Pharmacology of Anticonvulsants

Question 1

Define Epilepsy

Answer 1

A chronic brain disorder characterised by recurrent.
Abnormal electrical discahrges: loss of consciousness, abnormal movememnt, odd behaviour, distorted perceptions.

Question 2

Describe the goals of treatment and principles of long-term treatment.

Answer 2

Treatment Goals
Keep patients free of sezuires without dose-dependent toxicity phenomena.

Principles of Long-term therapy
1. It is better to treat a patient with only ONE anti-convulsant.
2. If fits are not controlled with the max dose of a drug, replace it with another, withdraw old drug in gradually decreasing doses while introduing the new drug
3. *THE ABRUPT WITHDDRAWAL OF THESE DRUGS MAY CAUSE STATUS EPILEPTICUS(life threatening)

Question 3

what’s epilepticus?

Answer 3

A seizure that lasts longer than 5 minutes, or having more than 1 seizure within a 5 minutes period, without returning to a normal level of consciousness between episodes is called status epilepticus.

Question 4

anti-epileptic drugs do not cure epilepsy, but rather control the seizures and usuallt have to be taken for life.

Describe the mech. of action, Indications, DI, Dose and AE for PHENYTOIN

Answer 4

MOA: blocks voltage-gated sodium channels
Indications: all forms of epilepsy(except absence seizures), status epilepticus.
Dose: 200 to 600mg, max=400mg
DI: Hepatic enzyme inducer
AE: N, V, Headache, Disorientation, Megaloblastic Aneamia, Gingival hyperplasia, Hirsutism, loss of bone density etc

Question 5

Describe the MOA, Indications, Dose, DI and AE for Carbamazepine

Answer 5

MOA: blocks sodium channels
Indications: First line monotherapy for generalised tonic-clonic and partial seizures
Dose: 200mg po bd for 2/52, then 300 mg max 900 mg bd.
DI: Induces hepatic enzymes, increases toxicity of tranylcypromine.
AE: Ataxia, Dizziness, Sedation, N, V, Rashes, Jaunduce, Dry mouth, Aplastic anaemia, Leukopenia, Hyponatriemia(in elderly)

Question 6

Describe the MOA, Indications, Dosage and AE of Lamotrigine

Answer 6

MOA Blocks sodium channels and HV-dependent calcium channels
Indications Focal, generalised, absence seizures, lennox-gastaut syndrome, bipolar disorder.
Dosage slow up titration of dose essential to minimize risk of serious and life-threatening skinn lesions(Stevens-Johnson Syndrome)
A/E: Ataxia, Dizziness, Blurred vison, Rash.

Question 7

Describe the MOA, Indications, and AE of Topiramate

Answer 7

MOA
Blocks voltage-dependent sodium channels. Reduce gih-voltage calcium currents. Targets glutamate(NMDA) sites

Indications Partial and primary generalised seizures(other: migraine, headache, obesity)

AE Drowsiness, Fatigue, weightloss, nervousness, renal stones, glaucome, hyperthermia, paraesthesia.

Question 8

Describe the MOA, Indications, Dosage, and AE of Gabapentin

Answer 8

MOA: An analogue of GABA (has no effects on GABA receptors)
Indications: Focal seizures
Dose Dose adjustment in renal disease is required.
AE Fatigue, Dizziness, Drowsiness, Ataxia

Question 9

Describe the MOA, Indications, Dosage, and AE of Vigabatrin

Answer 9

MOA Irreversibly inhibits y-aminobutyric acid transaminase (GABA-T) enzyme
Indications: Infantile spasms(west syndrome)
AE Dizziness, drowsiness, weight gain, mental confusion, psychosis.

Question 10

Describe the MOA, Indications, Dosage, and AE of Pregabalin

Answer 10

MOA binds to Auxiliary subunit of voltage-gated calcium channels.
Indications: Focus-onset seizures
Dose: dosage adjustments needed in renal disease
AE Weight gain, impaired memory, peripheral oedema.

Question 11

Describe the MOA, Indications, Dosage, and AE of Levetiracetam

Answer 11

MOA: High affinity for a synaptic vesicle protein
Indications: Focal, Myoclonic, generalised tonic-clonic seizures (other: perioperative neurosurgery)
AE: Mood alterations, ataxia, somnolence, dizziness, agitation.

Question 12

Describe the MOA, Indications, Dosage, DI and AE of Phenobarbitone

Answer 12

Indications: all forms of epilepsy excence absebce seizures
Dose: 60 to 180 mg/day po in 1-2 divided doses.
DI: Hepatic Enzyme Inducer
AE: Ataxia, Sedation, Nystagmus, Paradoxical stimulation, behavioural and learning problems, megaloblastic anaemia, idiosyncratic rash.

Question 13

Describe the MOA, Indications, Dosage, and AE of Ethosuximide

Answer 13

MOA: Inhibits T-type calcium channels, reduced propagation of abnormal electrical activity in the brain.

Indications: First line monotherapy for typical absence seizures
Dose:
AE: Nausea, vomiting, headache, sedation, ataxia, dizziness, euphoria, GIT distrubances(gastric pain), skin rashes(e.g SJS), bone marrow suppression.

Question 14

Describe the MOA, Indications, Dosage, DIand AE of Valproic Acid

Answer 14

MOA:
1. Blockade of sodium channel
2. Blockade of GABA transaminase
3. Blockade of T-type calcium channels.
Indications: Focal and Primary generalised seizures; all forms of epilepsy, first choice for patient of ART
Dose500mg po bd, max 2500mg daily.
DI Inhbits hepatic Enzymes
AE N, anorexia, increase appetite, ataxia, sedation, hepatotoxicty, alopecia, and thrombocytopenia, teratogenicity.

Question 15

Describe the MOA, Indications, Dosage, and AE of Clonaxepam, Clobazam, Diazepam

Answer 15

MOA: bind to GABA inhbitory receptos to reduce firing rate
Indication: reserved for emergencies or seizure attacks

Clonazepam and Clobazam
Adjunctive therapy for particular types of seizures
Diazepam
Available for rectal admin(children)
To avoid or interrept prolonged generalised tonic-clonic seizures.