neuro: epilepsy Flashcards
epilepsy is a disease of the brain defined by any of the following conditions:
- At least two unprovoked seizures occurring>24 h apart
- One unprovoked seizure and a probability of further seizures similar to the general
recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10
years - Diagnosis of an epilepsy syndrome
provokedseizure
events occurring in close temporal rs with an acute CNS insult: metabolic, toxic, structural, infectious, inflammation
drugs that decr seizure threshold
TCA, carbapenems, baclofen
safety considerations: phenytoin
a/w incr risk of serious skin reactions in people of Han Chinese or Thai family background
safety considerations: cbz
a/w incr risk of serious skin reactions in people of Han Chinese, Thai, European, Japanese family background
safety considerations: LT treatment with some antiseizure meds such as cbz, phenytoin, primidone and sodium valproate
a/w decr bone mineral density and incr risk of osteomalacia
- ca and vit D supplementation for person at risk
antiseizure meds for women and girls
teratogenic: sodium valproate, topiramate, phenytoin
impair effectiveness of hormonal contraceptives: cbz, oxcarbazepine, phenytoin, topiramate
(estrogen-containing hormonal contraceptives can imapair effectiveness of lamotrigine
breastfeeding is generally safe and should be encouraged
generalised tonic clonic/ grand mal: tonic phase
stiffening of the limbs, breathing may decr or cease altogether, cyanosis of nail beds&lips&face
generalised tonic clonic/ grand mal: clonic phase
jerking of limbs and face, lasts 1 min, after which the brain is extremely hyperpolarised and insensitive to stimuli
- incontinence may occur, along w biting of the tongue or inside of the mouth, breathing may be noisy and appear to be laboured
- following the seizure, pt may have headache and appear lethargic/confused/sleep
myoclonic
Involves rapid, brief contractions of bodily muscles,
usually occurring on both sides of the body
concurrently
- On occasion, may involve just one arm or one foot
absence generalised seizure / petit mal
- Usually manifests as basic lapse in awareness that begins and ends
abruptly - Sometimes mistaken as persistent staring
- Lasts only a few seconds no warning, no after-effects
- Often undetected even if there 50-100 attacks per day
- More common in children than in adults
- First onset usually occurs at 4-12 years old; rarely after 20 years old
- May be mistaken for complex
absence seizures vs complex partial seizures
absence:
1. are never preceded by auras
2. last seconds (rather than minutes)
3. begin frequently and end abruptly
4. produce characteristic EEG pattern ‘3Hz spike waves’
generalised atonic seizure
- most severe form is the classic drop attack (astatic
seizure) in which all postural tone is suddenly lost,
causing collapse to the ground like a rag doll - short episode and followed by immediate recovery
- occur at any age, and are always associated with diffuse
cerebral damage and learning disability
risk of second seizure is higher in the presence of:
- epileptiform abnormalities on EEG
- Prior brain insult (e.g. stroke, brain trauma)
- Structural abnormality in brain imaging
- Nocturnal seizure
non-pharmacological treatment for epilepsy
- ketogenic deit
- vagus nerve stimulation
- responsive neurostimulator system
- surgery
AED that requires slow titration
lamotrigine and topiramate
AED that undergoes autoinduction
carbamazepine
AED to use in pt w migraine
topiramate, valproate
AED to use in caution for pt w depression or anxiety
levetiracetam: can cause irritability and aggresion
women w childbearing potential
avoid valproate, use l/l
If the first AED produces an adverse drug reaction or is not tolerated at low doses or does
not improve seizures consider
substitution
if the patient tolerates the first or second AED but with a
suboptimal response, consider
combination
ketogenic diet
may be used for pt who cannot tolerate or have not responded well to AED treatment
Comprises low carbohydrate, high fat in diet
Induction of ketosis
Prevention of seizures (used mainly in young children evidence)
Challenging to adhere long term
AED with possible cognitive adr
