Pharmacology of Antibiotics

Question 1

Principle of antimicrobial chemotherapy

Answer 1

use drugs to selectively kill bacteria (and viruses/fungi) without affecting the host

Question 2

Targets for antimicrobial chemotherapy

Answer 2

bacterial cell wall, ribosomes, folate metabolism, DNA gyrases

Question 3

Give examples of beta-lactam antibiotics

Answer 3

penicillins
eg. amoxicillin, benzylpenicillin, flucloxacillin

cephalosporins
eg. cefaclor, cefalexin

Question 4

Beta-lactam antibiotics mode of action

Answer 4

target bacterial cell wall synthesis

bind irreversibly to a transpeptidase (which cross-links peptidoglycans in the bacterial cell wall

Question 5

Are beta-lactam antibiotics bactericidal or bacteriostatic?

Answer 5

bactericidal - causes lysis of the bacteria

Question 6

What organisms are beta-lactam antibiotics effective against?

Answer 6

only dividing organisms as division requires cell wall synthesis, which is what they target, therefore leading to lysis

Question 7

beta-lactamases

Answer 7

secreted by resistant bacteria which deactivated some penicillins
clavulanic acid is included with some agents to inhibit beta-lactamases (co-amoxiclav)
other penicillins like flucloxacillin are resistant

Question 8

Example of glycopeptides

Answer 8

teicoplanin, vancomycin

Question 9

Glycopeptides mechanism

Answer 9

inhibit bacterial cell wall synthesis by inhibiting growth of the peptidoglycan chain
manage infections due to superbugs like MRSA
bactericidal
IV

Question 10

Examples of tetracyclines

Answer 10

doxycycline, tetracycline

Question 11

Tetracycline mechanism

Answer 11

inhibit protein synthesis by binding to the 30S subunit of the bacterial ribosome
prevents tRNA from binding to A site
actively accumulate in bacterial cells

Question 12

Are tetracyclines bactericidal or bacteriostatic?

Answer 12

bacteriostatic - stops from reproducing

Question 13

Examples of macrolides

Answer 13

clarithromycin, erythromycin

Question 14

Macrolides mechanism

Answer 14

prevent translocation of 50S subunit of the bacterial ribosome along the mRNA
prevents protein synthesis

Question 15

Are macrolides bactericidal or bacteriostatic?

Answer 15

bacteriostatic

Question 16

Allergy to penicillin

Answer 16

it is immunogenic
use macrolides as an alternative
problem: macrolides are cytochrome P450 inhibitors and have lota of drug interactions

Question 17

Examples of aminoglycosides

Answer 17

gentamicin, neomycin, tobramycin

Question 18

Aminoglycosides mechanism

Answer 18

bind irreversibly to 30S subunit of bacterial ribosomes
leads to misreading of mRNA
therefore interferes with protein synthesis
synergy with penicillin: increases uptake of aminoglycosides

Question 19

Are aminoglycosides bactericidal or bacteriostatic?

Answer 19

bactericidal and used to manage Gram-negative bacteria

Question 20

Examples of quinolones

Answer 20

ciprofloxacin, norfloxacin

Question 21

Quinolones mechanism

Answer 21

inhibitors of bacterial DNA gyrase (topoisomerase II) and topoisomerase IV
Gram-negative: DNA gyrase inhibited and supercoiling of DNA inhibited whcih is essential for DNA repair and replication
Gram-positive: topoisomerase IV inhibited, interference with separation of DNA strands

Question 22

Are quinolones bactericidal or bacteriostatic?

Answer 22

bactericidal

Question 23

Examples of folate inhibitors

Answer 23

trimethoprim, sulphonamides

Question 24

Trimethoprim mechanism

Answer 24

structurally similar to folate and is a folate antagonist

inhibits bacterial dihydrofolate reductase which converts folate to tetrahydrofolate

Question 25

Is trimethoprim bactericidal or bacteriostatic?

Answer 25

bacteriostatic

Question 26

Sulphonamides mechanism

Answer 26

analogs of p-aminobenzoic acid (PABA)
inhibit the growth of bacteria by competitively inhibiting the enzyme dihydropteroate synthase
is involved in the synthesis of folate from PABA
therefore reducing availability of DNA and RNA precursors

Question 27

Metronidazole

Answer 27

pro-drug
used against anaerobic bacteria and protozoa
activated by anaerobic bacteria to cytotoxic products
damages helical structure of DNA, protein and cell membrane