wk5 Flashcards
Classifications
of Antibioitics
Spectrum of activity
Type of microorganism it fights
Bacteria, viruses, fungi, protozoa
Goals of Antimicrobial Therapy
Kill or disable pathogens without killing the host
Considerations for Antimicrobial Therapy
Pathogen must be SUSCEPTIBLE to the drug
Drug must REACH SITE OF INFECTION in high enough [ ] to kill or inhibit the pathogen
Animal must TOLERATE high [ ] of the drug
Other factors
Client compliance
Cost
MIC
Minimum inhibitory concentration
Lowest [ ] of drug which will inhibit growth
Antimicrobial must reach infection site in high enough [ ] to exceed the MIC
SENSITIVE
MIC is low enough to not produce significant side effects in the patient
RESISTANT
MIC is so high that there are significant side effects
Antibiotic Resistance
Genetic changes Mutations of chromosomes R plasmids Additional piece of DNA responsible for antibiotic resistance “R” = “resistance” Transferred to other bacteria
Plasmid
A circle of double-stranded DNA that is separate from the chromosomes, and which is found in bacteria and protozoa. A plasmid contains genes normally not essential for cell growth or survival.
How can resistance be prevented?
Administer the appropriate dose at correct intervals, for the appropriate time, & in the appropriate manner
Educate clients importance of following the instructions, including giving for the entire prescribed time
How does Resistance happen?
Inappropriate use of antimicrobials
Residue
Presence of a drug or chemical in animal tissues or food products
Adm of drug or chemical to animal
Contamination of food
Most antimicrobial residues are not degraded by cooking or pasteurization
Exposure can cause 2 effects in humans
Hypersensitivity
Killing off of susceptible (beneficial) GIT bacteria leaving resistant (pathogenic) bacteria to proliferate
What are withdrawal times?
Use of drugs in animals intended for food must be withdrawn a specific number of days
Allows enough time for drug to be excreted
sites that antimicrobials may effect to kill or inhibit bacteria or fungi
Cell wall
Cell membrane
Inhibit protein synthesis
Interfere with critical enzymes or bind with intermediate compounds the bacteria need
Impair production of bacterial nucleic acids (RNA and DNA)
How drugs work on Cell wall
drugs work while cell wall is forming during bacterial division; bacteria are lysed as they draw in water thru osmosis
Penicillin, cephalosporins
Cell membrane
makes organism leaky
Antimicrobials can enter or cytoplasmic components can leave
Drugs work on dividing or static bacteria
Antifungals
Inhibit protein synthesis
some drugs enter the bacterium, combine with the ribosomes and disrupt normal protein production
Cell stops dividing or dies
Lincosamides, macrolides, tetracyclines, aminoglycosides
Interfere with critical enzymes or bind with intermediate compounds the bacteria need
bacterium is unable to function
Sulfonamide antibiotics
Impair production of bacterial nucleic acids (RNA and DNA):
bacterium or fungus is unable to divide; may be unable to produce critical proteins
May also attack mammalian DNA!*
Inability to reproduce, fetal abnormalities, or death
Some antifungals can cause fetal abnormalities
Quinolones work at sites on the pathogen’s nucleic acid that are not found in mammalian cells
Penicillins
Only effective against actively dividing bacteria*
Mostly gram pos and some neg
Don’t use with bacteriostatic drug!**
Penicillin is effective against
Most gram (+) and some gram (-) bacteria Bactericidal
Bactericidal
Block enzymes essential for cell wall assembly
Different enzymes are involved 🡪 different penicillins affect different enzymes
Penicillin Pharmacokinetics
Well-absorbed from GIT and injection sites (except pen-G = inj only) Hydrophilic .: does not reach therapeutic levels in the eye, brain or prostate Excreted unchanged by kidneys – also actively transported into urine .: can attain much higher [ ] in urine than blood Many gram (-) bacteria are resistant to penicillins EXCEPT at the high [ ] in the urinary tract
Penicillin Cross-resistance
If bacteria become resistant to one type of penicillin, it is also resistant to most other penicillins
β-lactamase
Some bacteria, esp Staphylococci, acquire resistance by producing an enzyme, β-lactamase**** that attacks a part of the penicillin molecule: the β-lactam ring