topiramate: usually speech fluency
AED to use in hepatic impairment
gabapentin, pregabalin, levetiracetam, topiramate, clobazem
AED to use in renal impairment
carbamazepine, phenobarbitol, phenytoin, valproate
lamotrigine
AED with no DDI`
gabapentin, pregabalin, levetiracetam
potent enzyme inducers
1st gen
- carbamazepine
- phenytoin
- phenobarbitol
potent enzyme inhibitor
valproate
moderate cyp inducer
oxcarbazepine, topiramate
moderate cyp inhibitors
oxcarbazepine, topiramate
When an enzyme inducing ASM is discontinued, activity of affected enzymes
return to baseline
- drugs that are metabolised by the affected enzymes may require dose adj
issue w enzyme-induced AED: ddi
- antidepressants and antipsychotics
- immunosuppressive therapy
- antiviral therapy
- chemotherapeutic agent
phenytoin correction for
albumin < 40g/L
carbamazepine pk
Undergoes autoinduction (induces its
own metabolism)
Clearance increase and half-life
shorten carbamazepine
concentration decline and stabilize in
accord with the new clearance and
half-life
Maximal autoinduction usually occurs
2-3 weeks after dose initiation
Implication:
Do not start with desired maintenance
dose at the first dose, but gradually
increase over the initial few weeks
absence of myoclonic seizures, do not use:
cbz, gbt, oxcarbazepine, phenytoin, pregabalin
AED that may cause behavioural disturbances
levetiracetam
AED that can cause n/v
carbamazepine, valproate
rare but serious idosyncratic reactions of AED
Blood dyscrasia (Aplastic anaemia, agranulocytosis
Hepatotoxicity (1st-generation ASMs phenytoin, valproate, carbamazepine)
Pancreatitis (e.g., sodium valproate)
Lupus-like reaction
Exfoliative dermatitis
Toxic epidermal necrolysis/Stevens-Johnson syndrome
AED that has been a/w pancreatitis
sodium valproate
chronic SE of phenytoin
gingival hyperplasia (gum enlargement): may be observed in almost half of all patients receiving chronic phenytoin therapy
hirsutism: commonly observed in children and young adults on chronic phenytoin therapy
encephalopathy: most commonly a/w prolonged phenytoin treatment at high doses
^ may also occur w phenobarbitone
peripheral neuropathy: patients on LT phenytoin treatment at high doses experience sensory loss - may or may not improve w decr in AED dose, may respond with folate supplementation
^ may also occur w phenobarbitone and cbz
osteomalacia: incr clearance of vit D, leading to secondary hyperPTH, incr bone turnover, and reducing bone density
^ often a/w phenytoin, phenobarbitone and cbz (hepatic enzyme inducers)
chronic SE of valproate
alopecia
increased weight gain, gradually reverses spontaneously with discontinuation of treatment
chronic SE of topiramate
anorexia and weight loss, reversible w discontinuation of drug
- actl indicated as a possible weight loss agent
other isolated adr a/w nearly all AED
blood dyscrasias, megaloblastic anemia (altho predominantly in pt receiving phenytoin, but also a/w cbz and phenobarbitone)
AEDs causing neonatal congenital defects
malformation risk: topiramate, phenytoin, phenobarbitone
cognition: valproate
AED that requires pharmacogenetic testing
carbamazepine: HLA-B*1502 testing
- prior to starting
- strong assoc btw carriage and risk of cbz-induced sjs/ten
lamotrigine initial dosing
risk of severe cutaneous reaction higher with high starting dose, rapid dose escalation, concomittant valproate
- in pt taking valproate: 25mg EOD to maintenance dose of 100-200mg/d
- in pt not taking anyth else: 25mg OD, maintenance of 225-375mg/d in 2 divided doses
- in pt taking smth else but not valproate: 50mg/d to maintenance of 300-500mg/d in 2 divided doses
aromatic AED
cbz, ltg, oxcarbazepine, phenytoin, phenobarbital
non-aromatic AED
val, levetiracetam, gabapentin, topiramate
ref range of phenytoin
10-20mg/L
ref range of valproate
50-100mg/L
ref range of cbz
4-12mg/L
ref range of phenobarbitone
15-40mg/L
when can we consider discontinuing AEDs?
after a person has been seizure free for 2yrs
epilepsy is considered to be resolved for indiv who had
an age-dependent epilepsy syndrome but are not past the applicable age
or remained seizure-free for last 10 yrs, w no seizure meds for last 5 yrs
