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Infectious Disease > Bactericidal Cell Wall Inhibitors > Flashcards

Bactericidal Cell Wall Inhibitors Flashcards

1
Q

Chemistry of bactericidal cell wall inhibitors?

A

Penicillins, cephalosporins, monolactams, and carbapenems all have b-lactam ring in the center. Some of these are inactivated if the ring is cleaved by B-lactamases.

monolactams and carbapenems are are reisistant to B-lactamases

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2
Q

What is used with penicillins and cephalosporins to inhibit b-lactamases?

A

Clavulanic acid binds and inhibits B-lactamase.

  • augmentin is trade name for amoxicillin and clavulanic acid.
  • Timentin is trade name for ticarcillin and clavulanic acid.
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3
Q

What results in higher serum levels of penicillin?

A

probenicid, it acts by competing with penicillin for the organic anion transport system which is primary route of penicillin excretion –> results in higher levels of penicillin in the serum.

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4
Q

Mechanism of Penicillin G?

A

B-lactam binds PBPs and inhibits cross linking of bacterial cell wall components

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5
Q

Spectrum of Penicillin G?

A

Gram postive cocci -> strep and staph
gram positive rods –> listeria and actinomyces
gram neg cocci -> Neisseria
most mouth anaerobes (clostridium)
***Not effective against gm - aerobes or B lactase producing organisms w/o conjugative therapy

  • penicillinase sensitive

dosage forms:
IM, IV, PCN VK: oral (poor bioavailability)

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6
Q

DOC for which pathogens?

A

nonresistant staph and strep, N. meningitidis, B. anthracis, C. tetani, C, perfingens, Listeria, syphillis

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7
Q

Pharmokinetics of Penicillin G?

A

IV/IM for Penicillin G
PO for Pen V
Eliminated by kidneys

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8
Q

Side Effects of Pen G and V?

A

Hypersensitivity reactions, rare neurologic toxicity (seizures), Neutropenia, nephrotoxicity

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9
Q

MOA of B-lactams?

A

bactericidal –> bind to PBPs and inhibit transpeptidation which stops cross linking of polysaccharides and cell wall is destroyed and bacterial cell dies.

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10
Q

Classes of B-lactam compounds?

A

Penicillins, Cephalosporins, and B-lactamase inhibitors combined with PCN’s

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11
Q

Penicillin classifcation

A

Penicillin G

Antistaphlococcal PCNs: nafcillin, dicloxacillin, oxacillin, cloxacillin

Broad spectrum PCNs:
2nd generation: ampicillin, amoxicillin

3rd generation: carbenicillin, ticarcillin

4th generation: piperacillin

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12
Q

Combos with b-lactamase inhibitors

A

amoxacillin/potassium clavulanate= augmentin (PO)

ampicillin/sublactam=unasyn (IV)

Ticarcillin/potassium clavulanate= timentin

Piperacillin/tazobactam sodium= zosyn (sepsis)

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13
Q

General points of PCNs

A

All PCN’s should be given on an empty stomach except oral amoxicillin

Allergic rxns to one PCN are cross reactive to others, reactions can be urticarial to anaphylaxis to serum sickness

All abs can cause C. diff colitis

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14
Q

PCN G benzathine and PCN G procraine

A

IM forms: 1 injection lasts 10-12 days
used for strep and sometimes syphillis, gonorrhea now is resistant

IV form: meningitis and endocarditis

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15
Q

Usual dosage of PCN G

A

1-24 million units/day every 4-6 hours
erysipelas: IV 1-2 million units q 4-6 hours x 7-10 days

neurosyphilis: IV 18-24 million units q 4-6 hours x 10-14 days

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16
Q

Penicillin G safety

A

Preg Cat: B -> presumed safe
lactation: safe

Renal dosing: adj for creatine clearance adjust`

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17
Q

Adverse Reactions of PCN G

A

local: site reaction
significant reactions:
CNS -> coma, seizure
hematologic and oncologic: neutropenia, positive direct coombs test
Hypersensitivity: anaphylaxis, reaction, serum sickness

