39. Antibiotics Flashcards
(59 cards)
1
Q
Why with developing antimicrobial resistance do we not make new antibiotics?
A
- number of antibioitcs reaching market has dropped hugely over past 10 years
- resistance reduces effective life of a product
- too little profit, government restrictions, lack of new biological targets
2
Q
3 antibiotic modes of action
A
- bactericidal
- bacteriostatic
- bacteriolytic
3
Q
Explain bacteriostatic antibiotics
A
- hold everything in steady growth state
- total cells stays the same over time and so does viable cells
4
Q
Explain bacteriocidal antibiotics
A
- after addition of it, number of viable cells rapidly decreases
- total number of cells stays the same
5
Q
Explain bacteriolytic antibiotics
A
- both total and viable cells decrease drastically in numbers
- kills bad and normal cells
6
Q
Common bacterial targets for antibiotics are …
A
- cell membrane
- cell wall
- protein synthesis
- RNA polymerase
- DNA synthesis
- folate metabolism
7
Q
Penicillins target what?
A
cell wall
8
Q
Sulphonamides target what?
A
folate metabolism
9
Q
Fluroquinolones target what?
A
DNA synthesis
10
Q
Macrolides target what?
A
protein synthesis
11
Q
Tetracycline target what?
A
protein synthesis
12
Q
Why do antibiotics target what they do?
A
- unique components to invading organism
- non toxic to host (relatively)
13
Q
Structure of penicillins
A
- beta lactam ring
- a lactam is a cyclic amide
- a beta-lactam is a lactam with a heteroatomic ring structure, consisting of 3 carbon atoms and 1 nitrogen atom
14
Q
List types of penicillins
A
- benzylpenicillin
- beta-lactamase-resistant forms e.g flucloxacillin
- broad-spectrum penicillins e.g amoxicillin
- extended-spectrum penicillins
- reversed-spectrum penicillins
15
Q
Benzylpenicillin are the … form and not very active against …
A
- original
- gram negatives
16
Q
Explain early penicillins
A
- acid labile
- given orally (not very well absorbed) or parenteral route (slow IV, preverable IM, high availability)
- narrow spectrum of activity - gram positives but only a few gram negs
17
Q
Main difference between benzylpenicillin and broad-spectrum penicillins
A
- broad spec more effective against gram negative bacteria
18
Q
Penicllin development
A
- needed derivatives of penicillin which could treat a wider range of infections
- offered a broader spectrum of activity than original penicillins e.g ampicillin
- amino group facilitates penetration of outer membrane of gram neg bacteria
- further development led to amoxicillin with improved duration of action
- much better absorption profile
19
Q
Beta-lactamase-resistant forms are important against …
A
beta-lactamase producing bacteria
20
Q
Extended spectrum penicillins are important against …
A
pseudomonads
21
Q
Reversed spectrum penicillins have greater activity against …
A
gram neg than gram pos
22
Q
Why is beta lactamase bad for penicillin?
A
- defence mechanism from bacteria
- breaks down lactam ring so antibiotic can’t act
23
Q
How does a penicillin target the cell wall?
A
- penicillins - beta-lactam antibiotics
- inhibit the enzyme (transpeptidases) which are responsible for reaction to establish cross links in peptidoglycan cell wall
- bacteria swell and rupture
- only effective against multiplying organisms
24
Q
How are bacterial cell walls strong?
A
- complex polymer peptidoglycan forms straight chains cross-linked together
- made of N-acetylglucosamine and N-Acetylmuramic acid
25
Absorption of penicillin
- vary when given orally
- delayed release preparations available (procaine and benzanthine)
26
Distribution of penicillin
- widely distributed in body
- although concentrations in tissues and body fluids vary
- don't normally enter CSF (except with meninges inflammation)
27
Metabolism of penicillin
short half life (30-80 minutes)
28
Excretion of penicillin
- mainly through kidney with 90% excreted by tubular secretion
- clearance reduced in neonates
- reduce excretion rate by use of probenecid, which inhibits tubular secretion
29
Adverse reactions to penicillins
- hypersensitivity (seen with all penicillins, rash, fever, anaphylactic shock, serum sickness, 10-15% will show repeat reaction)
- GIT disturbance (altered gut flora)
- haemostatic effects - blood clotting
30
Give chain of folate biosynthesis
- pABA with dihydropteroate forms folate
- folate with dihydrofolate forms tetrahydrofolate
- goes to synthesis of thymidylate etc to form DNA
31
How does sulphonamide work?
