1.     Repetition and summary of drug mechanisms of action (MoA)

MoA of anticancer drugs (PowerPoint)

- open the PowerPoint file in edit mode and follow the instructions

A) Fill in the missing blanks in schemes with MoA of anticancer drugs

Identify the intracellular targets of different classes of cytotoxic anticancer drugs (cytostatics) 
Fill in the blanks in the scheme. Legend to Figure 1:

Give examples of different classes of cytotoxic anticancer drugs according to their mechanism of action.
Fill in the blanks in the scheme. Legend to Figure 2:

Give examples of individual agents belonging to each pharmacological group of cytotoxic anticancer drugs (1-6)

B) Fill in the missing blanks in the scheme with the principles of MoA of targeted anticancer drugs

Match the targets in Figure 3 with examples of monoclonal antibodies or tyrosine kinase inhibitors
Notice different targets of monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs)
Fill in the blanks in the scheme. Legend to Figure 3:

C) Pharmacological properties of anticancer drugs

Open the Excel file below and follow the instructions: 

2.     Repetition and summary of cytostatic toxicity

 

Give examples of different cytostatic toxic effects that you can remember from the lecture or the textbook
Distinguish the early and delayed cytostatic adverse effects
Give examples of typical toxic effects of the individual drug classes revised in the previous tasks 1A) and 1B)  
Make a simple drawing of a human and try to localize typical adverse effects of cytostatics - “Chemoman“ / “Toxman“ picture

3.     Chemotherapy-induced nausea and vomiting

• Explain the pathophysiology of vomiting induced by cytostatics
• Open the European Society for Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) guidelines (2016 update) 
• Learn about  consensus recommendations for the use of prophylactic antiemetics in advanced cancer patients

 

 Check the Czech oncological society JEP website and the information available at:  

Task A) Classification of cytostatics according to their emetogenic potential 

• Give examples of cytostatic agents according to their emetic potential with the use of ESMO guidelines above: 

1. Cytostatics with high or moderate emetogenicity: 
2. Cytostatic with low or minimal emetogenicity:

Task B) Prevention and therapy of chemotherapy-induced vomiting 

 

• Summarize antiemetic drug groups and individual agents according to their mechanism of action (MoA)
• Which antiemetics are used in oncological patients? Give examples of agents used for prophylaxis and therapy of nausea and vomiting:

1. 5-HT3 receptor antagonists: 
2. NK1 receptor antagonists: 
3. D2 receptor antagonists (and drugs with a combined MoA):

• Give examples of other drugs used in antiemetic combinations: 

Task C) Give examples of clinically used antiemetic drug combinations and their administration routes:

  

4.     Nephrotoxicity and urotoxicity of cytostatics

Give examples of typical nephrotoxic cytostatics
Explain the pathophysiology of their adverse effects
Suggest medication for prophylaxis of nephrotoxicity/urotoxicity of cytostatics

A) Prophylactic i.v. hydration regimen 

Suggest a hydration regimen for a patient treated with cisplatin. You can find it in the SPC. 

B) Mannitol-induced diuresis, furosemide-induced diuresis

Revise mechanism of action, adverse effects and their other possible indications 

C) Adjustment of the urinary pH   

Give pharmacological characteristics of methotrexate (MTX), its MoA, administration routes, oncological and non-oncological indications and adverse effects

Methotrexate inhibits nucleic acid synthesis by blocking the activation of folic acid.
Explain how do we adjust the pH of the urine in patients treated with higher doses of MTX
Can we use leucovorin to reduce MTX nephrotoxicity?
Why do we use leucovorin (i.e. folinic acid)? 
Explain the mechanism of the leucovorin rescue therapy “mechanism of leucovorin reversal of methotrexate cytotoxicity“ 
What is the administration route of leucovorin?
What is the reason for co-administration of 5- fluorouracil and leucovorin?

D) Urotoxicity

Give examples of typical urotoxic cytostatics

Give pharmacological characteristics of cyclophosphamide (MoA, administration routes, indications, adverse effects)
Explain the pathophysiology of urotoxicity of cytostatics  
Are there any drugs available for use in prophylaxis of urotoxicity?
Explain the MoA of mesna as an antidote
What is the administration route of mesna?

5.     Drugs used in the therapy of oncological pain and bone metastases

 

A) Analgesics 

The WHO analgesic ladder should be followed in treating cancer pain. Check the article below:

Complete the pain ladder in the Worksheet C with examples of drugs

Revise analgesics used in oncology, their MoA, indications, administration routes, contraindications and adverse effects
Which routes of administration are common for strong opioids? 
Which psychotropic agents can be used as co-analgesics?

B) Treatment of cancer pain, bone metastases

Bisphosphonates and denosumab are used in prophylaxis and therapy of bone metastases and associated bone pain.     

Fill in the blanks in the scheme that you can find in the Worksheet C

6.  Bone marrow toxicity (syn. Myelotoxicity) 

With the use of haemopoietic growth factors and leukocyte proliferation stimulation, we can reduce the risk of severe neutropenia development and the incidence of febrile neutropenia in oncological patients and shorten its duration. 

Prophylactic use of G-CSF decreases the risk of severe neutropenia. It will also decrease the incidence of infections due to febrile neutropenia in patients receiving myelosuppressive anti-cancer therapy. 
Thus, the patients will have a shorter stay in the hospital and reduced consumption of antibiotics and other supportive medications. At the same time, it will lower the risk of life-threatening complications of the therapy. 
There is a recombinant G-CSF available and its two technological modifications with different pharmacokinetic properties. 
Compare the pharmacokinetic properties of the following drug preparations (fill in the blanks in the Worksheet D):

1. filgrastim
2. pegfilgrastim
3. lipegfilgrastim