Structure and Mode Of Action Of Antibiotics and Antifungals

Question 1

Example of Lincosamide and uses

Answer 1

Clindamycin - staphs and Streps commonly
Bacteroides fragilis and other anaerobes.
Used in toxic shock to block M protein which blocks SIRS.
Toxoplasmosis/ parasitic Protozoa and malaria

Question 2

Action of lincosamides bacteriostatic or bacteriocidal?

Answer 2

Bacteriostatic

Question 3

Major targets for antibacterial agents

Answer 3

1. Inhibits cell wall synthesis (DNA)
2. Interferes with DNA synthesis snd replication (nucleic acids and DNA replication)
3. Inhibits protein synthesis (mRNA and ribosomes)
4. Disrupts cell membrane (proteins)

Question 4

Cell wall synthesis inhibitors

Answer 4

Beta lactams (penicillins, cephalosporins and carbapenems)
Glycopeptides e.g. Vancomycin and teicoplanin
Monobactams e.g. Aztreonam
Bacitracin
Fosfomycin
Isoniazid e.g. Mycolic acid/TB

Question 5

Mode of action of ‘Lincosamides’ e.g. Clindamycin,

Answer 5

• interfere with the synthesis of proteins

- bind to 23s portion of 50s subunit of bacterial ribosomes and cause dissociation of RNA from the ribosome

Question 6

What is a beta lactam?

Answer 6

Broad spectrum abx containing a beta-lactam ring.

Question 7

Three examples of a beta-lactam abx

Answer 7

Penicillins
Cephalosporins
Carbapenems

Question 8

Examples of macrolide and its uses

Answer 8

• Some gram positive I.e. S.pneumonia and limited gram negative i.e B. Pertussis, H. inf, some resp tract and soft tissue infections
• Effective against L. Pneumophila, mycoplasma, mycobacterium, some rickettsia and chlamydia.
• substitute for penicillin allergic
• Clarithromycin, Azithromycin and Erythromycin.

Question 9

Action of macrolides (clary, ery and Azithromycin) bacteriostatic or bacteriocidal?

Answer 9

Bacteriostatic

Question 10

Mode of action of macrolides (ery, Azithromycin, clary)?

Answer 10

Macrolide ring inhibits protein synthesis. - blocks peptidyl transferase from adding to growing peptide attached to tRNA to the next AA. - > inhibits ribosomal translation
Macrolides actively concentrate within leukocytes - transported to site of infection.

Question 11

Example and uses of Aminoglycoside

Answer 11

• Active against most gram negative aerobic and facultative anaerobic bacilli.
• generally not active against MRSA, gram negative anaerobes and gram positive bacteria.
• Gentamicin, Kanamycin, Amikacin, Tobramycin.
• gentamicin can be used against GN orgs + staphs. Used for RTI, UTI, blood, bone and soft tissue infections.

Question 12

Action of Aminoglycoside bacteriocidal or bacteriostatic?

Answer 12

Bacteriocidal

Question 13

Mode of action of Aminoglycosides

Answer 13

Inhibit protein synthesis

‘Cell membrane effect’ - integrity of cell membrane can be lost due to Aminoglycoside exposure and transport.

Question 14

What class of abx does Vancomycin belong to?

Answer 14

Glycopeptide

Question 15

Uses of Vancomycin.

Answer 15

• 1st line IV for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections and MRSA meningitis.
• PO for severe C. difficile colitis

Question 16

Mode of action of Vancomycin

Answer 16

Inhibits proper cell wall synthesis in gram positive bacteria.
Vancomycin binds to D-ALA-D-ALA of NAM NAG peptides of cell wall -> prevents cell wall synthesis of polymers of NAM & NAG -> prevents backbone polymers from cross linking with each other.

Question 17

How does resistance develop to vancomycin?

Answer 17

Last D-ALA reissued replaced with D- lactate (loss of H binding interaction) -> vancomycin cannot bind and cell wall synthesised as normal.

Question 18

Beta-lactams (penicillins, carbapenems and cephalosporins) bacteriocidal or bacteriostatic?

Answer 18

Rapidly bacteriocidal

Question 19

Protein synthesis inhibitors

Answer 19

Macrolides (ery, clary and Azithromycin)
Aminoglycosides (Gent, Tobra, Amik, Kanamycin)
Tetracyclines (doxy and tetracycline)
Chloramphenicol, Rifampicin, Mupirocin, Linezolid.

Question 20

Disrupters of cell membrane

Answer 20

Polymixins e.g colistin

Lipopeptides e.g. Daptomycin

Question 21

Interfere with DNA synthesis and replication.

Answer 21

Sulphonamides e.g. Sulphamethoxazole
Diaminopyrimidines e.g. Trimethoprim
Quinolones e.g. Ciprofloxacin
Nitroimidazoles e.g. Metronidazole

Question 22

Bacteriostatic definition.

Answer 22

Prevents growth and division, don’t kill

Question 23

Bacteriocidal definition.

Answer 23

Kill bacteria

Question 24

What is a monobactam, it’s uses and an example.

Answer 24

Abx closely related to beta-lactams but with a slightly different ring structure.
Useful in beta-lactam allergic patients.
E.g Aztreonam

Question 25

Beta lactam structure of Penicillins

Answer 25

Beta lactam ring (4 C and 1 N) and Thiazolidine ring (4 C and 1 S)
1 modifiable residue

Question 26

Beta lactam structure of Cephalosporins

Answer 26

Beta lactam ring (4 C and 1 N) and Dihydrothiazine ring (4 C, 1S and 1N)
2 modifiable residues

Question 27

Beta lactam structure of Carbapenems

Answer 27

Beta lactam ring (4C and 1N) and carbapenem core (4C and 1N)
Three modifiable residues

Question 28

What can be done with chemical residues on beta lactam structures?

Answer 28

Changed/ substituted in order to make large numbers of different abx in each sub-group.
Allows the pharmaceuticals to be changed or antibacterial spectrum to be changed.