Download Free Medical Anticancer Drugs PowerPoint Presentation

Anticancer Drugs PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Cancer is characterized by uncontrolled multiplication and the spread of abnormal forms of the bodys own cells. It is characterized by a loss in the normal control mechanisms that govern cell survival, proliferation, and differentiation.

Tags : Anticancer Drugs, cancer,Tumor cells,Drugs,Tumor

Published on : Nov 06, 2020 | Views : 8383 | Downloads : 55

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Anticancer Drugs Dr. Mohammed Samir Hussein BCs of Pharmaceutical Science MD of Clinical Pharmacology
Slide 2-

Second Page Introduction ‘Cancer’ is characterized by uncontrolled multiplication and spread of abnormal forms of the body’s own cells. Characterized by a loss in the normal control mechanisms that govern cell survival, proliferation, and differentiation. A small subpopulation of cells, called “ tumor stem cells”, reside within a tumor mass. - Tumor cells They retain the ability to undergo repeated cycles of proliferation. They migrate to distant sites in the body to colonize various organs in the process called metastasis. - They are characterized by chromosome abnormalities reflecting their genetic instability
Slide 3-

Causes of Cancer Sex, age, race, genetic predisposition, Exposure to environmental carcinogens (most important) Viruses (Eg, hepatitis B and hepatitis C link to liver cancer) Retroviruses, a family of RNA viruses (oncogenes, Eg, bcl-2) induce oncogenic transformation Deletion or mutation of tumor suppressor genes (Eg, p53)
Slide 4-

The terms cancer, malignancy and malignant tumor are often used synonymously Cell-cycle and cancer
Slide 5-

Pathogenesis of Cancer Four characteristics that distinguish them from normal cells: Uncontrolled proliferation De-differentiation and loss of function Invasiveness Metastasis
Slide 6-

Pathogenesis of Cancer There are two main categories of relevant genetic change: 1. The activation of proto-oncogenes to oncogenes. Proto-oncogenes are genes that normally control cell division, apoptosis and differentiation which can be converted to oncogenes that induce malignant change by viral or carcinogen action. 2. The inactivation of tumour suppressor genes. Normal cells contain genes that suppress malignant change – termed tumour suppressor genes (anti-oncogenes) Mutations of these genes are involved in many different cancers The loss of function of tumor suppressor genes can be the critical event in carcinogenesis
Slide 7-

Pathogenesis of Cancer
Slide 8-

Types of anticancer drugs A second group of agents called cell cycle–nonspecific (CCNS) drugs can sterilize tumor cells whether they are cycling or resting in the G0 compartment. CCNS drugs can kill both G0 and cycling cells Eg, Doxorubicin, Cyclophosphamide & Cisplatin Many of the effective anticancer drugs exert their action on cells traversing the cell cycle and are called cell cycle–specific (CCS) drugs Eg, 5-Fluorouracil, Paclitaxel & Bleomycin Cell cycle–specific (CCS) drugs Cell cycle–nonspecific (CCNS) drugs
Slide 9-

Anticancer drug resistance Types: Primary resistance and acquired resistance. Drug resistance can be highly specific to a single drug Rapid repair of drug induced DNA damage Inefficient activation of drug A decrease in the amount of drug taken by the cell Increased concentration of target enzyme Over expression of Bcl-2 (Mutation) – give resistant target molecule Specific change in the genetic machinery of a given tumor cell with amplification Mutations in the p53 tumor suppressor gene Loss of p53 function leads to resistance to radiation therapy & anticancer drugs Increased expression of the multidrug-resistant gene (MDR1 gene) MDR1 encodes a cell surface transporter glycoprotein (P-glycoprotein) MDR leads to enhanced drug efflux MDR reduces intracellular accumulation anticancer agents Reasons
Slide 10-

Anticancer Drugs Alkylating agents Antimetabolites Cytotoxic antibiotics Plant derivatives 1 2 3 4 Hormones Protein kinase inhibitors Monoclonal antibodies Miscellaneous agents 5 6 7 8
Slide 11-

ppt slide no 11 content not found
Slide 12-

1. Alkylating agents 1. Nitrogen mustards : chlorambucil, cyclophosphamide, estramustine, melphalan 2. Nitrosoureas : Carmustine, lomustine 3. Platinum compounds : Carboplatin, cisplatin, oxaliplatin 4 .Other: Busulfan, dacarbazine , procarbazine , thiotepa
Slide 13-

Alkylating agents…. Intrastrand cross-linking of DNA They form covalent bonds with DNA/cell substituents Then form a carbonium ion (reactive intermediate.) They interfere transcription & DNA replication This causes defective replication and chain breakage. Alkylation at guanine N7 leads to excision of the guanine base causes main chain breakage Their principal effect occurs during DNA synthesis and the resulting damage triggers apoptosis (cell death) Mechanism of action
Slide 14-

