Antiparkinson Drugs
| DRUG | MOA | SIDE EFFECTS | CI | EXTRA |
|---|---|---|---|---|
| DOPAMINE PRECURSORS | ||||
| Levodopa/Carbidopa (Sinemet) (L-Dopa; Larodopa, Dopar) GOLD STANDARD USUALLY SAVED FOR LAST | Levodopa is decarboxylated to dopamine in both and peripheral tissues. By adding Carbidopa a peripheral decarboxylase inhibitor=More levodopa enters the brain and is converted into DA in brain Short half-life 3 or more doses | Short Term-N/V (Phenergan), ortho HypoTN, palpitation, arrhythmias, CNS changes (compulsive behaviors), Sleep Attacks, Blepharospams, dyskinesia Long Term—End dose phenomena, On-Off phenomena, 2nd levodopa failure | DIET HIGH IN PROTEIN OR VIT B-6; cardiac stimulants, anti-HTN drugs; HTN crisis with MAOIs; ↓seizure threshold; ↑ICP in glaucoma pt | DIET HIGH IN PROTEIN OR VIT B-6; cardiac stimulants, anti-HTN drugs; HTN crisis with MAOIs; ↓seizure threshold; ↑ICP in glaucoma pt |
| DOPAMINE AGONIST | ||||
| Pramipexole (Mirapex) Ropinirole (Requip) Apomorphine (Apokyn) Requip—Restless leg syndrome | Direct agonist for dopamine receptors in EPS; non-ergot dopamine agonist at dopamine receptors | N, somnolence, BLE edema, postural HypoTN, confusion, (do not use old dementia pt), impulse control disorder; hallucinations, confusion, dyskinesia, nightmares, drowsiness, Sleep Attacks | Psychiatric illness can ↑ mental condition Serious cardiac problems esp. in pts with HTx of MI, PVD Bromocriptine is an Ergot derivate that can ↑ pulm &retroperitoneal fibrosis (severe) | Requip: non-ergotamine derivative with ↓ cardiac, pulm, GI (SEs) but→↑ psychosis,(compulsive behavior) Apokyn: treat episode of immobility; Drug is give SQ, causes severe emesis give Trimethobenzamide (tigan) bc Zofran can cause HypoTN and ↓LOC Hypersexuality and increased erection can occur |
| COMT INHIBITOR | ||||
| Tolcapone (Tasmar) Entacapone (Comtan) Comtan is derived from the enzyme Catechol-o-methyltransferase = peripheral breakdown of levodopa. It inhibits the breakdown of DA in the peripheral =↑DA level | Inhibition of COMT leads to ↓ concentration of a by-product (3-O-methyldopa) that competes with levodopa for active transport into the CNS with the use of Carbidopa This agent prolongs the dopamine that you will have available | N/V/D, postural hypoTN, dyskinesia, hallucinations, sleep disorders | Tolcapone (Tasmar) has been associated with hepatotoxicity (hepatic monitor 2X per mt for 1st 6 mt) TAKEN OFF MARKET | Add on agent bc not supplying any DA Has a short half-life and must be taken with each dose of levodopa |
| MAO-B Inhibitors | ||||
| Selegiline (Eldepryl) Rasagiline (Azilect) Zelapar-ODT | A selective inhibitors of MAO-B enzyme(which metabolizes DA) → ↑ DA levels in the brain as a result ↑efficacy of levodopa when given together | Nausea, ortho hypoTN, insomnia Exceeding 10mg/day can cause severe HTN “cheese effect” | Meperdine(Demerol) and Fluoxetine (Prozac) are CI Other ODTs—Dilaudid, methadone, Propoxyphene (Darvon), tramadol | Metabolizes to an amphetamine—give in AM |
| Central-Acting Anticholinergic | ||||
| Benzotropine (Cogentin) Trihexyphenidyl (Artane) Procyclidine (Kemadrin) Biperiden (Akineton | ↓the excitatory effects of acetylcholine(central)↔better balance between DA and Acetylcholine—reduced tremors and muscle rigidity | Dry mouth, constipation, urinary retention, Anti SLUDGE; Mydriatic effect= ↑glaucoma CNS—impaired memory, confusion, hallucination Strict dose adjustmt in old bc of anticholinergic effects | Glaucoma, stenosing peptic ulcer, BPH or bladder neck obstruction, Achalasia, myasthenia gravis, megacolon | DDI: Amantadine (Symmetrel), other anticholinergic , MAOIs, Digoxin, Haloperidol, Levodopa (↓levodopa activity from ↓GI motility) Phenothiazine (↑antichol effects) |
| Glutamate Antagonist (antiviral) | ||||
| Amantadine (Symmetrel) | ↑DA from neurons (antagonist) , may also block reuptake of DA, block cholinergic activity (anticholinergic activity) | drowsiness, confusion most common; N, dizzy, confusion, some anticholinergic SE; Potential Psychosis in old; ↓seizure threshold; ankle edema Livedo reticularis of the legs w/wo cardiac failure (purple rash) | Anticholinergic may have an additive effect on mental function | Sudden withdraw can cause ↑ Parkinson symptoms or neuroleptic malignant syndrome (acute delirium) Monitor Liver FXN |