A patient diagnosed with pulmonary tuberculosis (TB) was started on antituberculosis therapy. After a month of treatment, the patient develops jaundice, which resolves upon discontinuation of the therapy. Now, antituberculosis therapy is to be restarted. Which of the following drugs is least likely to cause his jaundice?
A. Rifampicin
B. Streptomycin
C. INH (Isoniazid)
D. Ethambutol
E. Pyrazinamide
Correct Answer: D. Ethambutol
Explanation:
Jaundice during antituberculosis therapy is often a result of drug-induced liver injury (DILI), which can be caused by one or more of the drugs in the regimen. Among the drugs listed, ethambutol is least likely to cause jaundice.
Drugs Associated with Jaundice:
- Rifampicin:
- Rifampicin is a potent hepatotoxic drug. It is a known cause of liver enzyme elevations and, in some cases, jaundice. The liver toxicity is generally dose-dependent, but it can occur even at standard doses.
- Streptomycin:
- Streptomycin, being an aminoglycoside antibiotic, primarily causes nephrotoxicity (kidney damage), but it is not typically associated with hepatotoxicity or jaundice. It is used less frequently in modern regimens due to its nephrotoxicity and ototoxicity, but it is not commonly linked to liver dysfunction like the other drugs listed.
- INH (Isoniazid):
- Isoniazid (INH) is a well-known cause of hepatotoxicity, especially in the first few months of therapy. It is one of the most common drugs to cause drug-induced liver injury (DILI), which can lead to jaundice. INH should be used cautiously, particularly in patients with pre-existing liver conditions or those who drink alcohol.
- Pyrazinamide:
- Pyrazinamide is another drug in the TB regimen known to cause hepatotoxicity and jaundice. It can lead to acute liver injury, particularly in patients who have underlying liver diseases or alcohol use.
- Ethambutol:
- Ethambutol is least associated with liver toxicity among the drugs listed. It primarily causes ocular toxicity (optic neuritis), leading to visual disturbances. While liver enzyme elevations have been reported, these are rare and mild compared to the other drugs in the regimen.
Why Ethambutol is Least Likely to Cause Jaundice:
- Ethambutol is less likely to cause liver damage compared to rifampicin, INH, and pyrazinamide. It is not associated with hepatotoxicity as a common side effect, unlike the other drugs that are known to cause drug-induced liver injury (DILI).
- The main side effect of ethambutol is optic neuritis, leading to visual disturbances, which is a major concern, but it does not typically affect the liver to the extent that would result in jaundice.
Management and Monitoring:
- Liver Function Monitoring:
- For patients starting antituberculosis therapy, it is important to monitor liver enzymes (ALT, AST, bilirubin) regularly to detect potential drug-induced liver injury (DILI).
- If Jaundice Occurs:
- If jaundice occurs, the first step is usually to stop all antituberculosis medications and conduct a thorough work-up to assess the severity and cause of liver dysfunction.
- Once liver function improves, the regimen can often be restarted with individual drugs based on the patient’s tolerance, avoiding the offending agent (e.g., pyrazinamide, INH, or rifampicin) that caused the jaundice.
- Rechallenge with Drugs:
- If liver function has recovered, ethambutol can often be safely continued, as it is less hepatotoxic compared to the other drugs.
- For the other drugs, rechallenge should be done with caution, and hepatic monitoring should continue.
Conclusion:
In this patient who developed jaundice, ethambutol is least likely to be the cause of the jaundice compared to rifampicin, INH, and pyrazinamide, all of which are known to cause hepatotoxicity. Monitoring liver function during antituberculosis therapy is critical to avoid serious complications related to drug-induced liver injury.
Table of Common Antituberculosis Drugs and Their Hepatotoxicity Potential:
| Drug | Hepatotoxicity Risk | Common Side Effects |
|---|---|---|
| Rifampicin | High | Hepatitis, jaundice, liver enzyme elevation |
| Streptomycin | Low | Nephrotoxicity, ototoxicity |
| INH (Isoniazid) | High | Hepatotoxicity, peripheral neuropathy |
| Ethambutol | Low | Optic neuritis (visual disturbances) |
| Pyrazinamide | High | Hepatotoxicity, hyperuricemia, GI upset |
This table should help provide clarity on the relative hepatotoxicity risks associated with each antituberculosis drug.