Antiepileptic Drugs Flashcards
define epilepsy
the repeated occurrence of sudden excessive or synchronous discharges in cerebral cortical neurones resulting in a disruption of consciousness, disturbance of sensation, movements, impairment of mental function, or some combination of these
what are the two classifications of epilepsy
symptomatic or idiopathic
define symptomatic
symptomatic indicates that a probable casue exists: cerebrovascular lesions perinatal or postnatal trauma CNS infections tumours congenital malformations of the CNS
define idiopathic
idiopathic indicates that no obvious cause can be found:
usually no other neurological condition
genetic factors probably responsible
what are the two types of seizure
partial and generalised seizures
what are partial seizures
partial seizures involve repeated jerking of a limb or complex behavioural changes (psychomotor epilepsy) but no loss of consciousness
- in complex partial seizures consciousness may be altered
in these cases the abnormal discharge is localised to the relevant area of the cortex
what are generalised seizures
generalised seizures can take two forms:
-an initial generalised convulsion followed by jerking of the whole body (clonic convulsion) accompanied by sudden loss of consciousness; this is tonic-clonic epilepsy or grand mal
-episodic transient loss of consciousness (absence seizures); this is termed petit mal and is mostly seen in children
in generalised seizures the abnormal electrical activity involves the whole brain
a state in which generalised convulsions follow each other without consciousness being regained is termed status epilepticus and is a medical emergency
what is the goal of anti-epileptic drugs?
to dampen neuronal hyperexcitability that leads to or sustains an epileptic attack
how might they work?
reducing excitation
enhancing inhibitory effects
what is their effect?
generally antiseizure
how do AEDs decrease excitation?
decrease activity of voltage gated sodium and/or calcium channels
decrease efficacy of excitatory synapses
how do AEDs increase inhibition?
increase efficacy of inhibitory synapses
increase potassium channel activity
discuss drugs that decrease excitation
a) voltage and use dependent inhibition of sodium channels
- phenytoin
- carbamezapine
- valproate
use dependent blockade - inhibit high frequency discharge by binding preferentially to inactivated sodium channels
- THIS PREVENTS THE RETURN OF THE CHANNEL TO THE RESTING STATE WHICH IS NECESSARY FOR THE GENERATION OF ACTION POTENTIALS
CARBAMEZAPINE IS MOST PREFERRED AS IT HAS FEWER SIDE EFFECTS
phenytoin and carbamezapine both interact with other drugs because they induce the P450 liver enzymes
phenytoin can cause vertigo, confusion, insomnia and ataxia , thickeninig of gums and increase in body hair
carbamezapine can cause unsteadiness, sedation, mental disorientation and water retention
discuss drugs that decrease excitation
b) decrease activity of voltage gated calcium channels
- inhibition of T-type calcium channels:
ETHOSUXIMIDE
IT IS USED ONLY FOR ABSENCE SEIZURES FOR WHICH IT IS THE DRUG OF CHOICE
IT CAN PRECIPITATE TONIC-CLONIC EPILEPSY
can cause GI tract disturbances and sedation
discuss drugs that increase inhibition
a) blockade GABA metabolism
- VALPROATE
an inhibitor of GABA transaminase, the enzyme responsible for the breakdown of GABA. this leads to an increased amount of GABA in the brain
also blocks sodium channels
effective in both tonic-clonic and absence seizures
teratogenic
increased hair growth and GI disturbances
