W5 23 anti-bacterial drugs

Question 1

What are antibacterial drugs?

Answer 1

Substances/chemicals killing or preventing the growth of bacteria

Question 2

What is the difference between bacteriostatic and bactericidal?

Answer 2

Bacteriostatic = halts the growth of the bacteria without killing
Bactericidal = kills the bacteria, can’t come back after finishing antibiotic therapy

Question 3

What is selective toxicity?

Answer 3

Kills bacteria without harming the host

Question 4

Features of bacterial cells

Answer 4

Peptidoglycan cell wall (good target for selective toxicity)
Plasma membrane
Singular, circular chromosome
Protein synthesis
Energy metabolism - no mitochondria

Question 5

Bacteria has 3 classes of mechanisms for their metabolism. What is class I and is it a good therapeutic agent?

Answer 5

Class I reactions are the reactions that utilise the nutrients and resources from the environment to make the precursor molecules that are needed for the macromolecules of the cells and needed for the production of ATP. (Not a good therapeutic target because these reactions are similar in human cells).

Question 6

Bacteria has 3 classes of mechanisms for their metabolism. What is class II and is it a good therapeutic agent?

Answer 6

Class II reactions utilise the precursor molecules that are made by the cell to make the first building blocks of the macromolecules (hexosamines, amino acids, nucleotides)
Better targets than class I, some of these are specific for bacteria.

Question 7

Bacteria has 3 classes of mechanisms for their metabolism. What is class III and is it a good therapeutic agent?

Answer 7

Class III reactions lead to the production of the large macromolecules like peptidoglycan, proteins, RNA and DNA
Best targets - specific macromolecules to the bacteria, good selective toxicity

Question 8

What are some potential targets Class II reactions?

Answer 8

Folate metabolism
Folate utilisation
Sulphonamides

Question 9

What is the difference between folate metabolism in humans and bacteria?

Answer 9

Human cells don’t make folate, we take it up from the environment. Used to make DNA.
Bacteria make their own folate from precursor PABA, and unable to take up folate from the environment.

Question 10

How does inhibiting folate metabolism stop bacteria growth?

Answer 10

Interrupting the folate metabolic pathway in bacteria will inhibit DNA synthesis in these cells. Would be bacteriostatic, halting growth of the colony and division but not killing the bacteria.

Question 11

What’s the difference between sulphonamides and trimethoprim?

Answer 11

Sulphonamides as antibiotics stop the production of folate from PABA in bacterial cells, interfering with DNA production. Bacteriostatic.
Trimethoprim interfere with the utilisation of folate by bacteria (only in bacterial cells). Bacteriostatic.

Question 12

Why would we not use sulphonamides in dental practice?

Answer 12

Sulphonamides are competitive antagonists of PABA, so if there is excess PABA it won’t be effective. Procaine, an LA, produces PABA esters, so provide the competitive antagonist the the drug. So unuseful.
Pus has purines and pyramidine bases as breakdown products. Bacteria can use these when they cannot make folate to make their DNA.
Plasmid-mediated resistance

Question 13

What antibiotics inhibit peptidoglycan synthesis? (Targeting class III reactions)

Answer 13

Penicillins
Cephalosporins
Cycloserin
Vancomycin
Bacitracin

Question 14

What are penicillins the first drug choice for?

Answer 14

First choice drug for bone and joint infections
- can be given IM or IV
- absorption from GI tract variable

Question 15

Why has resistance to penicillin spread among bacteria?

Answer 15

Bacteria produce b-lactamases - an enzyme that deactivates penicillin
Some gram-negative bacteria are resistance due to a reduction of membrane permeability so don’t uptake it
Modified penicillin binding sites by mRSA

Question 16

Downsides of penicillin

Answer 16

GI disturbances like nausea and diarrhoea (treatable after antibiotics stop GI flora returns to normal)
Serious side effects - hypersensitivity reactions

Question 17

Is there resistance by bacteria to cephalosporins?

Answer 17

Yes, same reasons as penicillin

Question 18

What are the side effects of cephalosporins?

Answer 18

Unpleasant side effects - diarrhoea, nausea, intolerance to alcohol
Serious side effects - hypersensitivity reactions, neurotoxicity

Question 19

Which types of antibiotics inhibit protein synthesis (class III)?

Answer 19

Tetracyclines
Aminoglycosides
Erythromycin

Question 20

What is the mechanism of protein synthesis in bacterial cells?

Answer 20

mRNA brings message along
tRNA brings amino acid into the A side
Process and new site moves over to the P side and cycle gets repeated
(Can interfere at some sites at the ribosome that will not affect human cells)

Question 21

What mechanism do tetracyclines inhibit protein synthesis of bacteria, and why do humans not respond?

Answer 21

They compete with tRNA for the A site, prohibiting the insertion of the tRNA bringing new amino acids.
Tetracyclines cannot go into human cells, they are selectively taken up by prokaryotes. Selective toxicity.

Question 22

What is the spectrum of bacteria that tetracyclines can affect?

Answer 22

Wide spectrum - gram + and gram - bacteria
Mycoplasma, Ricketsia, Neisseria meningitis

Question 23

Are tetracyclines absorbed from the GI?

