cns drugs: parkinson's disease Flashcards
normally, dopamine (D2) receptors (G-alpha-inhibibitory) in the striatum affects _________ and _________ release. degeneration of dopaminergic neurons sloes dopamine release and leads to a loss of _____________.
Ach, GABA, motor fxn and control
tx of parkinson’s disease is aimed at ____________.
overcoming loss of dopaminergic neuron input
the synaptic cleft of neuron affected by parkinson’s has a _____________ amount of dopamine causing movement disorders
reduced
L-DOPA mechanism
- L-DOPA crosses BBB into substantia nigra
- then converted into dopamine via DOPA decarboxylase
- provides more dopamine to synapse
when during the course of parkinson’s tx is L-DOPA most effective? why?
- good for 3-4 years
- may have to diminish dose due to adverse affects
- pts become less responsive (more degeneration)
what drug is L-DOPA accompanied by during tx?
carbidopa, a peripheral dopa decarboxylase inhibitor
2 benefits of carbidopa
- allows more L-DOPA to get into CNS by stoping conversion to dopamine
- stops vomiting and nausea in pts (due to dopamine receptor activation in the gut
advantages of using dopamine receptor agonists like bromocriptone (d2), pergolide (d1 and d2), pramipexole (d3), and ropinirole (d2)
- not as toxic as L-DOPA
2. don’t require a neuron from substantia nigra for delivery
when are dopamine receptor agonist contraindicated?
pts with history of psychotic illness, heart attack or ulcer
adverse affects of dopamine receptor agonists
GI, static hypotension, confusion, hallucinations, headache etc
Metabolic enzyme inhibitors treat Parkinson’s disease by____________.
blocking metabolism of dopamine by MAO and COMT
2 MAO inhibitors
selegiline, rasagiline
2 COMT inhibitors
tolcapone, entacapone
what is apomorphine and how is it administered?
- dopamine receptor agonist
- produces a vomiting if given alone
- must be administered with anti-sickness drug domperidone
- Parenternal administration through continuous subcutaneous infusion from a portable pump
What is amantadine?
- Parkinson’s treatment drug (also influenza)
- enhances synthesis release or reuptake of dopamine from the surviving nigral neurons
What is the treatment algorithm for Parkinson’s disease?
- dopamine agonist
- add levodopa and carbidopa (increase dosage if needed)
- add comt or mao inhibitor
- adjunct therapy
- consider surgery
Adjunct therapy for Parkinson’s disease
for tremor: anticholinergic
for drug-induced dykineseias: amantadine
for “off” episodes: apomorphine
phenytonin and other anti-seisure drugs block _________.
high frequency firing of action potentials and look a lot like local anesthetics
GABA or glutamate potentiation serves to dampen synaptic nerve impulses to reduce convulsions?
GABA (inhibitory synapse)
3 mechanisms of GABA potentiation
- inhibition of GABA transaminase
- inhibition of GABA reuptake
- facilitation of Cl- channel opening
GABA transaminase in involved in _______________ of GABA.
metabolism
vigabatrin
irreversible inhibitor of GABA transaminase
trigabine
GABA reuptake inhibitor
what type of drug is used by dentists for emergency tx of seizure?
bensodiazephines (diazepam, lorazepam, clonazepam, clorazepate, clobazam, midazolam
benzodiapines facilitate _________ to promote GABA potentiation.
Cl- channel opening
barbituates __________ to potentiate GABA.
faciliate Cl- channel opening (phenobarbitol, mephobarbital, metharbital, primidone)
drugs that block which type of channels in the thalamus are effective anti-convulsants?
T-type calcium channels (ehtosuximdie, phensuximide, methsuximde, trimethadione)
drugs that block voltage-gated calcium channels (essential for NT release) are thought to diminish ________________.
glutamate-mediated neurotransmission (gbabpetin, pregabalin)
flbamate and topiramate block _____ to reduce convulsions.
NMDA receptors
pharmacologic tx effectively controls ____% of those affected by convulsions.
80
