Anti Epileptics

Question 0

Carbamazepine

Answer 0

VGSC blocker

Question 1

Voltage gated sodium channel blockers in epilepsy mechanism

Answer 1

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

Question 2

Carbamazepine pharmacokinetics

Answer 2

Well absorbed
75% protein bound
Linear pharmacokinetics
Initial T1/2~30 hours
CYP450 inducer - induces own metabolism
T1/2 ~ 15 hrs in repeated use

Question 3

Carbamazepine ADRs

Answer 3

CNS- dizziness, drowsiness, ataxia, motor disturbance, numbness, tingling
Gi upset, vomiting
Rash
Can alter BP
Hyponatraemia 
Rarely bone marrow depression

Question 4

Carbamazepine contraindications

Answer 4

AVN conductance problems

Question 5

Carbamazepine DDIs

Answer 5

CYP450 induction - reduces phenytoin, warfarin, OCP, systemic corticosteroids
Protein binding displacement
Antidepressants interfere with action

Question 6

Carbamazepine uses

Answer 6

Generalised tonic clonic
All types of partial
NOT ABSENCE

Question 7

Phenytoin

Answer 7

VGSC blocker

Question 8

Phenytoin pharmacokinetics

Answer 8

Well absorbed
90% protein bound
Linear PK at sub therapeutic doses, but non linear at therapeutic concentrations
T1/2 6-24 hrs

Question 9

Phenytoin ADRs

Answer 9

CNS- dizziness, ataxia, headache, nystagmus, nervousness
Gingival hyperplasia
Rashes- hypersensitivity, Stevens Johnson in 2-5%

Question 10

Phenytoin DDRs

Answer 10

Competitive binding - valproate, NSAIDS
Reduces OCP
Cimetidine increases phenytoin

Question 11

Phenytoin monitoring

Answer 11

Plasma levels

Salivary levels

Question 12

Phenytoin uses

Answer 12

Generalised tonic clonic
All types of partial
NOT ABSENCE

Question 13

Lamotrigine

Answer 13

Blocks VGSC

May also block Ca channels and reduce glutamate release

Question 14

Lamotrigine pharmacokinetics

Answer 14

Well absorbed 
Linear PK
T1/2 24 hours
No CYP450 effects
Enters phase 2 metabolism directly

Question 15

Lamotrigine ADRs

Answer 15

CNS-dizziness, ataxia, somnolence
Nausea
Skin rashes of varying severity
Overall fewer ADRs than other VGSC blockers

Question 16

Lamotrigine DDIs

Answer 16

OCP reduces Lamotrigine level in plasma

Valproate increases Lamotrigine levels in plasma

Question 17

Uses of Lamotrigine

Answer 17

Partial
Generalised including absence
Safer in pregnancy
Not first line in paediatrics as more ADRs

Question 18

GABA agonists in epilepsy

Answer 18

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

Question 19

Valproate mechanism

Answer 19

Mixed sites
Weak GABA inactivating enzyme inhibitor
Weak GABA synthesising enzyme stimulator
VGSC blocker
Weak Ca channel blocker

Question 20

Valproate pharmacokinetics

Answer 20

Well absorbed
90% protein bound
Linear PK
T1/2 - 15 hrs

Question 21

Valproate ADRs

Answer 21

Generally less severe
CNS- sedation, ataxia, tremor
Weight gain
Reduces transaminases in 40% but rarely leads to hepatic failure

Question 22

Valproate DDIs

Answer 22

Care with other AEDs
Antidepressants - SSRIs, MAOIs, TCAs- all inhibit action
Antipsychotics- lower convulsive threshold
Aspirin - competitive binding

Question 23

Valproate monitoring

Answer 23

Free concentration in plasma (not closely associated with efficacy)
Salivary levels

Question 24

Valproate uses

Answer 24

Partial | Generalised tonic clonic and absence

Question 25

Benzodiazepines pharmacology

Answer 25

Act on receptor site on GABA chloride channel | Allosteric binding

Question 26

Benzodiazepines pharmacokinetics

Answer 26

``` 90-100% protein bound Well absorbed Linear PK T1/2 15-45 hrs Lipid soluble ```

Question 27

Benzodiazepines ADRs

Answer 27

``` CNS-sedation, confusion, impaired coordination, aggression Tolerance, dependence, withdrawal Abrupt withdrawal triggers seizures Respiratory and CNS depression Dry mouth, blurred vision, GI upset ```

Question 28

Benzodiazepines reversal

Answer 28

Flumazenil

Question 29

Benzodiazepine uses

Answer 29

Lorazepam, diazepam - status epilepticus | Clonazepam - absence seizures, short term use

Question 30

Management of status epilepticus

Answer 30

ABC Exclude hypoglycaemia Benzodiazepines (IV or rectal) Phenytoin