KY is a 12-year-old boy who has been diagnosed recently with acute lymphoblastic leukaemia (ALL). He has been admitted to hospital for treatment.
KY’s initial therapy will comprise the corticosteroid dexamethasone, as well as the cytotoxic agent’s vincristine, L-asparaginase, daunorubicin, methotrexate and cytarabine. He experiences gastrointestinal upset but responds well to therapy; however, he does require close monitoring of his condition. KY receives adjunct therapy with the colony stimulating factor filgrastim.
KY’s four siblings are tissue-typed for bone marrow transplant. One of the children is considered a good match. While awaiting transplantation, KY develops a fever. He receives intravenous therapy with doxycycline to reduce the risk of sepsis. This crisis passes. After bone marrow transplant, KY makes good progress and moves into remission.
Answer the following questions:
1. Describe the mechanism of action of the corticosteroids and indicate the adverse effects that require monitoring during treatment with these drugs. (6 marks)
2. To which cytotoxic drug groups do each of the drugs in the case study belong? (5 marks)
3. Describe the mechanism of action of each of the drug groups identified in question two
(5 marks)
4. What are the common immediate and delayed adverse reactions associated with cytotoxic drugs? (4 marks)
5. Describe the clinical management of a client with increased susceptibility to infection. (5 marks)
6. To which antimicrobial drug group does doxycycline belong? Is it considered a bactericidal or bacteriostatic agent? Explain. (3 marks)
7. Define the term ‘antimicrobial drug spectrum of activity’. What is the spectrum of activity of doxycycline? Why choose a drug with this spectrum of activity? (2 marks)
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1. The mechanism of action of corticosteroids, such as dexamethasone, involves binding to specific receptors in the cytoplasm of cells. Once bound, corticosteroids enter the nucleus and modulate gene expression by binding to specific DNA sequences. This leads to the inhibition of pro-inflammatory genes and the induction of anti-inflammatory genes.
During treatment with corticosteroids, there are several adverse effects that require monitoring. These include:
- Gastrointestinal upset: This could manifest as nausea, vomiting, or stomach irritation. Close monitoring of KY's gastrointestinal symptoms is important to ensure proper nutrition and hydration.
- Immunodeficiency: Corticosteroids can suppress the immune system, making the patient more susceptible to infections. KY should be closely monitored for signs of infection, and appropriate measures should be taken to prevent and treat infections.
- Adrenal suppression: Long-term use of corticosteroids can lead to suppression of the adrenal glands, which produce natural steroids. This can result in a condition called adrenal insufficiency. Monitoring of KY's adrenal function and adjusting the dose of corticosteroids accordingly is important.
- Growth inhibition: Corticosteroids can affect growth in children, so monitoring KY's growth and development is necessary.
- Behavioral changes: Corticosteroids can sometimes cause mood swings, irritability, or changes in behavior. Monitoring KY's mental health and providing appropriate support is important.
2. The cytotoxic drugs mentioned in the case study belong to the following groups:
- Vincristine: It belongs to the group of drugs called vinca alkaloids.
- L-asparaginase: It belongs to the group of drugs called enzyme inhibitors.
- Daunorubicin: It belongs to the group of drugs called anthracyclines.
- Methotrexate: It belongs to the group of drugs called antimetabolites.
- Cytarabine: It belongs to the group of drugs called nucleoside analogs.
3. The mechanisms of action of the drug groups mentioned above are as follows:
- Vinca alkaloids (e.g., vincristine): They interfere with the formation of microtubules, which are essential for cell division. This disrupts the normal functioning of cells and inhibits their growth.
- Enzyme inhibitors (e.g., L-asparaginase): They inhibit the activity of specific enzymes necessary for the survival and growth of cancer cells. In the case of L-asparaginase, it deprives leukemia cells of the amino acid asparagine, which they need to grow.
- Anthracyclines (e.g., daunorubicin): They interfere with DNA replication and cause DNA damage in cancer cells. This prevents them from dividing and growing.
- Antimetabolites (e.g., methotrexate): They interfere with DNA and RNA synthesis by acting as fake building blocks. This disrupts the normal functioning of cancer cells and inhibits their growth.
- Nucleoside analogs (e.g., cytarabine): They mimic the building blocks of DNA and disrupt DNA synthesis and repair. This inhibits the growth and division of cancer cells.
4. The common immediate and delayed adverse reactions associated with cytotoxic drugs include:
- Immediate reactions: These can include hypersensitivity reactions, infusion reactions, and acute toxicities such as nausea, vomiting, or diarrhea.
- Delayed reactions: These can include bone marrow suppression, leading to decreased blood cell counts (anemia, neutropenia, thrombocytopenia), gastrointestinal disturbances, hair loss (alopecia), fatigue, and long-term organ toxicities (e.g., cardiotoxicity).
5. The clinical management of a client with increased susceptibility to infection, like KY, includes:
- Close monitoring for signs of infection, such as fever, chills, cough, or increased WBC count.
- Prompt initiation of empirical broad-spectrum antibiotics in the case of suspected infection.
- Strict adherence to infection prevention measures, such as hand hygiene, isolation precautions, and proper cleaning of equipment and surfaces.
- Encouraging vaccination and immunization to provide additional protection against infectious diseases.
- Education and support for the client and their family on proper hygiene practices, recognizing signs of infection, and when to seek medical attention.
6. Doxycycline belongs to the antimicrobial drug group called tetracyclines. It is considered a bacteriostatic agent, meaning it inhibits bacterial growth rather than killing the bacteria directly.
7. The term "antimicrobial drug spectrum of activity" refers to the range of microorganisms that a drug is effective against. The spectrum of activity of doxycycline includes many gram-positive and gram-negative bacteria, as well as some atypical bacteria and certain protozoa. It is also effective against some of the bacteria that commonly cause respiratory and urinary tract infections.
Choosing a drug with this spectrum of activity is beneficial because it provides coverage against a wide range of potential pathogens. This is particularly important in cases where the patient is immunocompromised, like KY, as it helps to prevent and treat infections caused by various microorganisms.