Biology of Disease Coursework II

Biology of Disease Coursework II

Biology of Disease Coursework II

Introduction

The following case histories are presented. They share a common underlying theme (pathogen “X”). Answer the specific questions asked on each case and then the general questions at the end. Your answers need to be detailed but not very lengthy. “Mode of action” means site and mechanism of effect. Answering merely e.g. “anti-inflammatory” or “antibacterial” is not sufficient.

Case 1

A 7 year-old boy (with no chromosomal abnormalities) was diagnosed with T-cell acute lymphoblastic leukaemia. Chemotherapy (allopurinol, dexamethasone, vincristine, daunorubicin, pegylated L-asparaginase (Oncaspar) and methotrexate was begun.

a) For each of these drugs outlines its mode of action.

He was slow to respond and so chemotherapy was intensified after 2 weeks to escalated doses of these drugs plus 6-mercaptopurine.

b) What is the mode of action of this drug?

This was complicated by a short episode of fever with neutropenia, which was treated with meropenem and gentamicin.

c) What is the mode of action of these drugs?

Four days after hospital discharge, following induction of remission of the leukaemia he was admitted again for high fever (39.9 oC) without neutropenia. He was therefore started on oral teicoplanin and ceftriaxone. d) What is the mode of action of these drugs? Why use teicoplanin? Several days later he was still feverish. Antimicrobial therapy was therefore changed to i.v. meropenem, gentamicin and teicoplanin (Robertson, P. A., & Ryan, M. D. 1992, pp. 224-227).

e) Why change the administration route?

The following day he was drowsy and suffering from pronounced weakness down the left side. His pupils were unequally dilated.

f) What is the significance of these observations?

He also had urinary incontinence and a high fever. A brain CT scan revealed several scattered areas of darkening involving both frontal lobes, temporal horn of the right lateral ventricle and the occipito-parietal lobes. Acyclovir and was added to the drug regime, due to a history of recent family contact with a case of chickenpox.

g) What is the mode of action of acyclovir?

Neurological deterioration continued over the next two days despite the broad antibiotic coverage with an antiviral adjunct, and the brain abnormalities had grown larger and were better demarcated than before. Intermittent clonic seizures of the right hand began lasting for approximately two minutes at a time. Phenytoin was added to the drug spectrum.

h) Why administer this further drug?

The following day amphotericin B and caspofungin were empirically added to the regime. Neurological responsiveness declined further over the next few days, so a brain biopsy was performed. This revealed a pathogen “X” on microscopic and histological examination. PCR was done on the surgical material to confirm the presence of pathogen “X”, and of pathogen “X” was cultured successfully from the sample. Therefore, therapy was modified to a combination of voriconazole, caspofungin, and amphotericin B.

i)What is the mode of action of these drugs?

Why can they be administered together? The patient's dose of dexamethasone was reduced over the next few days until discontinuation. Despite broad spectrum anti-bacterial anti-viral and anti-fungal therapy, the patient's fever was unabated and the ...