anticonvulsants Flashcards
Describe the general toxidrome of carbamezapine
Dose dependent CNS and anticholinergic affect
Discuss risk assessment of carbamezapine
Symptoms are dose dependent but onset varies depending on whether the preparation is immediate or controlled release
20-50mg/kg: mild to moderate CNS and anticholinergic effects
>50mg/kg: flucuating mental status with intermittent agitation and risk of progression to coma within the first 12 hours. Risk of hypotension and cardiotoxicity with extreme doses
Following larger overdoses anticholinergic affect may be predominant prior to coma. Coma can be anticipated to last several days if a massive OD is taken
Pregnancy: Teratagenic needs further antenatal monitoringn
Children: one 400mg tablet is enough to cause a significant intoxication in a toddler and suspected ingestion of this dose should warrent observation for at least 8 hours
Discuss toxic mechanisms of carbemezapine
Inhibition of sodium channels preventing AP.
Blocks norad reuptake
Antagonist at muscarinic nicotinic and NMDA central adenosine receptors
Discuss toxicokinetics of carbemezapine
A: slowly and erratically absorbed. Following large overdoses ileus secondary to anticholinergic effects may result in ongoing absorption for several days.
D: Small VD
M: Heptaic metabolism by CP450 3A4 to farm an active metabolite
E: Excreted in the urine
Discuss clinical features carbemaziapine overdose
Usually evident within 4 hours with a peak at 8-12 hours particularly with controlled release. Erratic absorption for several days frequently complicates large overdoses producing a fluctuating clinical course
- Milds to moderate CNS affects include nystagmus, dysarthria, ataxis, sedation, delirium, mydriasis and myoclonus
- Anticholinergic effects common in the early stages
- Coma requiring intubation may delayed by up to 8-12 hours
- Large overdoses may be complicated by seizure, hypotension and cardiac conduction abnormalities. Dysrhythmias are associated with massive overdose
Discuss investigations of carbemezapine
ECG, paracetamol and BGL
Carbamazpine levels
- useful to confirm diagnosis
- mild to moderate nil need to repeat
- Coma essential to repeat 6 hourly to monitor clinical course
level
- 8-12mg/L (therapeutic range)
- > 12mg/L (nystagmus and ataxia)
- > 20mg/L (CNS and anticholingergic effects)
- > 40mg/L (Coma, seizures and cardiac conduction abnormalitiers)
Large overdose can be associated with evidence of NA blockade and ECG needs to be repeated (wide QRS, large terminal r wave, 1st degree heart block)
Discuss management of carbamezapine OD
Resus as per usual – bicarb if arrest
Seizures and agitation can be managed with benzos
In rare event of ventricular dysrhythmias, resus should include the use of IV blous sodium bicarb
D: Activated charcoal for ingestion <50mg/kg, if CNS involvement on activated charcoal if airway secured
E:Multiple dose activated charcoal - ceased if bowel sounds disappear. HD is affected given small VD
-Can consider dialysis if prlonged coma with serum levels greater than40mg/L after 48 hours or HD instbaility
A: nil antidote
Discuss disposition
Children suspected of 20mg/kg should be observed for 8 hours
Well patients at 8 hours can be discharged
Discuss the new anticonvulsant agents (Gabapentin, lamotrigine, levetiracetem, oxcarbazepine, pregabalin, topiramate)
Generally much less toxic in overdose than older agents.
Most overdoses with these agents produce mild and transietn CNS symptoms only
Symptoms usually appear within 2 hours and resolve in 24 hours
Coma and seizures can occur but are rare.
Discuss TM and TK of the newer anticonvulsants
TM: most of these agents potentiate GABA neurotransmission either by enhancing GABA release or inhibiting GABA reuptake at the synapse. Lamotrigine and topiramate also have effect on voltage dependent Na channels and topiramate inhibits carbonic anhydrase.
TK: All well absorbhed orally with linear kinetcs. most undergo hepatic metabolism and renal excretion.
Discuss clinical features of the new anticonvulsants
Gabapentin
- Nausea vomiting tachycardai hypotension and drowsiness
- Usually mild if present at all and resolve within 10 hours
Lamotrigine
- Ataxia, nystagmus, slurred speech drowsiness, transient intraventricular conduction delay (Rare) and seizures (rare)
- Rapid onset and resolve within 24-48 horus
Levetiracetam
-Agitation, dpressed LOC, coma and resp depression
Pregabalin
-drowsiness only
Topiramate
- Ataxia sedation coma seizure hypotension and metabolic acidosis
- CNS rapid onset usually with hours and resolve in 24 hours
- NAGMA is secondary to carbonic anhydrase inhibation.
Discuss management of the new anticonvulsants
RESUS
ABCD
D: Generally bening course with above so rarely indicated. If significant CNS affect and within 2 hours can administer charcoal through NGT once airway secure
E: Nil
A: nil
D: 6-24 hour observation if well can be discharge home
Discuss risk assessment of phenytoin
Results from either repeated supratherapeutic dosing or acute overdose. Intoxication is usually benign and results in dose related ataxia and CNS depression.
Coma and seizure are rare even in massive doses
CVS affects are not associated with ingestion of phenytoin but are reported after rapid IV infusion of excessive dose
10-15mg/kg - standard dose
>20mg/kg - ataxia dysarthria and nystagmyus
>100mg/kg potential for coma and seizures.
Discuss clinical features of phenytoin overdose
Present with gradual onset of ataxia dysarthrai and nystagmus Onset of neurological toxicity develops slowly over hours followed by acute overdose. Features of toxicity include 1) horizontal nystagmus 2) dysarthrai 3) ataxia 4) tremor 5) vertical nystagmus 6) othalmoplegia
Symptoms typically resolve over 2-4 days.
Discuss IX of phenytoin
Levels are useful to confirm the diagnosis and correlate with toxicity
- nystagmus is associated with levels >20mg/L
- severe ataxia is associated with levels of 30-40mg/L
- Coma is associated with levels of >50mg/L
