A patient on a didanosine and stavudine based regimen presents with severe abdominal pain radiating to the back, elevated serum lipase, and distal symmetric numbness of both feet. These complications share which common pathogenic mechanism?
- A Direct neurotoxicity of the parent drugs on dorsal root ganglia
- B Autoimmune hypersensitivity mediated by HLA-B*57:01
- C Inhibition of host mitochondrial DNA polymerase gamma leading to organ toxicity ✓
- D Accumulation of squalene in pancreatic and nerve tissue
Correct answer: C. Inhibition of host mitochondrial DNA polymerase gamma leading to organ toxicity
Explanation
Didanosine and stavudine are the NRTIs with the greatest affinity for host mitochondrial DNA polymerase gamma. Depletion of mitochondrial DNA in pancreatic acinar cells, neurons and other tissues produces pancreatitis, peripheral neuropathy and, with longer exposure, lactic acidosis with hepatic steatosis. This class-wide mitochondrial toxicity explains why these agents have been largely abandoned in modern regimens. Hypersensitivity mechanisms apply to abacavir, not to these drugs.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.