ANTIEPILEPTICS Flashcards
What do you know about sodium valproate (Epilim)?
(MOA, indications, side effects, dosing)
Sodium valproate works by blocking sodium channels in a use-dependent way, and increases brain concentrations of GABA, (an inhibitory neurotransmitter). It is indicated for seizure prevention, esp in JME. It is also used as a mood stabiliser and migraine preventer.
Side effects include weight gain, curly hair and mood stabilisation. It can also cause hepatic toxicity, thrombocytopenia and pancreatitis.
Dosing for epilepsy: initially 600 mg daily in 1–2 divided doses, increased gradually (in steps of 200 mg) every 3 days; usual maintenance dose 1–2 g daily (20–30 mg/kg daily), maximum 2.5 g daily
What do you know about levetiracetam (Keppra)?
(MOA, indications, side effects, dosing)
Levetiracetam is thought to inhibit seizure activity by blocking N-type voltage-gated calcium channels and/or by binding synaptic vesicular protein SV2A and modulating neurotransmitter release.
It is a broad-spectrum anti seizure medication that is widely used as first-line monotherapy for focal and generalized tonic-clonic seizures
Well tolerated generally. Side effects include 8% risk of mood disorder. Sedation is another common side effect.
Dosing for seizures: initially 250-500 mg twice daily increased after 2 weeks to 500 mg twice daily; thereafter, increased according to response in steps of 250 mg twice daily every 2 weeks; maximum 1.5g twice daily. Benefit of this drug is relatively quick uptitration.
IV is equivalent to oral dosing.
In status load 60mg/kg - to a max of 4.5g
What do you know about lamotrigine (lamasil) ?
(MOA, indications, side effects, dosing)
Lamotrigine is thought to act by producing use-dependent blockade of voltage-gated sodium channels and by inhibiting glutamate release. This stabilises excitatory neuronal cell membranes and suppresses repetitive neuronal discharges that generate seizures in epilepsy.
It is indicated for focal and generalised seizures and absence seizures in children.
Associated with severe cutaneous adverse reactions (steven Johnsons syndrome) and can cause blood disorders occasionally
Important to know that enzyme inducer. It will make combined oral contraceptive pill less effective, and COC will reduce its effective concentration. Interacts with valproate to increase lamotrigine levels.
Dosing: Adult initially 25 mg once daily for 14 days, increased to 50 mg once daily for further 14 days, then increased by maximum 100 mg every 7–14 days; usual maintenance 100–200 mg daily in 2 divided doses
*Half starting dose and up titration schedule with concurrent sodium valproate use.
*Double starting dose and up titration with concurrent enzyme inducers
Pregnancy safe but needs frequent dose adjustment.
What do you know about carbamazepine?
(MOA, indications, side effects, dosing)
Carbamazepine is thought to act by producing use-dependent blockade of voltage-gated sodium channels and stabilising excitatory neuronal cell membranes.
It is indicated for seizure prevention, particularly focal onset. It is also used for neuralgia, mania, and diabetes insipidus.
Side effects include drowsiness and increased cardiovascular risk. Like lamotrigine also comes with risk of steven-Johnson’s syndrome and is an enzyme inducer.
Dosing: start low and go slow - initially 50-100mg BD (even less in elderly) increased by 100mg q 2 weeks to usual maintenance of 800 - 1200mg daily.
What do you know about Topiramate (Topamax)?
(MOA, indications, side effects, dosing)
Topiramate is thought to produce anticonvulsant effects through blockade of sodium channels, potentiation of GABA activity, and antagonism of kainate/AMPA glutamate receptors.
It is indicated as monotherapy in epilepsy however side effects limit its use. It is also used as migraine prophylaxis.
Side effects include weight loss, cognitive impairment, angle closure glaucoma (particularly high risk in the first month). It is teratogenic AND reduces efficacy of combined oral contraceptive in doses over 200mg.
Dosing for seizures: initially 25 mg once at night for at least 1 week then increased in steps of 25–50 mg 2 weekly to usual dose of 100mg BD but no more than 500mg total per day.
Dosing for migraine prophylaxis: 25 mg nocte increased weekly as follows: 25/25, 25/50, 50/50, 50/75 etc to max of 200mg daily.
What do you know about Clobazam?
(MOA, indications, side effects, dosing)
Clobazam is a long acting benzodiazepine, binds to the GABA(A) receptor, facilitating the inhibitory action of endogenous GABA by increasing neuronal membrane permeability to chloride ions.
What is the interaction between valproate and lamotrigine?
There is an interaction between them that results in lamotrigine being cleared at half the rate, therefore it is twice as strong (so half the dose)
There is an important reaction between sodium valproate and which antibiotic? What happens?
There is an interaction between sodium valproate and meropenem which results in valproate concentrations being halved. The mechanism is not known. Even if you increase the dose of valproate, the levels won’t increase
Carbamazepine interacts with which antibiotics?
Azithromycin/erythromycin. Stops metabolism of carbamazepine so levels sky rocket and patient gets toxic.
What is the issue with DOACs and antiepileptics?
Certain antiepileptics such as carbamazepine induce metabolism of DOACs likely reducing their efficacy in a hard to measure way. Perhaps use warfarin instead - even though this also interacts at least we can monitor what’s going on with INR. Or change antiepileptic.
Describe the metabolism of lamotrigine during pregnancy and post partum.
Lamotrigine metabolism speeds up during pregnancy so doses need increasing and levels need checking. Post partum levels rise quickly and patients can become toxic due to slowing of lamotrigine clearance back to normal if lamotrigine not reduced back to pre pregnancy levels over a few weeks
What is the “goal” in treatment of convulsive status epilepticus?
Stop the seizures (benzos, big guns, bed time)
What is the “goal” in the treatment of non convulsive status?
Keep the patient awake and breathing - don’t kill them with kindness. ie don’t give heaps of benzos and then kill frail patients with resp compromise. The risk is not as great as with convulsive status
What is T2 with regards to status epilepticus?
T2 is the time at which we start to see the adverse consequences of status epilepticus - Usually 30 mins - at this point neuronal damage has been proven.
What is T1 w regards to status epilepticus?
T1 is the time at which status epilepticus is impending. Usually 5 mins. At the 5 min mark 80% of seizures will not self terminate.
