Ethambutol Flashcards
What is the mechanism of action of ethambutol?
Ethambutol inhibits the enzyme arabinosyl transferase (encoded by the emb gene) in Mycobacterium, which blocks polymerization of arabinoglycan, an essential component of the mycobacterial cell wall. This action is bacteriostatic.
How can Mycobacterium tuberculosis develop resistance to ethambutol?
Resistance can develop via mutations in the embB gene leading to overproduction or structural change in arabinosyl transferase, reducing drug binding. Thus, more substrate is available to overcome ethambutol’s effect or the enzyme no longer binds the drug effectively. Ethambutol is always given in combination with other TB drugs to prevent resistance.
What is ethambutol’s role in TB treatment and its spectrum?
Ethambutol is a first-line agent in active TB, mainly to prevent emergence of resistance to other drugs. It has activity against Mycobacterium tuberculosis and also Mycobacterium avium-intracellulare (MAI, when used in MAC therapy with macrolides). It is not used for non-mycobacterial infections.
Outline key pharmacokinetic features of ethambutol.
Ethambutol is well absorbed orally and distributes well, including into CNS if meninges are inflamed. It is partially metabolized and primarily excreted unchanged in urine. Dose adjustment is required in renal impairment. It has a fairly short half-life (~3-4 hours) and is usually given daily. It crosses the placenta but is considered safe in pregnancy at standard doses.
What are the major adverse effects of ethambutol?
The hallmark toxicity is optic neuropathy. It typically causes loss of visual acuity and red-green color blindness (difficulty distinguishing red from green). This is usually dose-dependent and reversible if caught early and drug is discontinued. Other side effects are relatively rare but include peripheral neuropathy and rash. Hyperuricemia can occur (ethambutol can decrease renal urate excretion slightly), but gout is uncommon compared to pyrazinamide.
When is ethambutol contraindicated or when should it be used with caution?
Use with caution in patients with pre-existing optic neuritis or poor vision. In young children, monitoring for visual changes is difficult, so some guidelines suggest avoiding ethambutol in very young kids if possible (though it can be used if needed, with careful monitoring). Contraindicated in patients who absolutely cannot report visual symptoms. Adjust dose in renal failure to prevent toxicity.
Is there a mnemonic to remember ethambutol’s toxicity?
“Ethambutol = Eye-thambutol.” This emphasizes its effect on the eyes (optic neuritis causing color blindness). Remember the “E” for Ethambutol and Eyes.
