Exam 4 Flashcards
Griseofulvin; MOA, Use, Toxicity
MOA
Fungistatic
disrupts mitotic spindle
Use
Dermatophytes
1-4 month therapy
Used in SA, equine, & food animal ELDU
Toxicity
Ds
Depression, anorexia
Hepatotoxicity
Bone marrow suppression
Ataxia especially in cats
Maybe teratogenic & carcinogenic
Absorption enhanced by high fat meal
Flucytosine; MOA, Use, Toxicity
MOA
Fungistatic
Prodrug converted to antimetabolite
Disrupts protein synthesis
Use
Cryptococcus
Some candida
In combo w/ amphotericin B due to resistance
Toxicity
Contraindicated in cats
Mammal cells do not convert to active form BUT some GI flora may -> toxic to mammal
Bone marrow suppression
Mucus membrane ulcers
Amphotericin B; MOA, Use, Toxicity
MOA
Fungicidal
Binds ergosterol & Disrupts membrane function
Long ½ life
Mostly eliminated by urine
Use
Severe systemic infections
Histoplasma
Blastomyces
Cryptococcus
Coccidioides
NO DERMATOPHYTES
Toxicity
Nephrotoxicity
Anaphylaxis – vomiting & fever
DO NOT combine w/ Azoles
Ketoconazole; MOA, Use, Toxicity
MOA
Fungistatic
Requires acidic environment for oral absorption
Inhibits CYP450 & ergosterol synthesis
Use
Candida
Malassezia dermatitis in dogs
Dermatophytes in dogs & cats
Add on treatment for systemic infection
Maybe adrenal hyperplasia
Toxicity
Safer than amphotericin B
GI upset
Hepatotoxicity in cats
interference w/ progesterone & tostesterone
EXTREME drug interactions
Itraconazole
o Better efficacy against Candida, Aspergillus, Dermatophytes & systemic fungi than Ketoconazole
o Fewer adverse effects
o More expensive
Fluconazole
o No metabolism
o Excreted in urine
o Penetrates CNS & urinary tract
o Better oral bioavailability than Ketp or Itra
Clotrimazole
o Topical
o Nasal aspergillosis in dogs
o Infused into bladder for fungal candiduria in SA
o Otitis externa due to Malassezia
Miconazole
o Topical for dermatophytosis in SA
o Could use frequent IV for systemic
Terbinafine; MOA, Use
MOA
Inhibit enzyme squalene epoxidase ->
Decreased ergosterol synthesis
Use
Long term treatment for onychomycosis
Topically & systemically for dermatophytosis in SA
Idoxuridine
o Antiviral for the eye
Oseltamivir
o Used to reduce severity of parvovirus
o Poor efficacy
Oral Famiclovir
o Used for feline herpes virus
Zidovudine
o FIV
o FLV
o Banned in birds
Classes of Penicillins & Drugs
Natural
Penicillin G
Aminopenicillins
Amoxicillin
Ampicillin
Beta Lactamase Inhibitors
Amoxicillin clavulanate (Clavimox)
Classes of Cephalosporins & Drugs
1st Gen
Cephalothin
Cephalexin
Cefazolin
3rd Gen
Ceftiofur
Cefpodoxime
Cefovecin
Ceftriaxone
Tetracycline; Drugs, MOA, Spectrum, Tox, Use
Drugs
o Tetracycline
o Oxytetracycline
o Doxycycline
MOA
* Bacteriostatic 30s proteins
Spectrum
* All accept Staph. Pseudomonas & E. coli
* Not good for UTIs
Tox
* GI
* Death in horses
* Fever
* Renal & hepatic toxicity
* Esophageal lesions in cats
Use
* Respiratory dz & anaplasmosis in cows
* Intrauterine infusion in cows
* Neorikettsia Ristcii in horses
* Doxy is drug of choice for intracellular pathogens
Aminoglycoside; Drugs, MOA, Spectrum, Tox, Use
Drugs
o Gentamicin
o Amikacin
MOA
* Bacteriocidal 30s proteins
Spectrum
* ALL aerobes
Tox
* Nephrotoxicity
* Ototoxicity (irreversible)
* Neuromuscular blockade (reversable)
* Bone marrow suppresion
* Amikacin least toxic
* Do not use in hypovolemia
Use
* Gentamicin systemically in horses
* Amikacin in foals, dogs, cats
* Amikacin as intrauterine infusion in horses
* Gentamicin for regional limb perfusion