Renal: acute interstitial nephritis, renal tubular disease

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18
Q

Drug interactions of Penicillin G

A

BCG: used for TB - abx may diminish therapeutic effect of vaccine

methotrexate: PCNs may increase serum conc of metho

Probenecid: may increase serum conc of PCN

Tetracycline derivatives: may diminish effect of PCNs

Vit K antagonists (warfarin) - PCNs may enhance effect of Vit K antagonists -> monitor INR

OBCPs: pen may decrease OBCP efficacy

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19
Q

Penicillin VK

A

oral form -> 250-500 mg TID-QID
DOC for strep pharyngitis

AE’s: GI -> N/V/D
acute nephritis, convulsions, hemolytic anemia, positive coombs reaction

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20
Q

Antistaphyloccocal PCNs activity

A

activity: semisynth PCNs used for infection with B-lactamase producing staph, also used against PCN susceptible strep and pneumococci

**inactive against enterococci and methicillin resistant strains

21
Q

Antistaphylococcal PCNs - drugs

A

Dicloxacillin, oxacillin and nafcillin (not affected by beta-lactamase enzyme)

22
Q

Dosage forms of Antistaph PCNs

A

dicloxacillin: PO
Oxacillin: IM, IV
Nafcillin: IV

23
Q

Antistaph PCNs safety

A

Preg Cat: B
lactation: unknown

No dosage adj needed for renal or hepatic disease

24
Q

Adverse effects of Antistaph PCNs

A

GI (dicloxacillin)-> Nausea, diarrhea, abdominal pain

agranulocytosis, eosinophilia, hemolytic anemia, hepatotoxicity

25
Q

Antistaph drug interactions

A

Aripiprazole: PCN may decrease concentration
Ca channel blockers: Nafcillin may increase metabolism
contraceptives: Nafcillin may increase metabolism of estrogens
BCG: may diminish effects of BCG
Methotrexate: may increase serum concentrations
Probenecid: may increase PCN serum concentration
Warfarin: may diminish effect

26
Q

Broad spectrum PCNS

A

2nd gen: ampicillin, amoxicillin
3rd gen: carbenicillin, ticarcillin
4th gen: piperacillin

27
Q

2nd gen PCNs uses

A

cover same as PCN G also E. coli, proteus marabilis, Salmonella, Shigella and H. influenzae,
Amox is better absorbed

uses: otitis, sinusitis, lower RTI
Amox combined with clay acid will expand coverage to gm +, gm - and anaerobic organisms

28
Q

Safety of 2nd gen PCNs

A

Preg Cat: B,
Lacation: safe

Renal dosing: adjust if CrCl

29
Q

Adverse effects of 2nd gen PCNs

A

CNS: agitation, anxiety, confusion, seizure
Hematologic: agranulocytosis, anemia, eosinophilia, hemo anemia

Renal: crystalluria

30
Q

What will occur if 2nd gen PCN taken while infected with mono?

A

high % of patients have developed rash during therapy, don’t use in these patients

31
Q

Drug interactions of 2nd gen PCNs

A

Allopurinol: may enhance risk of hypersensitivity rxn of PCN
BCG: diminish effect of BCG
methotrexate: may increase metho coc
tetracycline: may diminish effects of PCNs
Warfarin: PCNs may enhance effect
OCPs: PCNs may decrease efficacy

32
Q

3rd generation PCNS, activity

A

carbenicillin and ticarcillin

activity: strep, enteric gram-neg bacilli (e. coli, klebsiella, pneumoniae, enterobacter cloacea, enterobacter aerogenes and proteus miriabilis), pseudomonas, and anaerobes
- IV only: std therapy as anti-pseudomonal med in hosp.

33
Q

Piperacillin spectrum

A

derivative of ampicillin, covers same spectrum as 3rd generation, but more active against Klebsiella, enterococci and bacteroides
**piperacillin w/ tazobacatm (zosyn): broad spectrum, used for cellulitis, postpartem endometritis, peritonitis, comm-acquired pneumonia, nosocomial pneumonia

34
Q

Good to know about PCNs

A

can cause bleeding problems
can cause nephritis
IN high doses can cause near complications and seizures
- common to see secondary infections such as vaginal candidiasis

35
Q

B-lactamase inhibitors

A

clavulanic acid, sublactam, tazobactam

activity: inhibitors of many bacterial b-lactamases, inactivate ahminoglycosides

Use: only in comb with PCN -> PCN determines spectrum:
-intra-abdominal/gynecological infections
-skin and soft tissue infections
RTI, sinusitis, and lung abcesses

-Don’t have any antimicrobial activity by themselves.

