Beta-lactams

Question 1

Beta-lactams

Answer 1

-includes penicillins and cephalosporins

-all have a beta lactam ring which is site of action of penicillinase

Question 2

Benzyl penicillin vs. Penicillin G

Answer 2

The exact same thing, just two different names

Question 3

Crystalline penicillin G

Answer 3

-Na or K salt with penicillin

Formulations:
1.sterile formulations for injection (IV formulation, sometimes IM, SC)
2. Soluble powder for drinking water- in Vet med

Question 4

Procaine Penicillin G

Answer 4

-used commonly in cattle and horses
-Short acting/daily injections procaine will slow down penicillin absorption
-give IM or SQ; NEVER IV

Formulations:
-white injectable penicillin
-oral feed premixes

Question 5

Benzathine Penicillin G

Answer 5

-long acting injectable penicillin (IM, some products are IV)
*not absorbed well

-Only in Duplocillin in Canada for LA

Question 6

Penicillin V

Answer 6

-acid stable so can be given orally
-not really used in vet med, other drugs are better

Question 7

Procaine Pen G in oil

Answer 7

-long acting
-IM or SC only

Question 8

Procaine and benzathine Pen G formulation

Answer 8

-long acting
-IM or SQ injection only

Question 9

Penicillin G Mechanism of Action

Answer 9

Act by disrupting synthesis of bacterial cell wall
-inhibits the penicillin-binding proteins (PBPs) on outside of bacterial cell membrane
-this interferes with enzymes (transpeptidases) needed for peptidoglycan synthesis (part of cell wall)
-causes lysis of growing bacterial cells

Question 10

Are penicillin G a bactericidal or bacteristatic?

Answer 10

Bactericidal- BUT only if bacteria is actively growing

Question 11

What types of bacteria does Penicillin G get used for?

Answer 11

GRAM +
-lots of peptidoglycan in cell wall
-high affinity of PBPs for beta-lactams

Question 12

Why does penicillian not work as well for gram - ?

Answer 12

-lesser peptidoglycan in cell wall and lower affinityof PBPs for beta lactams

Question 13

What are possible resistance mechanisms of bacteria against Penicillin G?

Answer 13

-Presence of penicillinase (exogenous often gram + which breaks down Penicillin) or Beta-lactamase enzymes (exogenous often gram - which break down penicillin)

-inability of Beta-lactam to penetrate bacterial cell wall

Question 14

Cephalosporin and penicillinase or beta-lactamases

Answer 14

Cephalosporin can make it through the enzymes and bacteria will be susceptible

Question 15

Penicillin G spectrum activity

Answer 15

-Many gram + (mostly strep, not most staph because they make beta-lactamase)

-Many anaerobes

Question 16

MIC numbers and penicillins

Answer 16

MIC values are great and comparing susceptibility

ex. Low number= will kill it off

Question 17

Bacteria you can use Penicillin G for

Answer 17

Gram +
-Actinomyces
-Trueperella pyogenes
-Some Bacillus anthracis, Corynebacterium, Erysipelothrix, rhusiopathiae, Listeria

Gram -
-Some histophilus, pasteurella

-most anaerobes
-fusobacterium, some clostridium, some bacteroides

Question 18

Bacteria typically resistant to Penicillin G

Answer 18

Question 19

Penicillin Oral Pharmacokinetics

Answer 19

-poor oral absorption of Pen G due to rapid hydrolysis in stomach acid
**Exception: Phenoxymethyl penicillin

-Pen G used in feed premix or drinking water BECAUSE not trying to get plasma concentrations, just for local effects in GI tract

Question 20

Penicillin Parenteral Pharmacokinetics

Answer 20

1. Crystalline pen G
   -only dosage used IV. Rapid absorption after IM or SC]
   -need every 6 hrs; high concentration but drops quickly
2. Procaine pen G
   -slowly absorbed IM then crystalline forms
   -causes vasoconstriction at injection site
   -lower but sustained plasma concentrations
   -absorbed more and quicker in neck then in hindquarters (also less carcass damage)
   -NEVER IV because CNS signs
   **milky= no IV
3. Benzathine pen G
   -poorly soluble, very slowly absorbed
   -produces sustained Pen G plasma concentration but not high enough to reach MIC= residues in meat and milk

Question 21

Distribution of Penicillin

Answer 21

-Weak acid (pKa= 2.7)
-highly ionized at physiological pH/plasma?

Question 22

Penicillin Volume of distribution

Answer 22

-Low VD
- will stay in plasma and extracellular fluid (honestly good because other infection is in the ECF)
-Some tissues may not get therapeutic conc, BUT increased distribution to tissues with inflammation

Question 23

Penicillin elimination and excretion

Answer 23

Elimination: Very little metabolism

Excretion: Renal (some GFR, some into renal tubule)
*no real need to adjust dose for renal disease

Question 24

Penicillin half life

Answer 24

1-2 hours
But variation depending on the formulations. Procaine/Benzathine forms will take longer because takes longer to absorb

Question 25

Penicillin as Time dependent antimicrobials

Answer 25

-efficacy not based on high Cmax
-Keep penicillin conc >MIC for as long as possible

Question 26

Dosing for Penicillin formulations

Answer 26

-Crystalline penicillin: may need TID/QID

-Procaine Pen G: once daily dosing

-LA procaine/benzathine Pen G: days between doses BUT Flip flop kinetics (prolonged absorption so longer half life)

Question 27

Adverse rxns of Penicillin

Answer 27

1. Hypersensitivity (from R1 side chains, not beta-lactam)
   -anaphylaxis/ local inflammation (Type I)
   -Autoimmune hemolytic anemia (Type II)
   -Vasculitis (Type III)
2. GI flora changes (diarrhea)
   -especially in hindgut fermenters (horses, rodents, rabbits)
3. Drug residues in food animals