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Pharmacology > Mechanism Of Action Of Antimicrobials > Flashcards

Mechanism Of Action Of Antimicrobials Flashcards

1
Q

What are the types of antimicrobial therapy?

A

Empiric- when you don’t know the etiology
Definitive/targeted-when you know the agent
Prophylactic-to prevent infection

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2
Q

What are the criteria for empiric therapy?

A 
Patient presentation (symptoms)
Patient history (live in nursing home,other diseases)
Current trends
Current guidelines
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3
Q

What is de-escalation?

A

When you go from a broad antibiotic to a marrow spectrum antibiotic
Prevent antimicrobial resistance and help with cost savings

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4
Q

What is MIC?

A

Minimum Inhibitory concentration

Lowest concentration to prevent visible growth

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5
Q

What is the difference between bactericidal and bacteriostatic?

A

Bactericidal-irreversibly destroy ability of organism to replicate
Bacteriostatic- reversibly impair ability of organism to replicate

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6
Q

What are the 5 mechanisms of action of antimicrobials?

A

Inhibition of cell wall synthesis
Direct damage of outer cell membrane of bacteria
Modification of DNA synthesis
Modification of protein synthesis
Modification of energy metabolism within the cytoplasm

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7
Q

What are the cell wall synthesis inhibitors?

A

Beta lactams
Glycopeptides
Lipoglycopeptides

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8
Q

What are the different beta lactams?

A

Penicillins
Cephalosporins(generations 1-5)
Carbapenems (group 1-2)
Monobactam (aztreonam)

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9
Q

What is the mechanism of action of beta lactams?

A

Inhibition of cell wall synthesis by binding to penicillin binding protein (PBP)

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10
Q

What are the spectrum and adverse events of natural penicillins (VK-oral, G-IV)?

A

Spectrum: Group A streptococcus, actinomycosis, pasturella multocida, syphillis and anthrax (not recommended as a first line by CDC)
ADR: Hemolytic anemia, clostridium difficile

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11
Q

What are the spectrum and ADR of aminopenicillins (amoxicillin-oral, ampicillin-oral and IV)?

A

Enterococcus faecalis, streptococcus pneumoniae at high dose

ADR:clostridium difficile

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12
Q

What are the spectrum and ADR of penicillase resistant- Dicloxacillin-oral, oxacillin, nafcillin, methicillin-iv?

A

MSSA

ADR: clostridium difficile

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13
Q

What are the spectrum and ADR of beta lactam/beta lactramase inhibitors- amoxcillin/clavulanate, ampicillin/sulbactam, piperacillin/tozabactam?

A

Very broad spectrum
Piperacillin/tozabactam use when there is a lot of risks factors ,and pseudomonas
ADR: clostridium difficile

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14
Q

What is the spectrum of 1st generation cephalosporins?

A

Gram. Positive aerobes mainly

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15
Q

What is the spectrum of second generation cephalosporins?

A

Slightly less active for gram positive aerobes compares to first generations but more active against gram negatives aerobes

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16
Q

What is the spectrum of 3rd generation cephalosporins-ceftriaxone (most used), ceftazimide

A

More active against gram negatives aerobes and less against gram positive aerobes
Ceftazimide- only 3rd generation for pseudomonas

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17
Q

What is the spectrum of 4th generation cephalosporins- cefepime?

A

Active against gram negatives mainly

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18
Q

What is the spectrum of 5th generation of cephalosporins- Ceftrazoline (IV only)?

A

Active against MRSA

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19
Q

What is the spectrum of cephalosporin/beta lactamase inhibitor combination?

A

It is new and has a broad spectrum

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20
Q

What are the spectrum and ADR of carbapenems?

A

Most broad spectrum of the beta lactams
Ertapenem does not cover pseudomonas
ADR: Risk of seizures, CNS toxicity
Imipenem has a higher risk

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21
Q

What are the spectrum and ADR of monobactams?

A

Used for gram negative only , for beta lactam allergy, pseudomonas
ADR: clostridium difficile

22
Q

What are the glycopeptides?

A

Vancomycin (oral and IV)

Televancin (iv only)

23
Q

What is the MOA of glycopeptides?

A

Inhibition of cell wall synthesis at a site different than the beta lactams

24
Q

What are the spectrum and ADR of vancomycin?

A

Used for gram positives especially S. Aureus (MSSA, MRSA included), Enterococcus
IV only for systemic infections
Oral only for C.Difficile
ADR: Red man syndrome, nephrotoxicity/ototoxicity (rare when used alone)

25
Q

What are the spectrum and ADR of televancin?

A

Same spectrum as vancomycin
Concentration dependent killing
ADR: metallic taste, foamy urine, GI
Black box warning-do not use in pregnancy due to abnormal fetal development

26
Q

What are the lipoglycopeptides?

A

Oritavancin- IV

Dalbavincin -Iv

27
Q

What are the spectrum and ADR of oritavancin?

A

Gram positive only same spectrum as vancomycin
Concentration dependent (one time dose)
ADR: nervous system disorders

28
Q

What are the spectrum and ADR of Dalbavancin?

