Anticonvulsants I Flashcards
what is the cause of seizures?
abnormally excessive and rhythmic firing of certain populations of hyper-excitable neurons in the brain
seizures are usually characterized by what physical manifestation?
convulsions
what are the underlying causes of seizures?
- CNS injury - altered excitation thresholds
- congenital abnormalities within brain
- genetic factors
- infections, hypoglycemia, hypoxia, toxic metabolites
definition: epilepsy
chronic neurological disorder characterized by recurrent seizures
what are the two types of seizures?
- partial (focal)
2. generalized
what are the subtypes of partial (focal) seizures?
- simple partial
- complex partial
- secondarily generalized
what are the subtypes of generalized seizures?
- tonic-clonic (grand mal)
- absence (petit mal)
- myoclonic, atonic, clonic, tonic
- unclassified
what is the most severe type of seizure?
tonic-clonic (grand mal)
what is the most common partial seizure?
complex partial
what is the most common generalized seizure?
tonic-clonic
is there loss of consciousness with simple partial seizures?
no
how does a complex partial seizure spread?
from a small area of the brain to other areas that affect alertness and consciousness
is there loss of consciousness with complex partial seizures?
altered with potential automatisms
which type of seizures affect the entire brain with global EEG change and bilateral manifestations?
generalized
what are the features of a petit mal (absence) seizure?
- sudden onset and abrupt cessation
- brief loss of consciousness
- typically seen in children
what are the features of grand mal (tonic-clonic) seizures?
- tonic spasms and major convulsions of entire body (bilateral)
- loss of consciousness
what are the four stages of grand mal (tonic-clonic) seizures?
- aura
- tonic phase
- clonic
- stuporous state and sleep
what is status epilepticus?
continuous or very rapid recurring seizures, usually of the tonic-clonic type - medical emergency and require immediate therapy
what characterizes an atonic seizure? what type of seizure is it?
- sudden loss of postural tone, often seen in children
2. subtype of generalized seizure
what are the three stages of the seizure mechanism?
- initiation
- synchonization of surounding
- propagation - recruitment of normal neurons
what are the cellular and molecular factors that lead to seizure?
- excitatory postsynaptic potentials
- sodium influx
- calcium currents
- paroxysmal depolarization
what are the cellular and molecular factors that lead to control of seizures?
- inhibitory postsynaptic potentials
- potassium efflux
- chloride influx
- pumps
- low pH
what is the goal of antiepileptic drugs?
restore normal patterns of electrical activity
what are the treatment options for seizures?
- antiepileptic drugs
- surgery
- vagus nerve stimulation
when is vagus nerve stimulation indicated for seizure treatment?
for drug resistant patients with partial seizures
what are the anticonvulsant drug classes?
- cyclic ureides
- tricyclics
- benzodiazepines
- GABA derivatives
- “others”
what are the cyclic ureide drugs?
- phenytoin and fosphenytoin
- primidone
- phenobarbital
- ethosuximide
what are the tricyclic anticonvulsant drugs?
- carbamazepine
2. oxcarbazepine
what are the benzodiazepine anticonvulsant drugs?
- diazepam
2. lorazepam
what are the GABA derivative anticonvulsant drugs?
- gabapentin
2. pregablin
what are the “other” anticonvulsant drugs?
- valproic acid
- lamotrigine
- acetazolamide
- tiagabine
- topiramate
which drugs are typically used for partial seizures?
- carbamazepine
- phenytoin
- valproate
which drugs are typically used for tonic-clonic seizures?
- carbamazepine
- phenytoin
- valproate
which drugs are typically used for absence (petit mal) seizures?
- ethosuximide
2. valproate
which drugs are typically used for status epilepticus?
diazepam, lorazepam, phenytoin, fosphenytoin
what is the MOA for anticonvulsant agents?
inhibit firing of certain hyper-excitable cerebral neurons by
- decreasing excitatory effects of glutamate and repetitive firing of neurons (block voltage gated sodium channels)
- increase inhibitory effects of GABA
- alter neuronal activation by altering movement of ions (sodium, calcium) across neuronal membrane
what are the presynaptic methods of diminishing glutamate release?
- inactivation of VG sodium channels
- inactivation of VG calcium channels
- increase potassium channel opening
what are the postsynaptic methods of diminishing glutamate release?
- blockage of AMPA receptors
2. blockage of NMDA receptors
what is the mechanism for anticonvulsive agents that inactivate sodium channels?
bind sodium channel in inactive state and keep it inactivated for a prolonged period of time - preventing sodium from entering cell
what is the mechanism for anticonvulsive agents that cause reduced activity of calcium channels?
reduce calcium influx - decrease NT release and prevent neuronal excitability
inactivation of which receptor type is most effective for petit mal seizures?
calcium
what are the targets for increasing the effect of GABA?
- inhibit GABA transporters (block GABA reuptake)
- inhibit GABA transaminase (block GABA metabolism)
- potentiate activation of GABAa receptors
what are the general side effects of anticonvulsants?
sedation, diplopia, nystagmus, ataxia, GI upset
which anticonvulsant is considered safest during pregnancy?
phenobarbital
valproate and ethosuxamide act on which receptor to decrease seizure activity? which type of seizures are these good for? what is the MOA?
- calcium channel
- petit mal
- reduce pacemaker current that underlies thalamic rhythm in spikes and waves seen in absence seizures
