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Pharmacology MD3001 > The mechanism and Action of Antibiotics > Flashcards

The mechanism and Action of Antibiotics Flashcards

1
Q

What are the central principles of antibiotic use?

A
  • 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.
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2
Q

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

A

Targets - Penicillin binding proteins.

Mechanisms - Preventing peptidoglycan cross-linking.

Eg, Penicillin G, Flucloxacillin

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3
Q

Describe the targets, mechanisms and examples of glycopeptides

A

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

Mechanisms - Prevents transglycolation and transpeptidation.

eg, Vancomycin.

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4
Q

Describe the targets, mechanisms and examples of cyclic peptides

A

Targets - C55 isopropyl pyrophosphate.

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

eg, Bacitracin

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5
Q

Describe the targets, mechanisms and examples of phosphonic acids

A

Targets - murA protein,

Mechanism - Inhibits first stage of peptidoglycan synthesis.

eg, Fosphomycin.

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6
Q

Describe the mechanisms of lipopeptides

A

Target - Cell wall stress stimulon.

Mechanisms - Calcium dependant membrane depolarisation

eg, Daptomycin

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7
Q

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

A

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

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

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8
Q

What are the Penicillins active against?

A
  • Gram positive and gram negative cocci.
  • Gram positive rods
  • Spirochaetes.
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9
Q

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

A
  • Staphylococcus (Infections of wounds and boils)
  • Streptococcus haemolytic types (septic infections)
  • Enterococcus (endocarditis)
  • Pneumococcus (pneumonia)
  • Neisseria gonorrhoeae (Gonorrhoea)
  • Neisseria Menigitids (meningitis)
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10
Q

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

A

Clostridium (Tetanus and gangrene)

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11
Q

What are some examples spirochaetes and the disease they cause

A
  • Treponema (syphilliis)

- Actinomyces (abscesses)

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12
Q

Name some examples of Beta lactamase-resistant penicillins

A

Methicillin, oxacillin, nafcillin, cloxacillin and dicloxacillin.

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13
Q

Name some examples of broad spectrum penicillin’s

A

Ampicillin and amoxicillin

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14
Q

Name some examples of extended-spectrum penicillins

A

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

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15
Q

Describe the structure and function of carbapenems

A
  • 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
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16
Q

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

A

S. aureus - Destruction by beta-lactamase.

Psudomonas spp - Failure to reach target enzyme.

S.pneumoniae - Failure to bind to the transpeptidase

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17
Q

Describe features of Beta-lactamase inhibitors

A

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

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18
Q

What are strong inhibitors of class A beta-lactamses?

A

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

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19
Q

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

A

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

20
Q

Describe features of cephalosporins and some examples

A
  • 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
21
Q

Describe features of Bacitracin

A

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

22
Q

Name and describe bacterial folate antagonists

A

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.

23
Q

Trimethoprim is commonly used for?

A

Community urinary tract infections

24
Q

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

A

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

25
Q

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

A

-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
26
Q

What are the adverse side effects of erythromycin?

A

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

27
Q

What are the adverse side effects of clarithromycin

A

Similar to erythromycin but also causes QT prolongation

28
Q

What are the adverse side effects of clindamycin

A

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

29
Q

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

A

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.
30
Q

Describe the use of aminoglycosides

A

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)

31
Q

What are the side effects aminoglycosides?

A
  • Renal toxicity due to damage to kidney tubules.
  • Ototoxicity with a progressive damage to and destruction of the sensory cells.
  • Neuromuscular block
32
Q

Describe the pharmacokinetics of aminoglycosides

A

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

33
Q

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

A
  • Caution in the elderly,
  • Caution with renal failure,
  • Interaction with other renal toxic drugs,
  • Caution in severe sepsis that is causing acute renal failure.
34
Q

What are tetracyclines used for?

A

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

35
Q

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

A

Tigecycline

36
Q

What are some of the side effects of tetracyclines?

A

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

37
Q

What are the features of chloramphenicol?

A

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

38
Q

What is the function of topoisomerase IV?

A

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

39
Q

What is the function of DNA gyrase

A

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

40
Q

What is the function of Quinolones?

A

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

41
Q

What can fluoroquinolones be used against? name an example?

A

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.

42
Q

What is metronidazole?

A

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

43
Q

What is metronidazole active against?

A

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.

44
Q

What are Nitrofurans?

A

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.

45
Q

What are polymixins?

A

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

Pharmacology MD3001 (14 decks)

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