CNS 1 -PD, AD, Epilepsy Flashcards
Dopamine replacement
Parkinson’s Disease
levodopa/carbidopa
Dopamine agonist (4)`
Parkinson’s Disease
pramipexole
ropinerole
bromocriptine- ergot alkaloid, rare use
rotigotine (patch)
COMT inhibitors (2)
Parkinson’s Disease
entacapone
tolcapone
Dopamine releaser
Parkinson’s DIsease
amantadine
MAO-B inhibitor (2)
Parkinson’s Disease
selegiline
rasagiline
Anticholinergics (3)
Parkinson’s Disease
trihexyphenidyl (artane)
benzotropine (cogentin)
biperadin (akineton)
Levodopa
PD
immediate precursor of dopamine
- transported across BBB via amino acid transporters and converted to dopamine in the brain
Levodopa MOA
PD
increase amount of dopamine in the brain
(giving dopamine back)
Carbidopa MOA
PD
inhibits peripheral decarboxylase
- maximizing L-dopa delivery to the brain
Entacapone MOA
PD
inhibits COMT (catechol- O- methyltransferase)
- maximizing L-dopa delivery to the brain
- increases plasma t1/2 of L-dopa -> increasing availability
L-dopa AE
PD
N/V
loss of effectiveness
dyskinesias
psychosis
postural hypotension
Dopamine agonists (D2) uses
PD
- monotherapy in younger pts, also for RLS
- adjunctive therapy w/ L-dopa (orthostatic HTN, dyskinesias)
Non-ergot derivatives (3)
PD
pramipexole (mirapex)
ropinirole (requip)
apomorphine (apokyn) - SQ
Non-ergot derivatives AE
PD
nausea
sleep attacks
insomnia
compulsive behaviors
Ergot derivatives (1)
PD
bromocriptine
MAO-B inhibitors MOA
PD
inhibit metabolism, prolong L-dopa effects
- may have neuroprotective effects
selegine (eldepryl), rasagiline (azilect)
Amantadine (symmetrel) antiviral PD
MOA: stimulates dopamine release
blocks dopamine reuptake
blocks cholinergic and glutaminergic receptors
uses: dyskinesias
Amantadine (symmetrel) antiviral AE
PD
insomnia
agitation
irritability
hallucinations
restlessness
Antimuscarinic (anticholinergic) MOA
PD
block relative excess cholinergic fxn in basal ganglia
uses: tremors, rigidity
Antihistamine (1)
PD
diphenhydramine (benadryl)
Acetylcholinetrerase inhibitors (AChE-Is)
AD
donepezil (aricept)
AChE-Is MOA
AD
increase cholinergic transmission by reducing ACh metabolism
uses: symptomatic therapy for mild to moderate AD
AChE-Is AE
AD
N/V
diarrhea
bradycardia
lightheadedness
insomnia
vivid dreams
Memantine (namenda) MOA
AD
blocks CA+ influx into neurons caused by excessive glutamate signaling
uses: symptomatic therapy for moderate to severe AD
Memantine (namenda) AE
AD
lightheadedness
confusion
headache
Anti-epileptic drugs (AED) MOA
- ion channel blockade
- blockade of voltage-gated Ca+ channels
- prolonged inactivation of Na+ channels - GABA potentiation
- direct action on GABA receptor
- indirect GABA effect -> decrease reuptake or metabolism, increase release
Phenytoin (dilantin) MOA
AED
suppresses action potential through inactivation of Na+ channels
uses: partial or generalized tonic clonic seizures
Phenytoin (dilantin) AE
AED
cerebellar-vestibular symptoms:
nystagmus
ataxia
diplopia
vertigo
arrhythmias
hypotension
gingival hyperplasia
BBW: Steven’s Johnson syndrome (SJS)
Phenytoin (dilantin) drug interactions
phenytoin may decrease by diazepam, cimetidine, alcohol, valproic acid
Carbamazepine (tegretol) MOA
AED
inactivates Na+ channels
uses: drug of choice for partial seizures and may be first for generalized tonic-clonic seizures
Carbamazepine (tegretol) AE
AED
vertigo
ataxia
diplopia
blurred vision (cerebellar-vestibular)
small risk of small bone marrow suppression
water retention
induction of hepatic enzymes
BBW: Steven’s johnson syndrome (SJS)
Valproic Acid (depakene, depakote) MOA
