Ch.31: Antibiotics (Vickroy) Flashcards
shared side effect of macrolides
GI effects
shared side effect of aminoglycosides
renal toxicity
shared side effect of aminopenicillins
GI effects
beta lactam abx include:
penicillins**
cephalosporins**
monobactams
carbapenems
properties of beta lactam abx
- widely used
- good safety profile
- good efficacy
- resistance a problem
- contain a beta-lactam ring that confers antibacterial activity, hydrolytic instability, and microbial resistance**
- acidic
- prone to hypersensitivity rxn
beta-lactam MOA
cell wall inhibitors: irreversible inhibit enzymes that crosslink peptidoglycan polymers in the cell wall, which weakens cell walls and they eventually burst. Also inhibit penicillin binding proteins
killing by beta-lactams is time or conc.-dependent?
time
spectrum of beta-lactams
mainly gram + ; minimal broad-spec activity
Pharmacokinetics of beta-lactams
Oral absorption
Rapid kidney clearance
Does NOT cross BBB
Not well bound to plasma proteins
3 mechs. of beta-lactam resistance
1) prod. of beta-lactamase
2) changes in penicillin-binding-proteins
3) impenetrable membrane pores
procaine penicillin MOA***
forms moderately insoluble salt to allow penicillin to have a slower release and longer duration of action
penicillins drug interactions
phenylbutazone
sulfonamides
salicylates
barbiturates
5 subgroups of penicillins. Which are broad spectrum?
1) natural
2) beta-lactamase resistant
3) Aminopenicillins (broad spec)
4) Extended-spectrum (broad spec)
5) Augmented (broad spec)
International Units
amt of a substance that is based on biological activity rather than mass.
- there is no equivalence between IU measurements for different antimicrobial agents
- 1 mg of penicillin G procaine = 1009 IU ***
augmented penicillins are a combination of:
broad spectrum agent + beta-lactamase inhibitor
cephalosporins are very similar to penicillins. Name a difference
Cephalosporins have a longer duration of action
difference between earlier and later generations of cephalosporins
earlier have less broad-spec activity, less resistant ot beta-lactamase, less expensive, etc.
cephalexin is what generation?
1st
ceftiofur is what gen?
3rd
cephalexin features of note
- 1st gen. cephalosporin
- dogs only
- tx for pyoderma
- good oral bioavailability
ceftiofur features of note
- 3rd gen. cephalosporin
- dogs and food animal
- give IM or SC
- good tissue distr.
- scrutinized in LA!
ELDU of cephalosporins allowed in minor species?
yes (not in major species)
cephalosporins have cross-hypersensitivity with penicillins?
Y
which has longer duration of action: ceftiofur or cephalexin?
ceftiofur
imipenem features of note
- in carbapenem class
- expensive**
- effective against anaerobes and G+ aerobes
- shouldn’tbe used in resistant classes
Are cell wall inhibitors effective against intracellular organisms?
N
do cell wall inhibitors cross BBB?
N
common use of penicillins
UTI
aminoglycosides bactericidal/static? conc/time-dependent?
cidal (conc.-dependent)
aminoglycosides chem. properties**
- highly water soluble
- organic bases
- structurally diverse
- due to these properties, they have limited scope of cross-resistance*
Aminoglycosides MOA
- irreversible inhibition of protein synthesis
- must be transported into orgs. by transporter since not lipid soluble
aminoglycosides spectrum
G -
ineffective against anaerobes
aminoglycosides are synergistic with:**
beta-lactams (against Gram - bacteria)
trough conc.
lowest conc. obtained before next dose of drug is given
aminoglycosides pharmacokinetics
- not orally absorbed**
- distr. in ECF
- renal elimination
- peak conc. correlate with antimicrobial efficacy
- trough conc. correlate with organ toxicity (higher trough conc. = higher toxicity)
predominant organs for aminoglycoside toxicity***
renal cortex
inner ear
mech. of resistance to aminoglycosides
- inc. enzymatic degradation
- dec. memb. transport
- altered ribosomal binding site
signs of aminoglycoside toxicity
- nephrotoxicity**
- ototoxicity (irreversible)
- neuromuscular weakness (reversible)
- anaphylactoid rxns
aminoglycoside contraindications
renal dz, dehydration, NM disorders, etc.
