Epilepsy Flashcards
Class 1 Drugs
Carbamazepine, phenobarbital, phenytoin, primidone
Maintain on specific product
Class 2 Drugs
Clobazam, clonazepam, esclicarbazepine, lamotrigine, oxcarbazepine, perampanel, rufinamide, topirimate, valproate, zonisamide. Maintaining on specific product down to clinical judgement.
Class 3 Drugs
Bivarcetam, ethosuxamide, gabapentin, lacosamide, levetiracetam, pregabalin, tiagabine, vigabatrin.
Can have any brand
Focal seizure treatment
Carbamazepine/lamotrigine first line.
Tonic clonic seizure treatment
Sodium valproate first line. Lamotrigine if valproate unsuitable (though may exacerbate myoclonic seizures).
Absence seizure treatment
Ethosuxamide or sodium valproate first line, lamotrigine alternative if both unsuitable
Myoclonic seizure treatment
Sodium valproate first line if newly diagnosed, topiramate and levetiracetam alternatives if unsuitable.
Atonic and tonic seizures treatment
Sodium valproate first line, lamotrigine if unsuitable
Risk factors
Premature birth, family history, head trauma, infections such as meningitis and encephalitis.
Complications
Sudden unexpected death in epilepsy (SUDEP), injury caused by seizure (such as RTA, falls, etc), depression and anxiety disorders.
SUDEP risk factors
Uncontrolled or frequent seizures Tonic-clonic seizures Seizures that begin at a young age. Many years of living with epilepsy. Missed doses of medicine. Drinking alcohol.
ADRs
ANTI-EPILEPTIC HYPERSENSITIVITY REACTION:
rash, fever, lymphadenopathy in first 1-8/52- STOP immediately (Linked with CP3L drugs)
sedation and dizziness, suicidal thoughts and behaviour (MHRA warning), acute psychotic reactions, weight gain or loss, skin rashes, impaired bone health, minor blood dyscrasias, elevation of liver enzymes
Enzyme inducers
Carbamazepine Eslicarbazepine acetate Oxcarbazepine Perampanel (at a dose of 12 mg daily or more) Phenobarbital Phenytoin Primidone Rufinamide Topiramate (at a dose of 200 mg daily or more)
Non enzyme inducers
Acetazolamide Clobazam Clonazepam Ethosuximide Gabapentin Lacosamide Lamotrigine Levetiracetam Perampanel (at a dose of less than 12 mg daily) Pregabalin Sodium valproate Tiagabine Topiramate (at a dose of less than 200 mg daily) Vigabatrin Zonisamide
Carbamazepine indications
First line in tonic clonic and focal seizures.
Trigeminal Neuralgia
Carbamazepine mechanism of action
inhibits neuronal Na channels
Carbamazepine ADRs
Dose related: GI upset and neurological effects (ataxia, dizziness).
Hypersensitivity (presents as rash).
Oedema and hyponatremia due to ADH like effect.
Carbamazepine and pregnancy
Risk of neural tube defects - folate supplementation recommended. Doses should be adjusted based on plasma drug concentration.
Carbamazepine warnings
Hepatic, renal or cardiac diseases.
Carbamazepine interactions
Drugs metabolised by CYP enzymes (such as warfarin, oestrogens, progestogens). CYP inhibitors (such as macrolides) increase concentration.
Drugs that lower seizure threshold (antipsychotics, tramadol, ciprofloxacin etc)
Carbamazepine levels
Taken immediately before dose: 4-12mg/L - takes 1-2 weeks to reach steady state
Non- epileptic seizures
Eg Febrile: not caused by abnormal electrical activity
Non BD dosed anti epileptics
Phenobarbital (ON), Carbamazapine (MR, OD), Lamotrigine (ON), Perampanel (ON), rest usually BD
Partial vs Generalised seizures
Partial (only affects part of brain): Focal
Generalised (affects whole of both hemispheres): Tonic clonic, absence, myoclonic, (a)tonic.
