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PA20319- Immunity, Infection and inflammation > Antibiotic modes of action and resistance > Flashcards

Antibiotic modes of action and resistance Flashcards

1
Q

Inhibitors of cell wall synthesis

A

B- lactams: penicillins, cephalosporins, carbapenems, monobactams

Glycopeptides: Vancomycin, teicoplenin

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2
Q

Synthesis of peptidoglycan

A

NAM/NAG alternatingly joined by glyosylase
Monomer join to PG via glycosylase
PG is x linked via aa side chains via transpeptidases

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3
Q

Beta-lactam mode of action

A

Bind to penicillin binding proteins (PBP’s-transpeptidase)

Prevents X linking from occuring leading to cell lysis

Also stimulates autolysins which breakdown the cell wall that also lead to cell lysis

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4
Q

Glycopeptide mode of action

A

Prevents glycosylase from adding PG monomers onto PG chain and prevents x-linking

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5
Q

Polymyxin (colistin) and lipopeptides

A

Act on cell membranes by binding to liposaccharides only on g-ve bacteria

Causes cell disruption leading to leakage

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6
Q

Fluoroquinolones

A

Ciprofloxacin, Levofloxacin

Binds to type 2 DNA gyrase (g-ve) and type 4 topoisomerase(g+ve)

Inhibits DNA replication and packaging and causes cell lysis

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7
Q

Aminoglycosides

A

Gentamycin, Bactericidal

Binds irreversibly to A site on 16s rRNA in 30s subunit

Causes misreading of codons along mRNA and interferes with translocation of tRNA from A to P site which disrupts membrane permeability

Inhibits protein synthesis

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8
Q

Tetracyclines

A

Doxycycline

Binds reversibly to A site on 16s rRNA in 30s subunit

Causes tRNA not to bind to A site. Selectivity through accumulating in cell and better binding to bacterial ribosome

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9
Q

Inhibitors of protein synthesis

A

50s: Macrolides, chloramphenicol, streptogramins, lincosamides, fusidic acid, oxazolidinones
30s: tetracyclines, aminoglycosides

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10
Q

Species of most concern?

A

MDR e.coli and TB

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11
Q

Aquiring resistance

A

Mutations and/or conjugation of plasmids

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12
Q

Beta lactam resistance

A

4 classes: A,C,D have serine at active site, B is a metallo lactamase requiring zinc

Beta lactamases can be produced which bind in peri plasmic space or medium

Or by altering Penicillin binding proteins through MecA gene. (causes methicillin resistence in s.aureus)

or reduce number/size of porins to decrease permeability and uptake

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13
Q

Beta lactamase inhibitors

A

Clavulanic acid (in co amoxiclav)

Tazobactam (in taxocin)

Sulbactam

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14
Q

Glycopeptide resistance (Vancomycin)

A

Change in aa sequeces reducing h bonds from 5 to 4 making it unstable

d-ala to d-lactate

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15
Q

Fluroquinolones (ciprofloxacin) resistance

A

Mutations alter structure of DNA gyrase or of topoisomerase 4 preventing binding

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16
Q

Tetracycline resistance

A

Efflux pumps

Actively pumps out drug molecules ensuring it never reaches the required concentration.

Basal rate is intrinsic resistance while upregulated is aquired

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17
Q

Multi drug efflux pumps

A

RND for g-ve, MFS for g+ve

AcrAB/TolC pump in e.coli
chromosomal RND pump
upregulation gives resistanc to fluoroquinilones, chloramphenicol etc

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18
Q

Main types of penicillins

A

Lactamase sensitive:benzypenicillin (pen g), benzythine benzylpenicillin, phenoxymethylpenicillin (pen v)

Lactamase resistant: Flucoxicillin, co-fluampicil, temocillin

Broad spectrum: amoxicillin, ampicillin, co-amoxiclav, augmentin

Antipseudomonal: piperacillin, tazocin, timentin

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19
Q

Benzypenicillin properties

A 
High blood conc achieved quick
non toxic
good diffusion into body tissues
low levels in CSF 
longpost antibiotic effect
20
Q

Uses of pen G

A 
Use immediately for meningitis
throat infection 
endocarditis
pneumonia
cellulitis 
osteomyelitis
21
Q

Meningitis causing microbes

A

Neisseria meningitidis
H.infuenzae
s.pneumoniae

22
Q

Side effects of penicillins

A

Hypersensitivity (rash/anaphylaxis)
Neurotoxicity (increase with renal failure)
Renal failure (High salt affects electrolyte balance)
Diarrhoea and pseudomembraneous colitis

