Download Free Medical ANTICANCER DRUGS PowerPoint Presentation

ANTICANCER DRUGS PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Anticancer Drugs", to know about the Anticancer Drugs.

Tags : Pharmacology, Anticancer Drugs

Published on : Jul 18, 2021 | Views : 3578 | Downloads : 7

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Assoc. Prof. Ivan Lambev www.medpharm-sofia.eu ANTICANCER DRUGS
Slide 2-

Possible causes of cancer Physical agents (radiation, mobile phones ?) Chemicals (carcinogens, including smoking) Hereditary factors Effectiveness of the immune system (virus infections: Ca collum uteri) Stress, > BMI (GI cancer), some drugs (cyclophosphamide, estrogens, tamoxifen)
Slide 3-

Uncontrolled proliferation Can be invasive Can metastasize Lack of function (lack of differentiation) Characteristics of cancer cells
Slide 4-

Normal cells Growth is controlled by growth factors and growth inhibitory factors Cancer cells Inactivation of tumor-suppressor genes Activation of proto-oncogenes
Slide 5-

ANTICANCER TREATMENT  surgery  radiotherapy (irradiation)  chemotherapy  supportive therapies NB! NB!
Slide 6-

The sensitivity of a cancer to treatment depends on the growth fraction – that is the fraction of cells undergoing mitosis at any time.
Slide 7-

The fraction of cell division in Burkitt’s lymphoma is 100% and this tumor is very sensitive. In contrast the growth fraction represents less than 5% of cells in a carcinoma of the colon and this explains its resistance to chemotherapy.
Slide 8-

However, metastases from colonic carcinoma, deposited in the liver and elsewhere initially, have a high growth fraction and are sensitive to chemotherapy, which is frequently given following surgical removal of primary tumor.
Slide 9-

Different forms of cancer differ in their sensitivity to chemothe- rapy. The most responsive are rapidly proliferating tumors: lymphomas leukemias choriocarcinoma testicular carcinoma
Slide 10-

Solid tumors show a poor response: colorectal carcinomas adrenocortical carcinomas squamous cell bronchial carcinomas
Slide 11-

An intermediate response is shown by other cancers: bladder head and neck oаt cell bronchogenic carcinoma sex-related cancers of the breast, ovary, endometrium, prostate
Slide 12-

Solid tumors – surgery or irradiation, plus CHEMOTHERAPY “Non-solid tumors” – CHEMOTHERAPY Metastases – CHEMOTHERAPY
Slide 13-

Myelotoxicity (reduction of leukocytes increases susceptibility to infections) Hair loss Adverse effects Most of the anticancer agents have a limited selectivity and damage all dividing cells. As a result general adverse effects are:
Slide 14-

Damage to GI tract Impaired wound healing Depression of growth Nausea and vomiting Carcinogenicity (in rare cases) Reproductive toxicity (PRC: D/X) Kidney damage Hepatotoxicity
Slide 15-

Resistance to cytotoxic drugs (primary or acquired) in 90% of cases – mechanisms: Increased rate of synthesis of target enzyme (dihydrofolate reductase and methotrexate) Increased repair of DNA (alkylating agents) Insufficient activation of prodrug – cytarabine (does not undergo phosphorylation) Multi Drug Resistance – increasing action of membrane efflux system (P-gp 170 and 190), etc.
Slide 16-

Strategy to avoid resistance Use 3 or 4 anticancer drugs together or in sequence, e.g. treatment of lymphomas: COP treatment (COP – acronym) – Cyclophosphamide – Oncovin® (vincristine) – Prednisolone
Slide 17-

Each drug should be an active anticancer drug in its own right. Each drug should have a different mechanism of action and target site within the cancer cell (this will increase efficacy and will reduce the resistance). Each drug should have a different site for any organ-specific toxicity. Criteria for selecting combinations
Slide 18-

The dosage of many antineoplastic drugs is carried out according to the body surface of the patient, calculated in square meters (m2) by means of nomogram according body mass in kg and height in cm. The best treatment regimens are become the "gold standard" for treatment of cancer. They are develop and annually update by world oncotherapeutic teams.
Slide 19-

Prof. A. Dudov, MD, PhD President of Bulgarian Cancer Scientific Society
Slide 20-

ppt slide no 20 content not found
Slide 21-

Anticancer (antineoplastic) drugs I. Cytotoxic drugs (cytostatics) - Alkylators - Antimetabolites - Plant-derived drugs and their analogs - Cytotoxic antibiotics - Platinum coordination complexes II. Endocrine agents - Glucocorticoids - Sex hormones and antihormones
Slide 22-

