Antibiotics

Question 1

Define bacteriostatic

Answer 1

Prevent bacterial growth

Question 2

Define bacteriocidal

Answer 2

Kill bacteria

Question 3

What are the different sites at which antibiotics have an effect?

Answer 3

Bacterial cell wallNucleic acidsProtein synthesisCytoplasmic membrane

Question 4

Give some antibiotics that act at the peptidoglycan cell wall

Answer 4

PenicillinsCephalosporinsGlycopeptides

Question 5

Give some antibiotics that have an effect on nucleic acids

Answer 5

AntifolatesQuinolonesRifampicin

Question 6

Give some antibiotics that have an effect on protein synthesis

Answer 6

Aminoglycosides
Macrolides
Tetracyclines
Chloramphenicol
Fusidic acid

Question 7

Give some antibiotics that have an effect on the cytoplasmic membrane

Answer 7

Polymixins

Question 8

When can you give antibiotics as prophylaxis?

Answer 8

Peri-operative
Short term e.g. after meningitis exposure
Long term e.g. asplenic patients

Question 9

What are some particular characteristics of vancomycin and gentamicin?

Answer 9

Both have ototoxicity and nephrotoxicity at high levels

Question 10

Give some general methods that bacteria can acquire resistance

Answer 10

Chromosomal gene mutation

Horizontal gene transfer

Question 11

Describe chromosomal gene mutation

Answer 11

Bacterial gene mutates, giving a trait for resistance. Antibiotic kills bacteria without this resistance, acting as a selection pressure. Gives rise to a population of antibiotic resistant bacteria.

Question 12

Describe horizontal gene transfer

Answer 12

Made up of three components

• Transformation
• Transduction
• Conjugation

Question 13

Describe transformation

Answer 13

DNA released from bacterial resistant cell, taken up by recipient cell

Question 14

Describe transduction

Answer 14

Phage binds to donor cell and is infected. Phage then binds to recipient cell and transfers the DNA to the recipient cell.

Question 15

Describe conjugation

Answer 15

Connection is made between donor and recipient cell, plasmid is replicated and then transferred between the two.

Question 16

What are the main methods by which a cell can gain antibiotic resistance?

Answer 16

• Antibiotic inactivation- Adaptations to metabolism- Alteration of drug binding site - Increased efflux mechanisms- Decreased membrane permeability

Question 17

Describe antibiotic inactivation

Answer 17

Producing an enzyme that inactivate the druge.g. beta lactamase

Question 18

Describe adaptations to metabolism

Answer 18

Metablic pathways altere.g. changes to dihydrofolate reductase leads to a resistance to trimethorpim

Question 19

Describe changes to drug binding site

Answer 19

Binding sites change so drug does not have affinity for it

Question 20

Describe increased efflux

Answer 20

Increased removal of a drug so that it cannot build up the therapeutic levels

Question 21

Describe decreased permeabiltiy

Answer 21

Cell membrane can change in order to confer resistance.

Question 22

Describe patterns of emergence of antibiotic resistance

Answer 22

Local selection (hospital)
Clonal dissemination (over the country)
Global spread

Question 23

What are the main ways by which we can avoid the spread of antibiotic resistance?

Answer 23

Antibiotic stewardshipInfection control- prevent spread of recognised resistant bacteria- prevent bacterial exposure to antibiotics

Question 24

Describe time-dependent killing

Answer 24

Need a prolonged presence of the antibiotics but do not need a high concentration

Question 25

Describe concentration dependent killing

Answer 25

Need a high concentration of the antibiotic but only for a short duration

Question 26

Describe the minimum inhibitory concentration

Answer 26

Lowest concentration of the antibiotic that will inhibit the visible growth of a microorganism after overnight incubation

Question 27

Describe the influenza life cycle

Answer 27

Bins to sialic acid sugar via haemaglutinin EndocytosisH+ in, ATP-dependent, viral membrane contact with endosomal membrane H+ into virus via M2 ion channel, low pH causes uncoating Virus released into cytoplasm Replicates using cells machinery New virus buds off, bound to sialic acid Neuraminidase cleaves attachment for viral release

Question 28

Give some M2 ion channel blockers

Answer 28

AmantidineRimantidine

Question 29

Why do you use M2 ion channel blockers?

Answer 29

Treatment and prophylaxis for influenza A

Question 30

Mechanism for M2 ion channel blockers

Answer 30

Prevent H+ entering virus via M2, so it cannot uncoat and be released into the cytoplasm

Question 31

ADRs for M2 ion channel blockers

Answer 31

DizzinessHypotensionCNS effects - hallucination, confusion, insomniaNephrotoxic at high doses Amantadine gives more pronounced ADRs, so tend to use rimantadine

Question 32

What is a particular challenge regarding resistance for M2 channel blockers?

Answer 32

Only need a single point mutation in order to have an effect. Changes shape, causing the binding site to change so it does not block the channel when it binds.

Question 33

Give some neuraminidase inhibitors

Answer 33

ZanamivirOseltamivir

Question 34

Indications for neuraminidase inhibitors

Answer 34

Treat influenza A and B within 48 hours to have the best effect.

Question 35

Mechanism for neuraminidase inhibitor

Answer 35

Inhibit neuraminidase enzyme- causes aggregation of virus at the cell surface

Question 36

ADRs for neuraminidase inhibitors

Answer 36

HeadacheNosebleedBronchospasmResp. depression (rarely)

Question 37

Describe zanamivir

Answer 37

Low oral bioavailability so given as an inhaled powder. Not used for prophylaxis

Question 38

Describe oseltamivir

Answer 38

High oral bioavailabliity, given both for treatment and prophylaxis. Should be given within 48 to have best effect on reducing mortality and decreasing duration of illness.