The mechanism and Action of Antibiotics

Question 1

What are the central principles of antibiotic use?

Answer 1

• Anti-bacterials target processes that humans don’t possess.
• Anti-bacterials target bacterial processes which are different from human.
• The toxicity of anti-bacterials is greater to bacteria than to humans.

Question 2

Describe the targets, mechanisms and examples of beta-lactam and cephalosporin antibiotics.

Answer 2

Targets - Penicillin binding proteins.

Mechanisms - Preventing peptidoglycan cross-linking.

Eg, Penicillin G, Flucloxacillin

Question 3

Describe the targets, mechanisms and examples of glycopeptides

Answer 3

Target - C terminal D-ala-D-ala.

Mechanisms - Prevents transglycolation and transpeptidation.

eg, Vancomycin.

Question 4

Describe the targets, mechanisms and examples of cyclic peptides

Answer 4

Targets - C55 isopropyl pyrophosphate.

Mechanism - Prevents carriage of building blocking of peptidoglycan bacterial cell wall.

eg, Bacitracin

Question 5

Describe the targets, mechanisms and examples of phosphonic acids

Answer 5

Targets - murA protein,

Mechanism - Inhibits first stage of peptidoglycan synthesis.

eg, Fosphomycin.

Question 6

Describe the mechanisms of lipopeptides

Answer 6

Target - Cell wall stress stimulon.

Mechanisms - Calcium dependant membrane depolarisation

eg, Daptomycin

Question 7

Name the three classes of bacterial cell wall inhibitors and their features?

Answer 7

1) Beta-lactams,
2) Vancomycin,
3) Bacitracin.

They inhibit bacterial cell wall synthesis which leads to death of the bacteria.

Question 8

What are the Penicillins active against?

Answer 8

• Gram positive and gram negative cocci.
• Gram positive rods
• Spirochaetes.

Question 9

Name some examples of pathogen and diseases of gram positive and gram negative cocci

Answer 9

• Staphylococcus (Infections of wounds and boils)
• Streptococcus haemolytic types (septic infections)
• Enterococcus (endocarditis)
• Pneumococcus (pneumonia)
• Neisseria gonorrhoeae (Gonorrhoea)
• Neisseria Menigitids (meningitis)

Question 10

Name an example of a gram positive rods and the diseases it causes?

Answer 10

Clostridium (Tetanus and gangrene)

Question 11

What are some examples spirochaetes and the disease they cause

Answer 11

• Treponema (syphilliis)

- Actinomyces (abscesses)

Question 12

Name some examples of Beta lactamase-resistant penicillins

Answer 12

Methicillin, oxacillin, nafcillin, cloxacillin and dicloxacillin.

Question 13

Name some examples of broad spectrum penicillin’s

Answer 13

Ampicillin and amoxicillin

Question 14

Name some examples of extended-spectrum penicillins

Answer 14

Carbenicillin, ticaracillin, azlocillin, piperacillin. Covers broad spectrum bacteria and psudomonas aeruginosa.

Question 15

Describe the structure and function of carbapenems

Answer 15

• Bind to Penicillin binding proteins permanently acylating them.
• They are active against gram Positive and gram Negative bacteria and anaerobes
• Poorly active against MRSA and not active against bacteria lacking a cell wall

Question 16

Describe how different antigens are resistant to beta-lactam antibiotics?

Answer 16

S. aureus - Destruction by beta-lactamase.

Psudomonas spp - Failure to reach target enzyme.

S.pneumoniae - Failure to bind to the transpeptidase

Question 17

Describe features of Beta-lactamase inhibitors

Answer 17

There are 4 classes, (ACD and B). ACD use serine to hydrolyse where as B uses zinc ions.

Question 18

What are strong inhibitors of class A beta-lactamses?

Answer 18

Clavulanic acid and sulbactam, however these cannot inhibit class C and D

Question 19

What can be used alongside Beta lactam antibiotics and why is this a good alternative?

Answer 19

Beta lactamase inhibitors. This is an alternative approach to the use of beta lactamase resistant antibiotics.

Question 20

Describe features of cephalosporins and some examples

Answer 20

• Good alternatives to penicillins and can be used in septicaemia, pneumonia, meningitis, biliary tract infections, urinary tract infections and sinusitis.
• Eg, cefuroxime and cefotaxime.
• Overuse can lead to C.difficile

Question 21

Describe features of Bacitracin

Answer 21

Bactericidal which interferes with the dephosphorylation of lipid carrier which moves the early cell wall components through the membrane.
- Can be used in an ointment to treat infections of the skin and eye by strep and staph

Question 22

Name and describe bacterial folate antagonists

Answer 22

Sulphonamides and trimethoprim. Bacteria must make their own supply of folate whereas human depend on dietary intake. Therefore folate pathway inhibitors are specific for bacteria.

