macrolides and lincosamides Flashcards
macrolides name types
-the mycins and osin drugs
- Tylosin (TylanTM, generic tylosin)
-Feed premix, medicated water, or injectable
– Variety of label claims in swine:
* swine dysentery
* porcine proliferative enteropathy (L. intracellularis)
– Reduction in liver abscesses in feedlot cattle
– Aid in treatment of respiratory disease and
necrotic enteritis in broiler chickens
– NOTE: compounded forms often used for small
animal GI conditions
Respiratory Disease macrolides for vet use
- Tilmicosin (Micotil, generics)
– For SC use ONLY in cattle and sheep
– Oral Pulmotil premix and liquid for swine, feedlot cattle, & rabbits - Tulathromycin (Draxxin, generics): SC in cattle, IM in swine
- Tildipirosin (Zuprevo): SC in cattle
- Gamithromycin (Zactran): SC in cattle for BRD
-all long acting, better to inject less viscous.
Azithromycin (Zithromax, generics)
-human formulation (pediatrics) used in vet med
– Variety of oral tablet and suspension formulations (taste good)
– Commonly used extra-label in small animal practice
Lincosamides 2 used in vet med
- Lincomycin
– Available as oral premix, oral solution, injectable solution
– Licensed for a variety of indications in swine, poultry, dogs/cats - Clindamycin: Antirobe® / Clinacin oral capsules or solution
– ↑ antimicrobial activity compared to lincomycin
– Commonly used for skin, dental, bone, or anaerobic infections - Also used for protozoal diseases (neospora, toxoplasmosis)
– Resistance emerges rapidly
Pleuromutilins (tiamulin)
- tiamulin
- DenagardTM liquid solution or feed premix
– treatment & prevention of swine dysentery caused by spirochete Brachyspira
Streptogramins in vet med 1
-virginiamycin
* Stafac®, V-maxTM feed premix
– Feedlot cattle: Reduction in liver abscesses
– Swine: Treatment of swine dysentery
– Broiler chickens: Prevention of necrotic enteritis caused by
Clostridium perfringens
Macrolides & Lincosamides:
Mechanism of Action
- Binds to bacterial ribosomal 50S sub-unit
– Not same site as phenicols, but same effect
– Causes incorrect tRNA translation/ Disrupts protein synthesis - Activity may be pH-dependent
– Basic amine groups on some macrolides are ionized in acidic pH, with ↓ entry into bacterial cell
– But still clinically effective - due to high [drug]
Macrolides & Lincosamides drug type
- bacteriostatic
– But depends which macrolide/pathogen combo - time-dependent
– But data for azithromycin shows some concentration-dependent effects too
Macrolides & Lincosamides:
Spectrum of Activity
- Most Gram (+) species
- Some Gram (-) bacteria
– the usual BRD & SRD pathogens - Some anaerobes (esp. clindamycin)
- Helicobacter (esp. azithromycin for humans ulcers)
- Intracellular pathogens like Lawsonia and Rhodococcus
- spirochetes (Brachyspira),
-Chlamydia, - protozoa: Toxoplasma/Neospora
(clindamycin)
Macrolides & Lincosamides don’t work/ less effective
- Most gram (-) enterics
- Pseudomonas
- Enterococcus
- Resistance emerges rapidly in many bacterial species
– Cross-resistance is common, if resistant to one type its probably resistant to all macrolides
Mechanisms of Resistance
- Inability to bind to bacterial ribosome
– rRNA methylation (erm gene)
– Mutations to ribosomal binding sites (uncommon) - Efflux pumps / ↓ cell entry
- Enzymatic inactivation of drugs
Plasmid-mediated resistance genes:
* Resistance develops and transfers quickly
– Cross-resistance to multiple macrolides / lincosamides is common, difference in # member ring.
Macrolides & Lincosamides:
Pharmacokinetics absorption
Absorption:
* Lots of variation in oral F between macrolides
– Azithromycin and clindamycin well absorbed (both small animal)
– Some macrolides/lincosamides require special coating (e.g. erythromycin)
– Food may alter absorption
Macrolides & Lincosamides:
Pharmacokinetics
Distribution
- Generally highly lipophilic drugs*** massive Vd
– Low plasma concentrations, not good for speticemia or when you need antimicrobial in blood
– But very high Vd - Specific tissues:
– Very high “lung” concentrations
– CSF: lincomycin & clindamycin have ↑ distribution, could be good ex neospora in the brain - Drug accumulates in leukocytes**
– Effective against (some) intracellular pathogens
– Delivered to site of infection
Macrolides & Lincosamides:
Pharmacokinetics elimination
-Varies depending on the drug
* Typically some hepatic metabolism
* Excretion via the bile or urine
-Some macrolides have very long T1/2 elim:**
* Tilmicosin, tulathromycin, gamithromycin, tildopirosin
* Once distributed into tissue (e.g., lung), drug is slowly
eliminated from the body
– Re-distribution back to plasma before elimination
- Long withdrawal periods – but not prohibitive (28 – 49 d)
