How Do Enzyme Inhibitors Work?

Enzyme inhibitors are a class of drugs used to treat Gaucher disease type 1 (an inherited disorder in which a certain fatty substance is not broken down normally and accumulates in the body, causing liver, spleen, bone, and blood problems) in people who cannot be treated with enzyme replacement therapy. The only drug that belongs to this class is “miglustat” which works by decreasing or preventing the production of a natural fatty substance “glucosylceramide” that accumulates in Gaucher disease and causes symptoms.

Gaucher disease is a rare, metabolic disorder in which deficiency of the enzyme glucocerebrosidase results in the accumulation of harmful quantities of certain fats (lipids), specifically the glycolipid glucocerebroside, throughout the body, especially within the bone marrow, spleen, and liver. Major signs and symptoms of Gaucher disease include:

• Hepatosplenomegaly (abnormally enlarged liver and/or spleen)
• Anemia (low levels of circulating red blood cells)
• Thrombocytopenia (low levels of platelets)
• Easy bruising
• Lung disease
• Bone abnormalities such as bone pain, fractures, and arthritis (swelling and pain in joints)

Enzyme inhibitors are administered orally, typically three times a day with or without food.

Enzyme inhibitors work in the following ways:

• They work by inhibiting the enzyme “glucosylceramide synthase,” an essential enzyme for the synthesis of most glycosphingolipids. 
• This prevents the production of a natural substance “glucosylceramide” that helps in improving the signs and symptoms of Gaucher disease.

Enzyme inhibitors are used in conditions such as:

• Gaucher disease (an inherited disorder in which a certain fatty substance is not broken down normally and accumulates in the body, causing liver, spleen, bone, and blood problems)
• Niemann-pick disease (a rare, inherited disease that affects the body's ability to metabolize fat [cholesterol and lipids] within the cells)

Some of the common side effects include:

• Diarrhea
• Nausea
• Vomiting
• Anorexia (lack or loss of appetite)
• Headache
• Abdominal pain
• Muscle cramps
• Flatulence (gas)
• Indigestion
• Constipation
• Dry mouth
• Weakness

Other rare side effects include:

• Unusual weight loss
• Dizziness (feeling faint, weak, or unsteady)
• Back pain
• Pain, burning, and numbness or tingling in hands, arms, legs, or feet
• Easy bruising or bleeding
• New or worsening hand tremors (shaky movements)
• Vision problems
• Thrombocytopenia (low blood platelet count) 
• Migraine (a headache that can cause severe throbbing pain or a pulsing sensation, usually on one side of the head)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of enzyme inhibitors include:

• Miglustat
• Zavesca