eplipsy in clinical practice Flashcards
what is epilepsy?
Neurological disorder characterised by
recurring seizures
define status epilepticus
prolonged convulsive seizure for 5 minutes or longer, or recurrent seizures one after the other without recovery in between
what is a tonic seizure?
short-lived (less than 1 minute), abrupt, generalised muscle stiffening with rapid recovery
what is a tonic-clonic seizure?
generalised stiffening and subsequent rhythmic jerking of the limbs, urinary incontinence, tongue biting
what is an absence seizure?
behavioural arrest
what is an atonic seizure?
sudden onset of loss of muscle tone
what is a myoclonic seizure?
brief, ‘shock-like’ involuntary single or multiple jerks
what is status epilepticus treatment?
• Outside of hospital (if had previous seizures)
–Rectal diazepam 10-20mg
–Buccal midazolam 10mg
–Can repeat once after 15minutes
• Early status (hospital or ambulance)
–IV lorazepam 4mg, repeat once after 10-20mins
what is the established treatment for status epilepticus?
–IV phenytoin infusion 15 – 18mg/kg
–Other options – fosphenytoin and/or phenobarbital
what is the statiys epilepticus treatment for refractory status?
(60 - 90mins after initial
treatment)
–Anaesthesia e.g. propofol, midazolam, thiopental
–Until seizure free for 12-24 hrs then gradually tapered
what are the general measures you would take during status epilepticus?
– Secure airway and resuscitate
– Administer oxygen
– Establish intravenous access
what are the emergency investigations you would take during status epilepticus?
– Bloods
– Chest x-ray
– May include brain imaging, lumbar puncture
what monitoring requirements would you take for statius epilepticus?
– Regular neurological observations
– Pulse, blood pressure, temperature, ECG, bloods
– EEG monitoring is necessary for refractory status
how should you initiate treatment?
Treat with a single AED (monotherapy) wherever possible
– If an AED has failed a 2nd drug should be started - Cross-taper:
• Continue 1st drug
• Then start 2nd drug and build up to an adequate or maximum tolerated dose
• Then taper off 1st drug gradually
when/how should you discontinue aeds?
Discontinuing AEDs - Patients should be seizure free for at least 2 years
– Slowly (over at least 2–3 months) and one drug withdrawn at a time
what are the different categories when brand switching?
- Category 1 – phenytoin, carbamazepine, phenobarbital, primidone
- Maintain on a specific manufacturer’s product
- Category 2 – valproate, lamotrigine, perampanel, retigabine, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbazepine, zonisamide, topiramate
- Continued supply of a particular brand should be based on clinical judgement and consultation with patient and/or carer, taking into account factors such as seizure frequency and treatment history
- Category 3 - levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide, vigabatrin
- Usually unnecessary to ensure that patients are maintained on a specific brand
when would suicical ideation be most prominant?
symptoms may occur as early as 1 week after starting
treatment
–Patients should be advised to seek medical advice if
any mood changes, distressing thoughts, or feelings
about suicide or self-harming develop
what is antiepileptic hypersensitivity syndrome?
• Rare but potentially fatal syndrome associated with some antiepileptic drugs
– carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, and rufinamide
• symptoms usually start between 1 and 8 weeks of exposure:
– fever, rash, and lymphadenopathy are most common
– Other systemic signs include liver dysfunction, haematological, renal, and pulmonary abnormalities, vasculitis, and multi-organ failure
• The drug should be withdrawn immediately
how does epilepys affect bone health?
Antiepileptics: adverse effects on bone
– long-term use of carbamazepine, phenytoin, primidone,
and sodium valproate is associated with decreased bone
mineral density
– may lead to osteopenia, osteoporosis, and increased
fractures
• Increased risk if:
• immobilised for long periods
• inadequate sun exposure
• inadequate dietary calcium intake
• Consider vitamin D supplementation if at risk
how does epilepsy affect women of child bearing potential?
There is an increased risk of teratogenicity
associated with the use of antiepileptic drugs
• Effective contraception if child-bearing
potential
–Consider interactions with oral contraceptives,
particularly with enzyme inducing AEDs
–Progestogen only pill and implant are not
recommended by NICE if on enzyme inducing
AEDs
what risk poses pregnant women an epilepsy?
ncreased risk of major congenital malformations
– Increased risk if used during the first trimester
– Increased risk if the patient takes two or more antiepileptic drugs
• Highest risk with valproate
– Should not be used in pregnancy unless no other alternatives
• But also risk with carbamazepine, phenobarbital, phenytoin, and topiramate
what should a woman do if pregnant and has epilepsy?
