Anti cancer drugs Flashcards
(28 cards)
CCNS
Drugs that can act in traversing cells as well as those that are resting or are in G0 phase.
Name three examples of nitrogen mustards.
- Cyclophosphamide
- Mechlorethamine
- Chlorambucil
These are commonly used alkylating agents.
What are the three examples of nitrosoureas?
- Carmustine
- Lomustine
- Streptozocin
These agents are also part of the alkylating agents group.
What is the mechanism of action of alkylating agents?
They form reactive molecular species that alkylate the nucleophilic group on DNA bases - particularly the N-7 position of guanine.
This causes - crosslinking of bases
- abnormal base pairing
- dna stand breaking
Alkylation also damages RNA and proteins
What is a unique feature of cyclophosphamide?
High oral bioavailability
This makes cyclophosphamide one of the most widely used alkylating agents.
What is required for the antitumor activity of cyclophosphamide?
Hepatic cytochrome P450-mediated biotransformation
This transformation activates cyclophosphamide for its therapeutic effects.
Clinical uses
Leukemia, cancer, neuroblastoma, non-Hodgkin’s lymphoma, breast cancer, ovarian cancer
These are conditions where the drug is applied therapeutically.
Toxicity
Myelosuppression
Alopecia
Gastrointestinal distress
Hemorrhagic cystitis - due to formation of ACROLEIN (can cause bladder inflammation) - can be decreased by hydration and IV of MESNA
Cardiac dysfunction
Pulmonary toxicity
How can the risk of hemorrhagic cystitis be decreased?
By hydration and IV of mesna
Mesna is a sulfhydryl compound that helps protect the bladder.
What syndrome is associated with inappropriate ADH secretion?
Syndrome of inappropriate ADH secretion
This can lead to water retention and hyponatremia.
Busulfan - clinical use
Chronic myelogenous leukemia
This is a type of cancer that affects the blood and bone marrow.
Busulfan - toxicity
Myelosuppression
Pulmonary fibrosis
skin pigmentation
Carcinogenic
DACARBAZINE - mechanism
Must undergo biotransformation to an active metabolite- Methyl-triazeno imidazole carboxamide (MTIC)
This process activates the drug for its therapeutic effect.
What ion does MTIC form?
Methyl carbonium ion- attacks the nucleophilic groups on dna - dna damage -cell death
This ion can react with nucleophiles in DNA.
DACARBAZINE - Clinical uses
Melanin
Hodgekin lymphoma
Dacarbazine- toxicity
myelosuppression
alopecia
GI distress
skin rash
photo toxicity
Procarbazine - mechanism
It is a reactive agent that forms hydrogen peroxide, generating free radicals that cause DNA strand scission.
This mechanism contributes to its effectiveness in treating cancer by damaging the DNA of cancer cells.
Procarbazine- toxicity
- Gastrointestinal irritation
- Myelosuppression
- CNS dysfunction
- Peripheral neuropathy
- Skin reactions
- Inhibits many enzymes including monoamine oxidase and those involved in hepatic drug metabolism
- Disulfiram-like reactions with ethanol
- Neurotoxic
These side effects can significantly impact patient care and treatment management.
Procarbazine- clinical uses
Hodgekin and non hodgekin lymphoma
brain tumor
Procarbazine - pharmacokinetics
Orally active and penetrates into most tissues including the cerebrospinal fluid; eliminated via hepatic metabolism.
This means Procarbazine can be administered orally and is distributed throughout the body, including the brain.
What is the risk of using Procarbazine with ethanol?
Disulfiram-like reactions may occur.
This reaction can lead to severe nausea and other symptoms if alcohol is consumed while on Procarbazine.
Nitrosaureas
-Carmustine
-Lomustine
-Streptozocin
Nitrosaureas - mech
Highly lipophillic so can penetrate the bbb- therefore used in brain tumors
Nitrosaureas - toxicity
