ANTINEOPLASTIC AGENTS Cancer refers to a malignant neoplasm or new growth.

Cancer cells manifest uncontrolled proliferation, loss of function due to loss of capacity to differentiate, invasiveness, and the ability to metastasize. Cancer arises as a result of genetic changes in the cell. There are three approaches for the management of cancer: 1. Radiotherapy 2. Surgery 3. Chemotherapy Most anticancer drugs are antiproliferative, and hence affect rapidly growing dividing normal cells. Classification Alkylating Agents e.g. Cyclophosphamide Cisplatin Antimetabolites e.g. Methotrexate, fluorouracil Cytotoxic Antibiotics e.g. Doxorubicin, bleomycin Mechanism of Action forming covalent bonds with DNA and thus impending DNA replication. blocks or destabilize pathways in DNA synthesis. Inhibit DNA or RNA synthesis or cause fragmentation to DNA chains or interfere with RNA polymerase and thus inhibit transcription. Inhibits mitosis General Side Effects Bone marrow toxicity. Impaired wound healing. Sterility. Loss of hair. Damage to gastrointestinal epithelium.

Vinca Alkaloids e.g. Vincristine, vinblastine

ANTIVIRAL AGENTS Viral replication consists of several steps: (1) adsorption to and penetration into susceptible host cells; (2) uncoating of viral nucleic acid; (3) synthesis of early, regulatory proteins, eg. nucleic acid polymerases; (4) synthesis of RNA/ DNA; (5) synthesis of late, structural proteins; (6) assembly (maturation) of viral particles; and (7) release from the cell. N:B: Reverse transcriptase inhibitors block transcription of the HIV RNA genome into DNA, thereby preventing synthesis of viral mRNA and protein. The protease inhibitors act on synthesis of late proteins and packaging (steps 5 & d 6). Fusion inhibitors block HIV attachment to cell surface Antiretroviral Agents Antiretroviral drugs are synthetic agents that have antiviral activity against HIV and are used in the management of HIV infection. There are several different classes of antiretroviral agents commercially available currently. Four are listed below 1. 2. 3. 4. Class NRTI Nucleoside reverse transcriptase inhibitors (NRTI) Protease inhibitors Non-Nucleoside reverse transcriptase inhibitors (NNRTI) Fusion inhibitors Examples Zidovudine (AZT) Lamivudine (3TC) Stavudine (d4T) Delavirdine (DLV) Nevirapine (NVP) Efavirenz Indinavir (AGJ) Lopinavir/Ritonavir Enfurvirtide (iv) S/E Myelosuppression gastrointestinal intolerance, HA HA, insomnia, GI discomfort Peripheral neuropathy, pancreatitis Rash, Stevens Johnson syndrome with 1-3wks of therapy Nightmares Nephrolithiasis, N,D GI disturbances (D), fat redistribution Bacterial pneumonia, site rxns

NNRTI

PI Fusion Inhibitors

Cephalosporins Cephalosporins can be classified into four generations depending mainly on the spectrum of antimicrobial activity and the date of introduction. First-generation compounds have better activity against gram-positive organisms and the later compounds exhibit improved activity against gram-negative aerobic organisms. Generation First Examples Cefadroxil Cefazolin (IV/IM) Cephalexin Cefaclor cefamandole (IV) Cefuroxime (iv, po) Ceftriaxone (IV/IM) Ceftazidime (IV) Cefixime Cefepime (IV) Notes Active against gram +ve org but gram ve activity poor. Used for UTI, celllitis Used for sinusitis, OM, LRTI Used for nocosomial infection gonorrhea S/E Hypersentivity rash D, disulfarim rxn with alcohol ingestion

Second Third

Fourth