37)Anticancer drugs

Question 1

Anticancer drugs

Answer 1

Drugs used in treatment against cancer

Question 1

Cytotoxic drugs

Answer 1

Alkylating agents:

• Nitrogen-iprites ⇢ Chlorambucil
• Methane sulfonates ⇢ Busulfan
• Nitrosoureas ⇢ Carmustine

Antimetabolites ⇢ block metabolic pathway in DNA synthesis

• Pyrimidine antimetabolites ⇢ 5-Fluorouracil
• Purine antimetabolites ⇢ Mercaptopurine
• Folic acid antimetabolites ⇢ Methotrexate
• Urea antimetabolites ⇢ Hydroxycarbamide

Cytotoxic antibodies ⇢ Daunorubicin

Plant derivatives

Question 2

Hormone drugs

Answer 2

Glucocorticoids

Sex hormone + antihormones

Question 3

Target drugs

Answer 3

Monoclonal antibodies

Protein (tyrosine kinase) inhibitors

Question 4

Pharmacodynamics

Answer 4

Cytotoxic agents ⇢ inhibit DNA synthesis within cancer cells

• Resting cells (G phase) ⇢ resistant to many anticancer drugs

Alkylating agents ⇢ covalently bond w/nucleophilic substances in the cell

Antimetabolites ⇢ Act on metabolism of cancer cells ⇢ Act as analogues in RNA/DNA synthesis process ⇢ blocking it

Plant derivatives ⇢ Inhibit tubulin polymerisation ⇢ disturbing microtubule assembly in mitosis

MAB ⇢ Interact w/DNA ⇢ Inhibit topoisomerases I + II & free radical production

Question 5

Pharmacokinetics

Answer 5

Alkylating agents ⇢ ⇡ Oral bioavailability ⇢ Metabolised into active metabolite in liver

Antimetabolites ⇢ Administered IV due to ⇡ GI toxicity ⇢ Metabolised in liver + excreted in urine

Plant derivatives ⇢ Administered IV w/ ⇡ VOD ⇢ Metabolised in liver + excreted in bile + faeces

MAB ⇢ Administered IV ⇢ Bind to plasma proteins ⇢ Do not cross BBB ⇢ intensive hepatic metabolism + excreted in bile

Question 6

Clinical uses

Answer 6

Alkylating agents

• Lung, ovarian + breast cancers
• Used for some systemic immunodeficiency diseases ⇢ lupus + rheumatoid arthritis

Antimetabolites

• Ovarian, bladder, breast, head + neck cancers

Plant derivatives

• Lymphoblastic leukaemia, multiple myeloma, solid ovarian tumours + breast cancers

Question 7

Adverse effects

Answer 7

Nausea + vomiting w/antiemetics given due to severity

Alkylating agents

• Dose related damage to rapidly growing tissues (eg bone marrow)

Antimetabolites

• Stomatitis, rash + urticaria

Plant derivatives

• Neutropenia + neurotoxicity

MAB

• Dose dependant cardio toxicity ⇢ due to dree radical formation

Question 8

DDIs

Answer 8

Antimetabolite methotrexate + penicillin/cephalosporins/NSAIDS ⇢ inhibit renal excretion

• Must not be applied w/Wide spec antibiotics ⇢ ⇡ Toxicity

Anticancer drugs mostly involved in interactions ⇢ cisplatin, methotrexate, lapatinib + fluorouracil