Tetracyclines
What infections are commonly treated with tetracyclines?
(Men Can't See How Penis Tips Bruise) Mycoplasma pneumoniae Chlamydiae Spirochete Helicobacter pylori causing gastric and duodenal ulcers Plague Tularemia Brucellosis
What are three ways a resistance gene encodes a protein for ribosomal protection?
1) Block tetracyclines from binding to ribosome 2) bind to ribosome and distort structure to still allow tRNA binding while tetracycline is bound 3) Bind to ribosome and dislodge tetracycline
What are the two important chemical structural components of tetracyclines?
1) four hydrocarbon rings 2) derivatives of polycyclic naphthacene carboxmide
What are the three mechanisms of resistance to tetracycline? Which is the most common?
1) impaired influx or increased effluvia by active transport protein pump- MOST COMMON 2) ribosome protection due to production of proteins that interfere with tetracycline binding to ribosome 3) enzymatic inactivation of tetracycline- LEAST COMMON
Which site on the ribosome does tetracycline block?
A site
Does acidic or alkalytic pH impair absorption of tetracyclines?
Alkaline pH
How are tetracyclines excreted?
Bile, urine, and feces
What is the mechanism of action of tetracyclines?
Bind to 30S subunit of ribosome and disrupt protein synthesis.
What are drug contraindications with doxycycline? Why?
Carbamazepine, phenytoin, barbiturates, and chronic alcohol ingestion; shorten-half life by induction of CP450, which metabolizes doxycycline
Why can tetracyclines not be given to children?
Chelation with calcium binds to and damages growing bones and teeth
What causes the most adverse affects of tetracyclines?
Direct toxicity of drug or alteration in microbial flora
Which tetracyclines cannot be dehydrated?
Doxycycline and Minocycline
What two tetracyclines are eliminated by non renal mechanisms?
Doxycycline and tigecycline
Tetracycline resistant strains may be susceptible to what other medications?
Doxycycline, minocycline and tigecycline
What medications can treat organisms with Tet(K)?
Doxycycline, minocycline, or tigecycline
What is the function of the Tet(AE) pump?
Efflux pump expressing gram NEGATIVE species resistant to older tetracycline, doxycycline, and minocycline
What is the function of the Tet(K) pump?
Efflux pump of staphylococci confers resistance to tetracycline
What are the two ways to inactivate tetracyclines?
Epimerization and dehydration
Tetracyclines are used in __________solution because it makes them more soluble.
Hydrochloride
What is tigecycline used to treat?
Infections resistant to other antimicrobial including conventional tetracyclines
What organ is likely to lose function from toxicity of tetracyclines?
Liver
Two top 200 tetracyclines are short, intermediate, or long acting?
Long acting- doxycycline and minocycline
Can tetracycline be taken with milk?
NO
How does tetracycline enter microorganisms?
Passive diffusion and active transport
Demoxycycline is likely to cause what -articulation in fair-skinned patients?
Photosensitivity
Tigecycline susbtrate for ultidrug efflux pumps of __________ and __________, intrinsic resistance to all tetracyclines including tigecycline.
Proteus species; P. Aeuroginosa
Tetracyclines are the drug of choice for infections caused by what???
Rickettsiae
Where is absorption of oral tetracyclines?
Small intestine
What are tetracyclines isolated from?
Streptomyces aerefaciens
What is the common cause of kidney injury from tetracyclines?
Taken expired preparations
Why is tigecycline still able to act on Tet(M) binding ribosome?
The structure is too large and bulky and creates steric hinderance on Tet(M) binding to ribosome
What medication can treat organisms with Tet(AE)?
Tigecycline
What should tetracyclines be taken?
Two hours after eating or one hour before eating
Why is minocycline useful for eradication of meningococcal infections?
Very high concentration in tears and saliva
Do tetracyclines cross placenta?
Yes
Does food impair absorption?
Yes- except doxycycline and minocycline
