Anticonvulsants Flashcards
Name 3 mechanisms of actions of anticonvulsants
- prolong inactivated state of voltage gated Na and Ca channels presynaptically: reduce likelihood repetitive action potentials, reduce necerotransmitter release, prevent seizure spread
- enhance effects of GABA (inhibitory) via GABA - A receptor complex:open ligand gated Cl channels causing suppression of discharges
- inhibit effects of excitatory neurotransmitter, glutamate, via NMDA receptor (and ampa R): prevent opening ligand gated Na and Ca channels
Name the 4 sites on the gaba-a r complex
• GABA site • Benzo • barbiturate • alcohol (All neuroinhibitory) 4 bs All very addictive.
Name 5 anticonvulsants that prolong the inactivated state of voltage dependent Na and Ca channels
- Phenytoin
- carbamazepine
- valproate
- oxcarbazepine
- lamotrigine
- topiramate
- gabapentin
Name 3 anticonvulsants that inhibit effects of excitatory neurotransmitter glutamate by modulating NMDA (and ampa) receptors (nmda antagonists)
• Topiramate • magnesium • felbamate Zonisamide (Lamotrigine) (Ketamine)
Name 3 classes anticonvulsants with examples that enhance effects of inhibitory neurotransmitter GABA
• GABA site (inhibit GABA transaminase irreversibly): vigabatrin
• benzodiazepines (bind at GABA A r site): diazepam, clonazepam
• barbiturates: phenobarbitone
(GABA agonists: gabapentin)
Name an important side effect of phenytoin and carbamazepine Due to their action on CYP 450
Inducers
Vit D hypermetabolised causing osteopenia.
Name 3 indications phenytoin
Generalised and partial seizures, status epilepticus
Name 2 important pharmacokinetic components of phenytoin
• High protein binding 95% (increased risk toxicity if displaced)
• liver metabolism saturable: zero order kinetics (small increase dose may cause unpredictable increase in Cp with toxicity)
Old drug, so risks toxicity high
Name 5 important adverse effects phenytoin
- CNS: cerebellar syndrome, sedation
- allergic effects with cross sensitivity to carbamazepine: rash, hepatitis
- skin and collagen: gum hypertrophy, coarsening of facial features, hirsutism
- haem: megaloblastic anemia
- teratogenic: malformations
Name 5 indications carbamazepine
• Partial seizures
• generalised seizures, excluding absence and atonic
Other
• mood stabiliser bipolar disorder prophylaxis
• trigeminal neuralgia and other chronic pain syndromes
• chronic dystonic disorders
• intractable hiccups , neurohypophyseal diabetes insipidus
Name 5 adverse effects carbamazepine
• Ataxia • nystagmus • dysarthria • vertigo • sedation Common but not severe, occur when levels > 8,5 mg/l
Name 2 drug interactions carbamazepine
- Maoi: contraindicated
* CYP450 inducer: reduce efficacy warfarin, theophylline, oc, other anticonvulsants
Name 2 indications phenobarbitone
Barbiturates
• generalised and partial seizures
Second line! Too sedative in adults, behavioural disturbances in children, very addictive
Name 2 indications sodium valproate
Partial and generalised epilepsy
First line
Juvenile myoclonic epilepsy
Name 3 adverse effects sodium valproate
• git • liver failure and hepatic necrosis, rare. • pancreatitis • Hair loss - Teratogen:ntd
Indication ethosuxamide?
Drug of choice for absence seizures children
Not others seizures, may make them worse
Indication gabapentin?
- Add on for absence seizures
* partial and generalised epilepsy monotherapy
Gabapentin AE?
Somnolence
Lamotrigine indications? (3)
- Partial seizures
- generalised
- absence
Contraindication lamotrigine?
Liver or renal failure
Lamotrigine adverse effects (2)
• Hypersensitivity rashes: Steven’s Johnsons, toxic epidermal necrolysis, angioedema
• flu-like symptoms
Rare
Name 2 indications topirimate
Generalised and partial seizures
Newer drug
Name 5 adverse effects topirimate
- Poor concentration and memory
- Impaired speech
- ataxia
- somnolence
- anorexia and taste perversion
- syndrome of acute myopia associated with secondary closed angle glaucoma
Vigabatrin indication
Last resort for epilepsy due to significant irreversible visual defects
Vigabatrin contraindication?
History of psychosis: hallucinations as side effect
Vigabatrin excretion?
Excreted unchanged by kidneys therefore not metabolised in liver
Vigabatrin adverse effects? (3)
- Drowsiness common!
- visual hallucinations!
- ocular potentially irreversible: retinal changes, visual field defects, photophobia
Oxcarbazepine indications? ( 2)
Partial and generalised seizures
Add on in partial seizures
Carbamazepine derivative
Clonazepam indications as antiepileptic? (5)
Benzo Long term for: • motor seizures childhood • absence • infantile spasms • complex partial seizures • myoclonic epilepsy as add on treatment • status epilepticus
Name the 4 properties of actions of benzos
•Anxiolytic
.Hypnotic
• muscle relaxant
• anticonvulsant- not for long term use except clonazepam
Name 4 benzos that are first line agents in status epilepticus
- Diazepam
- clobazepam
- lorazepam
- clonazepam
Name the 6 steps of treatment of status epilepticus
1 Iv Benzo eg diazepam 10 mg over 5 minutes. Rectal in kids
2. Repeat benzos if continue
3. Iv phenytoin loading dose to prevent relapse
4 identify precipitants eg hypoglycaemia, alcohol, overdose, low plasma concentration
5.icu with Anaesthetist to administer iv thiopentone / chloromethiazole /propofol if still no response
6. Paraldehyde rectally if no facilities
First line treatment Janz syndrome/juvenile myoclonic epilepsy?
Valproate
Which anticonvulsant safest in pregnancy?
Lamotingine
