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75 Cards in this Set
- Front
- Back
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What are the 3 mechanisms of action of Phenobarbitone?
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1. Binds to GABA-A receptor to increase the chloride channel open duration
2. Blocks the Na channel 3. Binds to non-NMDA glutamate receptor and decreases activity of glutamate |
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When is Phenobarbitone used?
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1. Status epilepticus
2. Neonatal seizures |
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Why is Phenobarbitone not used as a long-term antiepileptic?
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1. 25% have severe behavioural changes (neurologically abnormal children more at risk)
2. Adversely affects cognitive performance if used long-term 3. Causes hyperkinesia |
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What are the adverse effects of phenobarbitone?
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1. Rash - allergic skin reactions, rarely SJS, toxic epidermal necrolysis
2. Megaloblastic anaemia 3. Osteomalacia |
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Which antiepileptics are predominantly renally excreted?
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1. Gabapentin
2. Vigabatrin 3. Topiramate 4. Levetiracetam 5. Zonisamide "Go Via The Left Zone" or "Gabby's vibrant top levels the zone" |
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Which AEDs are CYP450 enzyme inducers?
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1. Phenytoin
2. Phenobarbitone 3. Carbamazepine |
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Name 2 CYP450 enzyme inhibitors?
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1. Erythromycin
2. Cimetidine |
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Which AEDs have predominant hepatic clearance?
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1. Phenytoin (>95%)
2. Phenobarbitone (75% liver, 25% renal) 3. Carbamazepine (>95%) 4. Sodium valproate (>96%) 5. Lamotrigine (90%) 6. Diazepam (99%) ie. all the others excluding GBP, VGB, TPM, LVT, ZNS |
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What are the 2 mechanisms of action of Phenytoin?
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1. Blocks Na channels (main action)
2. Decreases depolarisation dependent Ca uptake |
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When is phenytoin used?
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1. status epilepticus
2. partial seizures 3. GTC (1y or 2ndy) 4. Neonatal seizures |
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How does Phenytoin interact with warfarin?
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Phenytoin is an inducer of CYP450, and therefore increases the metabolism of other drugs and decreases their effects. This includes warfarin, steroids, theophylline, OCP and other antiepileptics. The inducers of CYP450 are phenytoin, phenobarbitone and carbamazepine - therefore don't use these drugs in combination with other AEDs.
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Phenytoin has zero-order kinetics and a narrow therapeutic index. What does this mean?
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Zero-order kinetics: initially phenytoin follows 1st order kinetics (elimination is proportional to the drug's concentration), but after a certain point zero-order kinetics are displayed i.e. Drug elimination is INDEPENDENT of the drug's concentration. This means you get unpredictable plasma levels. The narrow therapeutic index: toxicity appears at >100 umol/L and may be severe at >150 umol/L.
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Why is phenytoin a bad choice for use in adolescents?
Can you name 5 other side effects? |
1. coarse facies, acne, hirsutism, gingival hyperplasia - particularly undesirable in teenagers!
5 other SEs: 1. Rash, including SJS 2. Megaloblastic anaemia 3. Osteoporosis 4. Fetal malformation 5. Severe idiosyncratic rxs (hepatitis, skin) |
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What is red hand syndrome/purple glove syndrome - which is associated with Phenytoin?
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PGS is associated with IV infusion of Phenytoin. The limb where the infusion is going is becomes red then purple, oedema and pain are present. It can be so severe that compartment syndrome can occur. It is thought to be due to phenytoin extravasating into the tissues.
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What is Fosphenytoin?
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A water soluble prodrug of phenytoin for IM or IV use. It's expensive!
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What are the 2 mechanisms of action of Valproate?
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1. Blocks sodium channels (suppresses high frequency firing) - main action.
2. Increases calcium-dependent potassium conductance. |
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When is valproate used?
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Valproate is very broad spectrum and treats almost all seizures apart from infantile spasms.
It is also used in bipolar disorder and migraine. |
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How is valproate metabolised by the liver? Name 3 pathways.
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1. Conjugation - glucuronide
2. beta-oxidation 3. CYP450 |
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What are the most common side effects of valproate?
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1. GI upset - nausea, gastric irritation, diarrhoea
2. Hyperphagia - weight gain 3. Alopecia, when hair grows back it is often curly Less commonly: tremor, ataxia, behavioural disturbance NB: Fetal malformations, 1-2% risk of spina bifida. |
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What are 2 rare but serious side effects of valproate?
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1. Hepatotoxicity
2. Coma with increased serum ammonia and reduced serum carnitine. |
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Who is particularly at risk of idiosyncratic potentially fatal hepatotoxicity from valproate?
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1. Ordinary risk is 1/37,000.
This risk increases to 1/500 if: less than age 2 yrs, mental retardation or polypharmacy. 2. Usually occurs in 1st few months of treatment as abdo pain, anorexia, vomiting and weight loss. 3. Differential dx: pancreatitis from valproate. |
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How can valproate cause coma as a side effect?