III. Target drugs - Monoclonal antibodies (MAB) - Protein (tyrosine kinase) inhibitors - Inhibitors of production of TNF-α IV. Inhibitors of bone resorption and metastases V. Immunomodulators - Cytokines (ILs, IFNs) - Vaccines VI. Radiotherapy VII. Cancer supportive therapies
Slide 23-

CYTOTOXIC AGENTS The majority of cytotoxic agents inhibit the process of DNA synthesis within the cancer cells. Resting cells (those in the Go phase) are resistant to many anticancer drugs.
Slide 24-

Precursors Precursors Purine Pyrimidine Ribonucleotides Deoxiribonucleotides DNA RNA Proteins Methotrexate Mercaptopurine Alkylators Cis-platin Antibiotics Nitrosoureas Mitotic inhibitors Asparagine Asparaginase
Slide 25-

Action of cytotoxic agents on the cell cycle Cycle non-specific Alkylators Antibiotics Phase specific Antimetabolites Mitotic inhibitors
Slide 26-

 Alkylating agents These drugs were developed from the sulfur mustard gases used in the 1st WW trenches and which caused bone marrow suppression in addition to respiratory toxicity. Replacement of the sulfur atom by nitrogen allowed the first alkylating agents to be obtained.
Slide 27-

The important functional group is the di-(2-chlor-ethyl)-amine side chain: R—N CH2CH2Cl CH2CH2Cl The dichlorethylamine chains are highly reactive and produce alkylating groups which bind covalently to sites within the DNA such as N7 of guanine.
Slide 28-

ppt slide no 28 content not found
Slide 29-

Chlorambucil Cyclophosphamide a) First alky- lators are di-(2-chlor ethyl)- amines: Nitrogen mustards
Slide 30-

Cyclophosphamide and Chlorambucil are commonly used for Hodgkin’s and non-Hodgkin’s lymphoma, chronic lymphocytic leukemia. Cyclophosphamide is also used for immunosuppression in non-malignant disorders (severe rheumatoid disorders, myasthenia gravis, multiple sclerosis).
Slide 31-

Cyclophosphamide is a prodrug. One of its metabolites is acrolein. Acrolein causes bladder toxicity with haemorrhagic cystitis which can be prevented by prior treatment with Mesna. Bladder cancer may develop years after cyclophosphamide chemotherapy. Cancer
Slide 32-

b) Nitrosoureas (the other alky- lators) inhibit the synthesis of DNA, RNA, and proteins. Carmustine crosses BBB. It is used for brain tumors. Carmustine and Lomustine are used for the treatment of Hodgkin’s lymphoma.
Slide 33-

A number of useful chemothera- peutic agents have been produced by simple modifications to the structures of normal purine and pyrimidine bases.  Antimetabolites – produce lethal synthesis
Slide 34-

5-Fluorouracil (5-FU®: i.v.) – used for the treatment of carcinoma of stomach, colon, rectum, breast, and pancreas. Xeloda® (p.o.) – used in colorectal carcinoma. It is a prodrug of 5-FU with very high selectivity. Cytarabine: used in acute myeloid leukemias (It acts after phosphorylation) a) Analogues of pyrimidine 5-FU
Slide 35-

5-FU blocks thymidilate synthase
Slide 36-

b) Analogues of purine Mercaptopurine (6-MP) and Thioguanine (6-TG): used in childhood acute leukemia; Fludarabine Gemcitabine is an analogue of pyrimidine too. It inhibits DNA polymerase and impairs DNA synthesis. It is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancers, breast cancer.
Slide 37-

c) Folic acid antagonists Methotrexate, Pemetrexed, Ralitrexed Folic acid in its reduced form (THF – tetrahydrofolic acid) is essential for syn- thesis of the purine ring system. During these reactions THF is oxidized to dihydro- folic acid which has to be reduced by dihydrofolate reductase. Methotrexate inhibits dihydrofolate reductase and blocks purine and thymidine synthesis.
Slide 38-

Folic acid Methotrexate (It has immunosuppressive activity too.)
Slide 39-

Methotrexate is given for the treatment of: acute lymphoblastic leukemia non-Hodgkin’s lymphomas chorionepithelioma non-malignant disorders (such as psoriasis).
Slide 40-

Adverse effects of methotrexate Vasculitis Arachnoiditis Pharyngitis, pneumonitis Cystitis Vomiting Hepatotoxicity Renal dysfunction PRC: D
Slide 41-

 Plant-derived drugs and their analogs Vinca alkaloids Derivatives of Podophyllotoxin Taxans etc. They have cycle and phase specific action on the cell division.
Slide 42-

Vinca alkaloids are complex natural chemicals isolated from the periwinkle plant (Vinca rosea). Vinblastine Vincristine Vinorelbine (Navelbine®) They bind to tubulin and produce metaphase arrest. They are used in acute leukemia.
Slide 43-