Question 23

Trimethoprim is commonly used for?

Answer 23

Community urinary tract infections

Question 24

Co-trimoxazole is a combination of what? And when is it used?

Answer 24

Sulphamethoxazole and trimethoprim. It can be used in the treatment of toxoplasmosis. In combo with other drugs for treatment of pneumocytis jiroveci

Question 25

Name some examples of macrolides and their mechanism of action and what they can be used against

Answer 25

-Bacterial ribosomal inhibitors, eg, Erythromycin and clarithromycin. - Corynebacterium (diphtheria), - Campylobacter (Diarrhoea) - Chlamydia trachomatis - Toxoplasma gondii (in pregnancy) - In combo with other agents in helicobacter pylorii

Question 26

What are the adverse side effects of erythromycin?

Answer 26

Mild gut disturbances, hypersensitivity reactions, transient hearing disturbances and occasionally cholestatic jaundice.

Question 27

What are the adverse side effects of clarithromycin

Answer 27

Similar to erythromycin but also causes QT prolongation

Question 28

What are the adverse side effects of clindamycin

Answer 28

Many GI disturbances but also psudomembraneous colitis (inflammation of colon due to necrotising toxin produced by clindamyciin resistant C.difficile).

Question 29

Name and example of a lincosamide and what it is active against

Answer 29

Clindamycin. - Active against gram positive cocci and anaerobic species. Therefore it can be used in combination against anaerobic sepsis and necrotising fasciitis or in eye drops to treat staphylococcal conjunctivitis.

Question 30

Describe the use of aminoglycosides

Answer 30

The relative toxicity and parenteral administration means that these agents should be reversed for treatment of serious infections. And more rare issues like yersinia pestis (the plaque)

Question 31

What are the side effects aminoglycosides?

Answer 31

- Renal toxicity due to damage to kidney tubules. - Ototoxicity with a progressive damage to and destruction of the sensory cells. - Neuromuscular block

Question 32

Describe the pharmacokinetics of aminoglycosides

Answer 32

Does not cross the blood brain barrier and is excreted by the kidneys. It is then administered intravenously as it is poorly absorbed orally

Question 33

What are some of the cautions in the use of aminoglycosides?

Answer 33

- Caution in the elderly, - Caution with renal failure, - Interaction with other renal toxic drugs, - Caution in severe sepsis that is causing acute renal failure.

Question 34

What are tetracyclines used for?

Answer 34

Rickettsia, mycoplasma and chlamydia infections, brucellosis, cholera, plague and lyme disease. And chronic acne

Question 35

What medication is used in the management of resistant gram negative infections?

Answer 35

Tigecycline

Question 36

What are some of the side effects of tetracyclines?

Answer 36

GI upset, hepatic and renal dysfunction, photosensitivity, binding to bone and teeth causing staining, vestibular toxicity

Question 37

What are the features of chloramphenicol?

Answer 37

It is a broad spectrum which has low risk of aplastic anaemia which means it is limited to indications for serious infections when no other drug is available, eg, meningitis and brain abscess

Question 38

What is the function of topoisomerase IV?

Answer 38

It is involved in chromosomal partitioning, it catalyses ATP dependant relaxation of negatively and positively supercoiled DNA and unknowing of un-nicked duplex DNA

Question 39

What is the function of DNA gyrase

Answer 39

It forms a transient covalent bond with DNA, breaks the DNA, passing the DNA through the break and then repairs the break

Question 40

What is the function of Quinolones?

Answer 40

Converting gyrase and topoisomerase IV into toxic enzymes that fragment bacterial chromosome.

Question 41

What can fluoroquinolones be used against? name an example?

Answer 41

Ciprofloxacin which can be used against enterobacteriaceae, H.influenzae, Beta lactamase producing N. gonorrhea (single dose can cure honorrhoea). Campylobacter (diarrhoea), psudomonas aeruginosa and salmonella.

Question 42

What is metronidazole?

Answer 42

Antiprotozoal agent which under anaerobic conditions generates toxic radicals that damages bacterial DNA

Question 43

What is metronidazole active against?

Answer 43

Anaerobic bacteria such as bacteriodes clostridia and some streptococci. Effective in treatment of pseudomembranous colitis and when used with other drugs (omeprazole/amoxicillin) can treat helicobacter pylori.

Question 44

What are Nitrofurans?

Answer 44

Mechanism is unknown but has a broad spectrum activity against bacteria and resistance is rare. They can be used to treat UTIs due to enterobacteriaceae.

Question 45

What are polymixins?

Answer 45

Branches chain decapeptides. Mechainsim of action involves interaction with phospholipids of cell membrane and disruption of its structure. Topical use for cutaneous pseudomonas infections.