A. 34. Drugs used for treatment of neurodegenerative disorders. Nootropic drugs. Flashcards
drugs used in Parkinson’s disease
“Lets Call iT PARkinson’S DisEase Please”
Levodopa Carbidopa Tolcapone pramipexole Amantadine Ropinirole Selegiline
Diphenhydramine
Entacapone
Procyclidine
Benztropine, Trihexyphenidyl*
drugs used in Alzheimer disease
“Mom! Dona Riva dances at the Gala”
Memantine
Donepezil
Rivastigmine
Galantamine
what is Piracetam?
Nootropic agent
what are Nootropics?
drugs, supplements, and other substances that may improve cognitive function (memory, creativity, motivation) in healthy individuals
what is the mechanism of Piracetam?
binds to the protein SV2A on the synaptic vesicle –> interfere with neurotransmitter release
what is Piracetam’s therapeutic potential?
cognition enhancer and in the treatment of schizophrenia, depression, ADHD, and Parkinson’s disease.
how are the drugs for Alzeheimer given?
orally
what are Rivastigmine , Galantamine and Donepezil?
Acetylcholine-esterase inhibitors (centrally-acting)
1st line agent for Alzheimer’s disease?
Rivastigmine
Galantamine
Donepezil
*provide a modest reduction in the rate of loss of cognitive function
side effects of rivastigmine, galantamine, donepezil
Nausea, vomiting
Diarrhea
bradycardia
what is Memantine?
glutamate NMDA receptor blocker
side effects for memantine
“car”
confusion
agitation
restlessness
why is Levodopa given with Carbidopa?
cause Carbidopa acts as a peripheral dopa decarboxylase inhibitor (does not cross the BBB)
what is Levodopa and what does it do?
it’s a dopamine precursor
enters the brain via LAT
converted by DOPA decarboxylase to dopamine –> ↑ dopamine activity in the brain (↓ bradykinesia)
how are the drugs for Parkinson’s disease given?
orally
*diphenhydramine also has IV preparation for acute drug-induced parkinsonism (acute dystonia)
what is the duration of action of Levodopa?
6-8 hours
what is Levodopa+carbidopa for?
Parkinson’s disease
side effects of Levodopa+carbidopa
GI distress- nausea, vomiting anorexia
Dyskinesia (on/off phenomenon)
hypotension, arrhythmias (peripheral effect of dopamine)
psychosis, agitation, anxiety, hallucinations (central effect of dopamine)
what is the mechanism of action of Selegiline?
selective MAO-B inhibitor–> ↓ metabolism of dopamine –>↑ dopamine activity in the brain (↓ bradykinesia)
can we see a “cheese effect” when given Selegiline?
no
there is no tyramine interaction like in non-selective MAO inhibitors.
does selegiline have a short T1/2?
no, long
what type of metabolism is seen with Selegiline?
hepatic
form: 1. desmethylselegiline (neuroprotective)
and 2. amphetamine (psychostimulant)
when is selegiline given?
as monotherapy for Parkinson’s disease (early stage) or in adjunct to levodopa+carbidopa (advanced stage)
side effects of selegiline
“Pork DISH”
Psychosis Dyskinesia Insomnia Serotonin syndrome (when used with SSRI'S) Hypotension
name 2 COMT inhibitors
Entacapone
Tolcapone
where does Entacapone work?
periphery
where does Tolcapone work?
periphery+CNS
what is the daily dose of Entacapone?
5 times
what is the daily dose of Tolcapone?
3 times
side effects of Entacapone and Tolcapone?
sleep disorders
tolcapone: hepatotoxicity
when do we use Entacapone or Tolcapone?
Parkinson’s disease (adjunct to levodopa/carbidopa)
mechanism of COMT inhibitors
periphery: inhibition of COMT enhances levodopa uptake and efficacy
CNS: inhibition of COMT enhances dopamine activity
what converts Levodopa to 3-OMD (3-O-Methyldopa)?
COMT
what does 3-OMD do?
partial agonist (antagonist in the presence of a full agonist) competes with levodopa for transport and activity
name the Dopamine agonists
Ropinirole
Pramipexole
Bromocriptine
Pergolide
what is Ropinirole?
D₂ receptor agonist
non-ergot derivative
what is pramipexole?
D₃ receptor agonist
non-ergot derivative
what type of metabolism does Ropinirole go through?
hepatic
what type of metabolism does pramipexole go through?
renal
how many times are ropinirole and pramipexole administered?
3 times daily
does pramipexole have a short T1/2?
yes
what are bromocriptine and pergolide?
partial D₂ receptor agonists
Ergot alkaloid derivatives
side effects of dopamine agonists
Dyskinesia Psychosis hallucinations anorexia, nausea bromocriptine--> orthostatic hypotension
indications for Ropinirole AND pramipexole
- Parkinson’s disease -monotherapy/adjunct to levodopa
- pramipexole: potential antioxidant
- Restless leg syndrome (RLS)- first-line treatment!
indications for bromocriptine and pergolide
- Parkinson’s disease -monotherapy/adjunct to levodopa
- hyperprolactinemia
- acromegaly
what is the mechanism of action of Amantadine?
- Antiviral medication
- enhances the effect of endogenous dopamine (↑ the synthesis and inhibiting its uptake)
- muscarinic blockade
- NMDA blockade
how is Amantadine eliminated?
by the kidneys
when is Amantadine used?
for Parkinson’s disease (adjunct to levodopa/carbidopa)
side effects of Amantadine
Livedo reticularis
Psychosis
Gi disturbances
Ataxia
mechanism of action of antimuscarinics
muscarinic blockade–> ↓ the excitatory activity of cholinergic neurons in the striatum–> improves tremor and rigidity
*no effect on bradykinesia
names the antimuscarinic agents
Procyclidine Diphenhydramine Benztropine Trihexyphenidyl "Tri PARKing my mercedes BENZ"
is antimuscarinic recommended as monotherapy for early Parkinson’s disease?
no
what is the other indication for antimuscarinics except for Parkinson’s disease?
drug-induced extrapyramidal symptoms
side effects of Antimuscarinics
“atropine-like effects”:
dry mouth urinary retention constipation hyperthermia tachycardia Mydriasis blurred vision toxicity (3 C's)--> cardiotoxicity, convulsions, coma
contraindications of antimuscarinics
glaucoma
prostatic hyperplasia
