Anticonvulsants Flashcards
Pentylenetetrazol
induction of seizures
Epileptogenesis drug - induction of epileptic seizures for the study of them.
GABAa receptor blocker - usually the fast-inhibitory receptor. Blocking the receptor blocks entry of chloride Cl- thus membrane potential remains more positive and more depolarisation can occur.
Artificially mimics absense and myoclonic seizures
Electro-convulsive Therapy (ECT)
induction of seizures
Maximal electroshock
Can track spread of discharge
Induces partial seizures with secondary generalisation of the tonic clonic kind.
Kindling model (induction of seizures)
Repeated stimulation over a long period of time thus convulsions become self-generating.
Expression of extreme stimulation by applying brief bursts of high frequency stimulation over a long period of time
Induces focal temporal lobe epilepsy
Kainate
induction of seizures
Glutamate receptor agonist
Induction of status epilepticus (when epileptic fits follow one another without recovery of consciousness between them) due to over stimulation of glutamatergic neurons.
Pilocarpine
induction of seizures
Ach receptor agonist
Pro-convulsant when it enters brain; cause widespread and prolonged seizures
Induction of status epilepticus (when epileptic fits follow one another without recovery of consciousness between them) due to over stimulation of glutamatergic neurons.
Diazepam (valium), Alprazolam (xanax), Midazolam
From class of benzodiazepine drug family
Positive modulator of GABAa postsynaptic receptors - Increase affinity of the GABAa receptor to GABA - thus increased inhibition of EPSP.
Benzodiazepines only bind in the presence of alpha 1,2,3,5 subunits on GABA receptor.
Clinical use: acute seizure (e.g. status epilepticus, absence seizure).
Adverse effects: sedation, cannot be used for maintenance therapy.
Administered rectal or i.v. in emergencies
Phenobarbitone
Barbiturate drug
Positive allosteric modulator - potentiates the action of GABA by maintaining the opened state of the channel for longer - allowing more GABA entry and inhibition of EPSP in postsynaptic neuron.
Effective to all GABAa receptor subunits.
Not commonly used; but usually for focal seizure
Used occasionally for emergencies like status epilepticus.
Adverse effects: sedative (severe drowsiness), can exacerbate absence seizures.
t1/2 = >60h
Strong induction of liver enzymes, risk of drug interactions.
Ganaxolone
Neurosteroid (rapidly alter neuronal excitability through interaction with delta subunit of GABAa
Vigabatrin
Irreversible inhibitor or GABA transaminase
GABA transaminase is located within astrocytes and responsible for metabolism of GABA into Succinic semialdehyde (SSA).
Used for all type of seizures; effective in patients resistant to other drugs.
Adverse effects: Visual field disturbances - around 50% of people
Short t1/2 but lasting effects due to irreversible inhibition
Tiagabine
GAT-1 transporter inhibitor - thus inhibits GABA re-uptake into neurons and glial cells potentiating its effects in the synaptic cleft by increasing extracellular concentrations.
Used as add-on therapy for partial seizures
Adverse effects: Drowsiness, confusion
Half life: approx 7h
Sodium Channel Blockers (anti-convulsants)
Maintain Na+ channels in their inactive states thus increase the refractory period and decrease excitation in the neuron.
Ideal for focal & tonin-clonic (grand mal) seizures
Not useful for absence seizures as these are caused by T-type Ca2+ channels in the thalamocortical cells.
Phenytoin
Na+ channel blocker - binds and stabilises channel in fast inactivated state due to strong depolarisation in the area (use dependent block). Stabilises membrane potential.
Widely used, effective against all types except absence seizures. Anti-arrhythmic effects (need to monitor blood levels closely).
Adverse effects: Mild: Vertigo, ataxia, headache, nystagmus, diplopia (double vision).
Severe: gingival hyperplasia (changes in bone structure; enlarged gums), hirsutism (due to increased androgen release) marked confusion, paradoxical increase in seizure frequency.
Carbamazepine
Na+ channel blocker - binds and stabilises channel in fast inactivated state due to strong depolarisation in the area (use dependent block). Stabilises membrane potential.
Most widely used; except absence seizures
Can also be used to treat neuropathic pain and manic-depressive illness.
Adverse Effects: Visual disturbances, ataxia, water retention (due to increased risk of hyponatraemia).
Lacosamide
Na+ channel modulators
Increased slow-inactivation during prolonged depolarisation
Affinity of drug depends on state of sodium channel
Adjunct therapy for focal seizures
Adverse Effects: Ataxia, Diplopia (double vision)
Pregabalin
Gabapentin
Ca2+ channel blockers - P/Q type (found in neurons)
For adjunct therapy (assist to primary treatment) in partial seizures
Voltage gating properties: binds to the channel alpha2delta1 thus reduces trafficking of Ca2+ channels to the membrane which reduces Ca2+ entry into the nerve terminals and subsequent reduction of glutamate released.
Adverse effects: Ataxia, diplopia
