Macrolides Flashcards
Macrolides Spectrum – especially good against?
Ricketssia Chlamydia Mycoplasma Good distribution in the respiratory tract - Pasteruella - Mannheimia
Mechanism of action: macrolides
50s – inhibition of protein synthesis
Mode of action: macrolides
Bacteriostatic – higher concentration bactericidal (resp)
Mechanisms of resistance of macrolides
Modifying the binding site on 50s ribosome subunit Cross resistance decreased permeability degrading enzymes
Macrolides: active substances Veterinary – older (natural)
Erythromyocin Tylosin Spiarmycin Tilicosin – semisynthetic
Macrolides: active substances Veterinary – newer (semisynthetic)
Tylvalosin Tildipirosin Tulathromycin – triamilide (3 nitrogen) Gamithromycin – azalide
Macrolides: active substances Human medicine, companion animals (semisynthetic)
Human medicine, companion animals (semisynthetic) Azithromycin – azalide (2 nitrogen) Clarithromycin Roxithromycin
Macrolides:Antimicrobial spectrum
Gram positive Few gram negative (anaerobic) • Fastidious (pasturella, mannheimia) • Campylobacter spp! - enteritis in dogs, cats and humans (raw chicken meat is the main source) o Azithro o Clarithro o Erythro • Bracyspira hyodysentriae o Tylosin? - resisitance is 99% - not used anymore o Tylvalosin excellent choice for swine dysentry • Lawsonia intracellularis: proliferative enteropathy: macrolides is the first choice o Tylosin and Tylvalosin : swine o Doxacycline: horses • Bordetella spp o Kennel cough dogs o Atrophic thinitis in swine • Mycoplasma, chlamydophila spp • Borrelia spp • Rhodococcus equi o Azithro o Clarithro o Erythro Good against anaerobic infections • Foot rot • Oral cavity infections • Bite wounds
Pharmacokinetics macrolides: Absorption
Oral absorption is variable, usually good - Exception erythromyocin: acid sensitive - Tylosin phosphate (15%) tartarate (30%) Painful to inject - Not recommended for small animals Ø IV – not soluable in water IM and SC are good – but irritates
Pharmacokinetics macrolides Distribution
Good (bones, placenta, prostate) Cannot penetrate BBB Respiratory tract! Intracellular - Lawsonian + rhodococcus equi
Pharmacokinetics macrolides
Metabolism
Extensive in the liver 90% of the drug is excreted with the bile (excretion) CYP450 anxyme inhibitor -> interactions • Ionophor antibiotics (coccidosis) • Tiamuli - potent enzyme inhibitor
Pharmacokinetics macrolides: Toxicity
In active and inactive form: the risk of serious dysbacteriosis These drugs are very toxic to horses, excpt foals Rodents + rabbits are sensitive
Side effect macrolides
GI irritation • Vomiting diarrhea Dysbacteriosis (horse, herbivore rodents) • Fatal enterocolitis • Except foal, so can be treatetd for R.equi Tissue irritation Erythromyocin - especially motilin agonist • Enhances gastric emptying • Important in delayed gastric empyin in dogs and cats Main side effects • Dysbacteriosis o Foals can ahve it, but it is excreted with the faeces, mother sometimes eat the faeces so foal should be seperated from her • Tissue irritation o Not used in small animal meicine o Animal welfare
Erythromycin - spectrum in the different animals - special species for this drug - humans?
Rare usage Small animals
Campylobacteriosis Food producing animals
Respiatory tract infections -
- including mycoplasmiosis
Diamond skin disease
Horses
- R.equi + rifampicin (combined with) - drug against tuberculosis in human
- One of the best drugs
- 6 week treatment, orally to the foal
Humans
- Penicillin allergy
Spiramycin
- highest concentration in which tissue?
- use
- animals?
Higher tissue levels - reaches the highest concentration in inflamed gingiva Frequent usage in oral cavity infecitons (small animals) - stomatitis Large animals: infrequent (mastitis)
