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Bactericidal Cell Wall Inhibitors Flashcards

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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

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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

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A

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

22
Q

Dosage forms of Antistaph PCNs

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A

dicloxacillin: PO
Oxacillin: IM, IV
Nafcillin: IV

23
Q

Antistaph PCNs safety

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A

Preg Cat: B
lactation: unknown

No dosage adj needed for renal or hepatic disease

24
Q

Adverse effects of Antistaph PCNs

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A

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

agranulocytosis, eosinophilia, hemolytic anemia, hepatotoxicity

25
Antistaph drug interactions
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
Broad spectrum PCNS
2nd gen: ampicillin, amoxicillin 3rd gen: carbenicillin, ticarcillin 4th gen: piperacillin
27
2nd gen PCNs uses
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
Safety of 2nd gen PCNs
Preg Cat: B, Lacation: safe Renal dosing: adjust if CrCl
29
Adverse effects of 2nd gen PCNs
CNS: agitation, anxiety, confusion, seizure Hematologic: agranulocytosis, anemia, eosinophilia, hemo anemia Renal: crystalluria
30
What will occur if 2nd gen PCN taken while infected with mono?
high % of patients have developed rash during therapy, don't use in these patients
31
Drug interactions of 2nd gen PCNs
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
3rd generation PCNS, activity
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
Piperacillin spectrum
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
Good to know about PCNs
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
B-lactamase inhibitors
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
Cephalosporins
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
Cephalosporins susceptibility to B-lactamases
are susceptible to B-lactamases | and they have similar SE's as penicillin.
38
Most common 1st, 2nd and 3rd generation cephalosporins?
1st: cephalexin (keflex), 2nd: cefaclor (ceclor), 3rd: cefixime (suprax)
39
1st gen cephalosporins
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
Use of 1st gen cephalosporins
cephalexin: uncomplicated cellulitis cefazolin: more complicated cellulitis or IV prophylaxis prior to surgery
41
2nd gen cephalosporins
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
Uses for 2nd gen cephalosporins
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
3rd gen cephalosporins
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
Use of 3rd gen cephalosporins
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
4th gen cephalosporins
cefepime IV activity: gram + and -, including pseudomonas, staph aureus, strep pneuma, Haemphilus and Neisseria
46
4th gen cephalosporin use
penetrates BBB well -> meningitis, other serious infections and sepsis sometimes used with amino glycoside w/ tx pseudomonas SE: N/V/D, HA, rash
47
Cephalosporins points
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
Carbapenems
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
Carbapenem uses
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

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