Macrolides Flashcards
What other drugs are “Mycin” and should not be confused with macrolides?
aminoglycosides and trade name of a tetracycline
What macrolide is licensed for food animal general vet use? include formulations and treatment
Tylosin (premix or medicated water)
- swine dysentry and porcine proliferative enteropathy (L. intracellularis)
- reduction in liver abscesses in feedlot cattle
- aid in resp diseases and necrotic enteritis in broilers
What are the “respiratory” vet macrolides and their formulations?
Tilmicosin (micotil)
- SC ONLY (Cattle/sheep)
- oral Pulmotil premix and liquid for swine, feedlot cattle and rabbits
Tulathromycin (Draxxin)
- SC in cattle
- IM in swine
Gamithromycin (Zactran)
- SC in cattle
Tuldiprosin (Zuprevo)
- SC in cattle
Are these resp/BRD macrolides any different?
all are similar
all about marketing
What human drug is often used extra label in small animals?
Azithromycin
- oral tablets and suspensions
What 2 macrolides are licensed but not common
tylvalosin (Aivlosin)
- oral premix or water for pigs
- PPE (by L.intracellularis in pigs)
Erythromycin (gallimycin)
- feed premix licensed for poultry (non-specific)
- formerly in IMM tubes
- still recommended as therapy for some things in horses and small animals
Name 3 “like macrolides” lincosamides (include formulations and use)
Lincomycin
- oral premix, oral solution, injectable
- licensed for swine, poultry, dogs/cats
Clindamycin (antirobe)
- increase activity compared to lincomycin
- common for skin, dental. bone, anaerobic infections
- resistance emerges quickly
Pirlimycin (Pirsue)
- IMM
What drug is a “like macrolide” pleuromutilins?
Tiamulin (Denagard)
- liquid solution or premix
- Tx and prevention of swine dysentry association with brachyspira hyodysenteriae
What drug is a “like macrolide” streoptogramins?
Virginiamycin (Stafac)
- feed premix
- “Virax” for cattle
- swine dysentary
- broilers: prevention of necrotic enteritis (C. perfringens)
What is the MOA of macrolides and lincosamides?
binds to 50s subunit
- different spot tha phenicols
- incorrect tRNA translation/protein synthesis
Activity pH dependent
- basic amine group decrease bacterial uptake but still clinically effective
What is the PK-PD relationship of macrolides and lincosamides?
bacteriostatic
- depends on which macrolide pathogen combo
time dependent
- azithromycin (some concentration dep effect)
What is the spectrum of activity of macrolides and lincosamide?
effective
- most gram +, some gram - (BRD and SRD pathogens), some anaerobes (clindamycin esp), helicobacter (azithromycin), some mycoplasma, intracellular pathogens (lawsonia, rhodococcus), spirochetes (brachyspira), chlymydia, taxoplasma (clindamycin)
Less/not effective
- gram - enterics, pseudomonas, enterococcus,
What is the mechanism of resistance?
inability to bind to bacterial ribosome - RNA methylation (erm gene) - mutations to binding site effluc pumps enzymatic inactivaion of drugs plasma mediated resistance genes (cross resistance) - happens quickly
Which BRD bacteria shows resistance to which macrolides?
mannheimia hemolytica
- tulathromycin, ggamithromycin, tildipirosin, tilmicosin
- beginning of resistance
What is the PK of absorption for macrolides and lincosamide?
lots of variation in F between drugs
- special coatings (less irritations)
- food may alter
What is the PK of Distribution for macrolides and lincosamide?
high lipophilic drug
low plasma but high Vd
dont use for septicemia (use for resp)
special tissues
- high lung concentrations
CSF: lincomycin and clindamycin
concentrate in leukocyte
- intracellular pathogens
- delivered to site of infection
What is the PK of elimination of macrolides and licosamide?
some hepatic metabolism
excretion in bile or urine
long half life (tilmicosin, tullathromycin, gamithromycin, tildopirosin)
once distributed to lung it is slowly eliminated, redistributed back to plasma then eliminated
Do macrolides have long withdrawal periods/ are they prohibited in food animal?
not prohibited
- not in edible tissues
What are the adverse events of tilmicosin?
cardiovascular toxicity
- SC only in sheep and cattle
FATAL on IV (epinephrine worsens toxicity)
FATAL parenterally in humans, goats, dogs
- CA channel blockage / Ca depletion
tachycardia but neg inotrope
IV CA may be protective
What other AE are seen with macrolides and licosamides?
GI
- oral (diarrhea,vomiting)
- irritation/less motility
GI flora
- fatal colitis in horses (erythromycin)
- caution with rodents
injection irritation
- tilmicosin especially (must go SC)
- erythromycin IM very irritating
hyperthermia
- erythromycin with foals
What drug interactions should be considered?
some CYP inhibitors (erythromycin) - antagonism when used with phenicols - both bind to 50s - macrolides dont cause bone marrow toxicity
Which antibiotic causes antagonism of macrolides
Phenicols
What macrolide has prokinetic capabilities? mechanism?
erythromycin
- motilin recpetor agonist or cholinergic neurons
How do macrolides have anti-inflammatory and immunomodulation capabilites? which drug is commonly used for this property?
macrolides inhibit production of proinflammatory cytokines
- decrease neutrophil migration
Tylosin: GI antiinflammatory
