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)
Tylosin
- resistance?
- what animals are they used in and which are they not?
- indications for the different animals
Frequent resistance Not used in horses - very toxic, use doxycyclines instead Pigs • Frequently used against swine dysentry, but the resistance is about 95% • Still potent for lawsonia intracellularis (proliferative enteropathy) Pigs+ruminant+poultry • Respiratory tract infections sensitive for it • Necrotic enteritis Small animals • ARD - antibiotic responsive diarhea • Mysterious disease • Large dogs, causing chronic diarrhea • We dont know what bacteria causes ARD
Tilmicosin
- what species to give to and which should avoid
- where does it function best in the body?
Ruminants + pigs Goat Ø! Most toxic macrolide (cardiotoxic) -> horses, goat humans • Dont give these drugs to these species Cattle - SC • Can die from any other administraiton Pigs + poultry PO Sometimes given to poultry -> 3 days acting by only one administration Excellent levels in lungs (60:1 to plasma) • Fastidous + mycoplasma very sensitive We dont know why it is cardiotoxic - lethal ide effect
Tylvalosin
- application
- species
- spectrum
Oral application, new drug Pigs, poultry Outstanding against • B.hyodysentriae • L.intracellularis • Mycoplasmae + fastidious
Tulathromycin Gamithromycin
- application
- distribution (which drug)
- spectrum
- where does it have the highest concentration?
Injectable application, new drugs (ru, su) Excellent distribution - Triamilide - Azlide Outstanding against - Fastidious organisms + mycoplasmae - Gram + coverage decreases 100X higher concentration in the lungs – good for respiratory tract infections
Tildipirosin
- application
- distribution
- spectrum
- concentration
Injectable application, new drugs (ru, su) Excellent distribution Outstanding against - Fastidious organisms - No mycoplasma 100X higher concentration in the lungs – Respiratory tract infectinos
Azithromycin Clarithromycin
- application
- pharmacokinetics?
- spectrum
- best concentration tissue
Oral application, new drugs (small animals, humans) Excellent absorption and distribution Outstanding against - Gr+ - Fastidious gr- - Borrelia - Mycoplasma - Campylobacter - R.equi Good lung concentrations (azithro clarithro)
Lung concentration and effective days in Tilmicosin
30-60x 3 days
Lung concentration and effective days in Tulathromycin
50-180x 6 days
Lung concentration and effective days in Gamithromycin
480x 10-15 days
