Carbamazepine

Question 1

What type of drug is carbamazepine?

Answer 1

Anti convulsant

Question 2

How does carbamazepine work?

Answer 2

Carbamazepine inhibits neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability much like Phenytoin.

This inhibits spread of seizure activity in epilepsy, controls neuralgic pain by blocking synaptic transmission in the trigeminal nucleus and stabilises mood in bipolar disorder by reducing electrical ‘kindling’ in the temporal lobe and limbic system.

Also has anticholinergic, antidiuretic, anti arrhythmic, antidepressant (blocks NA release), muscle relaxant

Question 3

What are the common indications for the use of carbamazepine?

Answer 3

1. Epilepsy: as a first choice treatment for focal and generalised seizures
2. Trigeminal Neuralgia as first choice treatment to control pain and reduce frequency and severity of attacks.
3. Bipolar disorder: as an option for prophylaxis in patients resistant to or intolerant of other medication.

Question 4

What are the contraindications for using carbamazepine?

Answer 4

Pregnancy: neural tube defects, cardiac and urinary tract abnormalities and cleft palate.
Prior antiepileptic hypersensitivity syndrome is a contraindication to both carbamazepine and phenytoin
Porphyria

Question 5

When should carbamazepine be prescribed with caution?

Answer 5

Hepatic, renal, cardiac disease and BM depression

Question 6

What are the common interactions with carbamazepine?

Answer 6

• Carbamazepine induces cytochrome P450 enzymes, reducing plasma concentration and efficacy of drugs that are metabolised by P450 enzymes (e.g. warfarin, oestrogens and progestogens).
• Carbamazepine is itself metabolised by these enzymes, so its concentration and adverse effects are increased by cytochrome P450 inhibitors (e.g. macrolides).
• Complex interactions occur with other antiepileptic drugs as most alter drug metabolism.
• The efficacy of antiepileptic drugs is reduced by drugs that lower the seizure threshold (e.g. SSRIs, tricyclic antidepressants, antipsychotics, tramadol).

Question 7

Is carbamazepine a CYP450 inhibitor or inducer?

Answer 7

Inducer

Question 8

What are the common side effects of carbamazepine?

Answer 8

The most common dose-related adverse effects are:

• gastrointestinal upset (e.g. nausea and vomiting)
• neurological effects (particularly dizziness and ataxia)
• oedema and hyponatraemia due to an antidiuretic hormone-like effect of carbamazepine

Question 9

What is carbamazepine hypersensivitiy?

Answer 9

• Carbamazepine hypersensitivity affects about 10% of people taking the drug
• Commonly manifests as a mild maculopapular skin rash.
• Antiepileptic hypersensitivity syndrome affects about 1 in 5000 people taking carbamazepine or phenytoin, usually within 2 months of starting treatment.

Question 10

What is Antiepileptic hypersensivity?

Answer 10

Clinical features include:

• severe skin reactions (e.g. Stevens–Johnson syndrome, toxic epidermal necrolysis)
• Fever
• Lymphadenopathy
• Systemic (e.g. haematological, hepatic, renal) involvement
• Mortality of about 10%.

Question 11

Was is carbamazepine a first choice for?

Answer 11

Focal seizures

Question 12

How is carbamazepine excreted?

Answer 12

Heptaically metabolised

Renal Excreted