PK & PD Flashcards
ADME
Absorption, Distribution, Metabolism, Elimination
What two factors affect distribution?
Lipid solubility
Protein binding
T/F: Penicillin G has good oral absorption
False - not absorbed orally
How are potassium pen, procaine pen, and benzathine pen given?
Potassium - IV
Procaine - IM
Benzathine - IM
How is amoxiclav given in cats and dogs? Horses?
Orally
Not in horses though
Distribution of penicillins
Hydrophilic
Confined to plasma/ECF
Minimal protein binding
Penicillins have ________ metabolism
Minimal
How are penicillins eliminated?
Renal! (A reason that they are really good treatment of choice for urinary infections)
How are cephalexin and cefazolin best absorbed?
Cefazolin - IV
Cephalexin - oral (dogs and cats)
Distribution of 1st gen cephalosporins
Hydrophilic
Confined to plasma/ECF
Low to moderate protein binding
1st generation cephalosporins have _______ metabolism and are eliminated by the _______
Minimal; kidneys
Ceftiofur and cefovecin are not absorbed ______
Orally
Cefovecin (Convenia) is given _____
SC
How is cefpodoxime proxetil best absorbed? What about this drug improves bioavailability?
Oral
Proxetil is a pro-drug - cleaved off in the GIT prior to absorption, prevents early metabolism
Distribution of 3rd gen cephalosporins
Hydrophilic
Confined to plasma/ECF
Low to moderate to high protein binding depending on drug
What about cefovecin extends its half-life?
High protein binding
What 3rd generation cephalosporin has an active metabolite? Otherwise the other 3rd gens have minimal
Ceftiofur (to desfuroylceftiofur)
Elimination of 3rd gens?
Renal
In general, b-lactam antibiotics are _________ (choose one: bactericidal or bacteriostatic)
Bactericidal
B-lactams are time-dependent antibiotics. What does this mean?
Concentrations are greater than MIC of the bacteria for a specified % of dosing interval
(50% in immunocompetent, 80% for g (-), 90% for immunosuppressed)
You have an immunocompromised patient being treated with b-lactams. How does this change your dosing compared to an immunocompetent patient?
Decrease dosing interval b/c these drugs are time-dependent
Dosing more frequently will help keep drug concentrations above the MIC for a greater % of the dosing interval
T/F: for time-dependent antibiotics, it is best to increase dose to maintain higher concentrations
False - best to decrease dosing interval
T/F: Aminoglycosides are absorbed best orally
False - not oral; best IV/IM
Distribution of aminoglycosides
Hydrophilic
Confined to plasma/ECF
Minimal protein binding
Aminoglycosides have minimal metabolism and are eliminated via the _______
Kidneys
Aminoglycosides: bacteriostatic vs. bactericidal?
Bactericidal
Aminoglycosides are __________ dependent
Concentration - max [ ] (Cmax) 8-10x MIC of the bacteria
When considering the nephrotoxic effects of aminoglycosides, what is the most important thing to take into account?
Want trough concentrations to be <2ug/mL
T/F: in contrast to b-lactams, in order to increase the MIC when using an aminoglycosides, the best method would be to increase the dose.
True - Aminoglycosides are concentration dependent, B-lactams are time-dependent (best to decrease dosing interval)
Most fluoroquinolones are given orally and have moderate to excellent oral absorption. The only exception is __________, which may be given IV/IM.
enrofloxacin
Which fluoroquinolone is the most lipophilic?
Enrofloxacin
T/F: Fluoroquinolones are restricted to the plasma and ECF.
False - well distributed, intracellular
Which fluoroquinolone has an active metabolite? What is the active metabolite?
Enrofloxacin (metabolite is ciprofloxacin)
How are fluoroquinolones eliminated?
Mostly renal, some liver
Exception: pradofloxacin - only 21% renal
Fluoroquinolones are ___________ and __________ dependent
Bactericidal
Concentration dependent
Doxycycline should never be given ______ in horses
IV
Will drop dead
Doxycycline and Minocycline have ________ PO absorption in dogs and cats
Good
How is oxytet typically administered?
IV/IM
Despite being the most lipophilic of the tetracyclines, doxycycline has some trouble reaching certain sites due to…
High protein binding
Why might Minocycline be a good choice for treating bacterial cholangitis?
Hepatic elimination
Tetracyclines are bacteri_____ and _____ dependent
-ostatic; concentration
What is the benefit of giving potentiated sulfonamides together?
Bactericidal when given together; bacteriostatic when given alone
Macrolides are baller b/c they are ________ distributed and reach intracellular spaces.
WIDELY
T/F: Macrolides are widely distributed, reach intracelllular spaces, and cross the BBB.
False - everything is true besides crossing the BBB into the CSF
Don’t give clindamycin to ….
Horses
Chloramphenicol distribution…
Widely distributed
Intracellular
CSF, eye, etc
Macrolides, lincosamides, and phenicols are all ________
Bacteriostatic
What happens if nitroimidazoles are given IV too quickly?
Will accumulate quickly in the CNS and can lead to toxicity
What are the two main classes of antibacterial agents that cannot be absorbed orally in small animals?
Benzylpenicillins
Aminoglycosides
What classes have poor oral absorption in horses?
B lactams
Macrolides (adult horses)
Lincosamides
Penicillins, cephalosporins, and aminoglycosides are _________, resulting in limited distribution
Hydrophilic
T/F: Pradofloxacin’s absorption is decreased by food.
True
Tetracyclines are eliminated by both the liver and kidneys, but some are eliminated more by one organ than the other. How are minocycline, doxycycline, and oxytetracycline eliminated?
Mino - mostly hepatic
Doxy - mixed
Oxy - mostly renal
Explain why you might choose to use minocycline over doxycycline for CNS infections
Both minocycline and doxycycline are highly lipophilic and are well distributed, but doxycycline is more protein bound than minocycline, making it more difficult to get into the CNS
T/F: Plasma PK for tetracyclines is not predictive of success for treating IC infections. Explain your reasoning.
True - intracellular concentrations are 26x higher than plasma
