Anticonvulsants II Flashcards
what are the hydantoin antiseizure drugs?
phenytoin and fosphenytoin
which hydantoin antiseizure drug is more soluble and used for parenteral use?
fosphenytoin
where is phenytoin metabolized? by what system?
liver - MES system
how is phenytoin excreted?
urine
elimination of phenytoin follows what kinetics?
dose-dependent (zero order)
what is the MOA of phenytoin?
- blocks and prolongs inactivated state of voltage gated sodium channels
- enhances release of GABA
- prevents seizure progagation
what are the clinical uses for phenytoin?
generalized tonic-clonic, partial, status epilepticus
what are the dose related side effects of phenytoin?
sedation, ataxia, nystagmus, diplopia, cardiac dysrhythmias
what are the idiosyncratic side effects of phenytoin?
gingival hyperplasia
which drug interactions decrease phenytoin metabolism?
barbiturates (high), warfarin
which drug interactions increase phenytoin metabolism?
barbiturates (low), carbamazepine
which drug interactions displace the protein binding of phenytoin?
salicylates, valproic acid, kidney failure
which drug class is carbamazepine?
tricyclic
what is the MOA of carbamazepine?
inhibition of voltage gated sodium channels (same as phenytoin)
blocks high frequency firing of neurons and decreases synaptic release of glutamate
what is oxacarbazepine?
antiseizure drug similar to carbamazepine - shorter half life but active metabolite has longer duration and fewer drug interactions
what are the clinical uses of carbamazepine?
general clonic-tonic (grand mal), partial seizures, TRIGEMINAL NEURALGIA
how is carbamazepine metabolized?
hepatic MES - induces p450s to upregulate its own metabolism
what is the drug of choice for trigeminal neuralgia?
carbamazepine
carbamazepine has drug interactions with which other drugs?
phenytoin, valproate, phenobarbital
what is the MOA of the phenobarbital?
enhances phasic GABAa receptor responses - increased opening time of chloride channel
what are the side effects of cabamazepine?
syndrome of inappropriate ADH secretion - fluid retention and hyponatremia
what is the main clinical use for phenobarbital?
status epilepticus
what is primidone?
metabolized by liver (MES) to phenobarbital and phenyl ethyl malonic acid (PEMA)
what is the MOA of ethosuximide?
blocks presynaptic T type calcium channels (blocks high frequency firing of neurons)
what are the clinical uses for ethosuximide?
absence seizures (petit mal)
what are the drugs of choice for petit mal (absence) seizures?
ethosuximide, valproic acid
what is the MOA of valproic acid?
- inhibition of presynaptic T type calcium channels - blocks neuronal firign
- inhibition of GABA transaminase
what is the main clinical use of vvalproic acid?
absence (petit mal) seizures
what is the main adverse event of valproic acid?
hepatotoxic syndrome, teratogenic risk
what are the preferred initial agents for status epilepticus?
diazepam (valium) or lorazepam (longer acting)
what is the MOA of diazepam?
potentiates GABAa responses by increasing frequency of channel opening
what is the main clinical use of diazepam?
status epilepticus
what are the use limitations of diazepam?
- sedative
2. tolerance
which drugs apart from diazepam and lorazepam can be used as antiepilepsy drugs?
clonazepam, nitrazepam, clorazepate
what is the MOA of gabapentin?
blocks presynaptic voltage gated calcium channels - decreaes excitatory transmission
what are the clinical uses for gabapentin?
- generalied tonic-clonic (grand mal)
- partial seizures
- neuropathic pain - postherpetic neuralgia and fibromyalgia
what is pregabalin?
similar to gabapentin, GABA analog
what is the MOA of lamotrigine?
blocks presynaptic voltage gated sodium and calcium channels
what are the clinical uses for lamotrigine?
- partial
- grand mal
- petit mal
what is the main adverse effect of lamotrigine?
steven johnson syndrome - severe blistering / necrosis of skin
what are the “other” newer agents of anticonvulsants?
- felbamate
- topiramate
- tiagabine
definition: spasticity
exaggerated muscle stretch reflex syndrome that occurs following injury to CNS
definition: spasm
increase in muscle tension seen after certain musculoskeletal injuries and inflammation
what is the MOA of diazepam as a muscle relaxant?
increases inhibitory actions of GABA on alpha motor neurons in spinal cord
what is the MOA of baclofen as a muscle relaxant?
GABAb receptor agonist - increased potassium conductance, hyperpolarization, reduction in calcium influx, reduction in excitatory transmitter release
which drug treats spasms associated with excess exertion, MS, cerebral palsy, injury?
diazepam
which drug reduces spasticity with MS, spinal, and brain injury?
baclofen