23
Q

Cephalosporins

A

Made from cephalosporium acremonium, cephalosporin C

Specificty, selectivity determined by R groups 1 and 2

24
Q

Properties of cephalosporins

A

resistant to b-lactamases

good drugs but limited by c.difficle risk

affinity for pbp’s in g+ve
outer membrane penetration in g-ve

25
Q

Side effects of cephalosporins

A

Hypersensitivity (rash/anaphylaxis/inflammation)

Diarrhoea, nausea, c.difficile super infection

Vomiting, headaches, dizziness, renal toxicity, hemorrhage (rare)

26
Q

2nd gen cephalosporins

A

cefuroxime , cefaclor, cefadroxil

ceftriaxone, cefotaxime is 3rd gen

27
Q

Carbapenems

A

Imipenem, meropenem

v resistant to b lactamase
broad spectrum
for p.aeruginosa and ESBL

28
Q

Glycopeptides

A

Vancomycin oral for c.difficile

teicoplanin injection for systemic infections

Active against g+ve not g-ve

29
Q

PK of glycopeptides

A

High CSF penetration
Renal excretion

Side effects: pain, thrombophlebitis, renal toxicity, ototoxicity, blood disorders, anaphylactoid reactions

30
Q

Polymyxins

A

Colistin

Active on g-ve bacteria, last resort iv

Highly nephro and neurotoxic

31
Q

Lipopeptides

A

daptomycin

Active on g+ve bacteria causes depolarisation of membrane

Used for skin/soft tissue infections, endocarditis caused by resistant g+ve bacteria

Side effects: nephrotoxicity, myopathy, peripheral neuropathy, colitis

32
Q

Fluoroquinolones

A

ciprofloxacin, levofloxacin,

Synthetic, broad spectrum, bactericidal

Active against g-ve and intracellular pathogens. ltd use against streptococci and enterococci

Side effects: gi disturbance,cns, tendon damage, rash, photosensitivity, renal impairment. Interacts with CYP450

33
Q

Rifamycins

A

Rifampicin

Bactericidal, inhibits rna polymerase, given in combo to reduce resistance

Treats tb, meningitis, prosthetic infections

34
Q

Rifamycin PK

A

well distributed, >90% metabolised

side effects are hepatotoxicity, fever, rash, hypersensitivity, GI disturbance, orange/red secretion

increased metab of warfarin, OCP’s

35
Q

Nitroimidazoles

A

Metronidazole

Anaerobic infections, GI + genital +abdominal+dental infections

36
Q

Nitroimidazole PK

A

Well distributed including CSF, hepatic metabolism, renal excretion

Side effects are nausea, vomiting, diarrhoea/constipation, taste, candida super infection
neuropathy, hives, rash, red/brown urine

Makes people more sensitive to urine

37
Q

Nitrofurantoin

A

Targets fucking everything

Used for non catheterised UTI caused by g+ve and g-ve aerobic bacteria

38
Q

Aminoglycosides

A

For serious aerobic bacteria infections Eg. septacaemia, complicated UTI, nosocomial RTI

Active mostly against g-ve psuedomonas
Streptomycin for TB, mycoplasma

39
Q

Aminoglycoside PK

A

Can be given orally for gut decontamination as it is not absorbed
Poor penetration for cells and CSF
Renally excreted

Side effects:Reversible nephro/ototoxicity

40
Q

Tetracyclines

A

Broad spectrum

Oral for acne, rti, ssti’s

Staphylococci and streptococci now resistant

41
Q

Tetracycline PK

A

60-80% absorption but well distributed including foetal.
No CSF penetration
Renal and bile excretion

Side effects:GI superinfections, teeth discolouring, headache, vertigo, hepatotoxicity, phototoxicity

42
Q

Macrolides

A

Erytromycin, clarithromycin
Alternative to penicillin for treating strep infection

Oral for rti, sti, gi,ssti

43
Q

Macrolide PK

A

Acid labile so given as enteric coated
Rapid absorption, well distributed except CSF
Bile excretion

Side effects are gi superinfections, cholestatic jaundice, ototoxicity, allergy, arrythmia

44
Q

Fusidic acid

A

Narrow spectrum for staph infections

Effects EF-G which supply energy for translocation

45
Q

Chloramphenicol

A

Broad spectrum

Topical use in eye infection
Oral for meningitis or typhoid fever

46
Q

Chloramphenicol PK

A

Well absorbed everywhere, metab in liver, renal excretion

Side effects: bone marrow suppression, grey baby syndrome, gi flora disturbed, neuritis, aplastic anaemia

PA20319- Immunity, Infection and inflammation (13 decks)

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