8. Penicillins

Question 1

List the Basic Penicillins.

Answer 1

1. Penicillin G: given IV
2. Penicillin V: oral
3. Penamecillin: prodrug, metabolized into benzylpenicillin.

Question 2

List the Staphylococcus B-Lactamase Resistant Penicillins (Anti-Staphylococci).

Answer 2

1. Oxacillin
2. Nafcillin
3. Methicillin
4. Cloxacillin
5. Dicloxacillin
6. Flucloxacillin

Question 3

List the amino-penicillin ESP (Extended Spectrum Penicillins).

Answer 3

1. Ampicillin
2. Amoxicillin

Question 4

List the ureidopenicillin ESP (Extended Spectrum Penicillins)/ (Anti-pseudomonal).

Answer 4

1. Piperacillin
2. Ticarcillin

Question 5

What are the side effects of Penicillin therapy?

Answer 5

Penicillins are generally non-toxic and can be used in pregnancy.

1. Allergy: T1 HS rxn; may be cross-reactive with cephalosporins
2. Epileptic seizures: (↓ BBB pen → only at high serum levels, as in ↓ kidney function)
3. Hematological reactions: drug-induced AI hemolytic anemia (via anti-penicillin IgG binding RBC surfaces)
4. Morbilliform rash - sometimes occurs if given during viral infection (EBV, etc.)
5. (Interstitial nephritis - mononuclear infiltrate)

Question 6

What are the indications of basic penicillins?

Answer 6

1. Gram + cocci: used to be good for staph, now 99% staph are resistant; still good against Streptococci (esp. S. pyogenes)
2. Good for Pasteurella multocida (pet bites), Actinomyces (and other Gram + anaerobes in general, i.e. C. perfringens, oral strep, etc.); Leptospira; Borrelia; Treponema
3. Syphilis; fever after cat/dog bite; upper respiratory infections (otitis, tonsillopharyngitis); soft tissue infections (Staph/Strep)
4. Gram - cocci: good for Neisseria only (most meningococci, some gonococci)
5. NOT effective for: Enterococci, Gram - rods (H. flu, E. coli, salmonella), Gram - anaerobes (B. fragilis, etc.)

Question 7

How are the kinetic parameters of penicillins?

Answer 7

1. Penetrate CNS, eye + prostate only in inflammation (compromised barrier)
2. Does not enter abscesses
3. Cross placenta + enter breast milk
4. Excreted via kidney unchanged

Question 8

What is the route of administration for penicillin G?

Answer 8

Penicillin G - gastric acid unstable → IV only

Question 9

List the cell wall synthesis inhibitors.

Answer 9

1. B-lactams (penicillins, cephalosporins, carbapenems, monobactams)
2. Glycopeptides
3. Others

Question 10

What spectrum does Extended-Spectrum Penicillins cover?

Answer 10

Spectrum: similar spectrum to basic penicillins (Staph, Strep), plus activity against…

1. Gram - rods - E. coli, Shigella, Salmonella etc. causing GI infections, UTIs, etc.Gram - rods often produce beta-lactamases, so ESPs are often combined with beta-lactamase inhibitors (Topic C-10) in these cases. B-Lase inhibitors have 100x ↑ affinity for B-Lase than the abx themselves and thus competitively inhibit it
2. Gram - anaerobes (B. fragilis, often multi-resistant + causes abdominal infections: peritonitis, etc.)
3. Enterococci (about 50%, many are multi-resistant); Listeria and some lower respiratory tract infections; Borrelia in early stages

Question 11

What are the indications for Staph B-Lactamase Resistant Penicillins/ Anti-staphylococci penicillins?

Answer 11

They have larger R groups that inhibit B-lactamase binding so are generally good against Staph (except MRSA), but weaker against Strep than basic penicillins.

Question 12

What are the indications for penicillin G?

Answer 12

1. Rheumatic fever
2. mitral endocarditis (S. viridans/bovis)
3. intrapartum group B strep prophylaxis (agalactiae)
4. IM form for syphilis (primary, secondary or early latent)
5. Neisseria meningitis

Question 13

What is the route of administration of Penicillin V?

Answer 13

Penicillin V - acid stable → oral admin.

Question 14

What is Penamecillin?

Answer 14

Penamecilline is prodrug metabolized by esterases into benzylpenicillin.

Question 15

What are the indications for Penicillin V?