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A small number of patients develop progressive lethargy and coma, associated with increased serum ammonia levels and decreased serum carnitine levels. Valproate may block the metabolism of carnitine leading to the come. Stopping the valproate leads to recovery over a few days.
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What is the mechanism of action of Carbamazepine?
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1. Blocks sodium channels.
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When can you use Carbamazepine?
When must you NOT use carbamazepine? |
1. Good for simple and complex partial seizures and for tonic-clonic seizures secondary to a focal discharge.
2. NOT to be used in absence epilepsy or myoclonus - it can exacerbate these seizures. // |
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What antiepileptic drug has an increased risk of SJS in Han Chinese?
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Carbamezepine.
Individuals with HLA-B 1502 allele (Han Chinese or Thai origin) are at increased risk of SJS when CBMZ is used. Consider testing before starting CBMZ, PHT or OXC. |
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List 5 side effects of carbamazepine.
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1. Skin rash (maculopapular rash in 5%), SJS risk in Han Chinese (HLA-B 1502)
2. Hepatotoxicity 3. Transient leukopenia (10-20%) 4. Aplastic anaemia (1 in 200,000) 5. Reversible blurring of vision, dizziness, and unsteadiness are dose related (and may be dose-limiting). |
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How do you monitor for carbamazepine toxicity?
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1. FBC and LFTs monthly for the first 3 months of therapy.
2. Watch for leukopenia or hepatotoxicity during this time. 3. This is more helpful than checking CBMZ levels. |
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When is ethosuximide used?
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1. 1st line for treating typical absence seizures. It can normalise the EEG!
2. Also can be used for myoclonic seizures, atypical absence, atonic and tonic seizures (BNFC). 3. It has no effect on GTC seizures. |
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What is the mechanism of action of ethosuximide?
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1. Calcium channel blocker (T-type) - blocks the calcium channels associated with thalamo-cortical circuitry, therefore inhibits the 3Hz thalamic spike and wave discharge and normalises the EEG.
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Name 3 side effects of ethosuximide.
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1. GIT - nausea, 33% at onset, titrate slowly.
2. Rash, can lead to SJS 3. Blood dyscrasias. Generally there are fewer side effects than other drugs and hypersensitivity reactions are rare. |
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What are the 2 antiepileptic drugs that lead to weight gain?
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1. Valproate
2. Vigabatrin (The two V's!) |
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What is the mechanism of action of benzodiazepines?
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1. GABA-A receptor agonist: binds to a specific GABA site that enhances the opening frequency of the chloride channel.
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When are benzodiazepines used?
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1. 1st line in status epilepticus
2. Otherwise used as adjunctive treatment 3. Clonazepam is used in partial seizures, myoclonic seizures, LGS, akinetic seizures, infantile spasms 4. Clobazam is used as an adjunct in complex partial seizures. |
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List 6 drawbacks to using benzodiazepines.
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1. Short duration of action
2. Respiratory depression 3. Sedation 4. Tolerance develops 5. Rebound seizures on withdrawal 6. All cause behavioural change Hypersecretion in Clonazepam |
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What is the mechanism of action of vigabatrin?
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1. Increases GABA levels which results in inhibition of neurotransmission (by binding to the degradative enzyme GABA transaminase receptor).
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When is vigabatrin used?
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1. 1st line for infantile seizures, especially effective for those with tuberous sclerosis.
2. Adjunctive therapy for poorly controlled seizures. |
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How is vigabatrin cleared?
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Renal excretion.
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Why is vigabatrin not used in the USA? Name 3 other side effects.
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1. Visual field restriction has been noted in 40% of adults - usually asymptomatic but irreversible with a cumulative effect over 6 months.
2. Weight gain 3. Lethargy. 4. Psychomotor disturbance. May increase myoclonus. |
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What is the mechanism of action of Lamotrigine?
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Acts on Na channels. Stabilises the neuronal membrane and inhibits neuronal release (especially glutamate release).
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When is lamotrigine used?
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1. Effective monotherapy for some with LGS, absence seizures
2. Adjunctive therapy for complex partial and GTC seizures (broad spectrum and well-tolerated) |
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Lamotrigine interacts with other antiepileptics which has effects on its metabolism. Name 1 drug that inhibits LTG metabolism, name 2 drugs that induce LTG metabolism.
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1. Valproate inhibits LTG metabolism - therefore if using these together, need to drop the dose of LTG.
2. Carbamazepine and phenytoin induce the metabolism of LTG. LTG also autoinduces its own metabolism. The major pathway of metabolism is via liver glucuronidation. |
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When is a person particularly at risk of developing SJS with Lamotrigine?
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1. during the titration phase - especially if rapid escalation of dose
2. if polypharmacy - especially with valproate |
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List some common side effects of lamotrigine.
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1. headache
2. nausea 3. dizziness 4. blurred vision 5. diplopia 6. ataxia |
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What is the mechanism of action of Gabapentin?
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Increases brains turnover of GABA - by binding to glutamate synapses.
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When is gabapentin used?
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As adjunctive therapy for refractory partial seizures.
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List 4 side effects of gabapentin.
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1. May increase myoclonic seizures.
