Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

DD & BL Unit 2 > Antibiotics - General Concepts & Classifications > Flashcards

Antibiotics - General Concepts & Classifications Flashcards

1
Q

Mechanisms of antibiotic selective toxicity

A

Inhibition of a metabolic pathway found in bacteria but not humans - i.e. folate metabolism

Same pathway but differences in enzyme structure - i.e. bacterial vs. eukaryotic ribosome, bacterial gyrase vs. eukaryotic topoisomerase

Macromolecule that does not exist in humans - i.e. cell wall synthesis

Macromolecule differs between microbes and humans - i.e. fungal cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Natural (intrinsic) resistance

A

Microbes lack a susceptible target for drug action and thus are resistant to one or more class of antibiotics

Ex.

E. coli is resistant to penicillin because penicillin does not fit through the pores in the OM of E. coli; E. coli is susceptible to amoxicillin because its more hydrophilic

Mycoplasm is resistant to B-lactams because it has no cell wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Antibiotic tolerance / escape resistance

A

Microbes are sensitive to antibiotics and the drug is able to reach its target BUT the organisms can resist killing by other adaptive mechanisms, including

Growth in biofilms
Metabolic bypass
Anaerobic growth
Stationary phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Mechanisms of bacterial resistance to antibiotics (5)

A
  1. Altered target to which antibiotic cannot bind
    Ex: DNA gyrase mutations causing fluoroquinolone resistance, PBP mutations causing B-lactam resistance
  2. Enzymatic degradation of antibiotic
    Ex: B-lactamase degradation of penicillins and cephalosporins
  3. Increased antibiotic efflux
  4. Decreased antibiotic influx
    Porin channel mutations
  5. Alternative resistant metabolic pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Bactericidal Mechanisms of antibacterial action

A

Organisms are killed by the antibiotic:

Inhibition of cell wall synthesis
Disruption of cell membrane function
Interference with DNA function or synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Bacteriostatic Mechanisms of antibacterial action

A

Organisms are prevented from growing:

Inhibition of protein synthesis
Inhibition of intermediary metabolic pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which antibiotics readily enter the CSF?

A

Chloramphenicol
Sulfonamides
Cephalosporins (3rd/4th)
Rifampin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which antibiotics enter the CSF with inflammation?

A

Penicillins
Vancomycin
Ciprofloxacin
Tetracycline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which antibiotics enter the CSF poorly?

A

Aminoglycosides
Cephalosporins (1st/2nd)
Erythromycin
Clindamycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Examples of beneficial selective distribution of antibiotics (4)

A

Clindamycin - into bone (osteomyelitis)

Macrolides - into pulmonary cells (URIs)

Tetracyclines - into gingival fluid (periodontitis) and sebum (acne)

Nitrofurantoin - rapidly excreted into urine (UTIs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Examples of toxic selective accumulation of antibiotics

A

Aminoglycides - into the inner ear (ototoxicity) and renal brush border (nephrotoxicity)

Tetracyclines - into Ca2+ in developing bone (abnormal bone growth) and teeth (tooth discoloration)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mechanisms of antibiotic toxicity

A
  1. Direct Toxicity, due to lack of selective toxocity - usually GI irritation, hepatotoxicity, nephrotoxicity, neurotoxicity
  2. Indirect toxicity - hypersensitivity, DDIs via alterations in CYP450 metabolic activity
  3. Disturbances of host microflora - superinfection, ex: pseudomembranous colitis due to C. dif overgrowth
  4. Host factors - very old, very young, pregnant/nursing mothers, drug allergies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Penicillins - 6 Classes + Representative Drugs

A

MOA: Cell wall synthesis inhibition, stage 3 - inhibits cross-linking of peptidoglycan polymers at the cell wall; bactericidal

Prototype: Penicillin G

Acid Stable: Penicillin V

Penicillinase-resistant: Dicloxacillin

Extended Spectrum: Amoxicillin, ampicillin

Anti-Pseudomonal: Piperacillin-Tazobactam

Penicillin plus Beta-lactamase inhibitor: Clavulanic Acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cephalosporins

A

MOA: Cell wall synthesis inhibition, stage 3 - inhibits cross-linking of peptidoglycan polymers at the cell wall; bactericidal

1st: Cephalexin, Cefazolin
2nd: Cefuroxime
3rd: Ceftriaxone

4th & 5th

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Vancomycin

A

MOA: Cell wall synthesis inhibitor, stage 2 (inhibits linear polymerization of cell wall sub units); bactericidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Macrolides

A

MOA: Reversibly binds bacterial ribosome, inhibiting protein synthesis; bacteriostatic

Azithromycin

17
Q

Tetracyclines

A

MOA: Reversibly binds bacterial ribosome, inhibiting protein synthesis; bacteriostatic

