Cns Pharmacology Ii

Front 1

Pathophysiology of Parkinsons'

Symptoms

Back 1

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

Front 2

Levodopa

Back 2

L-dopa
crosses BBB--prejunctionally decarboxylated to Dopamine (by amino acid decarboxylase AAAD) to restore DA activity in
corpus striatum

Front 3

Carbidopa

Back 3

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

Front 4

L-Dopa side effects

contraindications

Back 4

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

Akinesias:
"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

Front 5

Entacapone
Tolcapone

Back 5

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

Tolcapone--hepatotoxicity
--need to give 2-3 X day

Entcapone--duration of action even shorter (~2hrs)

Front 6

Selegiline

Back 6

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.

Front 7

Amantadine

Back 7

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)

Front 8

Bromocriptine

Back 8

D2 (and D1) receptor agonists

given w/ L-dopa. Also used for hyperprolactinimia

SE: nausea, vomiting, hypotension--initial dose

Front 9

Pergolide

Back 9

D2 (and D1) receptor agonists

given w/ L-dopa. Also used for hyperprolactinimia


SE: nausea, vomiting, hypotension--initial dose

Front 10

muscarinic receptor blockers

Back 10

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

Front 11

muscarinic receptor blockers
list of drugs for PD

Back 11

benztropine
trihexyphenidyl

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

biperidin
orphenadrine
procyclidine

Front 12

Pramipexole
Ropinirole

Back 12

Anti-parkinsonian--combo w/ L-dopa

Pramipexole D3 agonist


Ropinirole D2 agonist--also used for restless leg syndrome

SE: uncontrolled sleepiness

Front 13

Drugs for Alzheimer's

Back 13

Acetylcholinesterase inhibitors (Donepezil, rivastigmine, tagrine (liver tox) and galantamine)

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