2. Drowsiness 3. Dizziness 4. Weight gain It's also expensive! |
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What are the mechanisms of action of Topiramate?
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This is not very well understood but basically it seems to do everything!
1. Blocks sodium channels 2. Blocks L type calcium channels 3. GABA-A receptor agonist 4. Increases GABA levels 5. reduces glutamate levels 6. Blocks carbonic anhydrase (inhibitor) |
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List 3 side effects of Topiramate.
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1. Word-finding difficulties (and other cognitive dysfunction) 10%
2. Kidney stones (1.5%) 3. Anorexia and weight loss |
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What are 2 antiepileptic drugs that cause hyponatraemia?
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1. Carbamazepine
2. Oxcarbazepine |
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What is the mechanism of action of oxcarbazepine?
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1. Blocks sodium channels
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How are oxcarbazepine and carbamazepine similar?
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1. These are similar in action.
2. They both can cause hyponatraemia. 3. 30% of patients who react to CBMZ will also react to OXC. 4. Both can exacerbate absence and myoclonic seizures |
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What is the mechanism of action of levetiracetam?
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Keppra works by novel action: synaptic vesicle modulation, it blocks N-type calcium channels and increases GABA release.
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When is levetiracetam used?
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Broad spectrum of action, but especially used in:
1. Refractory partial epilepsy 2. Juvenile myoclonic epilepsy 3. Progressive myoclonic epilepsy |
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List 4 side effects of Levetiracetam.
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1. Behavioural change
2. Psychosis 3. Somnolence, fatigue 4. Headache |
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What relatively new antiepileptic drug is a sulphonamide derivative?
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Zonisamide
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What could be used as 1st and 2nd line for GTC seizures?
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1. Valproate
2. Carbamazepine (MEL) |
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What could be used as 1st and 2nd line for partial seizures?
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1. Carbamazepine
2. Valproate |
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What drug is 1st line for absence seizures?
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1. Ethosuximide in childhood absence epilepsy
2. Valproate in juvenile absence epilepsy |
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What could be used 1st line for myoclonic epilepsy?
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1. Valproate
2. second line: lamotrigine |
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What could be used 1st and 2nd line for tonic/atonic seizures?
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1. Lamotrigine
2. Valproate |
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What is 1st line in infantile spasms?
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Vigabatrin
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What is 1st line in Landau Kleffner syndrome?
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1. Valproate +/- lamotrigine
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What is used for seizure management in Benign Rolandic Epilepsy (Benign Partial Epilepsy of Childhood BPEC)?
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1. Try to avoid treating seizures as they tend to go away by 15 yrs!
2. If have to, use carbamazepine. |
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What is 1st line therapy for AD frontal lobe epilepsy?
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1. Carbamazepine.
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What antiepileptics are recommended for treating Lennox-Gastaut Syndrome?
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Combination of Valproate + Lamotrigine + Clobazam.
LGS is often refractory. |
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What antiepileptic drugs block sodium channels as their mechanism of action?
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Major action in:
1. Phenytoin 2. Carbamazepine 3. Lamotrigine 4. Topiramate (multiple actions) "Pen carves a lame top" 5. Oxcarbazepine Minor action in: 1. Phenobarbitone 2. Valproate |
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What antiepileptic drugs block calcium channels?
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Major action in:
1. Valproate (T type) 2. Ethosuximide (T type) 3. Levetiracetam (N type) 4. Topiramate (L type) "Valerie sucks a level top" Minor actions in 1. Phenytoin 2. Phenobarbitone |
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What antiepileptic drugs act as GABA-A receptor agonists?
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1. Phenobarbitone
2. Benzodiazepines 3. Topiramate (multiple actions) 3. Levetiracetam "Barb bends a level top" |
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What antiepileptic drugs increase GABA levels?
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1. Vigabatrin
2. Topiramate (multiple actions "Vibrant top" |
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What antiepileptic drugs reduce glutamate?
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1. Topiramate (multiple actions)
Minor action: 1. Phenobarbitone |
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Name 3 antiepileptic drugs that make absence and myoclonic seizures worse.
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1 Carbamazepine/Oxcarbazepine
2. Vigabatrin 3. Gabapentin "Carve a vibrant Gabby" |
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What are the side effects of sodium channel blockers? "Pen carves a lame top"
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1. Drowsiness
2. Tremor 3. Diplopia 4. Headache 5. Vomiting Actually these SEs occur in all AEDS, but they are worst with the Na channel blocker group. |
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What are the adverse behavioural side effects of the GABAnergic drugs? "Barb bends a level top" and "vibrant top"
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1. hyperactivity
2. aggression 3. irritability 4. mood disturbance Actually these SEs occur in all AEDs but they are worst with the GABAnergic group. |
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Which antiepileptic drugs need monitoring?
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1. Phenytoin
2. Phenobarbitone Also useful in 3. Carbamazepine |
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Which antiepileptic medication is contraindicated for use with a ketogenic diet?
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Valproate.
Because ketogenic diet increases risk of hepatotoxicity, and valproate can cause idiopathic potentially fatal hepatotoxicity. |
