My q's - B-lactams

Question 1

The two classes

Answer 1

1. Penicillins

2. cephalosporins

Question 2

the further split groups of penicillins

Answer 2

a) natural penicillins: narrow spectrum of activity, affective against anaerobes & gram positive
e. g penicillin G

b) aminopenicillins: broad spectrum of activity, affective against anaerobes, gram positive and some negative
e. g amoxycilin or ampiellin

c) other penicillins

Question 3

the 3 generations of cephalosporins

Answer 3

first generation: similar spectrum of activity of aminopenicillins (less anaerobic activity, great againdt staphylococcus which is gram positive)
e.g cephalexin or cephazolin

second generation: affective against gram negative
e.g proteus or enterobacter

third generation: best against gram negative (better than 2nd gen), ok activity against gram positive
e.g ceftiofur

Question 4

How antimicrobials work against the cell wall

Answer 4

• gram positive microbes cell walls are simple, comprised of amino acids & sugars
• gram negative microbe cell walls are harder to penetrate through as they’re far more complex and have 2 layers

e. g of Penicillin penetrating a gram positive cell wall:
- penetrates through wall toward the Penicillin binding proteins toward the cytoplasmic membrane
- when they bind, hydrolysis occurs and the drug can begin to exert its effects

e. g of B-lactams penetrating a gram negative cell wall:
- penetrates to get to binding proteins at the cytoplasmic membrane
- hydrolysis occurs
- exerts its effects

Question 5

Penicillins used in practice

Answer 5

1. amoxicillin: used with clavulanic acid, works against gram positives, anaerobes and some negatives, either oral or injection formulation
2. Pencillin G & Procaine Penicillin (very similar): both effective against anaerobes, gram negative. can be used in production animals too
3. penethamate: treats mastitis in injectable form (powder added to sterile water). Cloxacillin also treats mastitis

Question 6

Cephalosporins used in practice

Answer 6

1. cephalexin: first gen, effective against gram positive, oral administration
2. cephazolin: first gen, IV as injection, gram positive
3. ceftiofur: works well for resp infections, third gen, effective against gram negative, used in production animals
4. cefovecin: third gen, works for gram neg, used for skin infections, long DOA (2 weeks)

Question 7

general pharmacokinetics of both B LACTAMS and Side effects

Answer 7

• weak acids
• rapid absorption
• good distribution around the body
• route of elimination: renal

side effects

• generally safe, can use in pregnant and young animals
• disturbance of the GIT is the main one

Question 8

1. minimum inhibitory concentration (MIC)
2. concentration dependent
3. time dependent

Answer 8

2. concentration dependent:
   - given less frequently due to longer DOA
   - the level of drug plasma concentration above the MIC will determine the killing rate of microorganisms
   - therefore, the killing rate increases as the drug plasma concentration increases over the MIC
   - examples of concentration dependent antimicrobials are: aminoglycosides, fluroquinolone and metronidazole
3. time dependent:
   - given in low doses but more frequently
   - the duration of time and drug plasma concentration above the MIC determines the killing rate of the microorganisms
   - therefore the killing rate is increased over a narrow drug plasma concentration
   e. g of time dependent antimicrobials: B-lactams, macrolides, tetracyclines

Question 9

why are the hesitant to use in production animals?

Answer 9

1. GIT side effects
   - can destroy gut microbes, causing upsets
   - changes in faecal appearance, diarrhoea and vomiting
2. causes hypersensitive reactions
   - more common in penicillins than cyclosporins
   - can lead to more serious conditions

Question 10

how can resistance occur?

how do we stop resistance from occuring?

Answer 10

Penicillin can mistake binding proteins for enzymes that bind to the drug and then block them from exerting their actions, becoming ineffective.

gram negative microbes can also develop a cell wall thats less permeable to B-lactams, making it too hard to penetrate to get to binding proteins

to stop resistance from occuring, can use B-lactamase inhibitors (e.g amoxycilin or ticarcilin) which bind to the enzymes before they can bind to the B-lactam, making the B-lactam be able to bind to the proper protein and exert their effects