If planning pregnancy, should be referred to specialist and take folic acid 5mg
how should you dose sodium valporate?
Gradual titration of dose - Initially 600 g daily
in 1–2 divided doses, then increased in steps
of 150–300 g every 3 ays; maintenance 1–2
daily
how can sodium valproate be given?
–Immediate release or modified release tablets
–Liquid
–IV
what are the common sodium valporate side effects?
Alopecia (curly regrowth), tremor, weight gain, menstrual irregularities, GI disturbance, headaches, confusion
what serious side effects are associated with sodium valportae?
Hepatotoxicity
–Pancreatitis
–Blood disorders
–Skin reactions e.g. SCARS, hypersensitivity
how does sodium valporate acts as an enzyme inhibitor?
–Increases risk of toxicity with lamotrigine, phenytoin,
phenobarbital, carbamazepine
–Increased adverse effects with olanzapine
what other effects do sodium valporate have when it comes to drug interactions?
–Carbapenems e.g. ertapenem, meropenem reduce
concentration of valproate
–Enzyme inducing AEDs e.g. phenytoin, phenobarbital,
carbamazepine
what monitoring is needed with sodium valporate?
• TDM - Plasma-valproate concentrations are
not a useful index of efficacy, therefore
routine monitoring is unhelpful
• LFTs – before treatment and during first 6
months
• FBC (including platelets, PT) – before
treatment and before any surgery
why must sodium valproate be avoided in preganancy?
• Highly teratogenic
–neurodevelopmental disorders (approx. 30–40% risk)
–congenital malformations (approx. 10% risk)
• Valproate must not be used in women and girls of
childbearing potential unless:
–The conditions of the Pregnancy Prevention
Programme (PPP) are met and
–only if other treatments are ineffective or not
tolerated, as judged by an experienced specialist
when dispensing sodium valporate what must be included?
– Original packs – must have warning label on box
– Discuss risks in pregnancy with female patients each time valproate
medicines are dispensed
– Ensure they have the Patient Guide and
– Have seen their GP or specialist to discuss their treatment and the
need for contraception
what is the pregnancy prevention programme?
– Highly effective contraception: a user independent form
such as an intrauterine device or implant OR two
complementary forms of contraception including a barrier
method
– Risk Acknowledgement Form: needs to be signed and up
to date every time a prescription is issued (GP to check)
– Annual review by specialist
– Refer to the specialist urgently (within days) in case of
unplanned pregnancy or where a patient wants to plan a
pregnancy
– Patient provided with patient guide
how do you dose carbazepine?
• Initiate at a low dose and build up slowly
• Initially 100–200 g 1–2 times a day, increased
in steps of 100–200 g every 2 eeks; usual dose
0.8–1.2 daily in divided doses
what is the max dose for a suppository for carbamazepine?
1g daily
what are the side effects for carbamezepine?
dizziness, drowsiness, GI disturbance, headache, ataxia
• Hyponatraemia
• Hepatotoxicity
• Blood disorders – leucopenia, thrombocytopenia
• Severe Cutaneous Adverse Reactions (SCARS) e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, Drug Hypersensitivity syndrome
what are the counselling points you would recommend with carbamepine?
recognise signs of blood, liver or skin disorders
what are the interactions availible with carbamazepine?
Effects of carbamazepine on other drugs as an enzyme inducer (CYP3A4)
– DOACS, warfarin, COC
• Phenytoin
• Carbamazepine can increase (via inhibition of CYP219) phenytoin levels
• Phenytoin can reduce conc. of carbamazepine (enzyme inducer itself)
what are the effects of other drugs on carbmazepine? ie what inc/ decreases its conc
Increase conc. of carbamazepine – clarithromycin, fluconazole, diltiazem, grapefruit Juice
– Decrease conc. of carbamazepine – phenytoin, rifampicin, theophylline, St. John’s Wort
what monitoring is needed with carbamazepine?
Pre-treatment (MHRA guidance):
–FBC, U&Es, LFTs
–Test for HLA-B1502 allele in patients of Han
Chinese or Thai origin Test
for HLA-A3101
allele in patients of European descent or
Japanese origin
–Increased risk of potentially life-threatening
skin-related adverse drug reactions, including
Stevens-Johnson-syndrome
what therapeutic drug monitoring needs to be done for carbamazepine?
–Plasma concentration for optimum response 4–12
mg/litre - measure after 1–2 weeks
–Not routinely monitored – only if toxicity or non-
compliance suspected
–Trough level
how would you dose phenytoin?
