THERAPEUTICS

Brands

• 3,4-diaminopyridine, Firdapse, Zenas

Generic?

• Yes

Class

• Potassium channel blocker

Commonly Prescribed for

(FDA approved in bold)

• Lambert-Eaton myasthenic syndrome (LEMS)

• Congenital myasthenia gravis (CMG)

• Multiple sclerosis (MS)

• Downbeat nystagmus, cerebellar gait disorder

How the Drug Works

• Potassium channel blocker. Reduces flow of potassium across nerve terminal membranes and increases calcium influx with prolongation of action potential. This promotes presynaptic release of acetylcholine and may improve weakness and autonomic dysfunction

How Long Until It Works

• About 20 minutes, but maximum effect might take a few days

If It Works

• Continue to use to reduce symptoms of LEMS or CMG at lowest required dose. In LEMS, disease-modifying treatments, such as plasma exchange, IV immune globulin, corticosteroids, and immunosuppressives such as azathioprine are useful. Identifying malignancy such as small-cell lung cancer is essential

If It Doesn’tWork

• LEMS: treat with immunological therapy. Removal of neoplasm may improve symptoms

• CMG: establish the type. Presynaptic forms may respond to 3,4-diaminopyridine. Acetylcholinesterase inhibitors may improve or worsen symptoms, depending on the disorder

Best Augmenting Combos for Partial Response or Treatment-Resistance

• May be combined with pyridostigmine, which increases the available amount of acetylcholine for receptor binding and may allow reduction of dose

Tests

• Obtain baseline CBC, electrolytes, glucose, blood urea nitrogen, creatinine, liver function tests. Repeat monthly for 3 months, then every 6 months while on treatment

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Some AEs are related to acetylcholine release, others are unknown

Notable AEs

• Paresthesias, perioral numbness, insomnia, abdominal pain

Life-Threatening or Dangerous AEs

• Seizures, delirium: most common at doses of 100 mg or greater

Weight Gain

• Unusual

Sedation

• Unusual

What to Do About AEs

• Lower dose, supplement with pyridostigmine in LEMS. For first seizure, lower dose or discontinue and evaluate for metastatic brain tumor. For recurrent seizure, discontinue