36
Q

Cephalosporins

A

as they progress from 1st to 3rd generation they increase in gm - coverage and lose gram positive coverage.

  • well absorbed from GI tract, and food enhances absorption.
  • allergic reactions are similar to PCNs (3-10% cross-reactivity)
37
Q

Cephalosporins susceptibility to B-lactamases

A

are susceptible to B-lactamases

and they have similar SE’s as penicillin.

38
Q

Most common 1st, 2nd and 3rd generation cephalosporins?

A

1st: cephalexin (keflex),
2nd: cefaclor (ceclor),
3rd: cefixime (suprax)

39
Q

1st gen cephalosporins

A

cefadroxil=oldest,
cephalexin= keflex
cefazolin= Ancef (IV)

activity: good against gram +: strep and staph (not MRSA), some gram -, good against anaerobic cocci

SE: GI, allergic reactions, C. diff

40
Q

Use of 1st gen cephalosporins

A

cephalexin: uncomplicated cellulitis
cefazolin: more complicated cellulitis or IV prophylaxis prior to surgery

41
Q

2nd gen cephalosporins

A

cefaclor PO (more susceptible b-lactamase hydrolysis, not as useful), cefuroxime; IV, cefoxitin IV, cefotetan IV

activity: gram +, better gram - against klebsiellae, H. influenza, none against pseudomonas

42
Q

Uses for 2nd gen cephalosporins

A

cefuroxime: sinusitis, otitis, RTI, comm acquired pneumonia (H. flu, K. pneumonia, and penicillin resistant pneumococci).
cefoxitin: anaerobic activity- prophylactic GI surgeries, peritonitis, and diverticulitis (active against gm - rods)

43
Q

3rd gen cephalosporins

A

cefotaxime IV, ceftazidime IV, ceftriaxone

activity: expanded gram - against meningicoccus, citrobacter, b-lactamase strains of homophiles and neisseria

ceftazidime- active against pseudomonas

cefotaxime and ceftriaxone: cross blood/brain barrier

44
Q

Use of 3rd gen cephalosporins

A

ceftriaxone and ceftotaxime: meningitis
empirical therapy for serious infections -> effective against PCN resistant strains pnemonococci

ceftriaxone: used to tx gonorrhea, lyme disease

SE: rash, N/V, LFTs, eosinophilia, HA

45
Q

4th gen cephalosporins

A

cefepime IV

activity: gram + and -, including pseudomonas, staph aureus, strep pneuma, Haemphilus and Neisseria

46
Q

4th gen cephalosporin use

A

penetrates BBB well -> meningitis, other serious infections and sepsis
sometimes used with amino glycoside w/ tx pseudomonas

SE: N/V/D, HA, rash

47
Q

Cephalosporins points

A

1st gen: cephalexin and cefazolin still used a lot

2nd gen: tx otitis, sinusitis, and RTI (Ceftin)

3rd and 4th: DOC for gram - meningitis, good alt to aminogly.
need to watch for resistance strains -> combo therapy good for pseudomonas,
Ceftriaxone: DOC for gonorrhea
Ceftazidime: effective for pseudomonas meningitis

48
Q

Carbapenems

A

Imipenem/cilastatin - better coverage than meropenem (IV(

activity: very resistant to cleavage (b-lactamase), effective against gram + (enterococcus faecalis, and listeria), gram - (H influenza, N gonorrhoaea, enterobacter, and pseudomonas), anaerobes (bactericides)

49
Q

Carbapenem uses

A

meropenem= meningitis, intra-abdominal infections, resistant UTIs, pseudomonas, and w/ or w/o aminoglyc for neutropenic pt

SE: N/V/D, rashes,
imipenem: renal failure and seizures

Infectious Disease (27 decks)

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