Therapeutics Flashcards
Risk factors of N&V secondary to chemotherapy?
- anxiety
- age less than 50 years old
- concurrent use of opioids
- the type of chemotherapy used
Which anti-emetics may be used to treat N&V in chemotherapy?
For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line.
For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone
What is cyclophosphamide and how does it work?
An alkylating agent used in the management of cancer and autoimmune conditions.
It works by causing cross-linking of DNA
Cyclophosphamide adverse affects
haemorrhagic cystitis
myelosuppression
transitional cell carcinoma
How can the incidence of haemorrhagic cystitis in cyclophosphamide use be reduced?
Use of hydration and mesna
What is mesna and why is it used?
2-mercaptoethane sulfonate Na
a metabolite of cyclophosphamide called acrolein is toxic to urothelium
- mesna binds to and inactivates acrolein helping to prevent haemorrhagic cystitis
Cytotoxic agents: antibiotic examples?
Bleomycin
Anthracyclines (e.g doxorubicin)
What is the action of bleomycin?
Degrades preformed DNA
What is the action of anthracyclines e.g. doxorubicin?
Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis
Cytotoxic agents: major adverse affect of bleomycin?
Lung fibrosis
Cytotoxic agents: major adverse affect of anthracyclines e.g. doxorubicin?
Cardiomyopathy
Cytotoxic agents: antimetabolite examples
Methotrexate
Fluorouracil (5-FU)
6-mercaptopurine
Cytarabine
Methotrexate mechanism of action?
Inhibits dihydrofolate reductase and thymidylate synthesis
Fluorouracil (5-FU) mechanism of action?
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)
6-mercaptopurine mechanism of action?
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
Cytarabine mechanism of action?
Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase
Cytarabine major adverse affects?
Myelosuppression
Ataxia
6-mercaptopurine major adverse affect?
Myelosuppression
Fluorouracil (5-FU) major adverse affects?
Myelosuppression, mucositis, dermatitis
Methotrexate major adverse affects?
Myelosuppression, mucositis, liver fibrosis, lung fibrosis
Examples of cytotoxic agents that act on microtubules
Vincristine, vinblastine
Docetaxel
Docetaxel major adverse affect?
Neutropenia
Docetaxel mechanism of action?
Prevents microtubule depolymerisation & disassembly, decreasing free tubulin
Vincristine, vinblastine mechanism of action?
Inhibits formation of microtubules
Vincristine major adverse affects?
Peripheral neuropathy (reversible) , paralytic ileus
Vinblastine major adverse affect?
Myelosupression
Example of cytotoxic agent which inhibits topoisomerase?
Irinotecan
Irinotecan mechanism of action?
Inhibits topoisomerase I which prevents relaxation of supercoiled DNA
Major adverse affect of irinotecan?
Myelosupression
Cisplatin - mechanism of action
Causes cross-linking in DNA
Hydroxyurea (hydroxycarbamide) mechanism of action?
Inhibits ribonucleotide reductase, decreasing DNA synthesis
Major adverse affects of cisplatin?
Ototoxicity
Peripheral neuropathy
Hypomagnesaemia
Hydroxyurea (hydroxycarbamide)
Myelosuppression
Hydroxyurea (hydroxycarbamide) and cisplatin are examples of what?
Cytotoxic drugs
What are immune checkpoint inhibitors?
Immunotherapy (alternative to cytotoxic chemotherapy)
. In contrast to therapies such as chemotherapy and tumour-targeted drugs that directly affect the growth and proliferation of tumour cells, these targeted treatments harness the body’s natural anti-cancer immune response. They boost its ability to attack and destroy the cancer cells.
Some cancer cells make high levels of proteins that turn T-cells off, reducing their desrtuction. Checkpoint inhibitors block this process and reactivate and increase the body’s own T-cell population, enhancing the immune systems own ability to recognise and fight cancer cells.
Where are the proteins CTLA-4 and PD-1 are found?
T-cells
Where are the PD-L1 proteins found?
On cancer cells
Types of checkpoint inhibitors?
Blockade of CTLA-4 (cytotoxic T lymphocyte-associated protein 4): Ipilimumab
Blockade of PD-1 (programmed cell death protein 1): Nivolumab (Opdivo) and pembrolizumab (Keytruda)
Blockade of PD-L1: Atezolizumab, Avelumab, Durvalumab
What is pilimumab (Yervoy) and what is it used to treat?