A

Same as vancomycin
Concentration dependent-one big dose (1500) or 2 doses a week apart
ADR:headache, rash

29
Q

What are the spectrum and ADR of daptomycin?

A

Used for gram positive only , S.aureus including MRSA

ADR: myopathy, rhabdomyolosis, eosinophilic pneumonia, c. Difficile

30
Q

What is the MOA of daptomycin?

A

Inhibits cell wall synthesis by creating transmembrane channels
Cannot be used for pulmonary infections due to its inactivation by surfactant

31
Q

What are the spectrum and ADR of Colistin?

A

No activity against gram positive bacteria, usedonly for gram negatives especially acinetobacter and pseudomonas
Limited susceptibility against enterobacter, klebsiella
ADR: neuromuscular paralysis, neurotoxicity, nephrotoxicity, C. Difficlile

32
Q

What is the MOA of colistin?

A

Inhibition of cell wall synthesis by binding with anionic LPS molecules and displacing calcium and magnesium from outer membrane

33
Q

What are the protein synthesis inhibitors antibiotics?

A 
Tetracyclines
Glycylcycline
Macrolides/ketolides
Aminoglycosides
Cindamycin
Linezolid
34
Q

What is the MOA of tetracyclines- doxycycline (most used),minocycline, tetracycline?

A

Inhibition of protein synthesis by reversibly binding to the 30S
Bacteriostatic

35
Q

What are the spectrum and ADR of tetracyclines?

A

Gram positive aerobes especially s.aureus including MSSA, MRSA, mycoplasma, chlamydia, rickettsia, tick bite
ADR: nausea/vomiting, diarrhea, exaggerated sunburn, discoloration of teeth in children

36
Q

What are the spectrum and ADR of glycylcycline (tigecycline)?

A

Gram positive aerobes, MRSA, enterococcus
Gram negative aerobes especially acinetobactor
Anaerobes, atypicals
Does not cover pseudomonas
Not good for blood circulation issues, black box warning

37
Q

What is the MOA of macrolides?

A

Ihnibition of protein synthesis by binding to the 50S
Erythromycin-increase GI motility (drug/drug interaction)
Derivatives- clarithromycin, azithromycin (n drug/drug interaction )
Bacteriostatic, time dependent

38
Q

What are the spectrum and ADR of macrolides?

A

Gram positives aerobes (S. Aureus, MSSA, S.pyogenes, S. Pneumoniae)
Clamydia, mycoplasma, legionella
Not active against Ecoli, Klebsiella, enterobacter and pseudomonas
ADR: QTC prolongation- monitor cardiac rhythm

39
Q

What is the MOA of aminoglycosides amikacin, tobramycin, gentamicin(mostly used)?

A

Inhibition of protein synthesis by binding irreversibly to 30s
Bactericidal
Concentration dependent

40
Q

What are the spectrum and ADR of aminoglycosides?

A

Gram positive aerobes (S. Aureus)
Mostly gram negative aerobes (pseudomonas)
ADR: nephrotoxicity, neuromuscular blockade
Risk factors-myasthenia gravis

41
Q

What is the MOA of clindamycin?

A

Inhibits protein synthesis by binding exclusively to the 50S

42
Q

What is the spectrum and ADR of clindamycin?

A

Gram positives aerobes(S.aureus including MRSA), anaerobes (bacteroids)
ADR: C. Difficile associated disease, no anti diarrheal treatment

43
Q

What are the spectrum and ADR of Linezolid?

A

Gram positive (MRSA), VRE (faecium), E.faecalis
ADR: Myelosuppression most ofeteh after greater than 2 weeks therapy , reversible with discontinuation
Monoamine oxidase inhibition added effects with other agents(SSRI)

44
Q

What are the fluoroquinolones?

A

First quinolone is nalidixic acid

Structural derivatives: ciprofloxacin, moxifloxacin,levofloxacin

45
Q

What is the MOA of fluoroquinolones?

A

Inhibit bacterial topoisomerases which are necessary for DNA synthesis

46
Q

What is the spectrum of fluoroquinolones?

A

Gram positive including MSSA,should avoid in MRSA
Gram negative
Atypical bacteria
For S. Pneumoniae use only levofloxacin and moxifloxacin , do not use ciprofloxacin
For P.aeruginosas use only levofloxaacin and ciprofloxacin and do not use moxifloxacin

47
Q

What are the ADR of fluorquinolones?

A

Cardiac- QTC prolongation

Drug interactions: divalent and trivalent cations, impair oral absorption lead to failures

48
Q

What is the MOA of metronidazole?

A

Inhibits DNA synthesis

Selective toxicity versus anaerobes

49
Q

What are the spectrum and ADR of metronidazole?

A

Wide anaerobe spectrum (c.difficile)

ADR: drug interactions with warfarin (potentiation of anticoagulant effect), ethanol

50
Q

What are the clinical uses of folate synthesis inhibitors?

A

Skin/soft tissue infections
UTI
PJP infections in HIV patients
Agent of choice for stenotrophomonas infections
Reasonable coverage for MRSA but optimal dosage is not known
Requires dosage adjustment when CrCl is less than 30ml/min
ARD: Rash, urticaria, epidermal necrolysis, Steven’s-Johnson

Pharmacology (4 decks)

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