A.30

Question 1

Antiepileptics used in absence of seizures. ‘‘Broad spectrum’’ antiepileptic drugs. Drugs used for treatment of status epilepticus

Answer 1

Ethosuximide,
Valproate,
Lamotrigine,
Diazepam,
Clonazepam,
Levetiracetam,
Vigabatrine

Question 2

Ethosuximide

Answer 2

MOA: T-type Ca2+ ch.blocker in thalamic neurons; Effect: anticonvulsant with specific action on absence seizures;
IND: absence seizures ONLY! (not effective against tonic-clonic);
Kinetics: p.o administration, metabolized by CYT3A4, T1/2= 50h;
SEs: hyperactivity, insomia, nausea, vomiting

Question 3

Clonazepam

Answer 3

MOA: BDZ, GABAA agonist (→Cl- influx→ reduces electrical excitability);
Effect: more selective anticonvulsant with less sedation, also hypnotic and anxiolytic;
IND: Tonic-clonic and absence seizures, panic+anxiety disorders;
Kinetics: administered p.o, metabolized by P450 system and glucuronide conjugation, T1/2=~30h;
SEs: sedation, tolerance (mainly to anticonvulsant activity), severe respiratory depression if combined with other CNS depressants (e.g. alcohol)

Question 4

Valproate

Answer 4

MOA: VG Na+ ch. blocker (→inhibits AP initiation & propagation), T-type Ca2+ ch. blocker, enhances GABA transmission (inhibits GABA transaminase to reduce GABA breakdown), decreases glutamate transmission; Effect: anticonvulsant & mood stabilizer;
IND: broad spectrum→ all forms of epilepsy (incl. absence seizures), manic phase of bipolar disorder, migraine (prophylaxis);
Kinetics: administered p.o, subject to glucuronidation and mitochondrial oxidation, T1/2=9-16h;
SEs: Hepatotoxicity, thrombocytopenia, GI symptoms (nausea&vomiting, panceatitis), Tremor, weight gain, TERATOGENIC (most of all!!!);
Extra: inhibits CYT P450 enzymes (→different from others that iduces it→ slows it down and causes buildup of other chemicals)

Question 5

Lamotrigine

Answer 5

MOA: inhibits Na+ ch., reduces glutamate release (↓postsynaptic excitation);
Effect: Anticonvulsant, reduces frequency of mood episodes in bipolar disorders;
IND: Focal and generalized seizures (including absence), bipolar disorder, NOT teratogenic;
Kinetics: adminstered p.o (100% BAp.o), Hepatic metabolism by CYP2C9 (catalizes glucuronidation), T1/2= 24-36h;
SEs: Stevens-Johnson syndrome (skin peels off→particularly in children), dizziness, nausea, headache, double vision, sedation;
Drug interactions: Valproate (inhibits CYP enzymes), Phenobarbitol (induces CYP enzymes), female hormones (induce CYP enzymes)

Question 6

Levetiracetam

Answer 6

MOA: SV2A-R blockade (→modifies release of neurotransmitter);
Effect: anticonvulsant;
Kinetics: p.o/i.v admin., mostly excreted unchanged by kidneys, T1/2=7h;
IND: tonic-clonic, partial, myclonic seizures in children(→broad spectrum), NOT TERATOGENIC;
SEs: sedation, paresthesia, exacerbate underlying psychiatric disorders, hypersensitivity (skin lesions), dizziness;
Contra-IND: people with underlying psychiatric disorders

Question 7

Diazepam

Answer 7

MOA: BDZ, GABAA agonist (→Cl- influx→ reduces electrical excitability);
Effect: anticonvulsant, also hypnotic and anxiolytic; IND: i.v for status epilepticus, sk. muscle spasms, anesthesia, preoperative sedation, anxiety;
Kinetics: administered p.o (i.v. for status epilepticus), metabolized by P450 system and glucuronide conjugation, T1/2=~60h;
SEs: sedation, tolerance (mainly to anticonvulsant activity), severe respiratory depression if combined with other CNS depressants (e.g. alcohol)

Question 8

Vigabatrine

Answer 8

MOA: irreversible GABA transaminase inhibitor;
Effect: ↓GABA metabolism→ ↑GABA release, Anticonvulsant;
IND: adjunct to other anticonvulsants;
Kinetics: p.o admin., mostly excreted unchanged, T1/2= 10h (though irreversible enzyme inhibition prolongs drug action), CYP2C9 inducer;
SEs: sedation, confusion, peripheral sight loss, hyperactivity in children, neurological SEs, weight gain, MRI-abnormalities

Question 9

Antiepileptics used in absence seizures

Answer 9

Ethoxsuximide, Clonazepam, Valproate, Lamotrigine

Question 10

Broad spectrum antiepileptics

Answer 10

Lamotrigine, Valproate, Levetiracetam

Question 11

Status epilepticus

Answer 11

any ongoing convulsion

Question 12

Drugs used for treatment of status epilepticus

Answer 12

1st line treatment: Midazolam, Diazepam, clonazepam IV in high dose
2nd line treatment: Phenytoin, Levetiracetam, Valproate
3rd line treatment: Phenobarbital
4th line treatment: use general anesthesia