CNS Drugs Flashcards
Name the barbiturates
phenobarbital, pnetobarbital, thiopental, secobarbital
Mechanism of barbiturates
facilitate GABAa action by increasing duration of Cl- channel opening, thus decrease neuron firing (increases duration)
Contraindication of barbiturates
in porphyria
Use of barbiturates
sedative for anxiety, seizures, insombia, induction of anesthesia (thiopental)
Toxicity of barbiturates
respiratory and cardiovascular depression
CNS depression (EtOH exacerbated)
INDUCES cytochrome p450
Overdose tx of barbiturates
supportive (assist respiration and maintain BP)
Name the benzodiazepines
diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, clordiazepoxide, alprazolam
Mechanism of benzodiazepines
facilitate GABAa action by increasing frequency of Cl- channel opening
decreases REM sleep
Name the benzos with short-half lives and NO active metabolites
Alprazolam, triazolam, oxazepam, midazolam –> higher addictive potential
Use of benzodiazepines
anxiety, spasticity, status epilepticus, detoxification (especially alcohol withdrawal and DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia)
Which benzos used for status epilepticus?
lorazepam and diazepam
Toxicity of benzodiazepines
dependence, additive CNS depression effects with alcohol
less risk of respiratory depression and coma than with barbiturates
Overdose tx for benzos
with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
Name the non-benzo hypnotics
zlopidem, zaleplon, esZopiclone
Mechanism of the non-benzo hypnotics
act via the BZ1 subtype of the GABA receptor
effects reversed by flumazenil
Use of non-benzo hypnotics
insomnia
Toxicity of non-benzo hypnotics
ataxia, headaches, confusion
short duration because of rapid metabolism by liver enzymes
only cause modest day-after psychomotor depression and few amnestic effects
decreased dependence risk than benzos
Name the dopamine agonists
ergot - bromocriptine
non-ergot (preferred) - pramipexole, ropinirole
Parkinson disease NT levels
loss of dopaminergic neurons and excess cholinergic activity
Name drug that increases dopamine availability
Amantadine
Mechanism of amantadine
increase dopamine release and decrease dopamine reuptake
Uses for amantadine
PARKINSON
antiviral against influenza A and rubella
Toxicity of amantadine
ataxia livedo reticularis (skin rash, purple and lace like)
How do drugs increase L-DOPA availability pre-BBB?
agents prevent peripheral (Pre-BBB) L-dopa degradation (because dopamine cannot cross BBB) –> increased L-DOPA entering the CNS
central L-DOPA available for conversion to dopamine
Name the drugs that increase L-DOPA availability entering brain
Levodopa (L-DOPA)/carbidopa
Entacapone, tolcapone
Mechanism of carbidopa
blocks peripheral conversion of L-DOPA to dopamine by inhibiting DOPA decarboxylase
also reduces side effects of peripheral L-dopa conversion to dopamine (nausea, vomiting)
Mechanism of entacapone and tolcapone
prevent peripheral L-dopa degradation to 3-O-methyldopa (3-OMD) by inhibiting COMT
How do drugs prevent dopamine breakdown?
agents act centrally (post-BBB) to block breakdown of dopamine –> increased available dopamine
Drugs that prevent dopamine breakdown in CNS
selegiline and tolcapone
Mechanism of selegiline
blocks conversion of dopamine to DOPAC by selectively inhibiting MAO-B in brain
Mechanism of tolcapone
blocks conversion of dopamine to 3-MT by inhibiting central COMT
Drugs that curb excess cholinergic activity
benztropine
Mechanism of benztropine
antimuscarinic
improves tremor and rigidity but has little effect on bradykinesia
Mechanism of Levodopa/Carbidopa combo
increase level of DA in brain
carbidopa inhibits peripheral conversion of L-dopa to DA via inhibition of dopa decarboxylase
Can dopamine cross BBB?
NO
Can L-DOPA cross BBB?
YES
Use of levodopa/carbidopa
parkinson disease
toxicity of levodopa/carbidopa
arrhythmias from increased peripheral formation of catecholamines
long term can lead to dyskinesia following administration, akinesia between doses = “on/off” phenomenon
Mechanism of selegiline
selectively inhibits MAO-B, which preferentially metabolizes dopamine over NE and 5-HT, thereby increasing the availability of dopamine in CNS
Use of selegiline
adjunctive agents to L-dopa in treatment of Parkinsons
Toxicity of selegiline
may enhance adverse effects of L-dopa
Mechanism of memantine
NMDA receptor antagonist
helps prevent excitotoxicity (mediated by Ca2+)
Toxicity of memantine
dizziness, confusion, hallucinations
Use of memantine
Alzheimer’s disease
Mechanism of donepezil, galantamine, rivastigmine, tacrine
AChE inhibitors
Use of donepezil, galantamine, rivastigmine, tacrine
Alzheimer’s disease
Toxicity of donepezil, galantamine, rivastigmine, tacrine
nausea, dizziness, insomnia
Drugs used for Alzheimers
memantine (NMDA antagonist)
donepezil, galantamine, rivastigmine, tacrine (AChE Inhibitors)
NTs altered in Alzheimers
decreased ACh
NTs altered in Huntington’s
decreased GABA, ACh; increased dopamine
Treatments for Huntington’s
tetrabenazine and reserpine
haloperidol
Mechanism of tetrabenazine and reserpine
inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release
Mechanism of haloperidol
D2 receptor antagonist
Mechanism of sumatriptan (and “-triptans”
5-HT1b/1d agonists
inhibit trigeminal nerve activation
prevent vasoactive peptide release and induce vasoconstriction
Use of sumatriptan
acute migraine, cluster headache attacks
Toxicity of sumatriptan
coronary vasocpasm (contraindicated in patients with CAD or prinzmetal angina) mild paresthesia