Morning Report: 10/8/2013

Thanks to Dr. Gichinga for today’s Morning Report!

Carbamazepine Toxicity

Carbamazepine (5H-dibenzazepine-5-carboxamide) is an iminostilbene derivative with a tricyclic structure. It is an antiepileptic drug widely used for treatment of simple partial seizures and complex partial seizures, trigeminal neuralgia, and bipolar affective disorder.

Carbamazepine is absorbed erratically after oral administration because of its lipophilic nature. It has a large volume of distribution; peak plasma levels occur 4-8 hours postingestion but may take up to 24 hours to peak. The primary site of metabolism is the liver; its metabolite also is active, which may increase duration of the symptoms of toxicity.

Pathophysiology

Works by blocking the sodium channels in the brain which reduces the propagation of abnormal signals thereby inhibiting the generation of repetitive action potential in the epileptic focus.

Symptoms

Drowsiness
Slurred speech
Ataxia
Hallucinations
Nausea/Vomiting
Tremors
Seizures
Oliguria
Blurred vision
Bullous skin formations

Physical Examination

Ocular
- Mydriasis
- Nystagmus
- Ophthalmoplegia
Cardiovascular
- Tachycardia
- Hypotension
Neurologic
- Ataxia
- Slurred speech
- Dystonia, myoclonic activity
- Varying degrees of CNS depression progressing to coma
- Seizures, headache, confusion, and athetosis
- Increased or decreased deep tendon reflexes
Respiratory depression, apnea
Delayed gastric emptying, abdominal pain
Oliguria, urinary retention
Skin
- Bullous skin eruptions: Toxic epidermal necrolysis (TEN) has been reported with use of this drug. Severe drug eruptions are rare, and life-threatening events occur in 4 per million persons a year. TEN can trigger a life-threatening systemic inflammatory reaction leading to respiratory failure.
- Rash, dermatitis: Drug rash with eosinophilia and systemic symptoms, also known as DRESS syndrome, reflects a serious hypersensitivity reaction to drugs. Clinically, a diffuse maculopapular rash, exfoliative dermatitis, facial edema, lymphadenopathy, fever, and multivisceral involvement may be observed. All of these symptoms are associated with a high mortality rate. A cross-reactivity between carbamazepine and phenytoin occurs, which may lead to or worsen DRESS syndrome. Discontinuation of the anticonvulsants and topical steroids should ameliorate the rash.
- Stevens-Johnson syndrome
Blood dyscrasias
- Pancytopenia
- Splenomegaly
- Lymphadenopathy
- Vasculitis
- Aplastic anemia
- Agranulocytosis

Toxicity:

Therapeutic levels range from 4-12mg/L, however if patient is on multiple anticonvulsants they tolerate lower levels at around 4-8mg/L.

Ataxia and nystagmus can be seen at levels >10.

Place the patient on a monitor.
Administer IVF as needed for hypotension.
Administer IV diazepam (5-10 mg, repeat q10-15min prn) or other BZD to control seizures.
Gastric lavage may be helpful if performed within 1 hour of ingestion.
Protect the patient’s airway by placing the patient in left lateral decubitus position or by intubating.
Induction of emesis is not recommended because of the risk of CNS depression and seizures.
Administer activated charcoal if the patient is able to protect his or her airway.
Multiple doses of activated charcoal (1 g/kg) can be administered every 2-4 hours to enhance total body clearance and elimination in the patient with significant toxicity.
A saline cathartic or sorbitol may be given with the first dose of charcoal, although evidence for their effectiveness is lacking. Do not repeat activated charcoal administration if an ileus is present.
Perform whole-bowel irrigation (WBI) after ingestion of extended-release drug formulation:
- Adults and adolescents: 1.5-2 L/h (20-30 mL/min) of PEG-ELS
- Small children: 0.5 L/h (25 mL/kg/h)
Administer sodium bicarbonate when QRS is wider than 100 msec due to carbamazepine toxicity (sodium channel blockade).