C.8

Question 1

Penicillins

Answer 1

Penicillin G,
Benzathin-penicillin,
Penicillin V,
Flucloxacillin,
Amoxicillin,
Ampicillin,
Piperacillin

Question 2

General features of all β-lactams

Answer 2

MOA: inhibition of transpeptidation of peptidoglycan monomers (PBP)
T1/2+how many times a day: 30-60min→3-6X a day
Spectrum determinants: penetration capability (aquaporins in the outer membrane), G(-) thick LPS layer, binding affinity for PBP
Resistance: β-lactamase enzyme; inhibition of penetration; mutated PBP (MRSA); efflux
Spectrum (order the families from narrow to broad): Penicillin<cephalosporins<carbapenems
Synergism with: aminoglycosides
General pharmacokinetics: variable GI absorption and acid stability, including BBB penetration, inflammation improves penetration; NO METABOLISM, generally renal excretion
Distribution: extracellular only; no effect against obligate IC bacteria (e.g. Mycoplasma)
SEs: allergy (penicillin)→IgE mediated anaphylaxis; Proconvulsive (epileptogenic) effect in high doses; Broad spectrum β-lactams can cause dysbacteriosis; Hematological SEs rarely (ITP, hemolytic anemia)

Question 3

Basic penicillins

Answer 3

Penicillin G, Penicillin V, Penamecillin

Question 4

Anti-staphylococcal penicillin

Answer 4

methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin

Question 5

Extended spectrum (not pseudomonas)

Answer 5

Aminopenicillins: ampicillin, amoxicillin

Question 6

Extended spectrum - pseudomonas penicillin

Answer 6

-Carboxypenicillins: Carbencillin, Ticarcillin;
-Ureidopenicillins: Mezlocillin, Azlocillin, Piperacillin

Question 7

Penicillin: True for all of them:

Answer 7

Bactericidal;
MOA: binds and inhibits PBP (=transpeptidase)→ no cell wall production;
Pharmacokinetics: p.o/parentral, short T1/2 + time-dependent effect + short PAE, extracellular distribution, poor penetration (to the eye, prostate, bone and CNS), penicillins can cross the placenta and be excreted in breast milk, 30% metabolized by liver and 70% excreted by the kidneys;
SEs: allergy (skin rash, anaphylaxis, morbilliform rash), GI (nausea, diarrhea, dysbacteriosis), Hematologic (anemia, thrombocytopenia, neutropenia), Irritation and local pain (if given I.M), Neurotoxicity (seizures - at high doses)

Question 8

for basic penicillin

Answer 8

Spectrum: Gram (+) cocci- Streptococci, Pneumococci, non-β-lactamase producing staphylococci, Gram (-) cocci- meningo- and gonococci, Gram (+) rods- Corynebacteria, Bacillus antracis, Clostridium, Gram (-) rods- Fusobacterium, Bacteroides spp (except B.fragillis), Pasteurella multocida, Spirochetes- Leptospira, Borellia, Treponema pallidum

Question 9

Penicillin G

Answer 9

ROA: acid labile→ parentral (i.v>i.m);
Dose: 1-4MU/day i.v. 4-6 divided doses;
T1/2: 30-40 min (in case of kidney failure 24h);
IND: i.v infusion by serious infections, sepsis, osteomyelitis, acute endocarditis (Staph, Strep), pneumococcal pneumonia, neurosyphilis, Lyme, Gonorrheae, Tetanus, Diphtheria

Question 10

Penicillin V

Answer 10

ROA: acid stable→ p.o;
T1/2: 30-45 min;
IND: mild/moderate infections, scarlet fever, erysipelas, phlegmone (streptococci), otitis, bronchitis, sinusitis; Disadvantage: poor BA, short T1/2, narrow spectrum

Question 11

Benzathin-Penicillin

Answer 11

ROA: i.m, slow release of penicillin G;
T1/2: 10-20 days;
IND: prophylaxis in rheumatic fever, prevention of syphilis transfer to fetus in pregnant infected women;
Dose: 1.2-2.4 MU/week i.m;
Extra: can be given in DEPOT form (1 shot - stays for 3-4 weeks)

Question 12

Flucloxacillin

Answer 12

ROA: acid stable→ p.o and parentral use;
Resistance: it has a bulky polar side chain→ resistant to β-lactamases;
IND: mild infections caused by lactamase-producing Staph (10% of S.aureus are resistant→ MRSA);
T1/2: 30-60min

Question 13

Amoxicillin, Ampicillin

Answer 13

Kinetics: acid stable (→p.o and parentral administration),
-ampicillin has poor BA- given mainly parentrally (dose: 3-4X0.5-1g i.m/i.v),
-amoxicillin has better absorption (dose: 3X0.5-1g p.o);
Spectrum: everything in basic penicillin + Enterobacteriaceae (E.coli, Salmonella, Shigella), H. influenza, L. monocytogenes, S. agalactiae, H.pylori (combined with metronidazole and PPIs);
IND: UTIs (E.coli, enterococci, proteus), respiratory tract infections, Otitis, sinusitis, enterococcal endocarditis (combined with aminoglycosides), Listeria monocytogenis meningitis;
Protection against β-lactamase: combination with β-lactamase inhibitors - sulbactam (+ampicillin), clavulonic acid (+amoxicillin);
SEs: allergic, morbilliform skin rash, anaphylactic shock, diarrhea, maculopapular skin rash.

Question 14

Piperacillin

Answer 14

Spectrum: that of aminopenicillins + B.fragilis, pseudomonas, Klebsiella;
SEs: dysbacteriosis (diarrhea), ampicillin rash - morbilliform exanthema EBV/CMV infection, allergy; IND: severe infections caused by G(-) bacteria (urogenital infections, endocarditis, sepsis), pseudomonas infections, immunosuppressed patients, nosocomial infections, Klebsiella pneumoniae, enhanced activity against G(-) bacteria;
ROA: i.v;
Combinations: Piperacillin + Tazobactam