principles of selective toxicity Flashcards
what are tje typical characteristics of a cancerous cell
- sustained proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Introducing angiogenesis
- Resisting cell death
general aims when treating with chemotherapy
- To eradicate the disease
- To try induce remission
- control symptoms
potential properties of cytotoxic drugs
- active against cycling/proliferating cells
- phase-specific drugs, these target only certain parts of the cell cycle
- Cycle-specific drugs, these affect cells throughout the cell cycle
- Affect DNA synthesis
limitation of cytotoxic drugs only in treating cancer
have less activity against nondividing cells (eg quiescent cells in G0) .’. if cancer cells are at this stage = not affected .’. cancer can come back
Important considerations when using cytotoxic drugs include
Does the drug require hepatic metabolic activation?
Is patient nil by mouth
what are alkalyting agents
a class of chemotherapy drugs that bind to DNA and prevent proper DNA replication
how do allkalyting agents work
form a reactive ion and insert into DNA of the cancer cell. .’.
-DNA stand breakage
- abnormal base pairing
- cross linkage
impair ability to replicate DNA and proliferate
also alkylation of RNA and proteins .’. impaired ability to function and surviv
how selective are cytotoxic drugs
selectivity of cytotoxic drugs is marginal. therapeutic index of 1. This means that the concentration of drug that causes cancer cell death = causes toxicity + side effects.
important things to consider when giving antibiotics
- identify organism asap
- have they had previous adverse reaction to antibiotics
- contraindiction with other medicines
- other medical considerations (eg renal failure, pregnancy, breast feeding)
potential targets of antibioics include
- Peptidoglycan cell wall synthesis of bacteria
- Protein synthesis
- Intermediary metabolism (this involves folate coenzymes)
- The biosynthesis of DNA or RNA or cell membranes
what is peptidoglycan
a polymer made of sugars and AA that forms cell wall around the bacterial cell surface membrane.
its semirigid+ tight knit molecular structure gives strength and allows bacterium to resist osmolytic lysis
structure of peptidoglycan
has polysaccharide portion and protein portion.
polysaccharide = NAG and NAM form long chains that form the backbone
protein portion = short chains of AA that link the layers of peptidoglycan together (do this by joining to NAM)
what is the role of transpeptidase
forms peptide bridges that cross-like the pentapeptides coming out of NAM
what is the role of antibacterials
inhibit cell wall synthesis
example of antibacterials
penicllin
what is a bacteriostatic antibiotic
is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise
what is a bacteriocidal antiobiotic
substance that kills bacteria
Examples of polyene macrolides
Amphotericin B
Nyasatin
Clnical use of amphotericin B
Broad spectrum activity
clinical use of nvastin
thrush (oral and vaginal)
Mechanism of HIV infection
Infects tcells -> reverse transcription .’. DNA formed -> inserted into host cell dna. Production of viral cell proteins – virus build up until cell bursts.
What is Zidovudine (ZDV)
A prodrug. Must be phosphorylated 3 times to become active (ZDVTP).
is a synthetic thymidine analogue.
effect of ZDV
phosphorylated to ZDVTP
competes with endogenous thymidine for reverse transcriptase.
ZDVTP imporporated into viral DNA strand -> terminiates synhesis .’. chain termination.
relationship between malaria and mosquitos
bitten by mosquito - > malaria parasite (at this stage a sporozioite) enters blood. -> matures in hepatocytes to merozoites ->breaks out and infects/destroys rbc form gametocytes (some male some female) in rbc, sucked up by mosquito .'. fertilise one another and form a zygote in the mosquito midgut