Answer 23

Absorption from GI variable

Question 24

What are the unpleasant side effects of tetracyclines and how are they treatable?

Answer 24

GI disturbances, dizziness and nausea, diarrhoea, vitamin B complex deficiency (since they kill the gut bacteria that help us absorb this)
Deficiency treated with supplements. GI disturbances stop after finishing therapy.

Question 25

What are serious side effects of tetracyclines?

Answer 25

Hepatotoxicity Renal damage (mainly affecting people with already damaged liver and kidney functions) Teratogenic - can cause dental hypoplasia and bone deformities in unborn babies (don’t give to women of reproductive age unless certain they aren’t pregnant).

Question 26

By what mechanism do aminoglycosides work?

Answer 26

Aminoglycosides interfere with anticodon recognition, so bacteria ribosomes misinterpret the mRNA message, producing an unfunctional protein.

Question 27

What spectrum antibiotics are aminoglycosides?

Answer 27

Efficient against gram - enteric organisms eg Streptococcus, Listeria, Pseudomonas aeruginosa Used mainly in sepsis

Question 28

How are aminoglycosides administered?

Answer 28

IM or IV, not intra-oral because they are not absorbed from the GI

Question 29

Side effects of aminoglycosides

Answer 29

Ototoxicity - toxic to the auditory nerve, can lead to nerve deafness Nephrotoxicity

Question 30

By what mechanism does erythromycin act?

Answer 30

It inhibits translocation of tRNA from A site to P site of the ribosome, after new amino acid has been added to the chain. Thus polypeptide chain cannot be continued, producing a short dysfunctional peptide fragment rather than full protein.

Question 31

Why is erythromycin good to use?

Answer 31

Similar to penicillins, but people are not as allergic. Given to penicillin-sensitive patients. Resistance might still occur however.

Question 32

What are all the side effects of erythromycin?

Answer 32

Unpleasant - GI disturbances, similar to penicillin, can be tolerated Treatable - opportunistic infections (mainly Candida albicans) Serious - cholestatic jaundice (very rare), hypersensitivity (rare)

Question 33

Clindamycin inhibits protein synthesis of bacteria. Many dentists use it. Describe it.

Answer 33

Broad spectrum, easily tolerated, can be given by mouth

Question 34

What is the issue with clindamycin?

Answer 34

If you use it, it will kill a lot of the gut bacteria, potentially providing C. difficile with a growth advantage. Can cause severe problems. Particular associated with pseudomembranous colitis. Will kill the patient within a week.

Question 35

What advice should you give patients on clindamycin?

Answer 35

Warn them that any (even minor) GI disturbance, diarrhoea, bloating, immediately stop the drug and return, and need treatment if they get pseudomembranous colitis.

Question 36

What drugs interfere with energy metabolism?

Answer 36

Metronidazole

Question 37

How does metronidazole work?

Answer 37

Effective against anaerobic bacteria and protozoa (including C difficile) In cells that don’t have mitochondria, the breakdown products of metronidazole will become cytotoxic and destroy the cell from within. Thus saves pt from pseudomembranous colitis.

Question 38

Side effects of metronidazole

Answer 38

Nausea, metallic taste Disulfiram-like reaction with alcohol (don’t drink on this!)

Question 39

How do bacteria share their antibiotic resistance genes?

Answer 39

Bacteria can share their plasmids with one another via: - conjugation - process of sharing a plasmid with a resistance gene from one live bacteria to another - transduction - viruses can transport genes from one bacterium to another - when a bacterium dies it releases contents to the environment and live bacteria can pick up these fragments of DNA and increase their arsenal of resistance for the future, sharing these further.

Question 40

How do genes in bacteria cause antibiotic resistance?

Answer 40

Genes in plasmid can: - make an enzyme to drag de the antibiotic - make efflux pumps that get rid of the antibiotic - make enzymes that alter the antibiotic rendering it inefficient against the bacteria itself

Question 41

How do resistance bacteria have a selective advantage over antibiotic sensitive bacteria!

Answer 41

They multiply more easily producing larger numbers, facilitating spread

Question 42

Which drugs have which mechanisms of drug resistance?

Answer 42

Altered drug targets or metabolic pathways - eg acyclovir, rifampicin Decreased access/increases export - eg chloroquine Drug inactivation - penicillin, aminoglycosides

Question 43

Contraindications of antibiotics

Answer 43

Site of infection determining effective dose Other drugs can interact Pregnancy - watch women at reproductive age Immune system - immunocompromised patients might need strong antibiotics Drug resistance - previous use of antibiotics Side effects - age, renal, hepatic function Hypersensitivity reactions

Question 44

How can site of infection determine effective dose of antibiotics!

Answer 44

Small ineffective doses will promote resistance and development of sensitisation and won’t kill the bacterium. Most infections are in bone, which need higher doses than soft tissues

Question 45

How might other drugs interact with antibiotics?

Answer 45

Might affect half life of the antibiotic Antibiotic might affect other drugs and increase their toxicity Combinations might be additive, synergistic, antagonistic. Can increase risk of adverse reactions.

Question 46

When can antibiotics be used in dental surgery?

Answer 46

Used to supplement: - persistent/advanced infections - complex gum or implant surgery - patients with a weak immune system - prevention of bacterial endocarditis in patients at HIGH risk