Chapter 3 CNS - parkinson's disease drugs Flashcards
levodopa (e.g. l-dopa)
- combination products w/ carbidopa: parcopa, rytary, sinemet
mechanism
* decarboxylated to dopamine (DA) in brain
* improves neurological, motor, and altered mood sx’s of parkinson’s
indication
above
effects
1) nausea/vomiting d/t simulation of emetic center (tolerance develops to GI effects)
2) modest orthostatic hypotension
3) arrhythmias in older patients
4) involuntary movements (dose limiting)
5) psych disturbances
6) inc’d sexual activity d/t actions on hypothalamus (rewards + pleasure system)
PO, less than 1% of levodopa penetrates CNS b/c of peripheral decarboxylation
* circumvent this by coadministrating w/ carbidopa (a dopa decarboyxlase inhibitor) to ensure it reaches CNS
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drug interactions
* pyroxidine (vitamin B6, is required by your body for utilization of energy in the foods you eat, production of red blood cells, and proper functioning of nerves.) – reduces effects of levodopa by stimulating decarboyxylation
* antipsychotics (block DA receptors)k
* MAO inhibitors (cause build up of sympathomimetic amines (withdraw 2 weeks before levodopa administration)
* Anticholinergic drugs synergistic with levodopa (may delay absorption by slowing gastric emptying) — dopamine (inhibits gut motility, except for colon, inc insulin, protective GI function)
* Antidepressant drugs (inc orthostatic hypotension)
rarely used w/o coadministration!
carbidopa (lodosyn)
- diminishes decarboxylation of l-dopa in peripheral tissues
- improve effect of l-dopa
- decreased required dose of l-dopa by about 75%
indications:
parkinson’s
effects
* reduces levodopa-induced nausea and vomiting
* does not alleviate most side effects caused by levodopa
* no known toxicities
PO, pils contain fixed amounts of carbidopa and levodopa
no problems when given alone
amantadine (symmetral)
- release DA from intact terminals
indication
* less effective than l-dopa for parkinson’s
* used to tx drug-induced extrapyramidal rxn’s
effects
* few side effects
* high doses – induce hallucinations, confusion and nightmares
PO, adjust with renal failure
interactions
* anticholinergic agents: enhance CNS side effects
- less effective than l-dopa, more effective than anticholinergics; ALSO AN ANTIVIRAL
bromocriptine (parlodel)
ergot-derivative dopamine receptor agonist
- powerful d2 agonist
indication
* parkinson’s disease (tolerance develops to l-dopa or when sx relief swings between doses)
* hyperprolactinemia; adjunct in tx of pituitary tumors
effects
* more nausea, hallucinations, confusion, and hypotension (Dopamine increased pulse pressure, heart rate and circulating epinephrine (E) and norepinephrine (NE) levels. Dopamine agonists tend to diminish blood pressure by inhibiting sympathetic neuronal discharge of NE and, to a lesser extent, by stimulating dopamine vascular receptors.) than l-dopa
* less dyskinesia (involuntary, erratic, writhing movements of the face, arms, legs or trunk)
* non specific CNS arousal
PO – initiate at low dose and individualize
* rapid, partial absorption
MAY BE USED WITH l-dopa + carbidopa
Rotigotine (neupro)
Pramipexole (mirapex)
ropinirole (requip)
nonergot-derivative dopamine receptor agonist
- dopamine receptor agonist
indication
* parkinson’s
* restless leg syndrome
effects
* somnolence
* hallucinations
* psychosis
* hypotension impulse
rotigotine transdermal patch
pramipexole and ropinirole PO
few interactions for all
Selegilene (eldepryl)
Rasagiline (azilect)
monoamine oxidase inhibitors
- irreversibly inhibits monoamine oxidase type B (but not type A)
- inhibits intra cerebral metabolic degradation of DA
indication
* Parkinson’s as adjunct to levodopa and carbidopa
effects
* somnolence
* hallucinations
* psychosis
* hypotension impulse
PO, rapidly absorbed, crosses blood brain barrier, metabolized in liver
Potentiates effects of sympathomimetics…
OVERALL — slows progressio nof parkinson’s w/ levodopa/carbidopa use
entacapone (comtan)
tolcapone (tasmar)
COMT (catechol-o-methyltransferase) inhibitor
- Seletive, reversible COMT inhibitor
- By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier.
indication
* Parkinson’s as adjunct to levodopa and carbidopa
effects
* somnolence
* hallucinations
* psychosis
* hypotension impulse
PO
Drugs metabolized by COMT. MAO inhibitors (An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.)
Trihexyphenidyl (artane)
Biperiden (akineton)
Procyclidine (kemadrin)
Benztropine (cogentin)
anticholinergic drugs
- antagonists at cholinergic receptors
- lessen Ach:DA imablance in striatum
- less EFFECTIVE than l-dopa for tremor and other symptoms
indication
* Parkinson’s as adjunct to levodopa and carbidopa
effects
* somnolence
* hallucinations
* psychosis
* hypotension impulse
PO
Drugs metabolized by COMT. MAO inhibitors (An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.)
movement disorder drugs
- tardive dyskinesia serious side effect of antipsychotic
- manifests as repetitive jerking, movement of tongue, face, and neck
- don’t d/c psych med!
1) valbenazine tosylate (ingrezza)
2) deutetrabenazine (austedo)
BOTH above are vesciular monoamine transported inhibitors (VMAT2)
* reduce mvmt sx of TD
Deutetrabenazine: used to tx choreic movements (sudden, unintended, and uncontrollable jerky movements of the arms, legs, and facial muscles) of hungtington’s disease (depression and suicide are huge risks with HD patients)
parkinson’s disease
- tremor (pill rolling) at rest
- bradykinesia
- cogwheel rigidity
d/t lwo dopamine neurotransmission in nigrostriatal pathway 2ndary to degradation of dopaminergic neurons that project from substantia nigra and striatum (caudate and putamen)
