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13 Cards in this Set

  • Front
  • Back
Pathophysiology of Parkinsons'

Progressive degeneration of Nigrostiatal DA tracts (substantia nigra/pars compacta)--DA/ACh balance disturbed. Too little DA/too much ACh

Signs & Symptoms:
Resting tremor, bradykinesia, muscle rigidity, postural instability--loss of postural reflexes, flat facies
crosses BBB--prejunctionally decarboxylated to Dopamine (by amino acid decarboxylase AAAD) to restore DA activity in
corpus striatum
Alpha-methyldopa hydrazine--- L-amino acid decarboxylase inhibitor that acts in the periphery--does not cross BBB

Increases CNS availability of L-Dopa (fixed combo drug L-Dopa/Carbidopa "Sinemet")
--dose can be reduced by 80%--less side effects
L-Dopa side effects

SE: dyskinesias (up to 80% of pt's)--may be reduced by decreasing dose but parkinson symptoms may increase

"end-dose akinesia"--rapid return of akinesia & muscle rigidity before end of dosing interval
"On-off akinesia"--rapid fluctuation showing no beneficial & beneficial effects of L-dopa therapy--may be sign of neuron degeneration
"akinesia paradoxica"--sudden freezing of movement

Behavioral: anxiety, insomnia, psychosis--if preexisting problem
vivid dreams, hallusinations

Nausea & vomiting--better w/ carbidopa & when drug taken w/ food

CV effects: postural hypotension--reduced w/ carbidopa.
arrhytmias, afib, tachy, htn

Mydriasis & acute glaucoma

Contraindications: Psychosis, narrow angle glaucoma, peptic ulcer disease
w/ MAOa--can cause HTN crisis
antiemetics/antipsychotics-- reduce L-dopa activity
COMT inhibitors-- used in combo w/ L-dopa/Carbidopa

blocks peripheral conversion of levodopa to 3-O-methyl DOPA, increasing both the plasma half-life of levodopa as well as the fraction of each dose that reaches the CNS

--need to give 2-3 X day

Entcapone--duration of action even shorter (~2hrs)
MAO-B Inhibitor--retards DA breakdown in Striatum
(isoenzyme MAO-B is the predominant form in the striatum)

Metabolites of Selegiline: Amphetamina & methamphetamine

Selegiline + merperidine/tricycllics--stupor, rigidity, agitation, and hyperthermia
SSRI's w/ selegiline--seems to be ok w/ PD pt's but use caution

selegiline does not inhibit peripheral metabolism of catecholamines (in doses less than 10mg/day), also does not cause the lethal potentiation of catecholamine action observed when patients taking nonspecific MAO inhibitors ingest indirectly acting sympathomimetic amines such as the tyramine found in certain cheeses and wine.
antiviral drug. Increased release of DA in CNS via unknown mechanism
used in early PD as adjunct to L-dopa. Therapeutic effect may diminish w/in weeks
SE: anticholinergic, livedo reticularis (edema/skin mottling)
D2 (and D1) receptor agonists

given w/ L-dopa. Also used for hyperprolactinimia

SE: nausea, vomiting, hypotension--initial dose
D2 (and D1) receptor agonists

given w/ L-dopa. Also used for hyperprolactinimia

SE: nausea, vomiting, hypotension--initial dose
muscarinic receptor blockers
suppress ACh activity to balance DA/ACh ratio

used w/ initial tx of PD w/ L-dopa

good for tremor, rigidity
little effect for bradykinesia and postural reflexes
muscarinic receptor blockers
list of drugs for PD

M-blockers--more lipid soluble than atropine. greater CNS access

Anti-parkinsonian--combo w/ L-dopa

Pramipexole D3 agonist

Ropinirole D2 agonist--also used for restless leg syndrome

SE: uncontrolled sleepiness
Drugs for Alzheimer's
Acetylcholinesterase inhibitors (Donepezil, rivastigmine, tagrine (liver tox) and galantamine)

SE: GI dysfunction & muscle cramps
NDMA inhibitor (Memantine)