24. Pharmacological basics of chemotherapy Flashcards
Chemotherapeutic drugs -?
Target of this drug does not belong to the body (cancer or infectious agent)
Classification of chemotherapeutics:
- Antimicrobial
- Antineoplastic (anti-cancer)
- Antiparasitic
What drugs are included in antimicrobial group of chemotherapeutics?
- Antibacterial
- Antifungal (limited significance in vet med)
- Antiviral (limited significance in vet med)
What is the difference between antibacterial and antibiotics?
Antibiotics are naturally occuring and antibacterial drugs not neccessary
What drugs are included into antiparasitic group of chemotherapeutics?
- Antiprotozoal
- Endoparasiticidal drugs
- Ectoparasiticidal drugs
What is the concept of selective toxicity?
The goal is to destroy the target without harming the organism
Types of targets in regard of selective toxicity:
- Unique targets
- Similar targets
- Common targets
Unique targets - ?
Target that exists in pathogen but is not present in the host (e.g. cell wall - penicillin)
Similar targets - ?
Affinity to target is much higher than to the host
Examples of unique targets?
- cell wall
- ergosterol (fungal cell membrane component)
- folic acid synthesis (one of the steps)
Examples of drugs having unique target: cell wall
- beta-lactams (penicillins, cephalosporins)
- glycopeptides (vancomycin)
- bacitracin
Examples of drugs having unique target: ergosterol
- ergosterol-synthesis inhibitors (azoles: itraconazole, ketoconazole)
- ergosterol-complex formers (polienes: nystatine, amphothericin B) - form a channel by binding ergosterol -> leakage -> destruction
Examples of drugs having unique target: folic acid synthesis
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)
Why are sulphonamides very safe? What do they act on?
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
Sulphonamides and ________ often applied together. Why?
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
What do beta-lactams act on?
cell wall
What do azoles act on?
ergosterol
What do glycopeptides act on?
cell wall
What do polienes act on?
ergosterol
What do sulphonamides act on?
folic acid synthesis that is present only in bacteria
What will happen to bacteria if concentration of antibacterial drug is below MIC?
Growth of bacteria will not be inhibited
What is MIC?
minimum inhibitory concentration
What is MBC?
minimum bactericidal concentration. Minimal concentration that will kill the bacteria
What is MPC?
mutant prevention concentration. Minimal conc that will inhibit growth even of bacteria that were able to develop resistance
What will happen if concentration of the antibacterial drug is between MIC and MPC?
“normal” bacteria’s growth will be inhibited but resistant mutant ones will not be affected!! VERY BAD!
What are 2 main modes of action of antibacterial drugs?
- Bactericidal (kills bacteria)
- Bacteriostatic (inhibits growth and immune system kills bacteria)
What are the conditions when bactericidal drugs should be used?
- life-threatening infections (no time to wait for immune response)
- immunosuppressed patients (FeLV, FIV)
2 possible modes of action of bactericidal drugs
Time or concentration dependent. If increase of dosage significantly increases speed of killing bacteria -> concentration-dependent. If only slightly -> time-dependent
What bactericidal drugs are time-dependent?
- penicillins
- cefalosporins
- potentiated sulphonamides
What is postantibiotic effect?
Delayed antibacterial effect after the concentration of the drug declined below MIC
(e.g. beta-lactams, aminoglycosides, fluorouinolones)
What does synergetic type of action mean?
2 drugs potentiate each other. Increase of effectiveness
Examples of synergetic action
- penicillin + streptomycin
- lincomycin (50S inhibitor) + spectinomycin (30S inhibitor) - mainly against mycoplasma
What does additive action mean?
Don’t potentiate each other, but broad the spectrum of action.
Example of additive action
gentamicin (aerobic) + metronidazol (anaerobic)
What does antagonist action mean?
drugs act on the same target -> compete with each other -> decreased effectiveness
Example of antagonist action
erythromycin + chloramphenicol (both inhibit 50S)
2 types of bacterial resistance
- Chromosomal resistance (spread vertically)
- Plasmid encoded (horizontally + vertically)
Example of chromosomal resistance
MRSA (methicillin resistant S. aureus)
Types of transferring of resistance among bacteria
- conjugation - transferring chromosomal or plasmid encoded resistance genes - THE MOST IMPORTANT ONE
- transduction - via bacteriophages
- transformation - from dead bacteria (minor significance)