Tetracyclines bacteristatic or cidal?
static
Tetracyclines MOA
REVERSIBLE inhibition of protein synthesis (but have to be actively transported into cells)
Tetracyclines acid or base?
Both! (Amphoteric compounds)
name 2 aminoglycosides
gentamicin, amakacin
Tetracyclines well absorbed orally?
Y
Tetracyclines spectrum
G+, G- anaerobes, mycoplasms
Mechs. of tetracycline resistance
- altered transporter
- active excretion
- enzymatic degradation
- assoc. with cross-resistance to aminoglycosides and sulfonamides*
Tetracycline toxicity
(can be substantial)
GI, superinfections, pain, arrhythmias, teeth/bone discoloration, nephrotoxic, etc.
Tetracycline pharmacokinetics
- well absorbed orally
- can be highly protein bound
- distr. well into most tissues
- renal elimination
tetracycline and Ca
-avoid adding it to anything with Ca (binds Ca and causes precipitates)
Name 2 tetracyclines
tetracycline
doxycycline
Doxy features ofnote
- long-acting*
- lipophilic
- don’t give w/o water
- irritant if given IM or SC
- tx for Ehrlichiosis
What should you monitor during extended use of tetracycline
hepatic and renal fx
Name 2 macrolides
erythromycin
azithromycin
macrolides basic chemical properties
- contain lactone ring
- basic
- highly lipid soluble
Macrolides MOA
REVERSIBLE inhibition of protein synthesis
-accumulated by neuts
macrolides bacteriostatic or cidal?
static (cidal at high dose)
macrolides spectrum
G+
G-
intracellular organisms (because lipophilic)**
Pharmacokinetics (PK) of macrolides
- well absorbed all routes
- distr. widely
- mixed elimination via kidney, liver, biliary
macrolides toxicity
GI (can be fatal in horses!)
resistance to macrolides
- strong cross resistance
mech: alteration of ribosomal binding sites
which has less GI effects: erythromycin or azithromycin?
azithromycin
chem. properties of phenicols
- bases
- lipophilic
- good distr. into tissues and fluids (including milk, fetus**)
Name 2 phenicols
chloramphenicol
Florfenicol
chloramphenicol MOA
reversible inhibitor of protein synthesis
chloramphenicol toxicity***
GI
reduced liver metabolism
bone marrow depression–> never use in food animals!!***
PK of chloramphenicol
- absorbed all routes
- widespread tissue distr.**
- hepatic elimination
- species-dependent half-life
Can florfenicol be used in food animal?***
yes
sulfonamides acids/bases?
acids
sulfonamides MOA
interfere with folic acid form. for purine synthesis (a DNA precursor)
sulfonamides bacteriostatic or cidal?
static
sulfonamides spectrum
G+
G-
resistance to sulfonamides
-fairly widespread, limits effectiveness
PK of sulfonamides
- well absorbed in GIT
- wide distr.
- mixed elimination
4 groups of sulfonamides and uses
standard (systemic infections)
highly water soluble (UTI)
poor water soluble (topical or GI infections)
potentiated (most widely used; uses a bactericidal combo of sulfonamides)
potentiated sulfonamides MOA
interferes with folic acid metabolism, which ultimately prevents DNA synthesis
main side effect of sulfonamide**
renal crystalization (esp. older agents) -hydrate to avoid
Name a sulfonamide potentiated agent
sulfamethoxine + trimethoprim
sulfonamides drug interactions
- prolongs duration of action of drugs that use the same carriers
- antagonized by PABA
fluoroquinolones MOA
inhibits DNA gyrase (topoisomerase II)
fluoroquinolone action time or conc. based?
conc. More specifically, it is dependent on the area under the plasma conc-time curve above MIC.
are fluoroquinolones effective against anaerobes?**
No
fluoroquinolones side effects
nephrotoxicity at high dose
GI
fluoroquinolones contraindications
pregnancy
chondrotoxicity/tendonopathy*
off label use in food animals
fluoroquinolones drug interaction
antacids, NSAIDs,sucralfate
Name a fluoroquinolone
enrofloxacin
