Dopamine agonist

Use: Parkinson's Disease

Mechanism: L-dopa crosses BBB and serves as dopamine precursor (1-2% reaches brain alone); carbidopa inhibits peripheral decarboxylation (dopa decarboxylase inhibitor) but not in brain

dramatic improvement of symptoms for 3-4 years but does not alter the progression of the disease; as pt loses DA neurons, effectiveness will decrease with time

Side effects: Nausea and vomiting (GI symptoms) (much less in combo with carbidopa); dyskinesias (more common with combo); behavioral problems i.e. depression confusion, delusions etc; "on-off" phenomenon; small chance of arrhythmia, tachy and v-asystole, postural hypotension; 

Interactions: HTN crisis when combo c MAOIs (wait 2 weeks after discontinuing MAOI before starting l-dopa)

Contraindications: psychosis, closed angle glaucoma, cardiac disease, active peptid ulcer, malignent melanoma

Contraindications: psychosis, closed angle glaucoma, cardiac disease, active PUD, malignant melanoma

Others: Carbidopa/levodopa (Sinemet®)

MAOI

Uses: Parkinsons disease (early to decrease ROS damage); 

Mechanism: inhibits MAO-B (CNS only); MAI-B is predominant form in the striatum and thus reduces striatal metabolism DA; Reversible MAOI

Effects: Increases effect of DA in the brain, relieving parkinson's symptoms

Advantages: Decrease free radical production from MAO-B oxidation of DA, so may slow progression of disease!

Adverse effect: DO NOT combine with meperidine (seretonin syndrome)

Others: Rasagiline (Azilect®)

COMT inhibitor

Use: Parkinson's (adjunct to l-dopa

Mechanism: Inhibits CNS and peripheryl Catechol-O-methyltransferase (COMT) which metabolizes DA; Tolcapone (Tasmar) penetrates CNS

Effect: Prolongs duration of action of dopamine in the synaptic cleft and prolong l-dopa action

Adverse effects: dyskinesias, confusion, nausea

Tolcapone has been associated with death from liver disease, requires pt consent

Side effect: orange urine! Liver failure

Others: Entacapone (Comtan®) - Inhibits peripheral COMT (no BBB cross)

Adverse: Tolcapone has been associaed with death from liver disease, require pt consent

Dopamine agonist (KNOW all 4)

Uses: Parkinsons disease

Mechanism: acts directly on DA receptors, primarily DA D2

Advantages:  *continue to be effective as the disease progresses*

Side effect: Bromocriptine is an ergot derivative -> erythromelalgia (red, swollen feet, intense burning pain); anorexia, nausea, vomiting, postural hypotension, cardiac arrhythmias for all agonists

Others: Pramipexole (Mirapex®) - NOT ergot (no erythromelalgia); sudden sleep during day (rare) D2, D3 agonist

Ropinirole (Requip®) - transdermal patch for Restless leg syndrome; D2

Apomorphine (Apokyn®) - rescue of off periods in PD! potent DA agonist; take antiemetic, causes bad nausea

Dopamine releaser

Use: Early or mild Parkinson's disease; 

Mechanism: unsure, may increase DA synth, release and reuptake

Rationale for adding to Tx: antiviral drug used for flu, elderly pts with Parkinson's improved

Side effects: can cause livedo reticularis - reddish/blue spotting on skine

*Use c caution in pts c hx of seizures or CHF

Anticholinergic

Use+rationale: Parkinson's disease; decrease the effects of ACh to match the loss of dopamine, restoring chemical transmitter balance; use in mild and moderate disease; improves rigidity, tremor, drooling, but little effect on bradykinesia

Mechanism: muscarinic receptor antagonists (Decreases ACH effect); restores DA/ACh balance in striatum; improves rigidity, tremor; little effect on bradykinesia

Others: Biperiden (Akineton®) Procyclidine (Kemadrin®) Trihexyphenidyl (Artane®)

ACE inhibitor

Use: Alzheimer's disease, increases brain activity and improves cognitive ability

Mechanism: Inhibit metabolism of ACH; increases the amount of ACH in the nerve terminal

Tacrine causea liver toxicity in 50% of pts

Others: Donepezil (Aricept®) Rivastigmine (Exelon®)

NMDA antagonist

Use: more severe alzheimers disease

Mechanism: Non-competitive antagonist of NMDA; Blocks pathological activation of NMDA receptors; may reduce neurotoxic effect of glutamate and slow degeneration