Antibiotics (L21)

Question 1

what are the 3 antibiotic modes of action?

Answer 1

bactericidal

bacteriostatic

bacteriolytic

Question 2

bactericidal

Answer 2

drop in the total number of viable cells, but not all cells are killed off

Question 3

bacteriostatic

Answer 3

both viable and total cells remain constant

Question 4

bacteriolytic

Answer 4

kills bacterial cells but allows them to be recognised by the immune system, causes total cells to drop aswell

Question 5

common bacterial targets

Answer 5

• cell membrane
• cell wall
• protein synthesis
• RNA polymerase
• DNA synthesis
• folate metabolism

Question 6

structure of penicillins

Answer 6

beta lactam ring is the central structure of penicillins

Question 7

what is a lactam?

Answer 7

a cyclic amide - allows interaction with enzymes on the bacterial cell wall

Question 8

what is a beta lactam?

Answer 8

a lactic with a heteroaromatic ring structure, consisting of 3 C atoms and 1 N

Question 9

what are the types on penicillin?

Answer 9

• benzylpenicllin - original form
• broad-spectrum penicillin - more effective against gram -ive bacteria (e.g. amoxicillin)
• beta-lactamase-resistant forms - important against beta-lactamase producing bacteria
• extended spectrum penicillin
• reversed-spectrum penicillin - greater activity against gram -ive than gram +ive

Question 10

benzylpenicillin

Answer 10

early penicillin
• breaks down when it hits acidic contents of stomach
• not very well absorbed - orally
• slow IV
• narrow spectrum of activity - gram +ives but only a few gram -ives

Question 11

broad-spectrum penicillin

Answer 11

stuck a different functional group of the side of the beta lactam ring

amino group facilitates penetration of outer membrane of gram -ive bacteria

much better absorption

Question 12

penicillin mechanisms of action

Answer 12

targets the cell wall
• inhibits transpeptidase
• causes bacteria to swell and rupture
• more effective against gram +ive bacteria

Question 13

what does transpeptidase do?

Answer 13

enzyme responsible for the reaction which establishes cross links in the peptidoglycan cell wall

Question 14

why is penicillin more effective against gram +ive than -ive bacteria?

Answer 14

gram +ive have a lot more peptidoglycan strands

gram -ive have a lot more beta lactamase in their cell envelope

Question 15

what does beta lactamase do?

Answer 15

breaks open the beta lactam ring

Question 16

structure of bacterial cell walls

Answer 16

strength and organisation of cell dependent on complex polymer - peptidoglycan strain chains cross-linked together

heteropolymeric - made of repeating units

Question 17

where do penicillins target the peptidoglycan chains?

Answer 17

the side chain connection

on the 4th peptide of the side chain

Question 18

penicillin absorption

Answer 18

vary when given orally

Question 19

penicillin distribution

Answer 19

widely distributed throughout the body but concs in tissues and body fluids varies

don’t normally enter CSF - except with meninges inflammation

Question 20

penicillin metabolism

Answer 20

short half-lives - 30-80 minutes

Question 21

penicillin excretion

Answer 21

mainly though the kidney - 90% excreted by tubular secretion

clearance reduced in neonates

reduce excretion rate by use of probenecid - inhibits tubular secretion

Question 22

adverse reactions to penicillins

Answer 22

hypersensitivity
• skin rashes, fever, anaphylactic shock, serum sickness

GIT disturbance
• altered gut flora

haemostatic effects
• blood clotting

Question 23

what do sulphonamides do?

Answer 23

inhibit folate biosynthesis

Question 24

how does sulphonamide work?

Answer 24

looks structurally similar to pABA

inhibits dihydropteroate synthetase

no DNA production

Question 25

why is sulphonamide selective?

Answer 25

humans take in folate from the diet - brought inside the cell bacterial cells have to make their own

Question 26

sulphonamide absorption

Answer 26

80-100% of drug given orally is absorbed from the stomach and intestines

Question 27

sulphonamide distribution

Answer 27

widely distributed including CNS

Question 28

sulphonamide metabolism

Answer 28

metabolism occurs in the liver by N-acetylation

Question 29

sulphonamide excretion

Answer 29

in urine 30 minutes

Question 30

adverse reactions to sulphonamides

Answer 30

photosensitivity stevens-johnson syndrome haemopoeitic disturbances

Question 31

what are fluoroquinolones?

Answer 31

broad spectrum antibiotics discovered in search for antimalarial drugs

Question 32

mechanism of action of fluoroquinolones

Answer 32

target DNA replication via type II topoisomerases

Question 33

type II topoisomerases

Answer 33

``` DNA gyrase • regulates super-coiling • facilitates movement of transcription and replication complexes though DNA helix • removes knots • helps fold DNA ``` DNA topoisomerase IV • homologue of gyrase • unlinks daughter DNA replicons

Question 34

what do fluoroquinolones typically inhibit?

Answer 34

DNA gyrate in gram -ive bacteria topoisoemrases in gram +ive bacteria

Question 35

fluoroquinolones absorption

Answer 35

oral route most effective

Question 36

fluoroquinolones distribution

Answer 36

very well absorbed in upper GI tract

Question 37

fluoroquinolones metabolism

Answer 37

potent inhibitor of CYP1A2

Question 38

fluoroquinolones excretion

Answer 38

mainly excreted in tubular secretion

Question 39

adverse reactions to fluoroquinolones

Answer 39

hypersensitivity GIT disturbance

Question 40

macrolides mechanism of action

Answer 40

target bacterial ribosomes and protein synthesis block translocation of the newly forming peptide • binds to site near RNA exit tunnel • causes peptidyl-transferase RNA drop off

Question 41

macrolides absorption

Answer 41

oral route requires protected tablets to avoid inactivation by gastric juices

Question 42

macrolides distribution

Answer 42

diffuses readily into most tissues but doesn't cross BBB crosses placenta

Question 43

macrolides metabolism

Answer 43

metabolised by demethylation (CYP3A4) can therefore potentiate effects of other drugs

Question 44

macrolides excretion

Answer 44

excreted in bile

Question 45

adverse reactions to macrolides

Answer 45

cholestatic hepatitis may occur after prolonged use of erythromycin estolate GIT disturbances seen at large doses transitory auditory impairment hypersensitvity reactions

Question 46

tetracyclines mechanism of action

Answer 46

target bacterial ribosomes and protein synthesis interrupts elongation phase of synthesis • inhibits tRNA binding

Question 47

tetracyclines absorption

Answer 47

absorption faster in fasting state and inhibited by concurrent ingestion of dairy products, metal ions and certain antacids

Question 48

tetracyclines distribution

Answer 48

widely distributed entering most tissues

Question 49

tetracyclines metabolism

Answer 49

relatively long half-lives 6-18 hours due to EHR

Question 50

tetracyclines excretion

Answer 50

excreted by bile and the kidneys via glomerular filtration