Chapter 3.5.11-3.5.13

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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


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