Increase dose gradually – narrow therapeutic range, increase in increments of 25-50mg
• Initially 150–300 g once daily, alternatively 150–300 g daily in 2 divided doses; usual maintenance 200–500 g daily
what route is availible for phenytoin?
Route: (note sodium and base are NOT bioequivalent) –Tablets/capsules (phenytoin sodium) –Chewable tablets (phenytoin base) –Suspension (phenytoin base) –IV (phenytoin sodium)
what side effects are associated with phenytoin?
Coarsening of facial features • Gingival hyperplasia • Bone marrow suppression • Vitamin D deficiency, bone fractures • Folate deficiency • Hepatotoxicity • Rash, SCARS • Signs of toxicity - nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia
what drug interactions are seen with phenytoin?
Phenytoin is susceptible to inhibitory drug interactions
– Saturable metabolism - significant increase in circulating phenytoin concentrations (toxicity) e.g. clarithromycin, valproate, fluconazole
• Phenytoin levels can be reduced by enzyme inducers e.g. St. John’s Wort, rifampicin
• Some drugs can increase OR decrease levels of phenytoin e.g. carbamazepine, ciprofloxacin
• Phenytoin is a potent inducer and can decrease levels of some drugs e.g. carbamazepine, digoxin, warfarin
what monitoring needs to be done with phenytoin?
• Pre-treatment - HLAB* 1502 allele in individuals of Han Chinese or Thai origin • Baseline: –LFTs –FBC –U&Es
what is the ideal plasma phenytoin concentration?
Plasma-phenytoin concentration: 10–20 g/litre
how would low albumin affect phenytoin levels?
Highly protein bound – if low albumin (<32g/L), free phenytoin conc. is increased
–Need to correct for albumin before can interpret level
–Corrected phenytoin = measured phenytoin level
( (adjustment* x albumin, g/L) + 0.1)
(*Adjustment = 0.0275; in patients with creatinine clearance <20 mL/min, adjustment = 0.02)
how would phenytoin be given for status epilepticus?
Intravenous infusion - Loading dose 20 g/kg (max. per dose 2 )
– Note: If patient is already on phenytoin then only need a ‘top up’ dose:
Top-up dose (mg) = [20 – (phenytoin level (mg/L)] x 0.7 x weight(kg)
• Maximum rate of administration is 50mg/min (25mg/min in elderly patients or pre-existing cardiac disease)
• Monitoring - Continuous BP, RR and ECG
• Administered using with 0.2 micron filter into large vein
• Maintenance dose (by IV) - 100 g TDS adjusted according to plasma-concentration monitoring
what are the common errors associated with taking phenytoin IV?
wrong weight estimated or patient not weighed
– failure to take account of existing phenytoin levels for loading dose
– misreading 100mg as 1,000mg and vice versa
– wrong diluent used
– failure to use an in-line filter
– wrong infusion rate
– loading dose continued for maintenance without dose change
– monitoring equipment not available
– failure to monitor the effectiveness of phenytoin and any toxic effects
how do you dose lamotrigine?
Slow dose titration
– Initially 25 g once daily for 14 days, then increased to 50 g once daily for further 14 days, then increased in steps of up to 100 g every 7–14 ays; maintenance 100–200 g daily in 1–2 divided doses
• Lower dose if given with valproate: initially 25mg on alternate days for 14days….
• Higher dose if given with enzyme inducers: initially 50mg once daily for 14days
what are the common side effects associated with lamotrigine?
• Common - agitation, arthralgia, diarrhoea, dizziness, drowsiness, dry mouth, fatigue, headache, nausea, sleep disorders, tremor
• Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis
– increased risk - concomitant use of valproate, initial lamotrigine dosing higher than recommended, and more rapid dose escalation than recommended
• Hepatic disorders
• Blood disorders
• Rare: disseminated intravascular coagulation
what are the interactions associated with lamotrigine?
• Valproate • Enzyme inducers e.g. carbamazepine, rifampicin • COC – increases clearance of lamotrigine by 2- fold –Lack of efficacy of lamotrigine –Ideally use alternative contraception –If use COC - double lamotrigine dose and stop pill free interval
how would you dose levetiracetam?
–Initially 250 g once daily for 1–2 weeks, then
increased to 250 g twice daily, then increased in steps
of 250 g twice daily every 2 weeks (max. per dose 1.5
twice daily)
what are the side effects of levetiracetam?
Headache, asthenia, irritability, ataxia, drowsiness
what drug interactions are associated with levetiracetam?
–Reduced clearance of methotrexate
–Drugs the cause CNS depressant effect
when is a dose reduction required in levetiracetam?
in renal impairment
