Levodopa (L-dopa)

-type of drug

-mechanism of action

-side effects

Type of Drug:

- dopamine precursor, replacement therapy

Mechanism of action:

- metabolic precursor of dopamine acting to raise levels in brain

- early tx has nearly complete improvement

- long term treatment results in "on/off" phenomenon due to buffering capacity loss (i.e. further loss of dopaminergic neurons) 

Side effects:

- tolerance and reduction in s/e as therapy continues

- anorexia, nausea, vomiting

- orthostatic hypertension

- cardiac arrythmias 

- abnormal choreoform movements (peak dose dyskinesia

- psychoses and other mental disturbances

Contraindications:

- narrow angle glaucoma

- history of cardiac arrythmias/infarction, psychiatric disorders

Drug-drug interactions:

- non-selective MAO inhibitors (MAO-B specific is fine)

- sympathomimetic amines

- dopamine antagonists

- antidepressants

Bromocriptine

Pergolide

-type of drug

-mechanism/use

-side effects

Type of drug:

- dopamine agonist

- ergot alkaloids

Mechanism:

- dopaminergic agonist of D2 receptors

- effect treatment of on/off phenomena

- longer duration of action

Side effect:

- initial treatment can cause profound hypotension

Pramipexole

Ropinole

-type of drug

-mechanism/use

-side effects

Type of drug:

- dopamine agonist

- non-ergots

Mechanism:

- dopaminergic agonist of D2 receptors

- effect treatment of on/off phenomena

- longer duration of action

Side effects:

- nausea, somnolence

- compulsivity behavior (unusual but does occur)

Amantadine

-type of drug

-mechanism/use

Type of drug:

- antiviral drug that may work by releasing dopamine from storage site

Mechanism:

- anticholinergic properties

- blocks NMDA glutamate receptors

- used in early stages of mild PD and in latter stages for dose-related fluctuations of levodopa/carbidopa

- modestly effective

Trihexyphenidyl

Benztropine

Diphenhydramine

Biperiden

Procyclidine

-drug class

-mechanism

-side effects

Drug class:

- anticholinergics

Mechanism:

- inhibit striatal muscarinic cholinergic receptors

- used during early stages and mild cases

- late stage used with levodopa/carbidopa esp for tremors

- used to reduce symptoms of IPD

Side effects:

- sedation

- confusion

- delerium

- cycloplegia

- dry mouth

- urinary retention

- constipation

Selegiline

-drug class

-mechanism

-side effects

Drug class:

- MOA-B inhibitor

Mechanism:

- first drug of choice for PD, modest effect

- MAO-B specific at <10 mg/day

- does not inhibit peripheral metabolism of DA

Side effects:

- tyramine rich foods

- tricyclic antidepressants

- serotonin uptake inhibitors

Rasagiline

-drug class

-mechanism

Drug class:

- MAO-B inhibitor

Mechanism:

- inhibits MAO-B

- neuroprotective

- reduces "off" time when used with levodopa

- maybe used in monotherapy in early PD

Entacapone

Tolcapone

-drug class

-mechanism

-side effects

Drug class:

- COMT inhibitor

Mechanism:

- block peripheral metabolism of levodopa

- can be used to reduce the dose of levodopa

- control "on-off" effects of levodopa

Side effects:

- E has short duration while T has a long duration

- Tolcapone has hepatotoxic effects therefore use when non-responsive to other therapies

Reserpine

Tetrabenazine

-drug class

-mechanism

-side effects

Drug class:

- catecholamine depleting agents

Mechanism:

- used to control large amplitude chorea by depleting catecholamine stores in patients with HD

Side effects:

- hypotension (tx w/ carbamazepine)

- depression (tx w/ fluoxetine)

Riluzole

-mechanism

Mechanism:

- inhibits glutamate release, NMDA receptor, voltage dependent Na channels

- extends survival time in ALS patients by preventing excitotoxicity

- well tolerated, N&D occasionally

Baclofen

-mechanism

Mechanism:

- GABA_B receptor

- most effective treatment of ALS

- sedation is an adverse effect

Clonidine

Guanfacine