Antiseizure, muscle relaxant Flashcards
What are the different types of seizures?
Partial (simple, complex) Generalized -Tonic-clonic (grand mal) -Absence (petit mal) = children -Myoclonic -Status epilepticus
What are the basic mechanisms of action for antiseizure agents? (3)
- affect abnormal membrane function (channels that lead to excessive depolarization)
- correct decreased inhibition (increase GABA function)
- reduce excitation (block glutamate receptors)
Phenytoin
target channel, mechanism, clinical uses
- sodium channels
- refractory period is increased => inhibits repetitive action potentials
- generalized tonic-clonic seizure or partial seizures
How is pharmacokinetics of phenytoin affect drug interaction?
it is highly protein bound
-may interact with drugs that are protein bound
How is clearance affected as phenytoin dose is increased?
-dose-dependent => first-order to zero-order as dose is increased
(often while in therapeutic range)
Toxicity of phenytoin (5)
- CNS - dose-dependent (nausea, anorexia, apathy, sedation, ataxia, nystagmus, diplopia)
- BELOW not dose dependent*
- gingival hyperplasia
- hirsutism
- teratogenicity (cleft palate)
- rash
What is another antiseizure drug that is similar to phenytoin that causes rare blood dyscrasias and spinal bifida?
Carbamazepine
How is Oxcarbamazepine different from carbamazepine?
less CNS side effects
less enzyme induction
Mechanisms of action for phenobarbital (2)
GABA receptor - chloride ion channel
-selectively suppress abnormal neurons by suppressing firing from the foci and inhibiting spread
Why is phenobarbital primarily used in infants despite its effectiveness against tonic-clonic seizures?
because of its sedative effects
Which drug is used to treat absence seizure?
Ethosuximide
What is the mechanism of action for ethosuximide?
reduces low-threshold (T-type) Calcium current in thalamic neurons
How safe is ethosuximide?
among the safest of antiseizure drugs
Which antiseizure drug is used for absence seizures as well as tonic-clonic & myoclonic seizures?
Valproic acid
Describe the mechanisms of action for valproic acid (3)
- blocks repetitive neuronal firing
- reduce T-type Ca++ current
- increase GABA concentration
What are some toxicities related to valproic acid? (3)
- idiosyncratic hepatotoxicity (also interferes with metabolism of phenobarbital, phenytoin, and carbamazepine)
- teratogenicity (spinal bifida)
- weight gain, hair loss
Which drug of benzodiazepines is used as a long acting drug effective against absence seizures and some types of myoclonic seizures?
Clonazepam
Which two of benzodiazepines is used I.V. in status epilepticus?
diazepam, lorazepam
Which antiseizure drug is an antagonist for NMDA receptor (glutamate receptor)?
Felbamate
Why is use of felbamate limited to partial seizures that are refractory to other drugs?
occurrence of aplastic anemia and hepatic failure (otherwise very effective)
Main use for pregabalin other than for partial seizures
management of neuropathic pain (diabetic, postherpetic, fibromyalgia)
-drug abuse limits use
What is a serious toxicity for lamotrigine?
Stevens-Johnson syndrome
=> malaise, fever
erythematous/purpuric macules
epidermal necrosis and sloughing
Main function of topiramate
blocks spread of seizure rather than raising seizure threshold
(also cause weight loss)
What is the mechanism of tiagabine?
inhibits GABA transporter
=> increases GABA in synapse
What is the mechanism of zonisamide?
inhibits T-type Ca++ channel and Na+ channel
What is the mechanism of vigabatrin?
irreversibly inhibits GABA transaminase
=> increase in GABA
Why is vigabatrin subject to restricted prescribing program?
permanent effects on vision
What is the biggest problem in using diazepam as a muscle relaxant?
sedation
What receptor does Baclofen target and how does it decrease the release of excitatory transmitters such as glutamate?
act on GABA-B receptors
- > hyperpolarization
- > presynaptic inhibition
Why is Baclofen better than diazepam?
much less sedation
Target for tizanidine?
alpha 2 receptor agonist
