Anti-epileptics

Question 1

What is the general MOA of anti-epileptics ?

Answer 1

Reduce generation and propagation of neuronal impulse from the epileptic focus.

Question 2

What is the specific MOA of anti-epileptics ?

Answer 2

1. Prolong inactivation of Na+ channels
2. Reduce Ca2+ channel entry
3. Enhance GABAA-mediated inhibition
4. Reduce glutamate NMDA-mediated excitation

Question 3

What are the classes of anti epileptics ?

Answer 3

• Cyclic ureides
• Tricyclics
  *Benzodiazepines

Question 4

What are the Cyclic ureides used in epilepsy ?

Answer 4

Phenytoin, fosphenytoin
Primidone
Phenobarbital
Ethosuximide

Question 5

What is the Tricyclics
used in epilepsy ?

Answer 5

Carbamazepine

Question 6

What are the Benzodiazepines
used in epilepsy ?

Answer 6

Diazepam
Clonazepam

Question 7

What is the effect of anti-epilpetics induced prolonged inactivation of Na+ channel ?

Answer 7

It reduces the ability of neurons to fire at high frequency.

Question 8

What are the drugs that prolong Na+ inactivation?

Answer 8

Carbamazepine, Phentoyin, lamotrigine, and Valproate.

Question 9

Why are drugs that reduce calcium conductance through T-type calcium channels are used in generalised absence seizure ?

Answer 9

Drugs such as sodium valproate, dimethadione, and ethozuximide inhibit the thalamic rhythm seen in absence seizure by reducing calcium conductance through the T-type Ca2++ channels in thalamic neurons.

Question 10

What are the modes through which anti-epileptics induce GABArgic inhibition and post-synaptic neuronal hyperpolarization?

Answer 10

*Increase in Cl- channel opening through GABAA-benzodiazepine receptor complex.
*Inhibition of inactivation of GABA by GABA-Transaminase
* Inhibition of GABA reuptake

Question 11

How does anti-epileptics reduce glutametergic transmission?

Answer 11

The excitatory neurotransmitter glutamate release is reduced by inhibiting pre-synaptic calcium conductance.

Question 12

What is the mode of action and indication of Phenobarbitone ?

Answer 12

It acts by inhibiting sodium and calcium conductance which reduce glutamatergic signalling. It also enhance GABAa mediated Cl- channel conductance causing post synaptic hyperpolarization. It is indicated as a 3rd line agent for the Tx of tonic-clonic seizures as an enzyme inducer. The main side effects are high sedation and behavioral changes.

Question 13

What is the action, indication, and side effects of Phenytoin ?

Answer 13

It prolongs inactivation of Na channels. It is administered orally or IV for tonic-clonic, partial, and status epilepticus. The side effects are occular ataxia, sedation, gingival hyperplasia, and hirsuitism.

Question 14

What is the action, indication, and side effects of Carbamazepine
?

Answer 14

It acts through prolonged inhibition of Na channels. It is given orally for partial , complex, and tonic-clonic seizures. The major side effects are Aplastic anaemia, agranulocytosis.

Question 15

What is the action, indication, and side effects of Benzodiazepines
?

Answer 15

They enhance GABAa- Cl channel transmission leading to hyper polarization of the post synaptic neuron. Diazepam is indicated for status epilepticus. While Clonazepam is indicated for absence and myoclonic seizures. It is also given IV for status epilepticus. The side effects are sedation and tolerance.

Question 16

What is the action, indication, and side effects of Ethosuximide
?

Answer 16

It inhibit the pre-synaptic release of glutamate by inhibiting T-type calcium channels. It is given orally for absence seizure and the main side effects are GI disturbances.

Question 17

What is the action, indication, and side effects of sodium Valproate ?

Answer 17

It inhibits sodium and calcium channels and enhance conduction through the Cl channel GABAa complex. It is indicated for the Tx of tonic-clonic, absence and myoclonic seizures. The dosing: Orally, 25-30 mg/kg/d, therapeutic levels: 50-100 mg/mL. The side effects are hepatotoxicity, CYP450 induction, Tremor and GIT disturbances.

Question 18

What is the action, indication, and side effects of gabapentin ?

Answer 18

It inhibits Voltage-gated Ca2+ channels containing alpha 2 delta -1 subunit thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters. It is indicated as an adjunct therapy for refractory partial seizures or as monotherapay. The side effects are sedation and ataxia.

Question 19

What is the action, indication, and side effects of Lamotrigine ?

Answer 19

It inhibits T-type Ca channels leading to reduced release of glutamate. It also inhibits Na channels leading to reduced glutametergic signalling. It is used as a monotherapy or adjunct therapy for refractory partial seizures. The side effects are Sedation, occular, GIT, rash

Question 20

What is the first step in the management of status epilepticus (0-5 min) ?

Answer 20

• Stabilize the patient ABCD.
• Initiate ECG monitoring
• If the glucose is < 60 mg/dl for adults provide 100 mg B1 IV followed by 50 ml/kg D50W.
• For children 2 or more years old D25W IV.
• For children < 2 years D12.5 W IV.

Question 21

What is the second step (5 to 20 min ) in the management of status epilepticus ?

Answer 21

• Provide one benzodiazepham either IM Midazolam/ IV lorazepam or Diazepam.
• If none of the three options are available IV Fosphenytoin/ Valproic acid/ Levitracetam.
• If they are also not available rectal diazepam or intranasal or buccal midazolam can be given.

Question 22

What is the 3rd step (20 to 40 min ) in the management of status epilepticus ?

Answer 22

• If the seizure persists a single dose of IV Fosphenytoin/ Levitracetam/ Valproic acid can be given.
• If they are not available a single dose of IV Phenobarbitol can be given.

Question 23

What is the 3rd step (40 to 60 min ) in the management of status epilepticus ?

Answer 23

There is no clear evidence based therapy in this stage. Therefore, the second line agents can be tried again or anaesthetic dose of IV medazolam, thiopental, phenobarbitol or propofol can be used.