Antimicrobials 2 Flashcards
(50 cards)
definining molecular structure of the ‘penicillins’
beta lactam ring
* Confers activity B
* Destroyed by enzymes secreted by some bacteria: “penicillinases” or “beta-lactamases”
* Temperature labile; warming or freezing can destroy the BL ring
penicillins are only effective against what kind of bacteria?
growing
mechanism of action of penicillins?
inhibit cell wall synthesis
Beta lactams covalently bind to & inactivate the transpeptidase enzyme
Defective cell wall > as cells divide, they lyse & die
what kind of bacteria do penicillins work best against and why?
Penicillins tend to work best against Gram-positive bacteria, which have a thick, unprotected peptidoglycan layer
In Gram-negative bacteria:
* Binding sites are different on transpeptidases
* External bilayer can be difficult to penetrate
* Some bacteria secrete penicillinases into the periplasm
penicillins pharmacokinetics
- Distribute well to extracellular fluids everywhere except CNS & prostate (unless inflamed), poor penetration into cells > low Vd
- Acid stability varies; some cannot be given orally due to acid hydrolysis
- Short half-lives (≤ 2 h)
- Elimination: No metabolism; renal excretion of unaltered drug
Main Adverse Effects of penicillins
1) Hypersensitivity
* Mild allergy to anaphylactic reaction
2) Colitis in hindgut fermenters
* Oral penicillins can disturb gut flora
3) Breakthrough seizures in epileptics
* Beta-lactams inhibit GABAa receptors in the brain > increases neuronal excitability
penicillins resistance profile and reasons
Fairly common
- Poor penetration of complex Gram-neg. cell wall
- Acquired bacterial penicillinases
- Plasmid-encoded > can be transferred to other bacteria
Penicillin G: spectrum, excellent against what type of bacteria, half-life, administration strategies, stability
Narrow spectrum Excellent against:
* Gram-positive aerobes
* Anaerobes
- Sodium salt has 30 min half-life > admin. frequently, or use a depot formulation
- Depot formulation consists of penicillin bound to a molecule such as procaine or benzathine > penicillin gradually dissociates from procaine at IM or SC injection site > longer duration of action
- Penicillin G is not acid stable, must be administered parenterally
amoxicillin: spectrum, what bacteria it is effective against
Example of an extended spectrum penicillin
- Gram-pos. aerobes, anaerobes, plus a variety of Gram-neg. aerobes, especially Enterobacteriaceae
- Activity against Gram-pos. aerobes & anaerobes is generally less than that of penicillin G
- Oral bioavailability exceeds 90%
what is ampicillin and its uses?
similar drug to amoxicillin but mainly used parenterally because of poorer oral bioavailability
>but this means more remains in GI tract > GI upset more likley
what is potentiated penicillin
Bacterial penicillinases can be inactivated with penicillinase inhibitors such as clavulanic acid
> called a “potentiated penicillin”
Penicillins Flash Card: mechanism of action
Inhibition of cell wall synthesis
Penicillins Flash Card: Main adverse effects
- Hypersensitivity
- Contact dermatitis risk > not used topically
- Potentially fatal colitis in hindgut fermenters (oral admin.)
- Reduction of seizure threshold
Penicillins Flash Card: general spectrum
- Penicillin G: Gram-pos. aerobes, anaerobes
- Amoxicillin: Same as pen G, plus several Gram-neg. aerobes
Penicillins Flash Card: Health Canada prudent use stats
First line: Penicillin G, amoxicillin Second line: Potentiated penicillins
Penicillins Flash Card: PK features
Excreted intact in the urine
Penicillin G is not acid-stable
Oral bioavailability of amoxicillin is ~90%
what drug class are the cephalosporins similar to? in what ways?
Similar to penicillins:
* Mech. of action
* Distribution
* Elimination
* Main adverse effects
what route of administration is not good for cephalosporins and why?
- Most are not acid stable > cannot be given orally
if an animal has a penicillin allergy will cephalosporins be safe?
About 5% of humans with a penicillin allergy are also allergic to cephalosporins > avoid in an animal with a penicillin allergy to be safe
3rd gen cephalosporins enter what hard to reach tissue reasonably well?
CNS
1st gen cephalosporins spectrum of activity
1st generation: Similar to amoxicillin
>Mainly Gram-pos. aerobes, + anaerobes, plus some medically important Gram-neg. aerobes
3rd gen cephalosporins spectrum of activity
- Less activity against Gram-pos. & anaerobic bacteria but better against Gram-neg. aerobes
cephalexin is what type of drug? usaed mainly in what animals?
1st gen cephalosporin, used mainly in small animals
ceftiofur is what type of antibiotic? mainly used for what?
3rd gen cephalosporin
resp. infections in livestock & horses; foot rot & metritis in cattle; UTI in dogs, etc.
