AMDs and Antifungals Flashcards
what is the MoA of Penicillins
inhibits cell wall synthesis
what are the main adverse effects of penicillins (3)
1) decrease seizure threshold
2) can cause fatal colitis in hindgut fermenters if given orally
3) hypersensitivities (not given topically)
what are the main PK features of penicillins (3)
1) penicillin G is not acid stable
2) amoxicillin has an oral bioavailability of 90%
3) excreted intact in the urine
how should we be treating penicillins
1) Penicillin G and amoxicillin
2) Potentiated penicillins
what is the general spectrum of Penicillin G
G+ aerobes, anaerobes
what is the general spectrum of amoxicillin
G+ aerobes, anaerobes, some G- aerobes
all penicillins end in
“cillin”
do penicillins have a long or short half life
short (<2h)
what is the Vd (high or low) of penicillins and why
low; they distribute to extracellular fluids well (not brain or prostate) but have poor penetration of cells
if an animal is hypersensitive to penicillins they are also likely reactive to
cephalosporins
what is the MoA of cephalosporins
inhibit cell wall synthesis
what are the major adverse effects of cephalosporins
hypersensitivity; colitis in hindgut fermenters if given orally; reduce seizure threshold
how should we use cephalosporins
first line: 1st gen
second line: 3rd gen
what are the major PK features of cephalosporins
- most are not acid-stable
- some 3rd gen (cefotaxime) enter CNS readily
- not destroyed by penicillinases (may be destroyed by β-lactamases)
what is the general spectrum of first generation cephalosporins
same as amoxicillin: G+ aerobes, anaerobes, some G- aerobes
what is the issue with cefovecin (Convenia)
it is a third generation cephalosporin given as a single SQ injection with a 2-week half-life that essentially guarantees inappropriate duration of therapy
what is a convenient (hint) AMD we should avoid using unless the patient is really aggressive or long duration of therapy needed
Cefovecin (Convenia)
what are the main uses of aminoglycosides
1) topical infections (ex. staph)
2) serious G- aerobic systemic infections
what is the MoA of aminoglycosides
inhibits protein synthesis; bactericidal
what are the major adverse effects of aminoglycosides
nephrotoxicity and ototoxicity
what are the major PK features of aminoglycosides
highly ionized so no oral or topical absorption; food residues are over 1y if given parenterally
how should we give aminoglycosides
1st line: topical administration
2nd line: systemic administration
what is the general spectrum of aminoglycosides
G- aerobes; mycoplasma; staph
what is the MoA of tetracyclines
inhibit protein synthesis (bacteriostatic)
what are the major adverse effects of tetracyclines (4)
- nephrotoxicity if dehydrated
- esophageal ulcers in cats
- tissue irritation
- incorporates into growing long bones and teeth
what are the major PK features of tetracyclines
lipid soluble useful against intracellular pathogens
how do we use tetracyclines
first line, especially important for atypical bacteria (mycoplasma, rickettsia, anaplasma, chlamydia…)
what is a highly lipid soluble tetracycline
doxycycline
what is the general spectrum of tetracycline in small animals? large animals?
small animals: atypical bacteria
large animals: atypical bacteria plus some G+ and G- aerobes and anaerobes
if giving tetracyclines what is an important feeding consideration
divalent cations in food (ex. calcium) will markedly decrease oral absorption
what tetracycline has the best oral availability
doxycycline
why is it a problem that tetracyclines will bind to multivalent cations (ex. calcium)
1) inhibits oral absorption if taken with calcium-containing foods
2) incorporates into growing long bones and teeth which creates food residues
what is the MoA of sulphonamides
inhibit folic acid synthesis
what are the main adverse effects of sulphonamides (3)
- nephrotoxicity in dehydrated patients
- hypersensitivity
- lacrimotoxicity in dogs
how should we use sulphonamides
first line!
what are the main PK features of sulphonamides
inactive in the presence of pus; distributes to all tissues
what is the general spectrum of sulphonamides for small animals and for large animals
small animals: UTIs, atypical bacteria
large animals: fairly broad spectrum
what does TMS stand for and what is it
trimethoprim sulfonamide; it is sulphonamide combined with a diaminopyrimidine inhibitor (trimethoprim) to help restore its effectiveness
sulfonamides alone are ____________ whereas trimethoprim sulfonamides are _____________
bacteristatic; bactericidcal
what is the MoA of macrolides
inhibit protein synthesis
what are the main adverse effects of macrolides
- oral erythromycin causes nausea and vomiting
- tissue irritation
- potentially fatal colitis if given orally to hindgut fermenters
how do we give macrolides
first line: erythromycin
second line: newer macrolides
what are some key PK features for macrolides
erythromycin: inhibits P450 and stimulates motilin
enters cells
concentrates in lungs
newer macrolides have long half lives
in an animal with allergies what is better to give over penicillin
erythromycin
macrolides are especially important for ________ disease
respiratory
what AMD is fatal to swine and fatal in general if given IV
tilmicosin (a newer macrolide)
what is the MoA of fluoroquinolones
inhibit DNA synthesis (DNA gyrases and topioisomerases)
what are the main adverse effects of fluoroquinolones
- retinal damage in cats with enrofloxacin
- decreased seizure threshold
- cartilage damage
how do we use fluoroquinolones
second line
what are the main PK features of fluoroquinolones
- concentrates in lungs
- most have a long half-life (not enrofloxacin)
- oral absorption 100%
what is the general spectrum of fluoroquinolones
similar to aminoglycosides….