Depress bone marrow function Cause hair loss and gastrointestinal disturbances Depression of gametogenesis (particularly in men), leading to sterility, An increased risk of acute non-lymphocytic leukaemia Some are causing severe nausea and vomiting Use 5-HT3 receptor antagonists (e.g. ondansetron) Nephrotoxicity Adverse effects
Slide 15-

2. Antimetabolites Folate antagonists : Methotrexate, pemetrexed, raltitrexed Pyrimdine Antagonist: Cytarabine, fluorouracil, gemcitabine, Purine Antagonists: Fludarabine, mercaptopurine, pentostatin, General MOA: Blocking the synthesis of DNA and/or RNA
Slide 16-

A. Folate antagonists Mechanism of action: Methotrexate, which inhibits dihydrofolate reductase Raltitrexed, which inhibits thymidylate synthetase Pemetrexed, which inhibits thymidylate transferase 2. Antimetabolites
Slide 17-

Uses: Methotrexate is also used as an immunosuppressant for RA, psoriasis and autoimmune disorders. Adverse effect: Depression of the bone marrow Damage to the epithelium of the gastrointestinal tract. Pneumonitis Nephrotoxicity (with doses 10 times greater than the standard doses) A. Folate antagonists 2. Antimetabolites
Slide 18-

B. Pyrimidine Antagonists Mechanism of action: Fluorouracil An analogue of uracil, interferes with 2′-deoxythymidylate (DTMP) synthesis. It is converted into a ‘fraudulent’ nucleotide, fluorodeoxyuridine monophosphate (FDUMP). This interacts with thymidylate synthetase but cannot be converted into DTMP. The result is inhibition of DNA (but not RNA or protein synthesis) Cytarabine (cytosine arabinoside): An analogue of the naturally occurring nucleoside 2′-deoxycytidine. The drug enters the target cell and undergoes the same phosphorylation reactions as the endogenous nucleoside to give cytosine arabinoside trisphosphate, which inhibits DNA polymerase enzyme. Gemcitabine: An analogue of cytarabine, inhibit DNA methylase enzyme 2. Antimetabolites
Slide 19-

Pharmacokinetics: It is given parentally. Adverse effect: Gastrointestinal epithelial damage Myelotoxicity. B. Pyrimidine Antagonists 2. Antimetabolites
Slide 20-

2. Antimetabolites Mechanism of action: Mercaptopurine Mercaptopurine is converted into fraudulent nucleotide Fludarabine: Inhibits DNA polymerase. Pentostatin : Inhibits adenosine deaminase – a critical pathway in purine metabolism C. Purine Antagonists
Slide 21-

3. Cytotoxic Antibiotics Doxorubicin Inhibits DNA and RNA synthesis; It is mainly through interference with topoisomerase II (DNA gyrase) action. Bleomycin: Causes fragmentation of DNA chains. Most effective in the G2 phase of the cell cycle and mitosis It acts on non-dividing cells (Go). Mechanism of action:
Slide 22-

Dactinomycin : Intercalates in DNA, interfering with RNA polymerase and inhibiting transcription. It also interferes with the action of topoisomerase II. Used in pediatric cancers Mitomycin Enzyme activation converts into bifunctional alkylating metabolite It cross-links DNA and may also degrade DNA through the generation of free radicals Mechanism of action: 3. Cytotoxic Antibiotics
Slide 23-

Doxorubicin Cardiotoxicity (in high doses) leading to dysrhythmias and heart failure It is due to the generation of toxic free radicals from drug Bleomycin: Mucocutaneous reactions and Pulmonary fibrosis. Mitomycin Kidney damage and pulmonary fibrosis Adverse Effects: 3. Cytotoxic Antibiotics
Slide 24-

3. Plant Derivatives Vincristine: The drugs bind to tubulin and inhibit its polymerization into microtubules, Thereby preventing spindle formation in dividing cells and causing arrest at metaphase. Their effects become manifest only during mitosis. Etoposide: It inhibits DNA synthesis by an action on topoisomerase II and also inhibits mitochondrial function. Irinotecan and topotecan: It Inhibit topoisomerase I Mechanism of action:
Slide 25-

Paclitaxel: It stabilizes (freezing them) microtubules in the polymerised state, inhibiting mitosis; They are generally used to treat breast and lung cancer Paclitaxel given with carboplatin, is the treatment of choice for ovarian cancer Unwanted effects: Hypersensitivity reactions , cumulative neurotoxicity. Resistant fluid retention Other drugs: vinblastine and vindesine. Vinflumine, a fluorinated vinca alkaloid, and vinorelbine (semisynthetic) Unwanted effects: Neurotoxic (paraesthesias -sensory changes) Mechanism of action: 3. Plant Derivatives
Slide 26-

4. Anticancer Hormones Glucocorticoids : Prednisolone MOA: They have marked inhibitory effects on lymphocyte proliferation So it is used in the treatment of leukemia and lymphomas. Their ability to lower raised intracranial pressure useful in brain tumors (Dexamethasone) They mitigate side effects of anticancer drugs (Nausea & vomiting) Making them useful as supportive therapy when treating other cancers, as well as in palliative care. Estrogens : Diethylstilbestrol and ethinyloestradiol Occasionally used in the palliative treatment of androgen-dependent prostate cancer Prostate cancer also be treated with gonadotrophin-releasing hormone (GnRH) analogues
Slide 27-