Answer 15

DOC for group A strep (strep throat, rheumatic fever)

Question 16

What are the kinetic parameters like for Penicillin V?

Answer 16

1. Poor bioavailability
2. 4x/day dosing
3. Narrow spectrum

Question 17

What is the route of administration of Oxacillin?

Answer 17

Oxacillin has good oral absorption and it is often combined with aminoglycoside (gentamicin) in severe, life threatening infections (osteomyelitis, endocarditis, etc.)

Question 18

What is the route of administration of Nafcillin?

Answer 18

Nafcillin is only parenterally administered.

Question 19

What are the indications for Methicillin?

Answer 19

Methicillin is no longer used because of nephrotoxic side effects and is therefore only used for diagnostics.

Question 20

What are the indications of anti-staphylococci penicillins?

Answer 20

1. Oral admin: mild or moderate localized skin / soft tissue infections (folliculitis, impetigo, abscesses) by methicillin-sensitive Staph.
2. IV admin: severe systemic Staph infections such as tricuspid endocarditis or osteomyelitis.

Question 21

What is the resistance mechanism behind the anti-staphylococci penicillins?

Answer 21

Resistance occurs when Staph have altered PBPs + thus ↓ beta-lactam binding.

Question 22

What are the side effects of aminopenicillins?

Answer 22

1. Aminopenicillins can cause dysbacteriosis due to effect on GI bacteria (potentially pseudomembranous C. difficile colitis)
2. (rash, or in serious cases Stevens-Johnson syndrome)
3. often combined with aminoglycoside (ampicillin + gentamicin) for severe cases

Question 23

What is the route of administration of Ampicillin?

Answer 23

Ampicillin is parenteral admin; often w/ sulbactam B-Lase inhibitor.

Question 24

What are the indications for Piperacillin?

Answer 24

Piperacillin is good for P. aeruginosa and resistant nosocomial infections.

Question 25

What is the MOA of Beta-Lactams?

Answer 25

1. Beta Lactams all inhibit peptidoglycan synthesis by transpeptidase rxn inhibition. 2. They bind to PBPs which are the transpeptidase enzymes themselves → bactericidal effect. 3. Generally ineffective against intracellular bacteria. 4. Generally low toxicity and ok in pregnancy.

Question 26

**What is the resistance mechanism behind Beta-Lactams?**

Answer 26

1. **Beta Lactamases** - break down the abx molecules (penicillin \> cephalosporins \> carbapenems \> monobactams). Extended Spectrum B-Lactamases - more effective + even break down carbapenems 2. **Altered PBPs** - conveys resistance against all B-lactam abx via ↓ binding. ex: MRSA - resists all the staph B-lactamase-resistant penicillins 3. **Permeability Decrease** - reduced or absent pores in cell (ex: Gram negatives) 4. **Efflux Pump** - less common

Question 27

What are the indications of Ticarcillin?

Answer 27

Ticarcillin is a carboxypenicillin, also good for P. aeruginosa, with clavulanate.

Question 28

Which are the broadest spectrum penicillins?

Answer 28

Ureidopenicillins are the broadest spectrum penicillins.

Question 29

What are the pharmacokinetic paramters of Piperacillin?

Answer 29

1. Parenteral admin only 2. Often combined with gentamicin or tobramycin 3. Also often w/ tazobactam B-Lase inhibitor

Question 30

**What are the indications of ampicillin?**

Answer 30

1. **severe anaerobic infections** (aspiration pneumonia, Enterococcus, Listeria meningitis) 2. accumulates in gallbladder → can be good for **cholecystitis**

Question 31

**What is the route of administration of Amoxicillin?**

Answer 31

Amoxicillin is orally administrated, often w/ clavulanic acid, a B-Lase inhibitor.

Question 32

**What are the indications of Amoxicillin?**

Answer 32

1. common for Strep pharyngitis 2. sinusitis, otitis media and pneumonia by Strep, H. flu, etc. 3. dental surgery prophylaxis - against oral anaerobes in pts with endocarditis risk 4. (part of H. pylori triple therapy; also for Borrelia) 5. (prophylaxis against encapsulated microbes in asplenia )

Question 33

**What are the side effects of Amoxicillin?**

Answer 33

1. **Hepatotoxicity** (common with amox + clav). 2. common cause of **morbilliform rash** when given during **EBV**.