Antibiotics

Question 1

Explain how we generally make antibiotics

Answer 1

As natural products from fungi or bacteria (usually soil dwellers) think of penicillin

• So we make them from natural products by fermentation and then modify them chemically
• Some totally are synthetic such as sulphonamides

Question 2

Where, in society, is most of the antibiotic use?

Answer 2

80% is in the community
- but in hospitals many people are on them including around 50% of all patients in the ICU

Question 3

In the community, what are the 2 main reasons for GPs prescribing antibiotics?

Answer 3

• Respiratory tract infections (50%)
• UTIs (15%)

Question 4

Why do we have to modify these natural antibiotics in a lab usually?

Answer 4

• remove toxicological effects
• metabolism
• modify effects …
• generally making them into better pharmacological agents

Question 5

What is a therapeutic margin?

Answer 5

The difference between an active dose (MIC) and the toxic effect of the drug
- so if the margin is small, it is v important to get the dose right

Question 6

Name an antibiotic with a wide therapeutic margin

Answer 6

Penicillin

Question 7

What is dysbiosis?

Answer 7

• The overgrowth of certain organisms
• When we give antibiotics we can cause disregulation of microbial antagonsim
• This normal microbiotia may prevent outgrowth of pathogens

Question 8

Name a common cause of pseudomembranous collitis

Answer 8

Antibiotics causing loss of normal flora causing outbreak of clostridum difficile

Question 9

What is pseudomembranous collitis?

Answer 9

Damaged, ulcerated, inflamed colon often caused by toxins from bacteria
- causes watery diarrhoea

Question 10

Explain what bacterial clearance is

Answer 10

Immunity works together with the antibiotics

Question 11

Name 3 ways that we can classify antibiotics

Answer 11

• Type of activity
• Structure
• Target site of activity

Question 12

What is the difference between bacteriocidal and bacteriostatic antibiotics?

Answer 12

Question 13

Why would we use bacteriostatic antibiotics?

Answer 13

As even though you are not killing it - the immune defence mechanisms clear the infections

Question 14

When can we not use bacteriostatic antibiotics?

Answer 14

When the host immune systems are not intact

Question 15

Some antibiotcs may be {?} at low dosages and {?} at high dosages

Answer 15

Some antibiotcs may be bacteriostatic at low dosages and bacteriocidic at high dosages

Question 16

What is meant by broad spectrum vs narrow spectrum antibiotics?

Answer 16

How many types of bacteria the antibiotic is affective against

Question 17

Is Penicillin G broad or narrow spectrum of activity?

Answer 17

Narrow spectrum antibiotics

Effective against very few types

Question 18

Name the 2 basic penicillins

Answer 18

• Benzylpeniclillin (PenG)
• Penicillin V

Question 19

What bacteria are basic penicillins effective against?

Answer 19

Active against streptococci, pneumococci, meningococci, treopnemes

Most strains of Staphylococcus aureus are resistant

Question 20

What bacteria can basic penicillins NOT treat?

Answer 20

Staphyloccocal bacteria

Question 21

Name an antistaphylococcal penicillin

Answer 21

Flucloxacillin

Question 22

Describe the pros and cons of PenG vs PenV

Answer 22

Pen G

benzlypenicillin (G= gold standard);

not acid stable therefore I/v or i/m good for some G negatives as well as G positves

penV

phenoxymethlypenicillin
oral (more acid stable than penG)
less active v G negatives, but same activity y G postives as PenG

Question 23

Why might we use amoxicillin or ampicillin over the basic penicillins?

Answer 23

Have a broader spectrum of activity as they can treat some gram negative organisms and enterococci

Question 24

What might we prescribe for pseudomonal bacteria such as in cystic fibrosis?

Answer 24

Piperacillin

Question 25

Explain what co-amoxiclav/Augmentin is

Answer 25

You are giving an inhibitor of a bacterial drug that would normally break down the drug + a wide spectrum drug such as amoxicillin

Question 26

Why do we call penicillins and cephalosporins beta lactams?

Answer 26

They both have the crucial beta lactam ring

Question 27

What is beta lactamase?

Answer 27

A bacterial enzyme that breaks down beta lactams "Beta-lactamases, are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins"

Question 28

How do beta lactam antibiotics (Penicillins and Cephalosporins) work?

Answer 28

Inhibit cell wall synthesis

Question 29

How do the protein synthesis inhibitor antibiotcs work?

Answer 29

Bind to 50s or 30s ribososmes that are only on prokaryotic cells to block protein sythesis

Question 30

Name 2 common proteins synthesis inhibitor antibiotcs

Answer 30

* Erythromyosin * Chloramphenicol * Streptomycin * Gentamicin * Doxycyline

Question 31

How do Quinolone antibiotics work?

Answer 31

Inhibit DNA gyrase (which is specific to bacteria as we use topoisomerase 4)

Question 32

How do trimethoprim and sulfonamides work?

Answer 32

Inhibit folic acid synthesis (thetrahydrofolic acid) * bacteria can synthesise folic acid but humans do not have these enzymes it so that is why it is not toxic to us

Question 33

Describe the gram + vs gram - bacterial cell wall

Answer 33

Question 34

How do cell wall synthesis inhibitors work?

Answer 34

Inhibit peptidoglycan-making enzymes

Question 35

Gram {?} cell walls are more vulnerable to cell wall inhibitors as gram {?} bacteria have a impermeable membrane - drugs have to move across this membrane

Answer 35

Gram positive cell walls are more vulnerable to cell wall inhibitors as gram negative bacteria have a impermeable membrane - drugs have to move across this membrane

Question 36

Are E coli and staphylococcus aureus gram + or gram -

Answer 36

E coli = negative Staph Aureus = positive

Question 37

What are trans-peptidases and carboxypeptidsases?

Answer 37

These are the enzymes that cross-link peptidoglycan and they are the enzymes that beta lactams bind to to inhibit

Question 38

Why might some beta lactams be able to work on gram negative bacteria?

Answer 38

If the beta lactam is modified to move through the outer membrane of the cell wall

Question 39

What is peptidoglycan?

Answer 39

Peptidoglycan or murein is a polymer consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane of most bacteria, forming the cell wall

Question 40

Fully explain how the folic acid synthesis inhibitors work

Answer 40

Question 41

How does Dapsone work?

Answer 41

Leprosy drug, inhibits the first enzyme in the folic acd pathway - only in bacteria

Question 42

Why might we prescribe prophylactic antibiotics?

Answer 42

Question 43

Explain what MIC is

Answer 43

Minimum inhibitory concentration = the minimum concentration of the antibiotic needed to clear the infection

Question 44

Name some reasons as to why MIC may vary

Answer 44

* This will depend upon the age, weight, renal and liver function of the patient and the severity of infection * Depend on the susceptibility of the organism * Will also depend upon properties of the antibiotic i.e. enough to give a concentration higher than the MIC (minimum inhibitory concentration) at the site of infection

Question 45

What is the difference between time-dependance and concentration-dependance antibiotics?

Answer 45

Some antibiotics just need a maximum dose to be achieved, others need a maintained level above the MIC (?)