Progestogens: Megestrol and medroxyprogesterone Used in treatment of endometrial cancer. Gonadotrophin: Goserelin & leuprorelin MOA: They inhibit gonadotrophin release Used to treat advanced breast cancer in premenopausal women and prostate cancer. Degaralix: GnRH antagonist used for the treatment of prostae cancer. 4. Anticancer Hormones
Slide 28-

Somatostatin analogues: Octreotide and Lanreotide They are used to relieve the symptoms of neuroendocrine tumors Hormone-secreting tumors of the gastrointestinal tract such as glucagonomas, carcinoid tumors and gastrinomas. These tumors express somatostatin receptors, activation of which inhibits cell proliferation as well as hormone secretion. 4. Anticancer Hormones
Slide 29-

Antiestrogens: Tamoxifen MOA: Effective against estrogen dependent breast cancer, compete with endogenous estrogen for the estrogen receptors, thereby inhibits the transcription of estrogen-responsive genes ADRs: Endometrial hyperplasia and cancer and Risk of thromboembolism Aromatase Inhibitors: Anastrozole, letrozole MOA: Suppress the synthesis of estrogens from adrenal cortex Effective in the treatment of breast cancer in postmenopausal women Ant-androgens: Flutamide, bicalutamide Effective against prostate cancer 4. Anticancer Hormones
Slide 30-

ppt slide no 30 content not found
Slide 31-

5. Monoclonal Antibodies Rituximab: Uses: It is used to treat lymphoma MOA: It lyses B lymphocytes by binding to the calcium channel forming CD20 protein ADRs: Hypotension and cytokine release reaction Trastuzumab: MOA: Binds to HER2 (Human epidermal growth factor 2), breast cancer express this HER2 receptor MOA: Induces cell cycle inhibitors p21 and p27 Bevacizumab: Uses: used for the treatment of colorectal cancer MOA: It neutralise VEGF (vascular endothelial growth factor) MOA: Thereby prevents angiogenesis and tumor cell survival
Slide 32-

6. Protein Kinase Inhibitor Imatinib: Uses: It is used to treat chronic myeloid leukemia (CML) MOA: It inhibits an oncogenic cytoplasmic tyrosine kinase (abl/bcr) MOA: It inhibits platelet derived growth factor (PDGF) tyrosine kinase
Slide 33-

Treatment regimens and scheduling (Clinical Pharmacology)
Slide 34-

Leukemias The Leukemias (ALL) – Acute lymphoblastic leukemia (ALL)- Childhood A combination of vincristine and prednisone plus other agents (90% of children enter complete remission). Prophylactic Intrathecal methotrexate therapy (standard component) Acute lymphoblastic leukemia (ALL)- Adult Cytarabine & anthracycline remissions in about 70% Require intensive supportive – filgrastim
Slide 35-

The Leukemias (ALL) – Chronic myelogenous leukemia Imatinib (First line) - The tyrosine kinase inhibitor Chronic lymphocytic leukemia Chlorambucil and cyclophosphamide – Widely used Cyclophosphamide is combined with vincristine and prednisone , can also be given with these same drugs along with doxorubicin. Also combined with Rituximab/Ofatumumab Leukemias
Slide 36-

HODGKIN’S LYMPHOMA HODGKIN’S LYMPHOMA B-cell neoplasm malignant (mechlorethamine, vincristine, procarbazine, and prednisone) - old (doxorubicin, bleomycin, vinblastine, and dacarbazine) NON-HODGKIN’S LYMPHOMA The anthracycline-containing regimen (cyclophosphamide, doxorubicin,vincristine, and prednisone)
Slide 37-

BREAST CANCER Six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF protocol) or of fluorouracil, doxorubicin, and cyclophosphamide(FAC) four cycles of doxorubicin and cyclophosphamide and six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) Tamoxifen – estrogen receptor antagonist Anastrozole - aromatase inhibitor Trastuzumab - against the HER-2/neu receptor (MCA)
Slide 38-

PROSTATE CANCER Luteinizing hormone-releasing hormone (LHRH) agonists— leuprolide and goserelin agonists ALONE or in combination with an antiandrogen (eg, flutamide, bicalutamide, or nilutamide) Abiraterone, an inhibitor of steroid Synthesis Estramustine is an antimicrotubule agent GASTROINTESTINAL CANCERS Oxaliplatin-based regimen in combination with 5-FU plus leucovorin or with oral capecitabine Bevacizumab anti-VEGF antibody
Slide 39-

Miscellaneous Drugs
Slide 40-

Overview of Anticancer Drugs
Slide 41-

Overview of Anticancer Drugs…
Slide 42-

THANK YOU FOR YOUR ATTENTION