Antibiotics and Anti-fungals

Question 1

Describe the distinctive features of:

a. Gram positive bacteria
b. Gram negative bacteria
c. Mycolic bacteria

Answer 1

a. Gram positive bacteria 
Thick peptidoglycan cell wall 
b. Gram negative bacteria 
Outer membrane that contains lipopolysaccharide (LPS)
c. Mycolic bacteria  
Outer mycolic acid layer

Question 2

State the steps involved in the production of THF from PABA.

Answer 2

PABA –> DHOp (enzyme = dihydropterase synthase)
DHOp –> DHF
DHF –> THF (enzyme = DHF reductase)

Question 3

What is DNA gyrase?

Answer 3

A type of topoisomerase (topoisomerase II)

It releases tension in DNA and is important in unwinding DNA to allow protein binding required for DNA replication

Question 4

What does RNA polymerase do?

Answer 4

Produces RNA from a DNA template

Question 5

What is the key difference between ribosomes in eukaryotes and prokaryotes?

Answer 5

Eukaryote = 40S + 60S Prokaryote = 30S + 50S

Question 6

State two classes of drugs that interfere with nucleic acid synthesis and name the enzymes that they inhibit.

Answer 6

Sulphonamides – inhibits dihydropterate synthase

Trimethoprim – inhibits DHF reductase

Question 7

These two drugs are sometimes used together. What is this preparation called?

Answer 7

Co-trimoxazole

Question 8

Name a group of drugs that interfere with DNA replication and state its targets.

Answer 8

Fluoroquinolones (e.g. ciprofloxacin) inhibits bacterial DNA gyrase and topoisomerase IV

Question 9

Name a group of drugs that interfere with RNA synthesis and state its main target.

Answer 9

Rifamycins (e.g. rifampicin) – inhibits RNA polymerase

Question 10

List 4 groups of drugs that interfere with ribosomes.

Answer 10

Macrolides
Chloramphenicol
Aminoglycosides
Tetracyclines

Question 11

Describe how peptidoglycan is synthesized, transported to the cell wall and incorporated into the cell wall.

Answer 11

A pentapeptide is created on N-acetyl muramic acid (NAM)
N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan
The peptidoglycan is then transported into the cell wall by bactoprenol
The peptidoglycan is then incorporated into the cell wall by transpeptidase enzyme, which cross-links the peptidoglycan pentapeptides

Question 12

Which groups of drugs interfere with peptidoglycan synthesis and how do they do this?

Answer 12

Glycopeptides (e.g. vancomycin) – they bind to the pentapeptides and inhibit peptidoglycan synthesis
This is used as a last resort for Gram-positive bacteria that are resistant to other antibiotics

Question 13

Name a drug that interferes with peptidoglycan transport andstate its target.

Answer 13

Bacitracin – this inhibits bactoprenol, hence preventing peptidoglycan transport

Question 14

Name a class of drugs that inhibit peptidoglycan incorporation and explain how they do this.

Answer 14

Beta lactams – they bind covalently to transpeptidase, which inhibits peptidoglycan incorporation into the cell wall

Question 15

What are the three subsets of beta lactams?

Answer 15

Carbapenems
Cephalosporins
Penicillins

Question 16

Name two drugs that interfere with cell wall stability and explain how they do this.

Answer 16

Lipopeptides – disrupt Gram-positive cell walls

Polymyxins – bind to lipopolysaccharide and disrupt Gram-negative cell membranes

Question 17

List five mechanisms of antibiotic resistance and give a brief description of each.

Answer 17

Additional target– the bacteria produce another target that is unaffected by the drug
Hyperproduction – the bacteria increase the production of the target so the antibiotics are less effective (this is energy inefficient)
Altered target site – there is an alteration in the drug target so that the drug is no longer effective
Alteration in drug permeation– down regulation of aquaporins (responsible for allowing drugs into cells) or the upregulation of efflux systems
Production of destruction enzymes– beta-lactamases hydrolyse the C-N bond in the beta-lactam ring rendering the beta-lactams inactive

Question 18

What are penicillins G and V normally used to treat?

Answer 18

Gram-positive bacteria

Question 19

Name two drugs that are relatively beta lactamase resistant.

Answer 19

Flucloxacillin and temocillin

Question 20

Name a broad-spectrum antibiotic that must be administered with another drug to become resistant to beta lactamases. What is this other drug?

Answer 20

Amoxicillin (no antibiotic resistance on its own)

Clavulanic acid

Question 21

What are the two courses of treatment for mycobacterial infections?

Answer 21

Isoniazid + Rifampicin (6 months)

Ethambutol + Pyrazinamide (2 months)

Question 22

What are the mechanisms of action of isoniazid and rifampicin?

Answer 22

Isoniazid – inhibits mycolic acid synthesis

Rifampicin – inhibits RNA polymerase

Question 23

What else is rifampicin indicated for?

Answer 23

Leprosy

Question 24

What are the four types of fungal infection, characterised based on the tissues/organs affected?

Answer 24

Superficial – outermost layers of skin
Dermatophyte – skin, hair or nails
Subcutaneous – innermost skin layers
Systemic – primarily respiratory tract

Question 25

What are the two main groups of anti-fungals? Give an example ofeach.

Answer 25

Azoles (fluconazole)

Polyenes (amphotericin)

Question 26

Describe the mechanism of action of azoles.

Answer 26

They inhibit CYP51p (enzyme of the CYP450 system), which is involved in ergosterol production

Question 27

Describe the mechanism of action of polyenes.

Answer 27

These interact with membrane sterols and form channels (punching holes in the membrane)