IM Sheet #8 By Haneen Bahzad

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IM Sheet #8 By Haneen Bahzad

Post by Sura on 8/12/2011, 2:31 am

http://www.mediafire.com/file/22r3p2q5uuhh0ub/Patients%20on%20Chemotherapy%20(2).doc
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Sura

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Re: IM Sheet #8 By Haneen Bahzad

Post by Shadi Jarrar on 23/12/2011, 8:32 pm

بسم الله الرحمن الرحيم

Patients on Chemotherapy





Internal medicine.

Dr. Feras Fararjeh.

lecture # 8

22 /11/2011

Done by Haneen Bahzad Hasan



What we neeed to know about patients in chemotherapy (CT) in general (general concepts) ? , cancer in general , who are the patients that we expect that they are receiving CT? , what are the most commonly used CT agents in practice? And what are the possible side effects of CT?





General Concepts



The purpose of treating cancer with chemotherapeutic agents is to prevent cancer cells from multiplying, invading, metastasizing, and ultimately killing the host (patient).

Most chemotherapeutic agents currently in use appear to exert their effect primarily on cell proliferation.

Note: cancer is an abnormal cells growth characterized by the loss of normal inhibitory mechanisms of the cell proliferation in the body in the organ of concern. For example, in leukemia there will be a problem in the proliferation and differentiation of there's cells in the bone marrow. Another example is the breast cancer : the problem is in breast glands.

Note: every cell in our body has 2 capabilities: 1. the capability to proliferate and 2. the capability to differentiate to another cell in the line of differentiation. For example RBC in the bone marrow: proerythroblast differentiate to erythroblast which will differentiate into reticulocyte that will end in RBC.



Cell multiplication is characteristic of many normal cells as well as cancer cells, so that’s why chemotherapeutic agents will have toxic effects on normal cells , particularly those with a rapid rate of turnover, such as bone marrow and mucous membrane, hair follicles.



The goal in selecting an effective drug is to find an agent that has marked growth inhibitory or controlling effect on the cancer cells and a minimal toxic effect on the host.

Cancer, is a malignant neoplasm. It is a term for a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body (metastasize). The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream.











*CT is chemotherapy.

* 10^10: we need 5 cycles to eradicate all disease cells.



In an ideal system, each time the dose is repeated, the same proportion of cells-not the same absolute number- is killed (fractional cell kill) .



In this example, 3 logs of cancer cells are killed with each treatment cycle, and there is a one log growth between each cycle of treatment. The net reduction is 2 logs with each treatment. Such a model is liable for some changes when it comes to clinical practice for the following reasons:

1) All cells in the tumor are not equally sensitive to chemotherapy.

Note: decrease is not equal at the same time.

2) Drug accessibility to tumor cells varies according to the site of the tumour within the host and local factors such as blood supply and regional fibrosis.

Note: for example, not all drugs will cross the blood brain barrier.

Note: poor blood supply and fibrosis will decrease the drug accessibility.

3) Cell sensitivity may change during the course of therapy.

Note: at first, we may obtain such a decrease in the log of cells but later on during the course of CT, the decrease will not be the same, bcuz of the development of cell sensitivity to CT agents , so the cancer cells may have resistance to CT agents bcuz of different mechanisms especially the efflux of CT agents outside the cells, so nowadays they use a combinations of CT agents to enhance sensitivity and to reduce the risk of developing resistance.





Main lines of cancer treatment includes:




  • Surgical (complete resection and palliative surgery).

complete resection: If tumor is surgically removable and there is no metastasize for palliative symptoms , the best to go for a surgery.

palliative surgery: for example, gastric tumor and its effects ( symptoms like nausea and vomiting ), orpancreatic tumor which make a bile duct compression , these will be treated by palliative surgery or when the patient is already diagnosed with metastasis of the cancer cells, the treatment will be by palliative surgery.


  • Medical (chemotherapy and molecular targeted therapy).
  • Radiotherapy alone or with a medical therapy



Combination chemotherapy is usually used with a number of drugs with different mechanisms of actions simultaneously administered, the main aim is to decrease tumor resistance and enhance response to CT.

