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PHA 333 > eplipsy in clinical practice > Flashcards

eplipsy in clinical practice Flashcards

1
Q

what is epilepsy?

A

Neurological disorder characterised by

recurring seizures

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2
Q

define status epilepticus

A

prolonged convulsive seizure for 5 minutes or longer, or recurrent seizures one after the other without recovery in between

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3
Q

what is a tonic seizure?

A

short-lived (less than 1 minute), abrupt, generalised muscle stiffening with rapid recovery

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4
Q

what is a tonic-clonic seizure?

A

generalised stiffening and subsequent rhythmic jerking of the limbs, urinary incontinence, tongue biting

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5
Q

what is an absence seizure?

A

behavioural arrest

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6
Q

what is an atonic seizure?

A

sudden onset of loss of muscle tone

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7
Q

what is a myoclonic seizure?

A

brief, ‘shock-like’ involuntary single or multiple jerks

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8
Q

what is status epilepticus treatment?

A

• 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

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9
Q

what is the established treatment for status epilepticus?

A

–IV phenytoin infusion 15 – 18mg/kg

–Other options – fosphenytoin and/or phenobarbital

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10
Q

what is the statiys epilepticus treatment for refractory status?

A

(60 - 90mins after initial
treatment)
–Anaesthesia e.g. propofol, midazolam, thiopental
–Until seizure free for 12-24 hrs then gradually tapered

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11
Q

what are the general measures you would take during status epilepticus?

A

– Secure airway and resuscitate
– Administer oxygen
– Establish intravenous access

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12
Q

what are the emergency investigations you would take during status epilepticus?

A

– Bloods
– Chest x-ray
– May include brain imaging, lumbar puncture

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13
Q

what monitoring requirements would you take for statius epilepticus?

A

– Regular neurological observations
– Pulse, blood pressure, temperature, ECG, bloods
– EEG monitoring is necessary for refractory status

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14
Q

how should you initiate treatment?

A

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

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15
Q

when/how should you discontinue aeds?

A

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

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16
Q

what are the different categories when brand switching?

A
  • 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
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17
Q

when would suicical ideation be most prominant?

A

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

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18
Q

what is antiepileptic hypersensitivity syndrome?

A

• 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

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19
Q

how does epilepys affect bone health?

A

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

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20
Q

how does epilepsy affect women of child bearing potential?

A

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

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21
Q

what risk poses pregnant women an epilepsy?

A

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

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22
Q

what should a woman do if pregnant and has epilepsy?

A

If planning pregnancy, should be referred to specialist and take folic acid 5mg

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23
Q

how should you dose sodium valporate?

A

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

24
Q

how can sodium valproate be given?

A

–Immediate release or modified release tablets
–Liquid
–IV

25
Q

what are the common sodium valporate side effects?

A

Alopecia (curly regrowth), tremor, weight gain, menstrual irregularities, GI disturbance, headaches, confusion

26
Q

what serious side effects are associated with sodium valportae?

A

Hepatotoxicity
–Pancreatitis
–Blood disorders
–Skin reactions e.g. SCARS, hypersensitivity

27
Q

how does sodium valporate acts as an enzyme inhibitor?

A

–Increases risk of toxicity with lamotrigine, phenytoin,
phenobarbital, carbamazepine
–Increased adverse effects with olanzapine

28
Q

what other effects do sodium valporate have when it comes to drug interactions?

A

–Carbapenems e.g. ertapenem, meropenem reduce
concentration of valproate
–Enzyme inducing AEDs e.g. phenytoin, phenobarbital,
carbamazepine

29
Q

what monitoring is needed with sodium valporate?

A

• 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

30
Q

why must sodium valproate be avoided in preganancy?

A

• 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

31
Q

when dispensing sodium valporate what must be included?

A

– 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

32
Q

what is the pregnancy prevention programme?

A

– 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

33
Q

how do you dose carbazepine?

A

• 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

34
Q

what is the max dose for a suppository for carbamazepine?

A

1g daily

35
Q

what are the side effects for carbamezepine?

A

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

36
Q

what are the counselling points you would recommend with carbamepine?

A

recognise signs of blood, liver or skin disorders

37
Q

what are the interactions availible with carbamazepine?

A

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)

38
Q

what are the effects of other drugs on carbmazepine? ie what inc/ decreases its conc

A

Increase conc. of carbamazepine – clarithromycin, fluconazole, diltiazem, grapefruit Juice
– Decrease conc. of carbamazepine – phenytoin, rifampicin, theophylline, St. John’s Wort

39
Q

what monitoring is needed with carbamazepine?

A

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

40
Q

what therapeutic drug monitoring needs to be done for carbamazepine?

A

–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

41
Q

how would you dose phenytoin?

A

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

42
Q

what route is availible for phenytoin?

A 
Route: (note sodium and base are NOT bioequivalent)
–Tablets/capsules (phenytoin sodium)
–Chewable tablets (phenytoin base)
–Suspension (phenytoin base)
–IV (phenytoin sodium)
43
Q

what side effects are associated with phenytoin?

A 
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
44
Q

what drug interactions are seen with phenytoin?

A

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

45
Q

what monitoring needs to be done with phenytoin?

A 
• Pre-treatment - HLAB* 1502 allele in individuals 
of Han Chinese or Thai origin
• Baseline:
–LFTs
–FBC
–U&Es
46
Q

what is the ideal plasma phenytoin concentration?

A

Plasma-phenytoin concentration: 10–20 g/litre

47
Q

how would low albumin affect phenytoin levels?

A

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)

48
Q

how would phenytoin be given for status epilepticus?

A

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

49
Q

what are the common errors associated with taking phenytoin IV?

A

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

50
Q

how do you dose lamotrigine?

A

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

51
Q

what are the common side effects associated with lamotrigine?

A

• 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

52
Q

what are the interactions associated with lamotrigine?

A 
• 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
53
Q

how would you dose levetiracetam?

A

–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)

54
Q

what are the side effects of levetiracetam?

A

Headache, asthenia, irritability, ataxia, drowsiness

55
Q

what drug interactions are associated with levetiracetam?

A

–Reduced clearance of methotrexate

–Drugs the cause CNS depressant effect

56
Q

when is a dose reduction required in levetiracetam?

A

in renal impairment

PHA 333 (42 decks)

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