Antimicrobials and lung infection Flashcards
How do tetracyclines enter bacteria?
- diffuse across outer cell membrane
- via active carrier mediated process through inner cell membrane (can be anaerobia, abscesses)
What is the action of tetracyclines?
- bacteriostatic, broad spectrum
- bind to 30s subunit and block mRNA, prevents tRNA from being added to peptide chain and preventing protein synthesis
Describe the pharmacokinetics of tetracyclines
- given IM or IV a oral is slow
- oral absorption is slowed by food (chelate metal ions in stomach)
- enter most tissues and body fluids
- generally don’t cross the BBB
- cross placenta and secreted into milk
What are the adverse affects of tetracyclines on young animals?
Affects teeth and bone growth in foetus and neonate
How are chlor-, oxy- and tetracycline metabolised and excreted?
- metabolism is minimal
- excreted unchanged in urine and bile
- undergo some enterohepatic recirculation (increases half like to 6-10hrs)
- urinary excretion via glomerular filtration (impaired renal function will increase the half life)
- long acting formulations persist at injection site
What are the properties of mino and doxycycline?
- semisynthetic derivatives of tetracycline
- more lipid soluble
- better brain, ocular tissue and bronchial secretion penetration
- good absorption after oral administration
How is minocycline metabolised and excreted?
Some metabolism, excreted in bile and faeces
How is doxycycline metabolised and excreted?
- no renal excretion
Describe the toxicity of tetracyclines
- well tolerated and can be used long ter,
- broad spectrum suppression of intestinal flora can lead to superinfection with resistant pathogens
- idiosyncratic liver damage in some animals is there is renal impairment
- renal tubular damage
- can be irritant
- occasional anaphylaxis when given IV
- deposited at sites of ossification in bone and teeth
- photosensitivity
What is the clinical use of tetracyclines?
- broad spectrum
- useful in mixed bacterial infections (esp. in lungs)
- doxy and monocycline have anti-inflammatory properties
What are indications for use of tetracyclines?
- Cattle - resp infections in calves, bovine pneumonia, anaplasmosis, udder infection
- Sheep - Q fever, enzootic abortion, foot rot, pasteurella haemolitica pneumonia
- Pigs - prevent and treat atrophic rhinitis and lower resp disease, eradicate leptospira
- Cats and dogs - UTI, otitis externa, chlamydia, upper resp tract infection
- Poultry - prevention adn treatment of enteric and resp infection (largely in feed)
Give examples of macrolide drugs
Erythtomycin Tilmicosin Tylosin Spiramycin Tulathromycin *Mainly gram +ve, some -ve, bacteriostatic
What is the mechanism of action of the macrolides?
Act on 50s subunit by binding to the P site. This inhibits the movement of tRNA from the A site to the P site. No more AA can be added to the chain so protein synthesis is inhibited.
What are the general properties of macrolides?
- High intracellular conc
- Broad distribution in tissues
- Don’t cross BBB
- Enter and are concentrated in phagocytes (targeted to site of infection)
- Decrease mucous production (decrease bacterial load in the lungs)
- May enhance host immunomodulatory response
- Anti-inflammatory actions
What are the pharmacokinetics of erythromycin?
- Weak base (ion trapped in acidic fluids)
- Available orally as base, sterate, phosphate salt or thiocyanate
- High lipid solubility
- Well distributed in tissues
- Well abosrbed orally, unstable in gastric acid (coated)
- Food lowers gastric absorption
- Partly inactivated by hepatic metabolism
- Urinary retention is low (<5%)
Describe the toxicity of erythromycin
- One of safest antimicrobial drugs
- Can be irritating (oral, IV, IM - severe pain)
- GI disturbances are common (stimulates SM)
- Serious in horses because of method of excretion
- Good sub for beta lactam
What are the properties of tylosin?
Better activity than erythromycin against mycoplasmas
What are the properties of spiramycin?
- Greatly concentrate in tissues
- penetrates well into milk, lacrimal fluids, resp secretions
- V long half life, persistent drug residues
- only licensed for periodontal problems
What are the properties of tilmicosin?
- Concentrates in tissues
- Can cause rapid depletion of Ca, heart problems, can be fatal in some species (horses, goats, man)
What are the clinical uses of common macrolides?
- Alternative to penicillin in penicillin sensitive animals
- Erythromycin - Campylobacter jejuni, mycoplasma
- Resp disease in pigs, cattle, poultry
- Spiramicin for peridontal infection in dogs and cats
- Dysentry, penumonia in pigs, calves, poultry
Name advanced generation macrolides and their properties
Azithromycin, clarithromycin, roxithromycin, tulathromycin
- HIgh bioavailability following oral administration
- Broader spectrum of activity
- Longer half lives
- Higher tissue concentrations allowing daily dosage
What are the properties of tulathromycin?
- DRAXXIN
- Bovine and porcine resp disease
- SC (cattle), IM (pigs)
- high distribution and slow elimination
- Good gram -ve spectrum
- High conc in lung (neutrophils and alveolar macrophages)
Give examples of fluoroquinolones
Enrofloxacin (Baytril) Danofloxacin Marbofloxacin Difloxacin Orbifloxacin Ibafloxacin
What is the mechanism of action of the fluoroquinolones?
- Bactericidal
- Enter bacteria through porins
- Binds to topoisomerase IV and topoisomerase II (coils up DNA) and inhibits DNA replication
What is the spectrum of activity of the fluoroquinolones?
- Gram +ve and -ve (aerobes)
- Intracellular bactera e.g. chlamydia, legionella, brucella
- Mycoplasma
- Inactive against obligate anaerobes
Describe the pharmacokinetics of the fluoroquinolones
- High oral availability and rapid absorption (80-100%)
- Oral availability lower in ruminants, give IV/SC
- Low protein binding
- Enter phagocytes
- High conc in tissues and fluids
- Partial liver metabolism
- Parent drugs and metabolites excreted in urine and bile
- High urinary conc of parent drug
- Enterohepatic recycling
- Baytril metabolised to active metabolites which have antimicrobial activity
What are the clinical uses of the fluoroquinolones?
- Treatment of serious gram -ve infection
- Use as first choice for UTI (Pseudomonas aeruginosa); prostate infection; skin, soft tissue, wound infection; serious resp infection; osteomyelitis by gram -ve aerobes
What are the clinical uses of fluoroquinolones in SA?
- Rabbits, mice, rats, exotics - skin and visceral infection
- Don’t cause GI disturbances
Describe the toxicity adn interactions of the fluoroquinolones
- Relatively safe
- Erode weight bearing cartilage
- Clearnace of other drugs metabolised in the liver may be reduced
- Some CNS problems associated with GABA (exacerbate epilepsy)
- Ocular problems in cars (enrofloxacin) - high doses and long term treatment
What are the properties of enrofloxacin?
- Broad spectrum
- Rapidly kills bactera
- High bioavailability and absorption
- Tissue conc exceed plasma conc
- Crosses placenta, aqueous humour and CSF
- Low plasma protein binding
- Predominantly renal excretion
What are the properties of marbofloxacin?
- V good for Enterobacteriaciae and Pasteurella
- Adequate plasma levels maintained for 24hr after SC injection
- Parent drug excreted in urine and faeces
- Well tolerated in dogs and cats
- Resp infection in cattle and pigs
