Principles of Chemotherapy

Question 1

Define chemotherapy.

Answer 1

The use of drugs which exploit the differences between foreign cells and cells in the body (host) with the aim to stop the progress of a disease by killing and or eradicating infectious agents from the body without irreversible damage to healthy tissues.

Question 2

What are chemotheraputic agents?

Answer 2

The are drugs which are selectively toxic against a range of parasites.

• Metazoa (multicellular organisms) - worms, insects.
• Unicellular organisms - bacteria, virus, fungi, protozoa.

Question 3

Explain qualitative selective toxicity.

Answer 3

Drug affects a target UNIQUE to the foreign cell.

Bacterial, viral, fungal, parasitic infection.

Question 4

Explain quantitative selective toxicity.

Answer 4

Drug affects a target COMMON to both the foreign and host cell - but more effective against foreign cell…need a higher concentration to affect the host, lower concentration to affect the foreign.
Bacterial, fungal, parasitic and anti cancer drugs.

Question 5

What do cytocidal drugs do?

Answer 5

They KILL cells.

Question 6

What do cytostatic drugs do?

Answer 6

They STOP cells dividing - allowing the immune system to ‘clear’ the infection.

Question 7

Is a cytotoxic drug either cytocidal or cytostatic?

Answer 7

No - can be both depending on concentrations.

Question 8

MIC?

Answer 8

Minimum inhibitory concentration - to inhibit.

Question 9

MBC?

Answer 9

Minimum bacteriocidal concentration - to kill.

Question 10

What is the chemotherapeutic index?

Answer 10

Concentration toxic to host cells/concentration toxic to the parasites.

Question 11

Ideally, should chemotherapeutic index be high or low?

Answer 11

Ideally high - ie if 100 - need 100x higher concentration to be toxic to human cells!

Question 12

What 2 biochemical differences between host and targets cells can be exploited?

Answer 12

Key enzymes of receptors (most antibiotics) or differences in replication rate (anti cancer).

Question 13

Explain how key enzymes or receptors can be used as the basis for selective toxicity.

Answer 13

Grame +ve bacteria have a peptidoglycan cell wall (drugs could interfere with its production)
Bacteria have to manufacteur folic acid from PABA by the enzyme dihydropteroate synthase (humans/mammals dont have this enxyme - obtain folic acid form diet).

Question 14

Explain how differences in replication rate can be used as the basis for selective toxicity.

Answer 14

Cancer cells replicate rapidly (So do hair cells which is why hair loss id a side effect of anti cancer drugs).

Question 15

How might you achieve selective distribution of the drug?

Answer 15

1) Selective accumlation of the drug in the parasite.
2) Selective activation of the prodrug
3) Restricted accumulation of the drug within a limited compartment.

Question 16

Explain how you can get selective accumulation of the drug in the parasite.

Answer 16

Eg chloroquine in malaria - transporter concentrates the drug to toxic levels in parasite.

Question 17

Explain how you can get selective activation of the prodrug.

Answer 17

Eg acyclovir is converted to the active, acyclo-GMP by the viral enzyme THYMIDINE KINASE - an enzyme only virus has…therefore targets cells that are infected with the virus - kills correct cells.

Question 18

How can you get restricted accumulation of the drug within a limited compartment?

Answer 18

Eg amoxicillin to treat urinary tract infecction - freely filtered by the glomeruli and gets concentrated in the bladder and kills bacteria.
Also…
…nystatin to treat oral or vaginal candidasis
…mebendazole to treat threadworms.