Module 3: Section 2C

Question 1

3 basic principles of antibiotics

Answer 1

1. Antibiotics do not work on viruses
2. Antibiotics may be bactericidal and bacteriostatic
3. An antibiotic must be selectively toxic

Question 2

Antibiotics do not work on viruses

Answer 2

• Antiviral chemotherapeutics have been developed to target specific viruses
• Antibiotics primarily treat bacteria

Question 3

Bactericidal

Answer 3

Kill the target bacteria

Question 4

Bacteriostatic

Answer 4

• Prevent further bacterial replication
• Growth will resume if antibiotic is removed or concentration decreases below an effective level

Question 5

An antibiotic must be selectively toxic

Answer 5

• Antibiotics must kill or inhibit the pathogen while harming the host as little as possible
• Safety is measured by the therapeutic index, the ratio of the toxic dose to the therapeutic dose
• A larger therapeutic index means a safer drug

Question 6

What do ED₅₀, TD₅₀, and therapeutic index mean?

Answer 6

• ED₅₀ is the dose effective for 50% of people
• TD₅₀ is the dose toxic for 50% of people
• The ratio TD₅₀ ÷ ED₅₀ is the therapeutic index, a larger value means a safer drug

Question 7

Antagonism

Answer 7

An interaction between 2 or more drugs that have opposite effects on the body

Question 8

Synergism

Answer 8

• An interaction between 2 or more drugs when the combined effect is greater then the drugs on their own
• Effect of drugs is magnified

Question 9

When combining antibiotics what occurs more antagonism or synergism?

Answer 9

Antagonism

Question 10

What are 2 common microbial processes that are commonly inhibited by antibiotics?

Answer 10

1. Folate synthesis
2. Cell wall synthesis

Question 11

Why is tetrahydrofolic acid important?

Answer 11

• It’s needed to make some nucleotides and amino acids
• Bacteria must make it themselves by converting pABA into tetrahydrofolic acid

Question 12

Inhibition of folate synthesis

Answer 12

• This pathway is essential for DNA synthesis and is a target for antibiotics
• Humans get folate from their diet, so this pathway only exists in prokaryotes

Question 13

2 types of drugs that inhibit folate synthesis

Answer 13

1. Sulfa drugs
2. Trimethoprim
   - Both are bacteriostatic antibiotics
   - Often prescribed together

Question 14

Penicillin

Answer 14

• First antibiotic
• Works by interrupting the assembly of the peptidoglycan layer
• Disrupting cell wall synthesis and causing bacteria to lyse

Question 15

Antibiotics targeting peptidoglycan synthesis

Answer 15

• Have high therapeutic index cuz peptidoglycan is unique to prokaryotes
• Is a ubiquitous target
• Is accessible because the antibiotics do not need to cross the cytoplasmic membrane

Question 16

When are peptidoglycan inhibitors not effective?

Answer 16

On quiescent (dormant) cells since they are targeting bacterial growth and division steps that rely on peptidoglycan remodelling

Question 17

How do drugs targeting peptidoglycan (PG) work? (General)

Answer 17

• They bind to and inhibit penicillin-binding proteins (PBPs) in the bacterial cell wall
• PBPs are needed for the final stages of PG assembly
• Blocking them causes structural weakness in the cell wall

Question 18

How do drugs targeting peptidoglycan (PG) work? Step 1

Answer 18

PBP’s build the glycan chains and amino-acid crosslinks in peptidoglycan

Question 19

How do drugs targeting peptidoglycan (PG) work? Step 2

Answer 19

Drugs that bind PBP’s inhibit the formation of crosslinks between PG chains

Question 20

How do drugs targeting peptidoglycan (PG) work? Step 3

Answer 20

Preventing PG cross-link formation activates autolysis to degrade the cell wall, leading to cell lysis

Question 21

Glycopeptides

Answer 21

A class of antibiotics used to target bacteria

Question 22

Vancomycin

Answer 22

• Type of glycopeptide
• Works by blocking he construction of the cell wall by inhibiting the elongation of PG chains

Question 23

What does vancomycin not work well with?

Answer 23

• Gram-negative bacteria
• The access to the PG is prevented by the outer membrane of gram-negative bacteria

Question 24

Teicoplanin

Answer 24

• More recently discovered antibiotic
• Glycopeptide
• Very soluble in lipid membrane so it can be used to target intracellular bacterial infections

Question 25

Polypeptides

Answer 25

- Work to inhibit PG subunit synthesis and transportation - Two drugs: Polymyxin and Bacitracin

Question 26

Polymyxin

Answer 26

- Work well against gram-negative bacteria - They can disrupt both membranes with their hydrophobic tails

Question 27

Bacitracin

Answer 27

- Inhibit lipid carriers in the cell wall - Does not work well with gram-negative bacteria

Question 28

Beta-lactams

Answer 28

- Group of antibiotics that contain four-membered B-lactam rings in their structure - Target bacteria by inhibiting the cross-linking of PG catalyzed by PBPs

Question 29

2 kinds of beta-lactam antibiotics

Answer 29

1. Penicillins 2. Cephems

Question 30

Cephems

Answer 30

Can be further divided into: Cephamycin and cephalosporins

Question 31

What do beta-lactamase enzymes do and how are they countered?

Answer 31

- Some bacteria make beta-lactamases that break the beta-lactam ring in antibiotics, inactivating them and giving the bacteria resistance - To fight this, beta-lactams are used with beta-lactamase inhibitors such as clavulanic acid, sulbactam, or tazobactam