Doxycycline
Minocycline

18
Q

Lincomycins

A

MOA: Reversibly binds bacterial ribosome, inhibiting protein synthesis; bacteriostatic

Clindamycin

19
Q

Aminoglycosides

A

MOA: Irreversibly binds bacterial ribosome, inhibiting protein synthesis; bacteriocidal

20
Q

Chloramphenicol

A

MOA: Reversibly binds bacterial ribosome, inhibiting protein synthesis; bacteriostatic

21
Q

Fluoroquinolones

A

Inhibition of DNA gyrase; bactericidal

Ciprofloxacin
Levofloxacin
Moxifloxacin

22
Q

Nitrofurantoin

A

Interference with bacterial DNA; bactericidal

23
Q

Metronidazole

A

Interference with bacterial DNA; bactericidal

24
Q

Drug classes eliminated by renal excretion

A

Requires dose adjustments in patients with renal impairment; renal function monitored by serum creatine (SCr) and creatinine clearance (CrCl)

Penicillins
Cephalosporins
Vancomycin
Aminoglycosides
Fluoroquinolones
25
Q

Drug classes eliminated by non-renal mechanisms

A

Generally metabolised in the liver; must consider DDIs and interpatient differences based on genetic polymorphisms

Doxycycline - non renally eliminated tetracycline

Quinolones - Ciprofloxacin is renally eliminated but is a non-substrate inhibitor of P450

Clindamycin - non renally eliminated

Rifampin - inducer of CYP450, potential for hepatotoxicity

Isoniazid - metabolism effected by genetic polymorphism of NAT; potential hepatotoxicity

Metronidazole - DDI with alcohol due to inhibition of aldehyde metabolism (Antabuse reaction)

Erythromycin - DDI due to inhibition of P450

26
Q

Cell wall synthesis inhibition - 3 stages

A
  1. Synthesis and assembly of cell wall subunits in the cytoplasm
  2. Linear polymerization of subunits at the cell membrane
  3. Cross-linking of peptidoglycan polymers at the cell wall
27
Q

Concentration-dependent killing

A

Kill bacteria faster in higher doses that result in high initial Cp levels - can be dosed less frequently

Aminoglycosides
Fluoroquinolones

28
Q

Time-dependent killing

A

Kill bacteria best when Cp is above MIC for longer durations

Beta-lactams
Vancomycin
Macrolides

29
Q

Post antibiotic effect

A

Antibiotics that continue action after Cp < MIC - allows less frequent dosing than predicted by their half lives

Aminoglycosides
Fluoroquinolones
Macrolides
Beta Lactams

30
Q

What is an antibiogram?

A

A locally published, yearly summary susceptibility report for common pathogens and the percent of strains susceptible to different antimicrobials

31
Q

Tube Dilution Susceptibility Testing

A

A standardized number of organisms are added to serial dilutions of antibiotic in liquid medium and incubated; the tube with the lowest concentration of antibiotic that has no visible bacterial growth is the MIC

32
Q

Disk Diffusion (Kirby-Bauer)

A

A suspension of the test pathogen is spread onto an agar plate; disks impregnated with defined concentrations of different antibiotics are placed onto the surface of the agar; after incubation, the diameter of the zone of inhibition around each disk is proportional to the sensitivity of the organism to that antibiotic and can be referenced by various charts and related to the MIC

33
Q

E test

A

A variation of the Kirby-Bauser (Disk Diffusion) approach; a strip is impregnated along its length with a gradient of concentrations of an antibiotic and placed onto an agar plate spread with a suspension of the test pathogen; after incubation, an ellipse-shaped area of no growth occurs and the point at which the ellipse contacts the strip is the MIC, read directly off of the strip

34
Q

Minimum Inhibitory Concentration

A

MIC is the lowest concentration of an antimicrobial agent that will inhibit the visible growth of a standardized number of micro-organisms after overnight incubation

35
Q

Minimum Bacteriocidal Concentration

A

MBC is the lowest concentration of an antimicrobial agent that will kill 99.9% of a standardized number of micro-organisms in a given amount of time

After overnight incubation and determination of MIC, a sample from each tube is plated on growth medium; the concentration of antibiotic that killed 99.9% of organisms (10 colonies or fewer) is the MBC

36
Q

How do MBC and MIC relate to the designation of an anti-microbial as bacteriostatic or bacteriocidal?

A

If MBC / MIC > 4 the agent is bacteriostatic

If MBC / MIC < 4 the agent is bacteriocidal

37
Q

Porins

A

Form hydrophilic channels in the outer membrane of gram negative bacteria only, allowing selective uptake of essential nutrients and other compounds, including some hydrophilic antibiotics

38
Q

Efflux pumps

A

Located in the bacterial cell membranes of gram positive and gram negative organisms; pumps may be specific for one drug or may work on many drugs

DD & BL Unit 2 (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions