Antibiotics and Anti-fungals

Question 1

Describe the distinctive features of: Gram positive bacteria, Gram negative bacteria and Mycolic bacteria

Answer 1

Gram +ve bacteria: Thick peptidoglycan cell wall
Gram -ve bacteria: Outer membrane contains lipopolysaccharide (LPS)
Mycolic bacteria: Outer mycolic acid layer

Question 2

State the steps involved in the production of THF from PABA. What is THF important for ?

Answer 2

PABA –> DHOp (dihydropterase synthase)
DHOp –> DHF
DHF –> THF (DHF reductase)
THF important in nucleic acid synthesis

Question 3

What is DNA gyrase?

Answer 3

A topoisomerase

Releases tension in DNA + 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 function of ribosomes? What is the key difference between ribosomes in eukaryotes and prokaryotes?

Answer 5

Produce protein from RNA templates
Eukaryote = 40S + 60S
Prokaryote = 30S + 50S

Question 6

State 2 classes of drugs that interfere with nucleic acid synthesis and name the enzymes that they inhibit.

Answer 6

Sulphonamides: inhibits DHOp synthase
Trimethoprim: inhibits DHF reductase

Question 7

Sulphonamides and Trimethoprim 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 inhibit bacterial DNA gyrase + topoisomerase IV

Question 9

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

Answer 9

Rifamycins inhibits bacterial RNA polymerase

Mainly used in tuberculosis

Question 10

List 4 groups of drugs that inhibit ribosomes.

Answer 10

Macrolides e.g. Erythromycin
Aminoglycosides e.g. Gentamicin
Chloramphenicol
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
PtG is transported across the membrane by bactoprenol
PtG is incorporated into the cell wall by transpeptidase enzyme, which cross-links PtG pentapeptides

Question 12

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

Answer 12

Glycopeptides (e.g. vancomycin): bind to pentapeptides + inhibit PtG synthesis
= a last resort for Gram+ve bacteria that are resistant to other antibiotics

Question 13

Name a drug that interferes with peptidoglycan transport and state its target.

Answer 13

Bacitracin: inhibits bactoprenol regeneration, hence preventing PtG transport

Question 14

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

Answer 14

Beta lactams: bind covalently to transpeptidase, inhibiting PtG 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 membrane stability and explain how they do this.

Answer 16

Lipopeptides: disrupt Gram +ve cell membranes
Polymyxins: bind to LPS + disrupt Gram -ve cell membranes

Question 17

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

Answer 17

Additional target: bacteria produce another target that is unaffected by the drug
Hyperproduction: increase production of the target so the antibiotics are less effective (though energy inefficient)
Altered target: alteration in drug target so drug is no longer effective (though enzyme is still effective)
Alteration in drug permeation: reduction of aquaporins or increase of efflux systems
Destruction enzymes: beta-lactamases hydrolyse C-N bond of b-lactam ring rendering b-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

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 resistance on its own)

Clavulanic acid

Question 21

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

Answer 21

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

Question 22

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

Answer 22

Azoles (fluconazole)

Polyenes (amphotericin)

Question 23

Describe the mechanism of action of azoles.

Answer 23

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

Question 24

Describe the mechanism of action of polyenes.

Answer 24

Interact with membrane sterols + form channels (punching holes in the membrane)

Question 25

Give an example of Gram positive bacteria, Gram negative bacteria and Mycolic bacteria

Answer 25

Positive: Staphylococcus aureus
Negative: Escherichia Coli
Mycolic bactéria: Mycobacterium Tuberculosis

Question 26

Give an example of when an azole and polyene would be used?

Answer 26

Azole: Candidiasis + Systemic infections
Polyene: Systemic infection