A careful review of the patient status should be undertaken to assess tolerability to chemotherapeutic drugs and should include: cardiac, renal, hepatic assessment of the patient as well as performance status scale and other medical co-morbidities.( all of them are needed to determine how much the patient is going to tolerate CT, in some patients we don't give them CT agents bcuz simply the function status is poor and we expect them to be extremely bad if we give them systemic CT).





Chemotherapy Setting



Chemotherapy maybe given aiming for cure or for palliation of symptoms.

Curative Intent: (there is no metastasizing to other sites in the body.)

1) Neoadjuvant: initial chemotherapy is designed to shrink the primary tumor and make it more respectable, thereby rendering local therapy less destructive or more effective. (before surgery or before radiotherapy) , for example: breast cancer and colon cancer.

2) Adjuvant: chemotherapy is given post surgical resection to eradicate any potential remaining malignant cells and when there is micro metastasis to other sites in the body.

Palliative intent:

Chemotherapy is given to palliate symptoms ( direct compression, obstruction or paraneoplastic manifestation ) of the malignancy, improving quality of life, and prolong life expectanct . Used usually when the disease is metastatic or the general condition of the patient doesn’t allow a curative surgery.











Cell Cycle



Description
Abbreviation
Phase
State
A resting phase where the cell has left the cycle and has stopped dividing.
G0
Gap 0
Resting
Cells increase in size in Gap 1.
G1
Gap 1


Interphase
DNA replication
S
Synthesis
Cell continue to grow and increase in cell size
G2
Gap 2
Cell growth stops at this stage and cellular energy is focused on the orderly division into two daughter cells
M
Mitosis
Celll division







Cellular factor affecting sensitivity to chemotherapy:

1) Cellular growth fraction.( it is the amount of cells in mitotic phase in the same tumor ,and increase in it ,will increase the sensitivity to CT )

2) Tumor differentiation.

v (Increase in tumor well differentiation will lead to increase sensitivity to CT by more regulation of the phases.)

v tumor poorly differentiated or undifferentiated ( mechanisms of cell proliferation are lost ) will lead to decrease in sensitivity.





Chemotherapeutic Agents

In relation to cell cycle, chemotherapeutic agents can be divided into three different categories:

1) Phase specific drugs: Agents that are most active against cells in a specific phase of the cell cycle for example G1, M, and G2.

2) Cell cycle specific drugs: Agents that are effective while cells are actively in cycle but that are not dependent on the cell being in a particular phase.

3) Cell cycle nonspecific drugs: A third group of drugs that appear to be effective whether cancer cells are in cycle or are resting ( in resting phase).







Chemotherapeutic Agents



Type
Agent
Class
Antimetabolite, Pyrimidine analog

Topoisomerase II inhibitor

Vinca Alkaloid
Cytarabine (S phase)

Etoposide (G2 phase)

Vinblastine (M phase)
Phase specific
Alkylating agents
Cyclophosphamide

Melphalan
Cell cycle specific

( all the cell cycle phases except the resting phase)
Nitrogen Mustard
Mechlorethamine
Cell cycle non specific





Classification of Chemotherapeutic Agents (according to the mechanism of action).





EXAMPLES
CLASS
Cyclophosphamide

Ifosfamide

Melphalan

Platinum analogues (Alkylating like) : there is

no alkyl group but behave like alkylating

agents (cisplatin, carboplatin)
Alkylating agents

(contain alkyl group which make

apoptosis of cell and stops the cell

at specific level)
Purine analogue (Fludarabine)

Pyrimidine analogue (Cytarabine)

Antifolates (Methotrexate) = foliate deficiency
Antimetabolites

( inhibit metabolites that require

by cells during synthesis, mitosis

and proliferation.)
Vinblastine ( vinca alkaloids)

Vincristine ( vinca alkaloids)

Paclitaxel( taxol, taxosene? and taxanes ?)
Plant alkaloids and

Taxanes

( derived from plants)




Irinotecan (I)

Etoposide (II)


Topoisomerase inhibitors I, II
Doxorubicin,adremysin? ,anthracyclines
Cytotoxic antibiotics

( have cytotoxic effect)







Chemotherapy side effects



Chemotherapeutic drugs have a wide range of side effects that depend on the type of medications used and dose of medications used. The most common medications mainly affect the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines.