(mitotic inhibitors)
Slide 44-

Podophyllum peltatum (May apple) Podophyllotoxin Epipodophyllotoxin Etoposide Teniposide Derivatives of Podophyllotoxin (epipodophyllotoxins)
Slide 45-

Etoposide Inhibits mitosis Acts in late S- or early G2-phases Used in treatment of lymphoma; lung, testicular, bladder and prostate cancer
Slide 46-

Taxans Docetaxel – in breast cancer Paclitaxel Inhibit the depolymerization of tubulin and block mitosis. (Taxus brevifolia)
Slide 47-

 Cytotoxic antibiotics (inhibit DNA replication)
Slide 48-

Daunorubicin Idarubicin Doxorubicin Epirubicin
Slide 49-

Mitomycin C – in cancer of the bladder (locally after TUR) Other antibiotics Bleomycin in: – testicular cancer – melanomas, sarcomas – squamous cell carcinomas
Slide 50-

Cis-platin binds to DNA and proteins. It has made a significant impact on the treatment of testicular teratoma and ovarian tumors. It has a long t1/2 (72 h) due to extensive protein binding and slow renal elimination. Renal toxicity is a major problem. Severe nausea and vomiting are often troublesome too. PRC: D.  Platinum coordination complexes
Slide 51-

II. Endocrine agents Some cancer arise from cell lines with steroid receptors. Steroid hormones cause remissions in certain types of cancer. They usually do not eradicate the disease, but can alleviate symptoms for a long period and do not depress the bone marrow.
Slide 52-

Glucocorticoids suppress lymphocyte mitosis and are used in combination with cytotoxic agents in treating of lymphomas, myeloma and to induce a remission in acute lymphoblastic leukemia.
Slide 53-

Hydrocortisone, Prednisone Dexamethasone, Prednisolone Glucocorticoids are also helpful in reducing oedema around a tumor. They have antiemetic activity too.
Slide 54-

 Estrogens suppress prostate cancer both locally and metastases, and provide symptomatic improvement. Gynecomastia is a common side effect. Ethinylestradiol Polyestradiol phosphate
Slide 55-

 Progestagens suppress endometrial cancer cells and lung secondaries: Gestonorone Medroxyprogesterone
Slide 56-

Androgens are used rarely in the treatment of carcinoma ovarii and uteri Testosterone Side anabolic effect:
Slide 57-

 Androgen antagonists suppress prostate cancer cells. Unwanted effects include: gynecomastia, decreased spermatogenesis, decreased libido. Bicalutamide, Cyproterone, Flutamide 1 2 3 PSA >> 5
Slide 58-

Cyproterone (Androcur®) p.o. i.m. – anti-aphrodisiac too.
Slide 59-

 Inhibitors of alpha-reductase Alpha-reductase converts testosterone in more active dihydrotestosterone. Finasteride is useful orally in the treatment of benign prostatatic hyperplasia.
Slide 60-

 Estrogen antagonists Fluvestrant, Toremifen Tamoxifen (p.o.) suppresses breast cancer cells. The trans isomer of Tamoxifen blocks competitively estrogen receptors. Adverse effects include hot flushes and amenorrhoea in premenopausal women and vaginal bleeding in postmenopausal women.
Slide 61-

 Aromatase inhibitors Aminoglutethimide Exemestane (Aromasin®) Formestane, Letrozole They inhibit aromatase and block conversion of androgens to estrogens. - Inhibition of aromatase reduces estrogen production in adipose tissue, skin, muscle, and liver of postmenopausal women (because ovarian aromatase is resistant to such inhibition!).
Slide 62-

Aromatase is also presented in the cells of two-thirds of breast carcinomas and about 80% of these tumors are estrogen- dependent. Aromatase inhibitors are used in postmenopausal women with advanced breast carcinoma. Side effects include symptoms of estrogen withdrawal, e.g. headache, hot flushes, and lethargy; dyspepsia, nausea, alopecia, skin rash, hypotension, tachycardia.
Slide 63-

Breast cancer
Slide 64-

Treatment with the aromatase inhibitor letrozole reduces the occurrence of distant metastases in Ca mammae
Slide 65-

 Gonadotrophin releasing hormone agonists (GnRHAs) Continuous daily administration of GnRHAs results in suppression of testicular and ovarian steroido- genesis due to decreased levels of LH and FSH with subsequent decrease in testosterone (in man) or estrogens (in women).
Slide 66-

Gonadotrophin releasing hormone agonists: Leuprolide (Leuproreline) Goserelin (Zoladex®) – 3.6 mg/30 days s.c. in: – palliative treatment of advanced prostatic carcinoma – endometriosis
Slide 67-

