PED1003/L23 Selective Toxicity & Antibiotics

Question 1

How do bacteriostatic drugs affect the number of total and viable cells?

Answer 1

Stops changes in both

Question 2

Why has the number of new antibiotics reaching the market dropped dramatically in the last 10 years? (3)

Answer 2

Resistance reduces effective life of a product
Too little profit
Government restrictions
Lack of new biological targets

Question 3

How do bacteriolytic drugs affect the number of total and viable cells?

Answer 3

Decrease both

Question 4

How do bacteriocidal drugs affect the number of total and viable cells?

Answer 4

Drop in viable cells
Total cells remain the same

Question 5

Give 3 common bacterial targets.

Answer 5

Cell membrane
Cell wall
Protein synthesis
RNA polymerase
DNA synthesis
Folate metabolism

Question 6

Describe the structure of a B-lactam ring.

Answer 6

Cyclic amide with heteroatomic ring structure consisting of 3 carbon atoms and 1 nitrogen atom

Question 7

Describe early penicillins. (3)

Answer 7

Acid labile
Not well-absorbed via oral route
Parenteral route - slow IV, high availability
Narrow spectrum of activity - Gram +ves and few Gram -ves

Question 8

What did the amino group in penicillin facilitate?

Answer 8

Penetration of outer membrane of Gram -ve bacteria

Question 9

How do B-lactam antibiotics work? (3)

Answer 9

Inhibit transpeptidases responsible for creating cross-linkage of peptidoglycan cell wall
Bacteria swell and rupture
Only effective against multiplying organisms

Question 10

Which 2 amino acids are joined in a transpeptidation reaction?

Answer 10

Lys - Gly

Question 11

Describe the absorption of penicillin. (2)

Answer 11

Varies orally
Delayed release preparations available

Question 12

Describe the distribution of penicillin. (3)

Answer 12

Widely distributed throughout
Concentrations in tissues and body fluids vary
Do not normally enter CSF

Question 13

What is the half-life of penicillin?

Answer 13

30-80 mins

Question 14

Describe the excretion of penicillin. (3)

Answer 14

Mainly through kidney with 90% excreted by tubular secretion
Clearance reduced in neonates
Reduce excretion rate by use of probenecid which inhibits tubular secretion

Question 15

Give 2 adverse reactions to penicillin.

Answer 15

Hypersensitivity
GIT disturbance
Haemostatic effect

Question 16

Which 2 enzymes are involved in folate biosynthesis?

Answer 16

Dihydropteroate synthetase
Dihydrofolate reductase

Question 17

Give the intermediates in folate biosynthesis. (5)

Answer 17

pABA
Folate
Tetrahydrofolate
Synthesis of thymidylate
DNA

Question 18

Describe how sulphonamide works. (2)

Answer 18

Similar structure to pABA
Competitive inhibitor for enzyme dihydropteroate synthetase

Question 19

What enzyme is inhibited by trimethoprim?

Answer 19

Dihydrofolate reductase

Question 20

Why is suphonamide selective? (2)

Answer 20

Bacteria must synthesise folic acid
Humans can take it from environment

Question 21

Describe the absorption of sulphonamides.

Answer 21

80-100% given orally absorbed from stomach and intestines

Question 22

Describe the distribution of sulphonamides.

Answer 22

Widely distributed including CNS

Question 23

Describe the metabolism of sulphonamides.

Answer 23

Occurs in liver by N-acetylation

Question 24

Describe the excretion of sulphonamides.

Answer 24

In urine - 30 mins

Question 25

Give an adverse reaction to sulphonamides.

Answer 25

Photosensitivity Stevens-Johnson syndrome Hemopoietic disturbances

Question 26

How do fluoroquinolones work? (2)

Answer 26

Target DNA replication via type II topoisomerases Effective against Gram +ve and -ves

Question 27

Which enzymes are inhibited in Gram +ve and -ve bacteria by fluoroquinolones?

Answer 27

+ve - DNA-gyrase -ve - DNA topoisomerase IV

Question 28

Describe the absorption of quinolones.

Answer 28

Oral admin most effective

Question 29

Describe the distribution of quinolones.

Answer 29

Very well absorbed in GI tract

Question 30

Describe the metabolism of quinolones.

Answer 30

Potent inhibitor of CYP1A2 -> drug-drug interactions

Question 31

Describe the excretion of quinolones.

Answer 31

Mainly excreted in tubular secretion

Question 32

Give an adverse reaction to quinolones.

Answer 32

Hypersensitivity GIT disturbance

Question 33

How do macrolides work? (4)

Answer 33

Target bacterial ribosomes and protein synthesis Block translocation Bind to site near RNA exit terminal Causes peptidyl-transferase RNA drop-off

Question 34

Describe the absorption of macrolides.

Answer 34

Oral admin protected tablets to avoid interaction by gastric juice

Question 35

Describe the distribution of macrolides. (3)

Answer 35

Diffuses readily into most tissues Does not cross BBB Crosses placenta

Question 36

Describe the metabolism of macrolides. (2)

Answer 36

Metabolised by demethylation (CYP3A4) Can potentiate effects of other drugs

Question 37

Describe the secretion of macrolides.

Answer 37

Excreted in bile

Question 38

Give an adverse reaction of macrolides.

Answer 38

Cholestatic hepatitis (prolonged use) GIT disturbances at large doses Transitory auditory impairment Hypersensitivity reactions

Question 39

How do tetracyclines work? (4)

Answer 39

Interrupt elongation phase of protein synthesis Several binding sites of 30S RNA subunit Sterically inhibits transfer RNA binding Unbinds, rebinds, futile loop

Question 40

Describe the absorption of tetracyclines. (2)

Answer 40

Greater in fasting state Inhibited by concurrent ingestion of dairy products, metal ions and certain antacids

Question 41

Describe the distribution of tetracyclines.

Answer 41

Widely distributed entering most tissues

Question 42

Describe the metabolism of tetracyclines.

Answer 42

Excreted via bile and in kidneys via glomerular filtration

Question 43

Describe the excretion of tetracyclines.

Answer 43

6-18 hour half-life