Tetracyclines and Sulfonamides Flashcards
What type of bacteria do we mainly use tetracyclines against?
Atypical bacteria
What is the mechanism of action of tetracyclines?
Inhibit protein synthesis (bacteriostatic)
What is the spectrum of activity of tetracyclines?
- originally broad spectrum but much resistance acquired in small animals
- still very effective however against livestock
- therefore widely used in all species against atypical bacteria
- broad spectrum use in livestock against GP ae., GN ae., anaerobes
What is oral absorption like for tetracyclines?
- generally very low
- divalent cations in food like calcium in milk and cheese can markedly inhibit oral absorption (doxycycline is the least susceptible to this)
What is distribution of tetracycline like in the body?
- most are distributed well in the ECF except CNS
- distribution into cell depends on lipid solubility, doxycycline is most lipid soluble therefore enters host cells well including prostate and CNS
Why do tetracyclines have a food animal residue concern?
They bind to multivalent cations such as calcium and become incorporated into growing bone and teeth
How are most tetracyclines eliminated?
Glomerular filtration into the urine
How else can tetracyclines be eliminated besides the urine?
Lipid soluble tetracyclines like doxycycline can be excreted into the lumen of the GIT and be eliminated into the feces.
What is the main acquired mechanism of resistance in tetracyclines?
- efflux pump: removes drug from bacterial cell
What are the main adverse effects of tetracyclines? (4)
- incorporation into growing bones and teeth
- nephrotoxicity: administration to dehydrated patients may be fatal
- tissue irritation
- esophageal lesions from doxycycline in cats: broken or undissolved tablets can get lodges causing lesions or stricture
Why are sulfonamides largely ineffective when used alone in small animals?
Resistance is widespread
What is meant by potentiated sulfonamides?
- since resistance is widespread, effectiveness of sulfonamides is restored when combined with trimethoprim
- TMS (trimethoprim sulfonamide) combinations are widely used in large animals
- TMS combinations are synergistic and bactericidal
What is the mechanism of action of sulfonamides?
- inhibition of folic acid synthesis
- folic acid is needed for DNA, RNA, protein synthesis
- note that bacteria use PABA to synthesize folic acid and pus contains huge amounts of PABA therefore sulfonamides are ineffective in the presence of pus
What is the spectrum of activity for sulfonamides?
- in small animals it is used for atypical bacteria and sporadic bacterial cystitis
- for large animals it is mainly used for atypical bacteria but also used against GP ae., GN ae., anaerobes
What is absorption and distribution of sulfonamides like?
- good oral absorption
- distributes well to all tissues
- tissue debris and pus contain PABA which outcompetes sulfonamides so ineffective in these cases
How are sulfonamides eliminated from the body?
- renal excretion and hepatic metabolism
- metabolites can accumulate in renal tubules causing renal damage; severe in dehydrated patients
What are the main adverse effects of sulfonamides? (3)
- effects are usually due to sulfonamide not TM
- more allergenic than most drugs
- Keratoconjunctivitis (KCS) in dogs, it destroys the lacrimal tissue in a does-dependent manner = dry eye
- nephrotoxicity: dangerous in dehydrated patients