A penicillin can sometimes be combined with another compound to produce a modified penicillin that is resistant to the β-lactamase enzyme
Clavulanic acid plus amoxicillin = Clavamox® (veterinary) or Augmentin® (human)
Packaged individually in foil 🡪 clavulanate absorbs moisture from air
Penicillin Precautions
Hypersensitivity reactions are most common adverse reaction*
If allergic to one, is likely to be allergic to others
Cross-reactivity**
May destroy beneficial GIT bacteria allowing pathogenic bacteria to proliferate
Superinfection**
Can result in severe diarrhea and death in some species: guinea pigs, ferrets, hamsters, rabbits, snakes, birds, turtles and chinchillas
Observe withdrawal times in food animals
Penicillins are readily available to food animal producers
Cephalosporins
β-lactam antibiotic
Disrupts cell wall synthesis
Classified by generations according to when they were first developed
Cephalosporin 1st Generation
= gram (+) bacteria (Strep and Staph) Cefadroxil (Cefa-Tabs® and Cefa-Drops®) Cephalothin (Keflin®) Cephalexin (Keflex®) Cefazolin
Cephalosporin 2nd Generation
gram (-) bacteria
Cephalosporin 3rd Generation
= gram (+) & (-) bacteria (most are inj) Cefpodoxime (Simplicef®) - oral Cefovecin sodium (Convenia®) - SQ
Cephalosporins
MOA
β-lactam antibiotics; bactericidal similar to penicillins affecting cell walls
Do not cross BBB
Does cross placenta and can pass into milk
[ ] in urine is high like penicillins
Cephalosporin Precautions
Hypersensitivity, but much lower than with penicillins
Superinfection with oral administration of 1st –generation drugs
May cause anorexia, V/D
Don’t use with bacteriostatic drugs
Cefpodoxime proxetil
Simplicef Prodrug Active metabolite is cefpodoxime Oral adm Sid Tx Staph, Strep, Proteus, E. coli, Pasteurella
Cefovecin sodium
Convenia Reconstitute Refrigerate SQ adm Duration 7-14 days Tx Staph, Strep, Pasteurella Skin infections shelf life 56 days
VTNE Question of the Day:
Why are most antibiotics contraindicated in rabbits and hamsters? A - Highly sensitive to renal toxicityB - Disrupts gram positive gut floraC - Their little hearts just can’t take itD - Highly permeable blood-brain barrier
B - Disrupts gram positive gut flora
Aminoglycosides
Used to Tx serious bacterial infections
Gentamicin, amikacin, neomycin, streptomycin, kanamycin, tobramycin, netilmicin
Cross-resistance is not as common as with penicillins
Aminoglycosides MOA
bactericidal via action on ribosomal protein production; actively transported thru cell membrane into bacterium by an oxygen-dependent mechanism .: highly-effective against aerobic bacteria but not anaerobes
Cell wall-inhibiting antibiotics like penicillins enhance the ability of aminoglycosides to enter and kill bacteria*
Aminoglycosides Pharmacokinetics
usually parenteral due to limited GIT absorption
Hydrophilic .: do not cross BBB or into eye
nephro- and ototoxicity***** with large or frequent doses. Cats
Can cross placenta and cause harm to fetus
Eliminated in kidneys – most of drug is excreted in urine
Quinolones / Fluoroquinolones
floxacin suffix
Bactericidal
1st one in late 1980s = Enrofloxacin (Baytril®)
Since then: marbofloxacin (Zeniquin®), orbifloxacin (Orbax®), difloxacin (Dicural®)
All approved for dogs and cats except difloxacin (dogs only)
Human drug = Ciprofloxacin
Quinolones / Fluoroquinolones MOA
interferes with DNA gyrase, preventing bacterial DNA supercoiling
Effective against common gram (-) and gram (+) bacteria in skin, resp, and urinary infections
Activity against Pseudomonas is superior to aminoglycosides
Not recommended for streptococcal infections
Ineffective against anaerobes
Quinolones / Fluoroquinolones Pharmacokinetics
Tx prostate infections**
Up to ¼ of enrofloxacin is metabolized to ciprofloxacin***
Quinolones / Fluoroquinolones Precautions
Absorption is greatly reduced with antacids or sucralfate
May lower seizure threshold
Exceeding label dose in cats may lead to changes in retina and blindness!*
Should be reserved for more severe infections to minimize development of resistance!**
Tetracyclines
Bacteriostatic 🡪 need functional immune system!
Most commonly used drugs for rickettsial dz (Rocky Mt spotted fever, salmon poisoning in dogs, hemobartonella), Mycoplasma pneumonia, chlamydial infections (ocular in cats), psittacosis in birds, and borreliosis (Lyme dz).