AED
blocks Na+ and Ca+ channels, also gaba effects
uses: first line for all seizure types, bipolar disorder, migraine prevention
Valproic Acid (depakene, depakote) AE
N/V
anorexia
hepatotoxicity
pancreatitis
rash
wt gain
hair loss
tremor or bone marrow suppression
hepatic enzyme inhibitor
- not recommended for pregnant women
Ethosuximide (zarontin) MOA
AED
inhibits Ca+ channels in thalamic neurons
uses: drug of choice for absence seizures
Ethosuximide (zarontin) AE
N/V
anorexia
phenobarbitol MOA
AED
potentiates GABA signaling through direct receptor binding
uses: effective for generalized tonic-clonic and partial seizures, primarily used in children
Aducanumab (aduhelm)
MOA: monoclonal antibody therapy that removes amyloid
uses: AD to lower amyloid levels in AD brain, does not slow the decline of cognitive fxn
AE: urticaria, angioedema
phenobarbitol AE
AED
marked sedation but some tolerance develops
irritability
hyperactivity in children
agitation
confusion in elderly
respiratory depression
induces hepatic enzymes
topiramate (topamax) MOA
AED
blocks Na+ and Ca+ channels
potentiates GABA and blocks glutamate receptors
uses: partial and generalized seizures, Lennox-Gastaut, monotherapy, migraine prophylaxis
topiramate (topamax) AE
AED
cerebellar/vestibular: ataxia, diplopia, dizziness
CNS: somnolence, cognitive slowing, nervousness
GI: nausea, vomiting, anorexia
metabolic acidosis
kidney stones
hypohydrosis
glaucoma
levetiracetam (keppra) MOA
AED
not fully understood that it involves a synaptic vesicle protein SV2A may modulate release of glutamate and GABA
- not metabolized by CYP
levetiracetam (keppra) uses
AED
myoclonic seizures
primary gen tonic-clonic
partial- onset seizures
migraine
bipolar
new onset pediatric epilepsy
Other anti-epileptic drugs (4)
oxycarbazepine (trileptal)
lamotrigine (lamictal)
gabapentin (neurotin)
pregabalin (lyrica)
Treatment drugs for status epilepticus
Initial drug: benzodiazepine (IV lorazepam or diazepam)
2nd drug: IV fosphenytoin or phenytoin
Sedative hypnotic drugs
barbiturates
benzodiazepines
BZ-like drugs
also used as:
anti-anxiety
anticonvulsants
sedation/anesthesia
hypnotic
muscle relaxation
alcohol withdrawal
Benzodiazepines (BDZs) MOA
enhance inhibitory activity of GABA by binding to benzodiazepine site on receptor
BDZ antagonist
flumanzenil (IV/IM)
Benzodiazepines (BDZs) AE
excessive or additive sedation w/other CNS depressants
confusion
anterograde amnesia
abuse potential
tolerance and cross tolerance w/ETOH
Zaleplon (sonata)
more selective because binds only to GABA receptors with alpha-1 subunits
- rapid absorption, short half life
Zolpidem (ambien)
binds BZ site selectively with minimal muscle relaxing and effects
- rapid onset, oral spray and sublingual tablets
AE: drowsiness, complex sleep behaviors (driving, cooking, sex)
Exzopiclone (lunesta)
not restricted to short term use 12 mo.
AE: unpleasant taste, HA, complex sleep behaviors, rebound insomnia
Suvorexant (belsomra)
dual orexin receptor antagonist (DORA)
uses: helps for sleep, reduce insomnia
Ramelteon (rozerem)
melatonin receptor agonist
uses: helps for sleep, reduce insomnia
AE: dizziness, fatigue
Antidepressants (4)
venlafaxine
paroxetine
escitalopram
duloxetine
Busprione (buspar)
MOA: partial agonist 5HT1a also D2 activity, selective anxiolytic, not a benxodiazepine
uses: anxiety
Propofol
MOA: promotes GABA release
AE: hypotension, can be abused
ketamine- esketamine (spravato)
MOA: S-Enantiomer of ketamine with analgesic anesthetic and antidepressant activities
uses: major depression disorders
