Chapter 3.5.11-3.5.13
Fluoroquinolones include which Drugs
"Enryo went to Cipros house for Marbal and a Prada bag" -Enrofloxacin -Ciproflocacin -Marbofloxacin -Pradofloxacin
Potentiated Sulphonamides group includes which drugs
-Sulphadiazine trimethoprim -Sulphamethoxazole trimethoprom
Short acting Sulphonamides group includes which drugs
-Sulphamethoxazole -Sulphamethazine (good for all animals) -Sulphadiazine
Fluoroquinolones clinical use
-advantages of oral administration due to high gram - aerobic pathogen potency -disadvantages with selection for resistant bacteria if dosed wrong -effective in treatment of urinary tract infections
Trimethoprim-Sulphonamide combination Toxicity and Adverse Effects
-adverse effects can mainly be attributed to sulphonamide -diarrhea occurs after oral administration in HORSES -neurologic abnormalities in HORSES can be seen as well
Nitroimidazoles, Clinical Use: Metronidazole is used to treat
-anaerobic infections -pleuropneumonia -lung abscesses -clostridial enterocolitis
TAKE AWAY: General Properties of Fluoroquinolones
-bactericidal -concentration dependent effects -broad spectrum -large Vd -metabolized in liver -large therapeutic index
TAKE AWAY: General properties of Nitroimidazoles
-bactericidal drugs -reasonable therapeutic index -large Vd -metabolized in the liver -few resistance problems are observed
Trimethoprim Antimicrobial Activity
-bacteriostatic -broad spectrum against gram + and -
TAKE AWAY: General Properties of Rifamycins
-bacteriostatic -good therapeutic index -synergism with macrolides
TAKE AWAY: General Properties of Diaminopyrimidines
-bacteriostatic or coccidiostatic -broad spectrum -large Vd -hepatic metabolism -main excretion is urine unchanged -DO NOT COMBINE WITH SULPHONAMIDES IN DOBERMAN PINCHERS
Rifampin Antimicrobial activity
-broad spectrum antibiotic -also works on facultative anaerobic organisms -bacteriostatic
Sulphonamides Toxicity and Adverse Effects
-can produce a variety of reversible side effects -urinary tract disturbances -hematopoietic disorders -dermatologic reactions
Nitroimidazoles, Toxicity and Adverse effects
-carcinogenic and mutagenic -banned for use in livestock -oral use in horses is associated with anorexia
Which species can use which groups of Sulphonamides
-dogs and cats= all -cattle= intermediate and potentiated -horses=intermediate, potentiated, poorly absorbed -birds and reptiles= potentiated -chickens and turkeys= intermediate
Sulphonamides idiosyncratic drug reactions includes
-fever -epistaxis -uveitis -keratoconjunctivitis sicca
Nitrofurans Drug Class includes
-furazolidone -nitrofurazone
Rifampin drug interactions
-increases intestinal expression of P-glycoprotein transporters -induction of hepatic and intestinal cytochrome P450 enzymes
Fluoroquinolones have what general characteristics
-large volume of distribution -bactericidal -concentration-dependent killing
"Others" Miscellaneous Drugs includes
-methenamine -novobiocin
Fluoroquinolones Toxicity and Adverse Effects
-mild and generally limited to GI disturbances like nausea, vomiting, diarrhea -chronic/high dose therapy causes articular cartilage lesions in young fast-growing animals
____are antimicrobials with broad-spectrum activity aginast gram + and - bacti but their toxicity limits their use
-nitrofurans -effective for the treatment of intestinal and urinary tract infections in humans and animals
Miscellaneous Antibiotics includes
-nitrofurans -nitroimidazoles -rifamycins -others
Trimethoprim Clinical Use
-only in combination with sulphonamides -alone or in combo they may be TOC for prostatic infections caused by gram -
Rifampin Pharmacokinetics
-rapidly absorbed after oral administration -penetrates phagocytic cells -induction of hepatic enzymes
Trimethoprim pharmacokinetics
-rapidly absorbed from intestine after oral administration -distributes widely -bacteriostatic -high Vd
Sulphonamides Pharmacokinetics