Some common examples:

1) Myelosuppression and immune suppression ( all CT agents cause it in higher doses )

2) Gastrointestinal side effects

3) Cardiotoxicity (specific CT agents causes cardiotoxicity )

4) Hepatotoxicity

5) Nephrotoxicity

6) Encephalopathy

7) Increased risk of secondary neoplasms ( all CT agents cause it)

8) Infertility in male and female

9) Teratogenicity (all CT agents are teratogenic)

10) Tumor lysis syndrome

*1and 2 are the most common side effects

Myelosuppression and immune suppression

Depends on the type of chemotherapy and dose given.

Leads bone marrow suppression to anemia, thrombocytopenia, and leukopenia (neutropenia a decrease of the neutrophil granulocyte count below 0.5 x 109/litre )

Neutropenia increases the risk of infections and the patients should be isolated and treated with broad spectrum antibiotics if an infection( bacterial , viral and fungal) is suspected.

Careful dental assesment should be carried out in patients who are expected to go into severe myelosuppression post chemotherapy as bad oral hygiene is associated with increased risk of dental abscess.



Gastrointestinal side effects

Chemotherapy induced nausea and vomiting, which can be acute or delayed. Nausea and vomiting occurrence depends on the drug used as some drugs

( like vinca alkaloids and cisplatin) are considered more emetogenic than others

Xerostomia, mucositis.

Mouth ulcers

Loss of appetite

Diarrhea



Chemotherapy induced Cardiotoxicity


  • Some chemotherapeutic drugs can lead to cardiomyopathy and heart failure and all symptoms of heart failure . This depends on the cumulative dose of the drug. In addition, previous or concomitant radiation to left hemithorax, risk factors for cardiovascular disease, and anemia may cause more cardiac toxicity. Some common examples of drugs with cardiac toxicity are adremycin? (anthracyclines).

Cardiac toxicity can be acute (within hours or immediate action) or chronic. Chronic toxicity can occur even after many years of finishing chemotherapy



Note: Taxotin, herceptin ( thrastazomap) in breast cancer.



Hepatotoxicity

· it depends on the drug that been used like etoposide VB60?

· in patients who have hepatitis and increase in liver enzymes, we should decrease the CT agents dose.



Nephrotoxicity

· The patient must have a normal kidney function before starting almost any chemotherapy. So you must always check the kidney function statues by taking a careful history if they have a risk factor for nephrotoxicity like diabetes, hypertension and then we can start CT if we think the kidney is normal.

· Cisplatin, melphalan and cyclophosphamide





Encephalopathy


  • Neurological symptoms in general, reversible mucodystrophy in brain, numbness and weakness.



Increased risk of secondary neoplasms

· Acute myelogenes

· Acute mayeloplastic leukemia

· Mayelodysplasia

· Mayelodysplastic syndrome

This risk may stay for 2-5 years after finishing CT.



Infertility

· In male : decrease or ineffective spermatogenesis.

· In female: premature amenorrhea and premature ovarian failure leading to premature menopause.



Teratogenicity

· we shouldn’t give CT agents except if it is a life saving for the patient.





Tumor lysis syndrome

A potentially lethal complication of anticancer treatment, it occurs when large numbers of neoplastic cells are killed rapidly, leading to release of intracellular ions and metabolic byproducts into the systemic circulation.

It is typically associated with acute leukemias and high-grade non-Hodgkin lymphomas {such as Burkitt lymphoma} .

Characterized by rapid development of hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acute renal failure (ARF)



THE END






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Shadi Jarrar
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تاريخ التسجيل : 2009-08-28
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