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)
draxxin darting
-not as successful than just injection
-more damage when darting (muscle damage)
Tilmicosin (micotil) adverse effects
-CARDIOVASCULAR TOXICITY! in people or other species
* Not an issue if used according to label SC dose in cattle and sheep
* BUT: Fatal when injected IV
- May be fatal if administered parenterally in
humans, goats, dogs, etc.
– Ca++ channel blockage / Ca++ depletion
– Tachycardia, but neg. inotrope (poor contractility)
– IV Ca++ may be protective
-high risk for clients and to have in the clinic, other practitioners till use it based on risk tolerance
Macrolides & Lincosamides:
Adverse Events GI
GI toxicity after oral administration:
* Vomit/diarrhea is common
– Especially oral erythromycin
- GI flora changes (clostridial overgrowth):
– Fatal colitis reported in horses after erythromycin use
– Caution when using lincosamides (clindamycin) in
rodents / lagomorphs** - But macrolides seem to be OK: oral tilmicosin approved for
use in meat rabbits!
Macrolides & Lincosamides:
Adverse Events
injection site reactions:
* Most injectable macrolides / lincosamides cause
some degree of injection site irritation
* Very irritating:
– Tilmicosin (must go SC)
– Erythromycin IM injections
Hyperthermia:
* Reported after erythromycin injections in foals
Macrolides & Lincosamides drug interactions
Drug interactions: generally minimal
* Some (but not all) macrolides are CYP inhibitors
– E.g. erythromycin
- Antagonism when used with phenicols** dont use with phenicols
– Both bind to similar parts of ribosomal 50S subunit - BUT: Macrolides don’t cause bone marrow toxicity
Macrolides:
Non-antimicrobial properties
Erythromycin: GI prokinetic (not recommended to use now)
* Motilin receptor agonist
Anti-inflammatory & immunomodulation:
* Macrolides inhibit the production of many pro-
inflammatory cytokines
– ↓ neutrophil migration
– Possible reason for clinical improvement when
treating respiratory disease?
- Tylosin: commonly used as GI anti-inflammatory
