principles of selective toxicity

Question 1

what are tje typical characteristics of a cancerous cell

Answer 1

• sustained proliferative signalling
• Evading growth suppressors
• Activating invasion and metastasis
• Enabling replicative immortality
• Introducing angiogenesis
• Resisting cell death

Question 2

general aims when treating with chemotherapy

Answer 2

• To eradicate the disease
• To try induce remission
• control symptoms

Question 3

potential properties of cytotoxic drugs

Answer 3

• 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

Question 4

limitation of cytotoxic drugs only in treating cancer

Answer 4

have less activity against nondividing cells (eg quiescent cells in G0) .’. if cancer cells are at this stage = not affected .’. cancer can come back

Question 5

Important considerations when using cytotoxic drugs include

Answer 5

Does the drug require hepatic metabolic activation?

Is patient nil by mouth

Question 6

what are alkalyting agents

Answer 6

a class of chemotherapy drugs that bind to DNA and prevent proper DNA replication

Question 7

how do allkalyting agents work

Answer 7

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

Question 8

how selective are cytotoxic drugs

Answer 8

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.

Question 9

important things to consider when giving antibiotics

Answer 9

• identify organism asap
• have they had previous adverse reaction to antibiotics
• contraindiction with other medicines
• other medical considerations (eg renal failure, pregnancy, breast feeding)

Question 10

potential targets of antibioics include

Answer 10

• Peptidoglycan cell wall synthesis of bacteria
• Protein synthesis
• Intermediary metabolism (this involves folate coenzymes)
• The biosynthesis of DNA or RNA or cell membranes

Question 11

what is peptidoglycan

Answer 11

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

Question 12

structure of peptidoglycan

Answer 12

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)

Question 13

what is the role of transpeptidase

Answer 13

forms peptide bridges that cross-like the pentapeptides coming out of NAM

Question 14

what is the role of antibacterials

Answer 14

inhibit cell wall synthesis

Question 15

example of antibacterials

Answer 15

penicllin

Question 16

what is a bacteriostatic antibiotic

Answer 16

is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise

Question 17

what is a bacteriocidal antiobiotic

Answer 17

substance that kills bacteria

Question 18

Examples of polyene macrolides

Answer 18

Amphotericin B

Nyasatin

Question 19

Clnical use of amphotericin B

Answer 19

Broad spectrum activity

Question 20

clinical use of nvastin

Answer 20

thrush (oral and vaginal)

Question 21

Mechanism of HIV infection

Answer 21

Infects tcells -> reverse transcription .’. DNA formed -> inserted into host cell dna. Production of viral cell proteins – virus build up until cell bursts.

Question 22

What is Zidovudine (ZDV)

Answer 22

A prodrug. Must be phosphorylated 3 times to become active (ZDVTP).
is a synthetic thymidine analogue.

Question 23

effect of ZDV

Answer 23

phosphorylated to ZDVTP
competes with endogenous thymidine for reverse transcriptase.
ZDVTP imporporated into viral DNA strand -> terminiates synhesis .’. chain termination.

Question 24

relationship between malaria and mosquitos

Answer 24

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

Question 25

what class of drugs are used to treat malaria

Answer 25

anti-folates

Question 26

what are anti-folates

Answer 26

given to treat malaria.
specific DHFR inhibitors, more selective to protozoal DHFR than human DHFR.

but at high doses also affects human DHFR

Question 27

why should antifolates not be given in critical situations where time is of essence

Answer 27

act at late stage of sexual reproduction.

are slow acting

Question 28

role of DHFS (and DHPS)

Answer 28

involved in human &parasite pathways to produce folate, ultimately results in production of amino acids, nucleic acids etc.

Question 29

why do antifolates effect parasitic DHFR more tan human DHFR

Answer 29

parasitic - molecular weight = 10x heavier

affinity to parasite is 2000x greater than to human

Question 30

effect of antifolates in parasites

Answer 30

inhibiting DHFR and therefore the parasite cannot produce biomolecules it requires to survive and thus it dies

Question 31

effect of antifolates in bacteria

Answer 31

compete with the normal substrate PABA for DHPS. imporated into folate pathway .’. generates pseudofolate (instead of tetradrofolic acid)
.’. bacteria cannot make proper AA .’. die

Question 32

what is proguanil

Answer 32

selective inhibitor of plasmodial of DHFR and thymidylate.

Question 33

what type of drug is useful in acute malarial attack and why

Answer 33

Proguanil affects the primary liver and asexual RBC stages of malaria
can eradicate infection early on

Question 34

effect of proguanil on p.vivax malaria

Answer 34

can destroy it but dies not affect the latent stages (where hides in body tisse) .’. relapase.
gametocytes also unaffected