A checkpoint inhibitor that blocks CTLA-4 (cytotoxic T lymphocyte-associated protein 4)
Advanced melanoma
What are Nivolumab (Opdivo) and pembrolizumab (Keytruda) and what do they treat?
Checkpoint inhbitors that block PD-1
(programmed cell death protein 1)
These are treatments for melanoma, Hodgkin’s lymphoma, non-small cell lung cancer and urological cancers.
What are Atezolizumab, Avelumab and Durvalumab and what do they treat?
Checkpoint inhibitors that block PD-L1 and is used to treat lung cancer and urothelial cancer. I
Administration of checkpoint inhibitors?
All CTLA-4 inhibitors and PD-1/PD-L1 inhibitors currently available are monoclonal antibodies (laboratory-produced molecules engineered to serve as substitute antibodies that each bind to a specific protein). They are all administered by injection/intravenous infusion. Mostly, they are given as a single-agent treatment but sometimes, they can be combined with chemotherapy or each other. For example, ipilimumab and nivolumab can be used in combination.
What side effects might checkpoint inhibitors cause and why?
This mechanism of action of these drugs can result in side effects termed ‘Immune-related adverse events’ that are inflammatory and autoimmune in nature. This is because all immune cells are boosted by these drugs, not just the ones that target cancer. The over-active T-cells can produce side effects such as:
- Dry, itchy skin and rashes (most commonly)
- Nausea and vomiting
- Decreased appetite
- Diarrhoea
- Tiredness and fatigue
- Shortness of breath and a dry cough.
Checkpoint inhibitors: management and monitoring
Management of such side effects reflects the inflammatory nature, often involving corticosteroids.
It is important to monitor liver, kidney and thyroid function as these drugs can affect these organs.
Radiotherapy is an important form of therapy for cancer and accounts for 50% of all treatment regimens.
There are many side effects of radiotherapy and they are best characterised into early and late onset side effects.
EXAMPLES OF EARLY SIDE EFFECTS
Tiredness/Fatigue
Skin erythema
Alopecia
Mucositis (diarrhoea, dysuria)
Radiotherapy is an important form of therapy for cancer and accounts for 50% of all treatment regimens.
There are many side effects of radiotherapy and they are best characterised into early and late onset side effects.
EXAMPLES OF LATE SIDE EFFECTS
Skin pigmentation changes
Pulmonary fibrosis
Infertility
What type of chemotherapy agent are doxorubicin and daunorubicin examples of?
Anthracyclines
Examples of anthracyclines
doxorubicin
daunorubicin
Important classical side effect of Anthracyclines (doxorubicin, daunorubicin)?
Cardiomyopathy
Important classical side effect of anti-HER-2 monoclonal antibodies (e.g. Herceptin) cause cardiomyopathy?
Cardiomyopathy
What is Herceptin and example of?
anti-HER-2 monoclonal antibody
Examples of platinum agents?
Cisplatin
Carboplatin
What are cisplatin and carboplatin examples of?
Platinum agents
Important classical side effects of platinum agents (cisplatin, carboplatin)?
cause peripheral neuropathy and sensorineural hearing loss
+Cisplatin has a risk of ototoxicity and nephrotoxicity
Important classical urinary system side effects of cyclophosphamides?
Haemorrhagic cystitis
TCC of the bladder
What does gynaecological side effect is related to tamoxifen use?
Endometrial cancer
Important resp side effect of belomycin
Lung fibrosis
Important neurological side effect of cytarabine?
Ataxia
What is Cetuximab and what is it used for?
Cetuximab is an example of a monoclonal antibody
Used in treating squamous cell carcinomas of the head and neck and to treat bowel cancer.
It targets epidermal growth factor receptor, blocking the activation of this receptor and inhibiting the growth and metastasis of the tumour.
What is adjuvant chemotherapy?
Adjuvant chemotherapy refers to chemotherapy that people receive after another cancer treatment, such as surgery
What is neoadjuvant therapy?
Neoadjuvant therapy includes treatmentsTrusted Source that doctors use as an initial step to shrink tumors and kill any cancer cells that have spread. After that, they will start the primary treatment.
What type of cancer is cyclophosphamide commonly used to treat?
Glialblastoma
Classes of chemotherapy
Alkylating agents
Taxanes
Vinka alkaloids
Platinum complexes
Platinum complexes
Antimetabolites
Anthracyclines
Antitumour antibiotics
Topoisomerase inhibitors
Neutropenic sepsis: questions to ask
Date of last chemo
Which agent
Any lines?
Drug and allergies