Macrolides; Drugs, MOA, Spectrum, Tox, Use
Drugs
o Erythromycin
o Tilmicosin
o Azithromycin
o Tylosin
o Tulathromycin
MOA
Bacteriostatic
Spectrum
* Newer all
* Older gram (+) aerobes
Toxicity
* GI
* Colitis in horses
* Hyperthermia in foals
* Tilmicosin cause severe cardio tox
Use
* Gamithromycin, Tulathromycin, Tilmicosin resp dz & foot rot in cows
* Tylosin for IBD in dogs
Amphenicol Drugs; Drugs, MOA, Spectrum, Use
Drugs
o Chloramphenicol
o Florfenicol
MOA
* Bacteriostatic 50s
Spectrum
* All accept Staph. Pseudomonas & E. coli
* Not good for UTIs
Use
* CNS infection
* Some rickettsiae
* Mycoplasma
* Florfenicol for respiratory dz & foot rot in cows
Lincosamide; Drugs, MOA, Spectrum, Tox, Use
Drugs
Clindamycin
MOA
* Bacteriostatic 50s
Spectrum
* All Gram (+)
Tox
* Do not use in horses
Use
* Wounds
* Abscesses
* periodontal dz
* osteomyelitis
Antimetabolite; Drugs, MOA, Spectrum, Tox, Use
Drugs
o Sulfadiazine
o Trimethoprim-sulfa
o Ormetoprim-sulfadimethoxine
MOA
Sulfas – bacteriostatic
Sulfas + folate = bacteriocidal
Disrupt dihydrofolic acid becoming tetrahydrofolic acid ->
Bacteria cannot complete protein synthesis
Spectrum
Aerobic gram (+) & (-)
NOT Staph, E Coli, Proteus, Klebsiella, Pseudomonas
Toxicity
Hypersensitivity
Keratoconjunctivitis sicca (do tear test before & monitor)
Nephrotoxicity (rare)
Clinical Use
GI infections
CNS & joint coccidisosis
Bacterial enteritis
Bacteria pneumonia
Skin & soft tissue infections
Cystitis & prostatitis in dogs
Trying to get away from use due to tissue residue issues
Fluroquinolone; Drugs, MOA, Spectrum, Tox, Use
Drugs
o Enrofloxacin
o All the -oxacin
MOA
* Bacteriocidal
Spectrum
* Aerobic gram (+) & (-)
* Pradofloxacin gram (+) anaerobic (cats only)
Tox
* Irreversible cartilage damage in growing animals
* Retinopathy & irreversible blindness in cats
* Seizures at high doses
* Inhibit cytochrome P450 metabolism
* Pradofloxacin cause bone marrow suppression in dogs – use in cats ONLY
Use
* Penetrate prostate, respiratory tract and CNS
* Achieve high conc. in urine
* Enrofloxacin & danofloxacin used for bovine resp. dz
* NO ELDU in food animals
Beta Lactams; Drug Classes, MOA, Toxicity
Drug Classes
Penicillins
Cephalosporins
Vancomycin
MOA
Bactericidal
Bind bacterial transpeptidase enzymes ->
Inhibit cell wall synthesis
Toxicity
Very safe
Most commonly hypersensitivity
GI flora change
Cepahlosporins - renal toxicity
Vancomycin – hypersensitivity skin reaction & renal tox
Prohibited in food animals
Spectrum of Activity for Penicillins
Aerobic or Anaerobic
Gram (+) or (-)
Natural penicillin & aminopenicillins not effective on Pseudomonas & Staph
Spectrum of Activity for Cephalosporins
Aerobes
Cefoxitin & Cefotetan can also do anaerobes
Spectrum of Activity for Imipenem & Vancomycin
Both drugs usually reserved for humans
Imipenem
* Aerobic or Anaerobic
* Gram (+) or (-)
Vancomycin
* Aerobes
* Gram (+) or (-)
Uses of Cefadroxil/Cephalexin, Cefazolin, Cephapirin, Cefoxitin, Ceftiofur, Cefovecin, Cefpodoxime, Carbapenems
Cefadroxil & Cephalexin
* Most common ceph used
* Poor PO in horses
Cefazolin
* Dogs, cats, horses
* Penetrates bone
Cephapirin
* For cows
Cefoxitin
* Abdominal sx prophylaxis in SA
Ceftiofur
* UTIs in SA
* Resp. infections in horse, cow, pig
Cefovecin
* One time injectable for skin infections in SA
Cefpodoxime
* Skin infections in dogs
Carbapenems
* Not labeled for vet med
* Severe resistant infections in SA & foals
Rifampin; MOA, Spectrum, Tox, Use
MOA
* Bacteriocidal at high conc.
