Question

please answer the following questions 1-3.

1)Why could corticosteroid use trigger invasive disease?

2)What is the difference between acute and chronic when it come to disease in general? What is another example of a disease which can be chronic or acute?

3)What is the mechanism of action of the three main antifungal drugs in use (polyenes, azoles, and allylamines)? What is hepatotoxicity? This link may help you.

Answer 1

1. Corticosteroids usuage leads to increased susceptibility to the invasive diseases. It is because corticosteroid hormones exert immunosuppressive effects that leads to immunodeficiency and causing host susceptibility to the invasive diseases.

For example, glucocorticoids usage leads to invasive fungal infection. These hormones inhibit NFkB and other transcription factors that leads to anti-inflammatory and immunosuppression.

2. Acute is sudden onset of symptoms and usually lost within short period of time whereas chronic disease take longer duration for the onset of symptoms and it lost longer compared to the acute disease.

Example, normal wound healing takes place within short period of time whereas wound in diabetic patients take longer due to impairment in the inflammatory phase of wound healing.

3.

Polyenes bind to the ergosterol present in the cell membrane of fungi and forms pores in the membrane. This leads to leakage of intracellular ions and impairment in membrane potential.

Azoles inhibit enzyme 14α-lanosterol demethylase which is involved in the synthesis of ergosterol, the sterol present in the membrane of fungi. This leads to depletion of ergosterol and accumulation of toxic sterols.

Allylamines inhibit enzyme squalene epoxidase which converts squalene to ergosterol, the sterol present in the cell membrane of fungi. Accumulation of toxic squalene intracellularly and loss of ergosterol in the cell membrane leads to death of fungi.

Hepatotoxicity means toxicity to the liver. Hepatocytes are liver cells and toxicity to the hepatocytes known as hepatotoxicity.