Anti-epileptics Flashcards
MOA of Carbamazepine?
Inhibits neuronal sodium channels
This drug is used for seizure prophylaxis in epilepsy. Specifically, this drug is a second-line option for focal seizures (with or without secondary generalisation).
It can also be used for trigeminal neuralgia, and sometimes in mood disorders
Carbamazepine
Adverse effects of this drug include worsening of myoclonic and absence diplopia, ataxia, agranulocytosis, hepatic toxicity, SIADH (oedema and hyponatraemia) Stevens-Johnson syndrome- particularly in HLA B 1502
Carbamazepine
Carbamezepine warnings: exposure in utero is associated with NTD’s, cleft palate, cardiac and urinary tract abnormalities. Women planning a pregnancy should consider taking high dose _____ ______ supplements before conception.
folic acid
Use caution when prescribing Carbamazepine with drugs that induce metabolism by the CYP enzymes (eg Warfarin, oestrogens, erythromycin, lidocaine, etc), so the effect of these drugs will be ___________ when taken together with Carbamazepine
reduced
This first-generation anti-convulsant is a non-specific sodium channel blocker and targets almost all voltage-gated sodium channel subtypes. It binds to INACTIVATED sodium channels
Phenytoin
This first-generation antiseizure medication is not often prescribed anymore due to the incidence and severity of side effects. It may be used in patients who have had their epilepsy controlled with it for a long time, and it can also be used in status epilepticus.
Phenytoin
Side effects of this drug include gingival hyperplasia, hirsutism, acne, megaloblastic anaemia (inhibits folate absorption) S-J syndrome, and SLE-like syndrome
Phenytoin
These two core drugs are INDUCERS of CYP450 metabolism, so can make certain drugs less effective (impact can continue weeks after discontinuation)
Carbamazepine and phenytoin
This drug is 90% protein-bound, so only the free drug is active. Caution in administering this drug in conditions which alter protein such as liver failure, kidney failure, and pregnancy
Phenytoin
How do phenytoin and Carbamazepine affect the efficacy of hormonal forms of birth control?
It reduces the effectiveness of the birth control (reduces oestrogen levels)
How does oestrogen-containing birth control effect serum levels of valproate and lamotrigine?
It reduces the effectiveness of these drugs (ie oestrogen is epileptogenic)
Which two antiseizure medications should never be switched from brand name to generic versions?
Phenytoin and Carbamazepine
Which two antiseizure medications are liver enzyme inducers?
Phenytoin and Carbamazepine
What is the most common cause of seizure in a patient with a history of epilepsy?
Inconsistent use of anti-seizure medication
Focal seizures are typically due to loss of surrounding __________ (via GABAergic interneurons)
inhibition
Antiseizure medication such as valproate targets the T-type _______ channel, making it a helpful treatment for absence seizures
Calcium
Common side effects of most seizure medications include sedation, poor coordination, imbalance, fatigue, and osteopenia (if used long term). What are two of the more serious side effects associated with ASM’s?
Suicidal ideation and respiratory depression
Voltage gated sodium channel blockers are useful for what type of seizures?
Focal seizures
Indications for these two core drugs include epilepsy, trigeminal neuralgia, migraines, neuropathic pain, restless leg syndrome, anxiety/panic, and fibromyalgia
Gabapentin and pregabalin
Indications for this drug include seizures, status epilepticus, epilepsy, and myoclonus
Levetiracetam
Indications for this drug include seizures, status epilepticus, epilepsy, myoclonus, and mood disorders. Not to be prescribed in women of childbearing age unless they have a pregnancy protection plan in place
Sodium valproate
Which three ASM core drugs are renally excreted (no hepatic metabolism)
Levetiracetam, Gabapentin, Pregabalin
Adverse effects of these drugs include weight gain, cough, and worsening of myoclonic and absence epilepsy
Gabapentin and Pregabalin
MOA: SV2A protein binding
Levetiracetam
MOA: Binds to the alpha-2-delta subunit of PRESYNAPTIC Calcium channels
Pregabalin
MOA: Binds to the alpha-2-delta subunit of calcium channels
Gabapentin
MOA: GABA-A receptor allosteric modulation
Diazepam
MOA: Acts on Sodium channels, ? GABA-A receptors, T calcium channels, GABA transaminase inhibition
Sodium valproate
Adverse effects associated with this drug include alopecia, tremor, thrombocytopenia, pancreatitis, FETAL ABNORMALITIES
Sodium valproate
FIrst line management of status epilepticus
Diazepam
Side effects of this drug class mainly include drowsiness and sedation. Can cause dependence if used repeatedly for more than a few weeks.
Diazepam
Which of the anti-seizure medications is an auto-inducer of its own metabolism?
Carbamazepine
Which anti-seizure medication is a cytochromie P450 inhibitor?
Sodium valproate
If someone is taking both sodium valproate and Warfarin, what effect would the sodium valproate have on the metabolism of Warfarin?
Warfarin would accumulate in the system, increasing risk of bleeding, as Valproate inhibits metabolism of warfarin
First line drug used in the management of ACUTE seizures?
Benzodiazepines:
Lorazepam (IV) in hospital
Midazolam (buccal/nasal)
Diazepam (rectal) outside the hospital
Which three core drugs can be used intravenously if there is concern for acute seizure recurrence?
Levetiracetam, fosphenytoin, sodium valproate
How long does it take Carbamazepine to reach steady state?
About 20-30 days, due to auto-induction
For most anti-seizure drugs (other than Carbamazepine), steady state is typically achieved in ______ half-lives
5
Give a high dose (aka ___________ ________) when the therapeutic range needs to be reached quickly- eg acute concern in A&E, risk of airway compromise
loading dose
When is the trough level of anti-seizure medication measured?
Immediately before their next dose is due
Core drugs with short half-lives (3)
Levetiracetam
Gabapentin
Pregabalin
___________ is 90% protein-bound, so alteration in proteins (liver failure, kidney failure, and pregnancy) will impact the free concentration
Phenytoin
Which hormone is epileptogenic?
Oestrogen
Which two ASM’s increase the metabolism of oestrogen-containing OCP’s, making them LESS effective?
Carbamezepine and phenytoin
In pregnancy and the post-partum period, renal blood flow and GFR increase by up to 50%, which is important for the drugs with renal excretion such as … (which will be cleared out of the system faster)
Levetriacetam
Gabapentin
Pregabalin
Which two antiseizure medications are considered safe in pregnancy (with regular monitoring and alterations)?
Levetiracetam and lamotrigine
Which four core ASM’s are associated with major congenital malformations?
SODIUM VALPROATE
Cabamazepine
Phenytoin
?Pregabalin
Which ASM requires women of childbearing age to be on a pregnancy prevention programme before being prescribed this drug?
Sodium valproate
(No one under 55 should be given this drug unless two specialists agree)
What advice is offered to women taking ASM’s and breastfeeding?
They should breastfeed immediately before taking their seizure medication
Sodium valproate is a liver enzyme _________
Inhibitor
Carbamazepine and phenytoin are liver enzyme __________
inducers