staph, G- aerobes, atypicals
what is the general spectrum of macrolides (old vs new)
old (erythromycin): some G- aerobes and some atypical; all G+ aerobes and anaerobes
new: all G- aerobes; some G+ aerobes, anaerobes and atypical
what drugs should we avoid using if at all possible (3)
fluoroquinolones, potentiated penicillins, 3rd gen cephalosporins
what are the 5 main types of antifungals and give an example
- polyenes (amphotericin B)
- azoles (itraconazole)
- pneumocandins and echinocandins (caspofungin)
- pyrimidines
- drugs used for dermatophytosis (terbinafine)
what is the toxicity and relative spectrum of polyenes? are they fungistatic or fungicidal?
broad spectrum
high systemic toxicity
fungicidal
what is the toxicity and relative spectrum of azoles? are they fungistatic or fungicidal?
very low toxicity
broad spectrum
fungistatic
are pneumocandins/echinocandins high or low toxicity?
low toxicity
what is the newest class of antifungal drugs
pneumocandins/echinocandins
what is the cell target for:
a) pneumocandins
b) azoles
c) polyenes
a) pneumocandins: cell wall
b) azoles: plasma membrane
c) polyenes: plasma membrane
how do the cell targets of antibacterials differ from antifungals
antibacterials are commonly protein synthesis or cell wall synthesis whereas antifungals are very commonly plasma membrane
what allows us to target the plasma membrane of fungi (what is different about the plasma membrane compared to animals cells)
they contain ergosterol instead of cholesterol
what are the two “formulations” of amphotericin B (a polyene) and what is the therapeutic difference
1) bile salts: will be eliminated in the kidneys and can cause kidney damage
2) lipid: will be eliminated in the reticuloendothelial system and can be used to target infections there
what is the absorption and distribution of amphotericin B
poor oral; given IV; distributes in extracellular fluid but poor CNS penetration
what is the half life of amphotericin B
LONG (26h in dogs)
what is the spectrum of amphotericin B and what is its main use(s)? how do we usually give it? how does use differ in large animals?
broad (not against dermatophytes); due to toxicity it is usually used topically or for life-threatening systemic mycoses; we usually give one dose of this followed by doses of azoles; not used in food animals and rarely used in equine
what is the main adverse effect of amphotericin B
dose-dependent nephrotoxicity (worse with bile salt formulations, better with lipid formulations)
how should we go about administering amphotericin B
slow (4-6h) in dextrose-containing IV fluid, may be good to give NaCl fluids before administration to lessen renal toxicity
what antifungal can you not give a pregnant dog
azoles (teratogenic)
what is the bioavailability of azoles
good oral bioavailability
what are the two “types” of azoles and an example? how do we use them?
1) imidazoles (ex. ketoconazole)
2) triazoles (ex. itraconazole)
Triazoles better for systemic use but both good for topical use so we use imidazoles first
what is the MoA of azoles and an important consideration due to this MoA
inhibits fungal P450 enzymes involved in ergosterol formation
it also inhibits some mammalians P450 enzymes making it inhibit the metabolism of other drugs given
why do we generally not use imidazoles systemically anymore
endocrine effects common with systemic therapy because they inhibit mammalian sterol synthesis
what drug is no longer used as an antifungal but is used to treat hyperadrenocorticism
ketoconazole (an imidazole azole)
what are the topical imidazole azoles
miconazole (otic and dermal)
clotrimazole (otic)
enilconazole (dermal)
what is caspofungin and what is it important for
echinocandin; useful against Candida spp.
what 2 classes/types of antifungals can be used synergistically against dermatophytes
terbinafine and azoles
what are the two ways to administer terbinafine
oral or topical
what is the best way to treat severe cases of dermatophytosis
oral and topical combinations of azoles and terbinafine in a clipped animal
is therapy long/short for itraconazole and why
long; it enters into newly forming keratin
what are the main adverse effects of itraconazole
- GI upset, nausea, vomiting
- skin problems
- inhibits some P450 enzymes
