THERAPEUTICS

Brands

• Mestinon, Mestinon Timespan, Regonal

Generic?

• Yes

Class

• Cholinesterase inhibitor

Commonly Prescribed for

(FDA approved in bold)

• Myasthenia gravis (MG)

• Reversal of non-depolarizing muscle relaxants

• Orthostatic hypotension

How the Drug Works

• It is a quaternary amine that reversibly inhibits the cholinesterase enzyme and improves the neuromuscular transmission in MG. It is poorly absorbed in the gut and does not cross the BBB

How Long Until It Works

• Orally about 30 minutes, IM form within 15 minutes, IV within 5 minutes

If It Works

• Continue to use to reduce symptoms of MG. Often combined with disease-modifying therapy such as immunosuppression or thymectomy

If It Doesn't Work

• Increase to the maximal dose: if no effect, question the diagnosis of MG. Remove potential offending medications. If not controlled at 240–360mg daily, consider immunomodulating treatment

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Generally not combined with other symptomatic treatments. For refractory MG, add immunotherapy

Tests

• None

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Cholinergic properties of the drug

Notable AEs

• Muscarinic AEs include diarrhea, abdominal cramps, nausea, increased salivation, miosis, increased bronchial secretions, rash, worsening of bronchial asthma, and diaphoresis. Nicotinic AEs, including fasciculation and muscle cramping, are less bothersome

Life-Threatening or Dangerous AEs

• Bradycardia – possibly leading to hypotension – is most common with IV use

• Cholinergic crisis – worsening weakness, usually with overdose of drug and severe cholinergic AEs – is very rare

Weight Gain

• Unusual

Sedation

• Unusual

What to Do About AEs

• Lower to tolerable dose, take with food

Best Augmenting Agents to Reduce AEs

• Treat GI AEs with anticholinergics that do not affect nicotinic receptors (so no weakness): glycopyrrolate 1mg, propantheline 15mg, or hyoscyamine sulfate 0.125mg. Use 3 times a day or take with each pyridostigmine dose. For diarrhea try loperamide or diphenoxylate hydrochloride-atropine. To prevent bradycardia and excessive secretions with IV form, use atropine 0.6–1.2mg IV immediately prior