Antibacterial Agents

Question 1

How do polymyxins work?

Answer 1

They bind to Lipid A on LPS and disrupt the membrane causing leakage of cytoplasmic contents.

Only work in gram negative bacteria (as LPS only in gram neg)

Question 2

How do B-lactams work?

Answer 2

1. Bind to PBPs (transpeptidases) and prevent X-linking
2. Mimic d-ala-d-ala residues on peptide side chain
3. Stimulate autolysins -> break down cell wall

Question 3

How do Glycopeptides work?

Answer 3

e.g Vancomycin, Teicoplanin

1. Binds terminal d-ala-d-ala on peptide side chain. Prevents transglycosylase enzyme from adding PG monomer onto the glycan chain
2. Prevents X-linking (by steric hinderance)

Not effective against gram-negative bacteria as they are too large to fit through the pores in the outer membrane

Question 4

How does cycloserine work?

Answer 4

Inhibits cell wall synthesis

Question 5

How does Bacitracin work?

Answer 5

Inhibits cell wall synthesis

Question 6

What is polyfax?

Answer 6

Polymyxin B & Bacitracin

Used topically for skin & eye gram negative infections & prevention of wound infection

Question 7

How do lipopeptides work?

Answer 7

e.g Daptomycin

They cause rapid depolarisation of the membrane which inhibits ATP synthesis (leading to loss of function)

Only active against gram positive

They are used for skin & soft tissue infections and also endocarditis

Question 8

How do sulphonamides work?

Answer 8

They are metabolic inhibitors of nucleic acid synthesis

They inhibit Dihydropterate synthetase (which converts para aminobenzoic acid to dihydropteroic acid)

Question 9

How does Trimethoprim work?

Answer 9

It is a metabolic inhibitor of nucleic acid synthesis

It inhibits Dihydrofolate reductase (which converts dihydrofolic acid to tetrahydrofolic acid -> purines and pyrimidines)

Question 10

What is trimethoprim normally used for?

Answer 10

Gram negative UTIs (Not pseudomonas)

Question 11

What is the combination product of Trimethoprim and Sulphamethoxazole (Sulphonamide) called?

Answer 11

Co-trimoxazole

Question 12

Which drug can lead to stevens-johnson syndrome?

Answer 12

Co-trimoxazole (combination of Trimethoprim and Sulphamethoxazole)

Question 13

How do Fluroquinolones work?

Answer 13

e.g Ciprofloxacin, Levofloxacin, Moxifloxacin etc

They are inhibitors of DNA replication

They inhibit DNA gyrase and type IV topisomerase

Can chelate so should be given on an empty stomach

Question 14

What is the main problem with using Ciprofloxacin?

Answer 14

It is very broad spectrum and so has a high risk of C. diff!

Question 15

What can Ciprofloxacin (fluroquinolone) be used for?

Answer 15

It is active against both gram positive and gram negative but PARTICULARLY gram negative

Also active against INTRACELLULAR pathogens

Limited use against streptococci and enterococci

Question 16

How do Rifamycins work?

Answer 16

e.g. Rifampicin

They are inhibitors of RNA polymerase

Bactericidal

Normally used for treatment of TB, prophylaxis of meningitis, infections involving prosthetic material

Question 17

What are the main side effects of Rifampicin?

Answer 17

• Hepatotoxicity
• Increased metabolism of other drugs
• Orange-red colour of secretions!

Question 18

How do nitroimidazoles work?

Answer 18

e.g. Metronidazole

They inhibit nucleic acid synthesis by disrupting the DNA

Can be used to treat C.diff

Question 19

How do Aminoglycosides work?

Answer 19

e.g. Gentamicin (Amikacin, Tobramycin, Steptomycin)

They mostly bind to the 30s subunit
Decrease assembly of initiation complex & binding of tRNA to A site

Some bind the 50s subunit
Decrease assembly of initiation complex

Question 20

What is Gentamicin (an aminoglycoside) normally used for?

Answer 20

Serious infections from AEROBIC bacteria

Active against many G-ves
Active against some G+ves

Question 21

What are the main side effects of aminoglycosides?

Answer 21

Nephrotoxicity and Ototoxicity

Question 22

How do Oxazolidinones work?

Answer 22

e.g. Linezolid

Binds the 23S rRNA in 50S subunit
Decreases assembly of the initiation complex

Active against gram positive bacteria

Question 23

How do Tetracyclines work?

Answer 23

e.g. Doxycycline (Minocycline, Tigecycline)

Binds to the 30S ribosomal subunit
Decreases tRNA binding to A site

Question 24

What are the main side effects associated with Tetracyclines?

Answer 24

Staining in teeth
Phototoxic reactions
Can lead to superinfections (candida albicans, proteus, pseudomonas)

Question 25

How do Macrolides/Ketolides work?

Answer 25

e. g. Erythromycin, Clarithromycin, (Azithromycin)
e. g. of ketolide is Telithromycin (more potent macrolide designed to overcome resistance)

Bind to the 50S subunit
Decreases translocation and release of tRNA

Question 26

How do Lincosamides work?

Answer 26

e.g. Clindamycin

Bind to the 23s portion of the 50s subunit

Question 27

What are lincosamides normally used for?

Answer 27

IV, IM or Oral treatment of Stapylococcal bone & joint infections, respiratory infections, peritonitis, septicaemia etc

Question 28

How does Fusidic acid work?

Answer 28

It binds to the EF-G-Ribosome complex
Decreases translocation of tRNA

Narrow spectrum antiobiotic

Question 29

What is Fusidic acid normally used for?

Answer 29

Staphylococcal skin infections

Question 30

How does Chloramphenicol work?

Answer 30

It binds to the 50S subunit
Prevents peptide bond formation

Broad spectrum antibiotic
Normally used for the treatment of eye infections

Question 31

What is the most important side effect of Chloramphenicol?

Answer 31

Aplastic anaemia

Rare but fatal, bone marrow cells die.
Normal haemopoetic cells absent. Space now filled with adipose tissue

Question 32

Which antibiotics give a long post effect?

Answer 32

• Benzylpenicillin

- Aminoglycosides