Antiepileptic Drugs Flashcards
What is Epilepsy?
a neurological disease characterised by spontaneous seizures-
what are the pathways of seizure propagation?
- initiation at cell level by increase in electrical activity, this causes syncing of surrounding neurons and subsequent spread to adjacent regions
- Ufibers connect regions to cortex, corpus callosum spread between hemispheres, the thalamocortical projection diffuse spread throughout brian
- central brain regions then spread to both hemispheres
what is a ‘focal/partial’ seizure?
Decrease in GABA mediated inhibition (exogenous factors, degeneration of GABAergic neurons) are major factors that aid in syncing of seizure focus
what is a ‘secondary generalized seizure’?
loss of GABA input (tonic phase) - AMPA and NMDA mediated excitation - oscillatory pattern of excitation and inhibition - GABA mediated inhibition prevails and patient flaccid
how do you clinically diagnose a primary generalized seizure?
- no Aura - this is how you tell it appart from the secondary generalized seizure.
how do you clinically diagnose absence seizures?
Absence seizures activation of T type calcium channels during awake state - therefore on EEG it will look like the patient is in stage 3 sleep =
what is ‘status epilepticus’?
Continuous seizure for more than 30 minutes and recurrent seizures without regaining consciousness between seizures for more than 30 minutes
what are the major classes of antiepileptic drugs?
- Voltage gated ion channel modulators (Na+, Ca2+, K+)
- GABAergic neurotransmission enhancers
- Glutamatergic neurotransmission reducers
- Other
What is the difference between resting state, activated state, and inactivated state sodium ion channels in in the CNS?
What kinds of calcium channels are present in the CNS?
- T- Type = open during membrane depolarization (mutated in patients with childhood onset absence epilepsy)
- L, P/Q type, N-type control entry of calcium into the presynaptic terminal (regulate neurotransmitter release)
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What is the MOA of phenytoin?
Binds to Na + channels to prolong duration in which channels are inactivated Prevents sustained repetitive firing of action potentials in hyperexcitable conditions
•Drowsyness, insomnia, ataxia, tremor, gingival hyperphasia, Stephen Johnson syndrome, blood disorders
•Hepatic metabolism – induction of cytochome p450, extensive drug interactions (e.g. oral contraceptives)
•Fosphenytoin is a prodrug form
what is the MOA of Carbamazepine?
Mechanism of action same as phenytoin but structurally unrelated
First order kinetics
Diplopia, ataxia, agranulocytosis, SIADH, Stephen Johnson syndrome
induction of cytochrome P450
What is the MOA of Gabapentin?
Inhibits L-, P/Q-and N-type calcium channels (reducing glutamate and noradrenaline release)
Focal seizures, neuropathic pain
Dry mouth, weight gain, GI disturbances, sedation, ataxia
Very few drug interactions
N.B. Does not interact with GABAergic system
What is the MOA of Lamotrigine?
Lamotrigine
Stabilises the neuronal membrane potential by slowing Na+ channel recovery from inactivated state
Inhibits L-, P/Q-and N-type calcium channels
Effective in atypical absence seizures
GI disturbances, insomnia, rash, Stephen Johnson syndrome, blood disorders
what is the MOA of Ethosuximide?
Ethosuximide
Reduce T-type Ca2+ currents in a voltage dependent manner
No effect on GABA or Na+ channels
Uncomplicated absence seizures
EFGHIJ- Ethosuximide causes Fatigue, GI distress, Headache, Itching, Stevens-Johnsons syndrome
how do GABAergic neurotransmission enhancers work?
activation requires the simulataneous binding of two GABA molecules to the receptor, one to each of the two binding sites at the interface of the alpha and beta subunits
