Anti-seizure medication

Question 1

What ASM’s promote inhibition?

Answer 1

Topiramate- partial and tonic clonic
Benzodiazepines-
Valproate- partial and generalised (A, MC, TC)

Question 2

What ASM’s reduce excitation?

Answer 2

Phenytoin- partial and tonic-clonic
Carbamazepine- partial and tonic clonic
Lamotrigine- partial and generalised
Valproate- partial and generalised
Topiramate- partial and tonic clonic
Levetiracetam- partial, MC and TC- abscence?

Question 3

Carbamazepine- characteristics

Answer 3

Sodium channel blocker, strong hepatic enzyme inducer (CYP3A4)- h.metabolism
SE: Dose dependent- diplopia, ataxia, sedation and fatigue
Hyponatremia- SIADH (increases ADH release)
Idiosyncratic- BM suppression, hypersensitivity, hepatic derangement, rash

Question 4

Phenytoin

Answer 4

Sodium channel blocker used in emergency settings (unresponsive SE)
Acute SE: dizziness, ataxia, fatigue, diplopia, nystagmus, rash, sedation
Chronic SE: gum hyperplasia, coarse face, hirsutism (facial hair) osteopenia ( inc vit D metabolism), low folate, peripheral neuropathy
Idiosyncractic- fever, rash, lymphadenopathy- teratogenic

Question 5

What induces and reduces phenytoin concentration?

Answer 5

Increased: enzyme inhibitors
Decreased: carbamazepine and antacids (other inducers)
90% protein bound- valproate displaces+ inhibits metabolism, increase free phenytoin/ toxicity

Question 6

Sodium valproate

Answer 6

Sodium/calcium channel blocker, GABA, glutamate receptor actions
Hepatic metabolism
TERATOGENICITY IN YOUNG WOMEN

Question 7

Sodium valproate- side effects

Answer 7

Generally well tolerated
V
A- appetite increase, weight gain
L-liver failure
P-pancreatitis
R-reversible hair loss
O-oedema
A-ataxia
T-teratogenicity, tremor, thrombocytopenia
E-encephalopathy (confusion as increased ammonia)

Question 8

Levetiracetam- drug profile

Answer 8

Few side effects but common ones include irritability, anxiety, fatigue, dizziness, behavioural changes, bone marrow and rarely psychosis
Rare hepatic failure
Acts on SV2A ligand (blocks synaptic vescile release)
Rapid and complete absorprtion, renal excretion and not inhibitor/ substrate CYP450 enzymes
CHOICE IN PREGNANCY

Question 9

Lamotrigine

Answer 9

Sodium channel modulator, safe teratogenicity wise
Typically well tolerated- idiosyncratic rash/ STEVENS JOHNSON SYNDROME (skin failure of mucosal membrane, blistering and bleeding of mouth etc)
Rash- minimised by slow titration, stop if develops
Insomnia, less cognitive effects, mood stabilising effects
CHOICE IN PREGNANCY

Question 10

Lamotrigine interactions

Answer 10

Combined oral contraceptive pill

Other AED’s- especially valproate

Question 11

Toparamate

Answer 11

Sodium/calcium channel blocker- GABA/ glutamate
Used in migraine
enzyme inducer and inhibitor, hepatically eliminated
SE- sedation, anorexia, WEIGHT LOSS, psychiatric, word finding difficulties
Rare SE- kidney stones, acute angle closure glaucoma
TERATOGENIC

Question 12

AEDs and mental health risk

Answer 12

Levetiracetam- SUICIDE RISK
Interaction with antidepressants
Generally ADs ok to use with ASMs- untreated depression?

Question 13

Bone health

Answer 13

Care with enzyme inducers, e.g carbamazepine

Vitamin D Catabolism

Question 14

AEDs and weight gain

Answer 14

Valproate (50% in first 1/2 months)- hyperinsulinaemia, insulin resistance, polycystic ovary syndrome- carbamazepine
Gabapentin+ topiramate indicated

Question 15

AED hypersensitivity syndrome

Answer 15

Rare, potentially fatal conditions within w1-8 of exposure
rash, fever, tender nodes, hepatitis (50% mortality), eosinophilia, pharyngitis, organ failure
Aromatic AED’s phenytoin/carbamazepine show cross reactivity

Question 16

Benzodiazepines- characteristics

Answer 16

STATUS EPILEPTICUS- diazepam, midazolam, lorazepam
GABA agonist
IV most definitive- IM in pre hospital SE
Lorazepam drug of choice in hospital