III. Target drugs They block receptors of the growth and other angiogenic factors: VEGF – vascular endothelial growth factor EGF – epidermal growth factor PDGF – platelet-derived growth factor PlGF – placental transfer growth factor TNF-α – tumor-necrosis factor alfa, etc.
Slide 68-

a) Monoclonal AntiBody (MAB) BEVACIZUMAB (Avastin®) – anti-VEGF agent blocks angiogenesis and the growth of new blood vessels. It is used to treat various cancers, including colorectal, lung, and kidney cancer, etc. Avastin®
Slide 69-

ppt slide no 69 content not found
Slide 70-

Colorectal cancer
Slide 71-

TRASTUZUMAB (Herceptin®) is part of a treatment plan for the adjuvant treatment of patients with HER2 overexpressing, node-positive HER2+ breast cancer. CETUXIMAB (an inhibitor of EGF receptor): used in metastatic colorectal cancer. www.breastcancer.org/symptoms
Slide 72-

b) Protein kinase inhibitors Imatinib (Glivec®): used for the oral treatment of chronic myelogenous leukemia Everolimus (Afinitor®) – mTOR inhibitor: mammalian Target Of Rapamycin) is used: in renal cancer, pancreatic neuroendocrine tumors, as an immunosuppressant to prevent rejection of organ transpalntants (including in drug-eluting coronary stents to prevent restenosis). Lapatinib, Pasopanib Sorefenib (used in renal and liver cancer)
Slide 73-

c) Inhibitors of the production of TNF-α: Thalidomide and analogs - in with Kaposi's sarcoma, glioblastoma, multiple myeloma, erythema nodosum leprosum)
Slide 74-

IV. Inhibitors of bone resorption and metastases
Slide 75-

The immune system probably contributes to the final removal of residual malignant cells, and most cytotoxic anticancer agents compromise immune responsiveness. V. IMMUNOMODIFICATORS
Slide 76-

 Cytokines – peptide regulators of inflam- matory and immune reactions. Interleukins, interferons, colony-stimulating factors, tumour necrosis factors.
Slide 77-

IL-2 produced by T-lymphocytes which activate cytotoxic killer cells. It is received by recombinant DNA technology. IL-2 has been given by i.v. infusion in patients with metastatic renal carcinoma. IL-2 causes many ADRs.
Slide 78-

Interferon alfa-2b (Intron® A) – in: chronic hepatitis, hairy cell leukemia AIDS-related Kaposi’s sarcoma renal carcinoma Interferons (alpha, beta, gamma) are glycoproteins produced as part of the natural host defenses to virus infections. They have antiviral activity, immunoregulatory function, reduce multiplication of cancer cells.
Slide 79-

Papular cutaneous Kaposi’s sarcoma Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8.
Slide 80-

 Vaccines BCG Immunotherapeuticum – locally in bladder cancer after TUR Silgard® and Cervarix® are vaccines against certain types of cancer- causing human papillomavirus (HPV – type 6, 11, 16, and 18) Cancer
Slide 81-

Cancer of the cervix uteri H P V Normal Early Stage IB Late Stage IB Stage IB
Slide 82-

HPV vaccines: SILGARD®: 0, 2, and 6 month i.m. (from 9 to 26 years old) CERVARIX® Cervarix® HPV
Slide 83-

Prof. G. Gorchev, MD, DSc: Medical University – Pleven
Slide 84-

ppt slide no 84 content not found
Slide 85-

 Radio-pharmaceuticals (radionuclides) - Irradiated with beta-rays): 131I, 32P (Sodium phosphate), 183Pal - palladium, 145Sm - samarium 89Sr (strontium)  Brahiterpiya (locally in prostate or vaginal cancer)  Photodynamic cancer therapy (irradiation with laser light, with consequent formation of free radicals): - Porfimer, Temoporfin VI. Radiotherapy
Slide 86-

VII. CANCER SUPPORTIVE THERAPIES
Slide 87-

ppt slide no 87 content not found
Slide 88-

ppt slide no 88 content not found
Slide 89-

Cisplatin Carmustine Cyclophosphamide Mitomycin C L-Asparginase Fluorouracil Methotrexate Etoposide Vincristine Emetogenic activity
Slide 90-

Colony-stimulating factors (CSFs) are used in special cancer therapy centers to reduce the severity and duration of neutropenia induced by cytotoxic anticancer chemotherapy; used in aplastic anaemia; used in anaemia in AIDS too.
Slide 91-

Molgramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor – rHuGM-CSF) Filgrastim (Recombinant Human Granulocyte Colony- Stimulating Factor – rHuG-CSF)
Slide 92-

ppt slide no 92 content not found
Slide 93-

“BURNOUT” syndrome
Slide 94-

www.medpharm-sofia.eu