Sometimes helps tear staining in dogs
Tetracyclines Older drugs
hydrophilic
Tetracycline and oxytetracycline
Tetracyclines Newer drugs
more lipophilic
Doxycycline and minocycline 🡪 longer half-life, broader spectrum of action, better penetration of tissues
Salmon Poisoning
DZ is caused by a rickettsial organism, Neorickettsia helminthoeca, which infects the parasite, Nanophyetus salmincola, a fluke
Salmon, trout, Pacific giant salamander
Tetracyclines MOA
bind to ribosomes and disrupt protein synthesis 🡪 inhibit bacterial function
Tetracyclines Pharmacokinetics
Doxy- & minocycline are more lipophilic .: orally absorbed much better
Tetracycline & oxytetracycline are readily CHELATED in the gut by mineral divalent cations
Doxycycline’s absorption is only reduced by 20%
Oxytetracyline = most commonly used INJECTABLE tetracycline
Distributed to most tissues
High [ ] in saliva and bronchial secretions
Hydrophilic 🡪 no significant [ ] in CNS; can’t penetrate mammalian cells to reach intracellular pathogens
Lipophilic 🡪 cross BBB, can enter eye and prostate
Well-absorbed IM
Excretion
Tetracycline/oxytetracycline 🡪 primarily renal .: decrease dose with renal DZ; excreted by liver into intestines – some then chelated, some reabsorbed ENTEROHEPATIC CIRCULATION***
Doxycycline mostly excreted into the intestine
divalent cations
Ca++ = dairy products*****
Mg++ = oral antacids; kaolin, pectin (Kaopectate); bismuth subsalicylate (Pepto-Bismol)
Fe++ = iron supplements
Cu++
Tetracyclines Precautions
Chelation with Ca++ 🡪 discolors adult teeth* (mottled yellow) if tetracycline is given during their development; at high doses may slow bone development
Superinfections in GIT following PO adm
Cattle 🡪 Rumin stasis
Dogs 🡪 GIT mucosal irritation 🡪 V/D, anorexia
Cats 🡪 fever, depression, abd pain
Horses 🡪 especially sensitive to rapid IV injection of doxycycline causing arrhythmias, collapse and death (chelation of Ca++?)
Bacteriostatic 🡪 interfere with penicillins and cephalosporins***
Expired tetracycline/oxytetracycline decompose to a nephrotoxic compound 🡪 Fanconi’s syndrome
VTNE Question of the Day:
Which drug family is associated with tooth enamel problems? A - AminoglycosidesB - QuinolonesC - MacrolidesD - TetracyclinesE - Cephalosporins
D - Tetracyclines
VTNE Question of the Day:
A parrot is presented with psittacosis, to be treated with IM oxytetracycline at 100mg/kg, every 2-3 days for 30 days. If the parrot weighs 500 grams and the concentration of the drug is 100mg/ml, how many milliliters are necessary for a single dose?A - 0.05 milliliterB - 5 millilitersC - 0.5 milliliterD - 1.5 millilitersE - 90 milliliters
C - 0.5 milliliter
Sulfonamides
First antimicrobials to have widespread use
.: many strains of bacteria are resistant
May be combined with other drugs to make them bactericidal vs –static & increase efficacy
Common sulfonamides used in vet med
Sulfadimethoxine (Albon®)*****
VTNE Question of the Day:
Which drug family is most associated with nephrotoxicity (kidney damage) as an adverse effect? A - Sulfonamides B - AminoglycosidesC - PenicillinsD - LincosamidesE - Cephalosporins
B - Aminoglycosides
Parasitism
When one species lives at the expense of another
Ectoparasite
Parasites on the outside of the body
fleas & ticks “infested”
Endoparasite
Parasites on the inside of the body
heartworms “infected”
Definitive host
contains adult stage (sexually mature)
Intermediate host
contains immature stage
Some parasites have >1 intermediate host
Zoonotic potential
Toxoplasma gondii
Ancylostoma caninum = hookworm
Toxocara canis visceral larval migrans (VLM)
VLM
visceral larval migrans
Fenbendazole
Panacur
GI Tract parasites (Toxocara Canis)
Antinematodal
Benzimidazole
Pyrantel pamoate
Nemex®, Strongid-T®
Antinematodal
Tetrahydropyrimidines
Clinical uses: ascarids, strongyli, pinworms, hookworms
Imidazothiazoles
Febantel
Dogs and cats: hooks, rounds, whips
Avermectins
Antinematodal
Dosage forms:
Ivermectin (Heartgard®, Ivomec®)**
Moxidectin (ProHeart®, Quest Equine Oral Gel®)
Doramectin
Clinical uses: lots of bugs, esp in large animals read pg 265-267
Other agents:
Drontal Plus® (praziquantel/pyrantel pamoate/febantel) tapes, hooks, rounds and whips in dogs
Anticestodal
tapeworms
Bunamidine (Scoloban®)
Epsiprantel (Cestex®)
Praziquantel (Droncit®)*****
Antitrematodal
liver and lung flukes
Praziquantel (Droncit®)*****
Tapes and lung flukes in dogs and cats
Antiprotozoal
Drugs for Txing coccidia & other protozoans
Sulfadimethoxine (Albon®) dogs, cats, chickens and turkeys
Many other drugs for livestock and poultry
Drugs for Txing Giardia
Metronidazole (Flagyl®) dogs and cats
Drugs for preventing Giardia
Heartworm Disease
Dogs and wild canids – also cats & ferrets
Dirofilaria immitis
vs Dipetalonema reconditum
Adulticides
Melarsomine dihydrochloride (Immiticide®)**
Arsenic compound deep IM inj in lumbar region
Microfilaricides
Given 3-4 weeks after adulticide
Ivermectin and milbemycin extralabel use!
Heartworm Disease Preventatives
Ivermectin (Heartgard® products)
Milbemycin oxime (Interceptor®, Sentinel®)
Moxidectin (ProHeart®)
Selamectin (Revolution®)
-cidal
Kills
Cidal drugs kill outright
–static
prevents replication
Static drugs depend more on a functioning immune system
