aggravation, delirium, psychosis, memory impairment.

Question 11

Trihexyphenidyl

Answer 11

Parkinson’s. Muscarinic Antagonist.
Used alleviate Tremor and Rigidity (not bradykinesia) as a mono therapy or adjunct. Block effect of increased firing of striatal cholinergic interneurons.
SE: blurred vision, dry mouth, urinary retention, constipation, glaucoma aggravation, delirium, psychosis, memory impairment.

Question 12

Amantadine

Answer 12

Parkinson’s.
Alleviates bradykinesia, rigidity (not tremor) in patients with mild to moderate disease prior to initiation of L-DOPA.
Mech: increases DA release, blocks cholinergic muscarinic receptors & glutamatergic NMDA receptors. NMDA receptor is glutamate receptor on nn.
SE: hallucinations & confusion, nausea, dizziness, rash of the low extremities. Caution with PT wi/ CHD & glaucoma.

Question 13

Donepezil

Answer 13

Alzheimer's Disease: AChE inhibitor
Increases ACh in pre-synaptic vesicles.
Modest improvement in patients.
Good oral bioavailability.
Cyp3A4 & Cyp2D6 metabolism
SE: diarrhea, tremors, bradycardia, anorexia, N/V

Question 14

Galantamine

Answer 14

Alzheimer's Disease: AChE inhibitor
Increases ACh in pre-synaptic vesicles.
Modest improvement in patients.
Good oral bioavailability.
Cyp3A4 & Cyp2D6 metabolism
SE: diarrhea, tremors, bradycardia, anorexia, N/V

Question 15

Rivastigmine

Answer 15

Alzheimer's Disease: AChE inhibitor
Increases ACh in pre-synaptic vesicles.
Modest improvement in patients.
Good oral bioavailability.
Plasma cholinesterase metabolism
SE: diarrhea, tremors, bradycardia, anorexia, N/V

Question 16

Tacrine

Answer 16

Alzheimer’s Disease: AChE inhibitorAlzheimer’s Disease: AChE inhibitor
Increases ACh in pre-synaptic vesicles.
Modest improvement in patients.
Good oral bioavailability.
Cyp3A4 & Cyp2D6 metabolism
SE: diarrhea, tremors, bradycardia, anorexia, N/V

Question 17

Memantine

Answer 17

Alzheimer’s Disease: NMDA Receptor inhibitor
Low affinity.
By blocking NMDA receptors, it protects neurons from Ca2+ overload that can lead to neuronal death (excitotoxicity) Too much glutamate activation of receptors leads to massive calcium influx.
Improves daily activities and cognitive fx.
Additive benefits with Donepezil
SE: dizziness, headache, confusion, agitation, constipation