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%)