-rapidly absorbed from the GI tract leading to wide distribution -high Vd -eliminated by combination of renal excretion and biotransformation -nephrotoxicity is a concern
Fluoroquinolones pharmacokinetics
-rapidly and well absorbed from GI -ingestion with food may delay time to peak concentrations -rapid and extensive tissue distribution -excreted unchanged in urine by glomerular filtration and active tubular secretion
We use Intermediate Acting Sulphonamides to treat
-respiratory -genitourinary -enteric and soft tissue infections -coccidiosis
Fluoroquinolones can be useful in serious infections such as
-septicaemia, pneumonia caused by gram - bacteria -treatment of skin and many soft tissue infections -intra-abdominal infections
Groups of Sulphonamides includes
-short acting -intermediate acting -potentiated -poorly absorbed -topical
TAKE AWAY: General Properties of Sulphonamides
-stable weak acids -bacteriostatic and coccidiostatic -reasonable therapeutic index -painful after IM injection -potentially neurotoxic in higher concentrations
We use Potentiated Sulphonamides to treat
-systemic -respiratory -urinary and cutaneous infections -coccidiosis
Metronidazole Pharmacokinetics
-weak base that is moderately lipophilic -almost complete systemic absorption -widely distributed in tissues -primarily hepatically metabolized
Rifampin toxicity and adverse effects
-well tolerated by horses -monotherapy should be avoided due to rapid emergence of resistance
Primary use of Sulphonamides, in order
1. Toxoplasmosis (with pyriethamine) 2. Chlamydiosis 3. Pneumocysitis carinni 4. Nocardosis
Fluoroquinolones are antagonized with which drug groups?
Chloramphenicol and Rifampin
____Fluoroquinolones are for the most part less active against gram + bacteria and poor activity against anaerobic bacteria
Enrofloxacin, Ciprofloxacin, Marbofloxacin
Fluoroquinolones adverse CNS effects are due to
GABA receptor antagonism
In small animals, Metronidazole appears to be effective in the treatment of
Giardia in cats, but Fenbendazole might be more effective in dogs
Metronidazole is used as part of combination therapy in the treatment of
Helicobacter associated gastritis in dogs and cats
Most important synthetically modified member of the rigamycins
Rifampin
Novobiocin is used in the local treatment of
Staph aureus infections, including mastitis in dairy cows and in an oral product for dogs for treatment respiratory tract infections
Which Sulphonamide is the only BACTERICIDAL drug in the bunch?
Sulphadiazine-trimethoprim (potentiated)
Diaminopyrimidines includes which drug
Trimethoprim
Metronidazole is used for it's excellent activity against
anaerobes and protozoa
In small animals, Metronidazole is used in the therapy of
anaerobic infections
Fluoroquinolones are antagonized by___And synergistic with_____?
antagonized= chloramphenicol and rifampin synergism= beta-lactams and aminoglycosides
In addition to antibacterial activity, Rifampin also has some ___Activity
antiviral and antifungal
Sulphonamides drug interactions
appear not to antagonize the bactericidal effect of penicillin BUT procaine of procaine penicillin will antagonize Sulphonamides
Metronidazole Antimicrobial activity
bactericidal to most gram negative and many gram positive anaerobic bacteria, and a variety of protozoa
Sulphonamides antimicrobial activity
broad-spectrum agents, but it's limited by resistance
We use Topical Sulphonamides to treat
burns, otitis externa
Which Fluoroquinolone is most effective against Pseudomonas aeruginosa
ciprofloxacin
Fluoroquinolones used to treat enterococci
ciprofloxacin and ampicillin or vancomycin
Fluoroquinolones used to treat Staph aureus and Pseudomonas aeruginosa
ciprofloxacin and imipenem or amikacin
Nitroimidazoles, Drug Interactions
commonly used for therapy of bacterial pleuropneumonia in horses when combined with -beta lactam -gentamicin -enrofloxacin -metronidazole
DO NOT use Trimethoprim and Sulphonamides in combination in which species?
