QuestionSBA
QuestionChoice
Pleural effusions can be associated with malignancy, and these are usually exudative. Pleural effusions are usually associated with reduced air entry and dull percussion notes as opposed to fine crackles
32740
c
Exudative pleural effusion
QuestionChoice
This is unlikely to be the diagnosis here. Although the patient is likely to be at risk of developing infections such as pneumonia, no other signs of infection are present. Pneumonia does not usually produce fine crackles throughout the lung fields on auscultation
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b
Community-acquired pneumonia
QuestionChoice
Pulmonary fibrosis is a recognised side effect of bleomycin, and fine crackles on auscultation should prompt this diagnosis. A chest x-ray should be performed, and the medication may need to be stopped
32738
a
Pulmonary fibrosis
QuestionChoice
Transudative pleural effusions are usually caused by fluid overload, such as organ failure (kidney, liver, heart) or through iatrogenic causes. Pleural effusions are usually associated with reduced air entry and dull percussion notes as opposed to fine crackles
32741
d
Transudative pleural effusion
QuestionChoice
Asthma can cause breathlessness, but this is not usually progressive in nature. Auscultation of the chest would reveal polyphonic wheeze or, in a severe attack, may be silent
32742
e
Asthma
QuestionComment
Toxicity bear! :D 
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Endoscopic retrograde cholangiopancreatogra-chap
Concept
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# Summary 


Cytotoxic drugs, or chemotherapeutics, are medicines which are capable of destroying cells at particular stages of the cell cycle. Typically, they have more effect on rapidly dividing cells, such as cancer cells. The action of chemotherapeutic agents varies with different classes of medication available and each class will have specific side effect profiles.


# Side effects

Common side effects of many cytotoxic drugs include:

- Increased risk of infection
- Anaemia
- Easy bruising
- Fatigue
- Gastrointestinal upset
- Appetite loss
- Mucositis
- Hair loss
- Skin & nail changes
- Emotional & cognitive changes
- Increased risk of infertility

Before each cycle of chemotherapy, blood tests including FBC, U&Es & LFTs are carried out to assess for toxicity, and to check fitness for chemotherapy treatment.

# Specific chemotherapy drugs

Some chemotherapy drugs carry an increased risk of some side effects. It is important to be aware of these in exam settings and in clinical practice as a patient may present with long-term side effects of anticancer treatments.

### Doxorubicin

Doxorubicin is a member of the anthracycline family of **cytotoxic** antibiotics. It inhibits topoisomerase II, an enzyme which joins the DNA double helix, therefore halting the cell cycle. Doxorubicin also generates free radicals which damage the DNA and cell membrane structures. It is used to treat **haematological cancers** and solid tumours including **breast cancer**.

Doxorubicin can cause **cardiomyopathy**, which presents up to 15 years after treatment. Doxorubicin's cardiotoxic effects range from isolated ECG changes to pericarditis and established cardiomyopathy. Before treatment begins cardiac function should be assessed with an ECG and/or echocardiogram.

### Cisplatin

Cisplatin is a platinum-based agent which works by crosslinking with DNA purine bases, causing DNA damage and disrupting repair mechanisms. It is used to treat **testicular, ovarian, lung, bladder, cervical** and **head and neck** cancers.

Key side effects of cisplatin use are **peripheral neuropathy** and **hearing loss**. It is also known for causing severe nausea and vomiting.

### Cyclophosphamide

Cyclophosphamide is an alkylating agent which damages DNA, and is activated by the liver. It is used to treat a number of cancers including **haematological** cancers and **breast** cancer. It is also used as an immunosuppressant.

Cyclophosphamide can cause urothelial toxicity, specifically **haemorrhagic cystitis** and, in the longer term, transitional cell carcinoma of the bladder. Mesna is used with high dose cyclophosphamide to reduce the concentration of active metabolite in the urinary tract and reduce the risk of this occurring.

### Bleomycin

Bleomycin is a cytotoxic antibiotic that works by inhibiting DNA synthesis. It is used to treat metastatic **germ cell** cancers, **head and neck** cancers and some **non-Hodgkin's lymphomas**.

One key side effect to be aware of is **lung fibrosis**. Respiratory side effects typically begin 1-6 months after treatment completion, although may occur sooner if a hypersensitivity reaction occurs.

### Cytarabine

Cytarabine is an antimetabolite chemotherapeutic drug. It prevents the synthesis and repair of DNA. It is used to treat **haematological** cancers.

Cytarabine can cause **ataxia** due to an acute cerebellar syndrome, especially at higher doses. This may also cause **dysarthria.**

### Methotrexate

Methotrexate is an **antifolate** drug, commonly used as an immunosuppressant but is also used in treatment for a number of cancers including **haematological** cancers, **gestational trophoblastic** disease and **breast cancer**.

Side effects to be aware of include **bone marrow suppression, gastrointestinal toxicity, photosensitivity, liver and pulmonary toxicity**. Folinic acid is typically given alongside and FBC should be monitored closely.


# References

[BNF: Cytotoxic drugs](https://bnf.nice.org.uk/treatment-summaries/cytotoxic-drugs/)

[BNF: Cisplatin](https://bnf.nice.org.uk/drugs/cisplatin-specialist-drug/)

[BNF: Bleomycin](https://bnf.nice.org.uk/drugs/bleomycin-specialist-drug/)

[BNF: Cytarabine](https://bnf.nice.org.uk/drugs/cytarabine-specialist-drug/)

[BNF: Methotrexate](https://bnf.nice.org.uk/drugs/methotrexate/)

[NHS: Chemotherapy side effects](https://www.nhs.uk/conditions/chemotherapy/side-effects/)

[Cancer research UK: Cytarabine](https://www.cancerresearchuk.org/about-cancer/treatment/drugs/cytarabine)

[An overview of doxorubicin formulations in cancer therapy](https://journals.lww.com/cancerjournal/fulltext/2014/10040/an_overview_of_doxorubicin_formulations_in_cancer.9.aspx)

[Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies](https://www.sciencedirect.com/science/article/pii/S0022282812001150)

[Cancer research UK: doxorubicin](https://www.cancerresearchuk.org/about-cancer/treatment/drugs/doxorubicin)

[StatPearls: Cyclophosphamide](https://www.ncbi.nlm.nih.gov/books/NBK553087/#:~:text=Cyclophosphamide%20is%20a%20medication%20primarily,anti%2Dneoplastic%20effects%20through%20alkylation.)

[Drugbank.com: Bleomycin](https://go.drugbank.com/drugs/DB00290)

[Chemotherapy agents with known pulmonary side effects and their anaesthetic and critical care implications](https://www.sciencedirect.com/science/article/abs/pii/S1053077015005698)

[Cytarabine induced acute cerebellar syndrome during hyper-CVAD treatment for B-cell acute lymphoblastic leukaemia](https://pmc.ncbi.nlm.nih.gov/articles/PMC5437478/)

[Drugbank.com: Methotrexate](https://go.drugbank.com/drugs/DB00563#)
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Bleomycin can cause pulmonary fibrosis, characterised by fine crackles on auscultation and progressive breathlessness in affected patients.
A 74-year-old male diagnosed with Non-Hodgkin's lymphoma and started on bleomycin. He presents to General Practice complaining about progressive breathlessness. On auscultation of his chest, you notice bilateral fine crackles.

What is the likely diagnosis?
a