* Interferes w/ RNA synthesis
Spectrum
* Gram (+) aerobes
Tox
* Liver toxicity
Use
* Rhodococcus equi
Metronidazole; MOA, Spectrum, Tox, Use
MOA
* Bacteriocidal
* Undefined
Spectrum
* Anaerobic gram (+) & (-)
Tox
* Vestibular toxicity
* Maybe neurotoxicity in cats
Use
* Anaerobic infections
* Dogs & horses ONLY
Methanamine
Acidic environment -> formeldahyde ->
Urinary antiseptic ->
Used for uncontrolled UTIs
Polymyxin B; MOA, Use, Spectrum of Action, Adverse Effects
MOA
Disrupts wall of gram (-)
Use
Eye infections
Low controlled dose for endotoxin in equine colic
Spectrum of Action
Pseudomonas
Salmonella
E. coli
Adverse Effects
Dose dependent nephrotoxicity, neuromuscular blockade, CNS tox
Make sure pt is hydrated
Drugs to Consider for Treatment of MRSA
o Chloramphenicol
o Tetracycline
o Aminoglycosides (best because bacteriocidal)
o Rifampin
Drugs to Consider for Treatment of Pseudomonas
o Amikacin & gentamycin
o ceftazidime, cefotaxime
o ticarcillin, piperacillin, carbenicillin
o Fluroquinolone w/ beta-lactam
o Imipenem (last resource)
Drugs to Consider for Treatment of Nocardia, Mycoplasma, & Rickettsiaceae/Anaplamataceae
Nocardia
Sulfonamides
Mycoplasma
Tetracyclines
Macrolides
Amphenicols
Rickettsiaceae/ Anaplamataceae
Tetracyclines
amphenicols
Antibiotics that target both aerobe, anaerobe, gram (+) & (-)
o Ampicillin w/ enrofloxacin (NOT in young animals)
o Amoxicillin/clindamycin/metronidazole + fluoroquinolones (dogs; avoid in young)
o Amoxicillin/clavulanic (cat; limited effect against anaerobes)
o Imipenem (not an option for empirical and ambulatory treatment)
o Penicillin and gentamycin or amikacin (no for ambulatory treatment)
o Ticarcillin‐sulbactam
o Ceftazidime
o Cefotaxime
Which Drugs are Bacteriocidal and which are Bacteriostatic
Bacteriocidal Drugs
o Beta‐lactams
o Vancomycin
o Aminoglycosides
o Metronidazole
o Fluoroquinolones
o TMS
o Rifampin
Bacteriostatic Drugs
o Macrolides
o Tetracyclines
o Chloramphenicol
o Clindamycin
Which Drugs are Hydrophilic and which are Lipophilic
Hydrophilic Antibiotics
o Beta‐lactams
o Vancomycin
o Aminoglycosides
Lipophilic Antibacterials
o Macrolides
o Fluoroquinolones
o Tetracyclines
o Chloramphenicol
o Clindamycin
Time Dependent Antibiotics and how to enhance dosage regimen
o Beta‐lactams
o Macrolides
o Lincosamides
o Sulfonamides
o Antibiotics effective when plasma conc. Exceeds 4 x MIC for MOST of dosing interval
o Can enhance dosage regimen by reducing interval or using CRI
Concentration Dependent Antibiotics and how to enhance dosage regimen
o Aminoglycosides
o Fluoroquinolones
o Most effective when exceeds 8 x MIC for at least a short time
o Can enhance dosage regimen increase dose or reduce interval
Complicated Infections
o Prior antibiotic therapy was unsuccessful
o Immune compromise
o Infection likely involves more than 1 bacteria
o Environment where resistant bacteria may be present such as hospital
o Bacteria is likely resistant
Culture & Sensitivity Rules
o 90% that test susceptible will be
o 60% that test resistant will be susceptible
o Intermediate discourages standard dose because it may be resistant to standard
o C/S based on plasma/serum conc. not tissue
Microbiological/ Epidemiological Vs PK/PD Vs Clinical Breakpoints
o MIC decided by CLSI
Microbiological/Epidemiologcial
Population MIC /zone diameter
PK/PD
AUC/MIC
Cmax/MIC
%dose interval / MIC
Clinical
Outcome data from field trials at standard doses
Host Factors that Decrease Antibiotic Efficacy & Drugs Effected
Hypertonic environment
Affect beta lactams accept cefovecin & cefpodoxime
Acidic Environment
Macrolides
Fluoroquinolones
Aminoglycosides
Penicillin (inactivates at pH 6)
Purulent debris
Aminoglycosides
Vancomysin
Low O2
Aminoglycosdies
High O2
Metronidazole
Which Antibiotic is commonly used CRI
Beta Lactams
Length of Treatment for Acute Vs Chronic Bacterial Infections
Acute
5 days
7-10d
reassess in 2 days
Chronic
>21d
re-culture & assess 7 days prior to discontinuation
re-culture & assess 1-2wks after discontinuation
