24. Pharmacological basics of chemotherapy

Question 1

Chemotherapeutic drugs -?

Answer 1

Target of this drug does not belong to the body (cancer or infectious agent)

Question 2

Classification of chemotherapeutics:

Answer 2

1. Antimicrobial
2. Antineoplastic (anti-cancer)
3. Antiparasitic

Question 3

What drugs are included in antimicrobial group of chemotherapeutics?

Answer 3

1. Antibacterial
2. Antifungal (limited significance in vet med)
3. Antiviral (limited significance in vet med)

Question 4

What is the difference between antibacterial and antibiotics?

Answer 4

Antibiotics are naturally occuring and antibacterial drugs not neccessary

Question 5

What drugs are included into antiparasitic group of chemotherapeutics?

Answer 5

1. Antiprotozoal
2. Endoparasiticidal drugs
3. Ectoparasiticidal drugs

Question 6

What is the concept of selective toxicity?

Answer 6

The goal is to destroy the target without harming the organism

Question 7

Types of targets in regard of selective toxicity:

Answer 7

1. Unique targets
2. Similar targets
3. Common targets

Question 8

Unique targets - ?

Answer 8

Target that exists in pathogen but is not present in the host (e.g. cell wall - penicillin)

Question 9

Similar targets - ?

Answer 9

Affinity to target is much higher than to the host

Question 10

Examples of unique targets?

Answer 10

• cell wall
• ergosterol (fungal cell membrane component)
• folic acid synthesis (one of the steps)

Question 11

Examples of drugs having unique target: cell wall

Answer 11

• beta-lactams (penicillins, cephalosporins)
• glycopeptides (vancomycin)
• bacitracin

Question 12

Examples of drugs having unique target: ergosterol

Answer 12

• ergosterol-synthesis inhibitors (azoles: itraconazole, ketoconazole)
• ergosterol-complex formers (polienes: nystatine, amphothericin B) - form a channel by binding ergosterol -> leakage -> destruction

Question 13

Examples of drugs having unique target: folic acid synthesis

Answer 13

Bacterias are producing folic acid but animals receive it with food -> unique agent

PABA (paraaminobenzoic acid) -> dihydro-folic acid reaction requires enzyme: dihydropteroate-synthetase. This enzyme can be inhibited by sulphonamides (because they are structural analogues of PABA)

Question 14

Why are sulphonamides very safe? What do they act on?

Answer 14

Sulphonamides act on unique target: dihydropteroate synthetase enzyme that participates in conversion of PABA to dihydrofolic acid. Mammals don’t have this reaction in their body, they receive dihydro-folic acid from food

Question 15

Sulphonamides and ________ often applied together. Why?

Answer 15

Trimethoprim. Acts on similar target: dihydrofolate reductase (converting non-active dihydro-folic acid to active tetrahydro-folic acid). So sulphonamides and trimethoprim potentiate each other because act on 2 different steps of the same reaction

Question 16

What do beta-lactams act on?

Answer 16

cell wall

Question 17

What do azoles act on?

Answer 17

ergosterol

Question 18

What do glycopeptides act on?

Answer 18

cell wall

Question 19

What do polienes act on?

Answer 19

ergosterol

Question 20

What do sulphonamides act on?

Answer 20

folic acid synthesis that is present only in bacteria

Question 21

What will happen to bacteria if concentration of antibacterial drug is below MIC?

Answer 21

Growth of bacteria will not be inhibited

Question 22

What is MIC?

Answer 22

minimum inhibitory concentration

Question 23

What is MBC?

Answer 23

minimum bactericidal concentration. Minimal concentration that will kill the bacteria

Question 24

What is MPC?

Answer 24

mutant prevention concentration. Minimal conc that will inhibit growth even of bacteria that were able to develop resistance

Question 25

What will happen if concentration of the antibacterial drug is between MIC and MPC?

Answer 25

"normal" bacteria's growth will be inhibited but resistant mutant ones will not be affected!! VERY BAD!

Question 26

What are 2 main modes of action of antibacterial drugs?

Answer 26

1. Bactericidal (kills bacteria) 2. Bacteriostatic (inhibits growth and immune system kills bacteria)

Question 27

What are the conditions when bactericidal drugs should be used?

Answer 27

- life-threatening infections (no time to wait for immune response) - immunosuppressed patients (FeLV, FIV)

Question 28

2 possible modes of action of bactericidal drugs

Answer 28

Time or concentration dependent. If increase of dosage significantly increases speed of killing bacteria -> concentration-dependent. If only slightly -> time-dependent

Question 29

What bactericidal drugs are time-dependent?

Answer 29

- penicillins - cefalosporins - potentiated sulphonamides

Question 30

What is postantibiotic effect?

Answer 30

Delayed antibacterial effect after the concentration of the drug declined below MIC (e.g. beta-lactams, aminoglycosides, fluorouinolones)

Question 31

What does synergetic type of action mean?

Answer 31

2 drugs potentiate each other. Increase of effectiveness

Question 32

Examples of synergetic action

Answer 32

- penicillin + streptomycin - lincomycin (50S inhibitor) + spectinomycin (30S inhibitor) - mainly against mycoplasma

Question 33

What does additive action mean?

Answer 33

Don't potentiate each other, but broad the spectrum of action.

Question 34

Example of additive action

Answer 34

gentamicin (aerobic) + metronidazol (anaerobic)

Question 35

What does antagonist action mean?

Answer 35

drugs act on the same target -> compete with each other -> decreased effectiveness

Question 36

Example of antagonist action

Answer 36

erythromycin + chloramphenicol (both inhibit 50S)

Question 37

2 types of bacterial resistance

Answer 37

1. Chromosomal resistance (spread vertically) 2. Plasmid encoded (horizontally + vertically)

Question 38

Example of chromosomal resistance

Answer 38

MRSA (methicillin resistant S. aureus)

Question 39

Types of transferring of resistance among bacteria

Answer 39

1. conjugation - transferring chromosomal or plasmid encoded resistance genes - THE MOST IMPORTANT ONE 2. transduction - via bacteriophages 3. transformation - from dead bacteria (minor significance)