- not used in clinical practice
- target metabolism
- PABA precursor to folic acid - sulphonamides are a derivative of PABA, look similar sturcturally
- can bind to same enxymes in synthetic pathway and stop it from working
- work specifically on dihydropteroate whereas trimethoprim (a type of sul) works on dihydrofolate reductase
32
Is sulphonamide selective?
- bacteriostatic in nature
- stops folic acid entering the bacterial cell
33
Absorption of sulphonamide
- 80-100% of drug given orally is absorbed from stomach and intestines
34
Distribution of sulphonamide
- widely distributed including CNS
35
Metabolism of sulphonamide
occurs in liver by n-acetylation
36
Excretion of sulphonamides
- in urine after around 30 minutes
37
Adverse reactions to sulphonamide
- photosensitivity
- Stevens-Johnson syndrome (less than 1% frequency)
- hemopoietic disturbances
38
Explain fluoroquinolones
- broad spectrum
- effective against Gram pos and neg
- discovered during search for antimalarial drugs
- targets DNA replication via type II topoisomerases
39
What do quinolones typically inhibit?
- DNA-gyrase in Gram negatives
- topisomerase in Gram-positives
40
What does DNA-gyrase do?
- regulates amount of supercoiling
- facilitates movement of transcription and replication complexes through DNA helix
- removes knots and helps fold DNA
41
What does DNA topoisomerase IV?
- homologue of gyrase
- unlinks daughter DNA replicons
42
Absorption of quinolones
oral admin more effective
43
Distribution of quinolones
- very well absorbed in upper GIT
44
Metabolism of quinolones
potent inhibitor of CYP1A2
45
Excretion of quinolones
mainly excreted in tubular secretion
46
Adverse reactions to quinolones
- hypersensitivity
- GIT disturbance
47
Explain prokaryotic ribosomes
- 70S size
- 50S comprises 2 subunits of 23S and 5S
- 50S is the main site of protein synthesis
48
Action of macrolides
- block translocation of newly forming peptide
- binds to site near RNA exit tunnel
- causes peptidyl-transferase RNA drop off
49
Absorption of macrolides
- oral admin requires protected tablets
- to avoid inactivation by gastric juice
50
Distribution of macrolides
- diffuses readily into most tissues
- doesn't cross blood brain barrier
- does cross placenta
51
Metabolism of macrolide
- metabolised by demethylation (CYP3A4)
- can potentiate effects of other drugs
52
Macrolides are excreted in ...
bile
53
Adverse reactions to macrolides
- cholestatic hepatitis can occur after prolonged use of erythromycin estolate
- GIT disturbances at large dose
- transitory auditory impairment
- hypersensitivity
54
How do tetracyclines work?
- interrupts elongation phase of synthesis
- several binding sites on 30S RNA subunit
- sterically inhibits transfer RNA binding - unbinds, rebinds, futile loop
55
Absorption of tetracyclines
- greater in fasting state
- inhibited in concurrent ingestion of dairy products, metal ions, certain antacids
56
Distribution of tetracyclines
widely
- enters most tissues
57
Metabolism of of tetracyclines
- relatively long half lifes (6-18 hrs) due to enterohepatic recirculation
58
Excretion of tetracyclines
via both bile and kidneys via glomerular filtration
59
List types of antibiotics
- penicillin
- sulphonamides
- fluoroquinolones
- macrolides
- tetracyclines