Antiepileptic withdrawal principles
Withdraw slowly
Withdraw under specialist supervision
Withdraw one at a time if on combination therapy
Driving: Epilepsy/multiple unprovoked seizures
Need to inform DVLA
Must be 12 months free of seizures for car & motorcycles, must be 10 years free w/o epilepsy medication for bus/lorry.
First unprovoked seizure: must not drive for 6 months (1 year if underlying risk factors).
Driving: First unprovoked seizure
Need to inform DVLA
Must not drive for 6 months (1 year if underlying risk factors) - Bus/lorry - 5 years, after which must have assessment showing risk <2% annually.
Anti-epileptics in pregnancy - teratogenicity
Inc risk of teratogenicity:
Highest risk VALPROATE (minor and major risks, developmental delays, etc)
Increased risk: Carbamazepine, Phenytoin (antifolate), phenobarbital, primidone, lamotrigine (CP3L)
Cleft palate: Topirimate in first trimester
Contraception and epilepsy
Enzyme inducers - inc metabolism of hormonal metabolism, inc risk of unplanned pregnancy
Pregnancy and plasma concentration
Need to monitor plasma concentration of: Phenytoin, carbamazepine, lamotrigine
Anti-epileptics and pregnancy
Refer to specialist if planning to become pregnant
5mg folic acid reduces risk of neural tube defects if taken taken before pregnancy and for first 12 weeks.
Monitor foetal growth: topiramate and levetiracetam
Vit K injection in newborn to prevent haemorrhage
Notify UK Epilepsy and pregnancy register
Withdrawal effects in newborns (particularly benzos/phenobarb)
Anti-epileptics and breastfeeding
Monitor feeding difficulties, weight gain, drowsiness, developmental milestones
ZELP present in milk in high quantities (Zonisamide, Ethosuxamode, Lamotrigine, Primidone
Phenobarbital and Primidone (largely metabolised to phenobarb) inhibit suckling reflex
AVOID abrupt withdrawal of breastfeeding - risk of withdrawal esp with phenobarb/primidone
Phenytoin MOA
binds to Na receptors of neuronal cells in inactive state, increases inactivity, reduces seizures.
Phenytoin uses
Focal/tonic clonic. Exacerbates absence, myoclonic.
Phenytoin therapeutic range
10-20mg/L, 40-80mmol/L
Plasma Phenytoin drug monitoring
Non-linear relationship between dose and plasma conc, so small dose changes lead to large plasma concs.
Highly protein bound - high risk in pts with low protein binding, (eg, pregnant, elderly, paeds, hepatic imp)
Phenytoin signs of Toxicity
SNAtCHeD Slurred Speech Nystagmus (uncontrolled repetitive eye movements) Ataxia Confusion Hyperglycaemia Double/blurred vision
Phenytoin ADRs
Changes of appearance: coarsening of facial features, gingival hypertrophy (good oral hygiene), acne
Blood dycrasias - counsel signs of infection (leucopenia that’s severe, progressive or associated with symptoms requires withdrawal)
Hypersensitivity reaction - report fever, rash, swollen lymph nodes (Rash - can continue if mild and not recurring, otherwise stop)
Low vitamin D - Rickets and osteomalacia (phenytoin increases vit d metabolism
hepatotoxicity
suicidal ideation (as with all anti-epileptics)
IV (fos)phenytoin ADRs
Phenytoin- Bradycardia/hypotesion
Fosphenytoin- asystole, cardiac arrest, VF, heart block, bradycardia, hypotension. (Fosphenytoin 1.5g=1g Phenytoin sodium, Fosphenytoin IV/IM only, can be given more rapidly than phenytoin.)
Phenytoin Interactions
Seizure threshold reduced by SSRIs, quinolone, tramadol, antipsychotics, mefloquine, TCA and related antidepressants. Inc conc (toxicity) - amiodarone, cimetidine, miconazole, fluconazole, chloramphenicol, metronidazole, trimethoprim etc. Red conc (treatment failure) - SJW, rifampicin (Inducers)