dobermans (also not good when debris or necrosis is present)
Novobiocin is combined with procaine penicillin G to treat
dry cow therapy
Sulphonamides bacteriostatic action can be reversed by what?
excess of PABA, so any tissue exudates/necrotic tissue should be removed if animals are to be treated with Sulphonamides
Trimethoprim-Sulphonamide combinations have what antimicrobial activity?
generally broad and usually bactericidal action against many gram + and - bacteria
Trimethoprim + Sulphonamide is used in treatment of
gram negative, prostatic infections (combo is BACTERIOCIDAL)
Principle process for Trimethoprim
hepatic metabolism
Novobiocin is an inhibitor of
hepatic metabolism, skin rashes may occur in cows treated with intramammary infusions
Because of ___rifampin is cautiously used in dogs
hepatoxicity
In a small proportion of animals Sulphonamide therapy can produce what kind of reactions?
idiosyncratic, which are unpredictable and rare events occurring 10 days-3 weeks after first exposure
We use Poorly absorbed Sulphonamides to treat
inflammatory bowel disease
Trimethoprim toxicity and adverse effects
it is relatively safe and non-toxic, hyperkalemia may occur under unusual circumstances
Methenamine is used for
long-term prophylaxis of recurrent urinary tract infections in dogs and cats
Rifampin has synergistic activity with
macrolides against R. equi but is antagonistic with gentamicin or amikacin
Novobiocin has renewed interest in treatment for
methicillin-resistant and methicillin-susceptible staph infections in dogs
Nitroimidazoles, the only relevant one in vet med is
metronidazole, it also has potential carcinogenicty
Pradofloxacin has a broader spectrum of activity that includes
more gram + bacteria and anaerobic bacteria
Nitrofurans are rapidly metabolized after administration, which persists in
muscle and liver for weeks to months
Enrofloxacin can cause which toxic efects
neurotoxic effects, seen in horses, dogs, cats
Carcinogenicity of ___led to their ban in livestock
nitrofurans and nitroimidazoles
___are bacteriostatic in nature and bactericidal when high concentrations are used
nitrofurans, only have a moderate passage through membranes and moderate oral bioavailability
Diaminopyrimidine-Sulphonamide Combinations is the drug of choice in treating
nocardia infections, but high oral dosage must be used for prolonged periods
Methenamine should not be used in patients with
preexisting hepatic insufficiency
Sulphonamides are antagonized by
procaine benzyl penicillin
Fluoroquinolones can cause what in cats with high doses?
retinal degeneration with treatment of enrofloxacin
Topical Sulphonamides group includes which drugs?
silver sulphadiazine
Novobiocin is less active against
strep and the more fastidious gram - bacteria
Intermediate acting Sulphonamides group includes which drugs
sulphadimethoxine
Poorly absorbed Sulphonamides group includes which drugs?
sulphasalazine
Trimethoprim is synergistic with which drug?
sulphonamides
Fluoroquinolones Drug Interactions
synergistic with beta lactams, aminoglycosides, vancomycin against Staph aureus and Pseudomonas and enterococci
We use Short Acting Sulphonamides to treat
systemic and genitourinary infections, nocardiosis OFTEN COMBINED WITH TRIMETHOPRIM
Only veterinary approved products in the US that falls under Miscellaneous category
topical wound formulations of nitrofurazone and furazolidone for use in non-food animals
Rifampin is primarily used in foals for
treatment of Rhodococcus equi
Adverse effects of Metronidazole in the dog and cat have been reported and include
vomiting, hepatotoxicity, neutropenia, neurologic signs
Sulphonamides are less commonly used as single agents due to
widespread acquired resistance and relatively low potency compared to more modern drugs
Sulphonamides Clinical Use
widespread resistance limits the effectiveness, but it's primary uses include: -toxoplasmosis -chlamydiosis -pneumocystitis carinii -nocardiosis -treatment of chronic colitis