Anti Epileptics Flashcards
Carbamazepine
VGSC blocker
Voltage gated sodium channel blockers in epilepsy mechanism
Bind in the refractory period
Keep channels inactive for longer
Reduces probability of high abnormal spiking activity
Only active when there is heavy depolarisation in the neurone - normal potentials still fire
Detach once the membrane potential returns to normal
Carbamazepine pharmacokinetics
Well absorbed 75% protein bound Linear pharmacokinetics Initial T1/2~30 hours CYP450 inducer - induces own metabolism T1/2 ~ 15 hrs in repeated use
Carbamazepine ADRs
CNS- dizziness, drowsiness, ataxia, motor disturbance, numbness, tingling Gi upset, vomiting Rash Can alter BP Hyponatraemia Rarely bone marrow depression
Carbamazepine contraindications
AVN conductance problems
Carbamazepine DDIs
CYP450 induction - reduces phenytoin, warfarin, OCP, systemic corticosteroids
Protein binding displacement
Antidepressants interfere with action
Carbamazepine uses
Generalised tonic clonic
All types of partial
NOT ABSENCE
Phenytoin
VGSC blocker
Phenytoin pharmacokinetics
Well absorbed
90% protein bound
Linear PK at sub therapeutic doses, but non linear at therapeutic concentrations
T1/2 6-24 hrs
Phenytoin ADRs
CNS- dizziness, ataxia, headache, nystagmus, nervousness
Gingival hyperplasia
Rashes- hypersensitivity, Stevens Johnson in 2-5%
Phenytoin DDRs
Competitive binding - valproate, NSAIDS
Reduces OCP
Cimetidine increases phenytoin
Phenytoin monitoring
Plasma levels
Salivary levels
Phenytoin uses
Generalised tonic clonic
All types of partial
NOT ABSENCE
Lamotrigine
Blocks VGSC
May also block Ca channels and reduce glutamate release
Lamotrigine pharmacokinetics
Well absorbed Linear PK T1/2 24 hours No CYP450 effects Enters phase 2 metabolism directly
Lamotrigine ADRs
CNS-dizziness, ataxia, somnolence
Nausea
Skin rashes of varying severity
Overall fewer ADRs than other VGSC blockers
Lamotrigine DDIs
OCP reduces Lamotrigine level in plasma
Valproate increases Lamotrigine levels in plasma
Uses of Lamotrigine
Partial
Generalised including absence
Safer in pregnancy
Not first line in paediatrics as more ADRs
GABA agonists in epilepsy
GABA has a major role in post synaptic inhibition (natural anticonvulsant)
GABA exhibits benzodiazepine and barbituate binding sites - binding enhances GABA action
Increases inward Cl current, hyperpolarising neurones
Valproate mechanism
Mixed sites Weak GABA inactivating enzyme inhibitor Weak GABA synthesising enzyme stimulator VGSC blocker Weak Ca channel blocker
Valproate pharmacokinetics
Well absorbed
90% protein bound
Linear PK
T1/2 - 15 hrs
Valproate ADRs
Generally less severe
CNS- sedation, ataxia, tremor
Weight gain
Reduces transaminases in 40% but rarely leads to hepatic failure
Valproate DDIs
Care with other AEDs
Antidepressants - SSRIs, MAOIs, TCAs- all inhibit action
Antipsychotics- lower convulsive threshold
Aspirin - competitive binding
Valproate monitoring
Free concentration in plasma (not closely associated with efficacy)
Salivary levels
Valproate uses
Partial
Generalised tonic clonic and absence
Benzodiazepines pharmacology
Act on receptor site on GABA chloride channel
Allosteric binding
Benzodiazepines pharmacokinetics
90-100% protein bound Well absorbed Linear PK T1/2 15-45 hrs Lipid soluble
Benzodiazepines ADRs
CNS-sedation, confusion, impaired coordination, aggression Tolerance, dependence, withdrawal Abrupt withdrawal triggers seizures Respiratory and CNS depression Dry mouth, blurred vision, GI upset
Benzodiazepines reversal
Flumazenil
Benzodiazepine uses
Lorazepam, diazepam - status epilepticus
Clonazepam - absence seizures, short term use
Management of status epilepticus
ABC
Exclude hypoglycaemia
Benzodiazepines (IV or rectal)
Phenytoin
