Exam 7: Tetracyclines and Macrolides Flashcards
What is the structure of tetracyclines?
4 rings…
What shouldn’t you consume with Tetracyclines? Why?
Dairy products or antacids
They bind to Calcium, decreasing their absorption
Which Tetracycline is preferred for IV administration? When is it used?
Doxycycline (long-acting Tetracycline)
Used for serious infections and when oral use causes GI upset.
What precaution should you take when taking a Tetracycline? Why?
Drink with lots of water, standing up
They are prone to causing esophageal ulceration
How are tetracyclines excreted? Exception?
By the kidneys through glomerular filtration
Also in the bile/feces
Doxycycline is excreted mostly non-renal mechanisms (useful for patients with renal failure)
Tetracycline Mechanism
Inhibit bacterial protein synthesis by binding to the 30S Ribosomal Subunit, preventing addition of amino acids onto peptide chains
Enter the bacteria via passive diffusion and active transport
STATIC AGENTS
Mechanisms of Resistance to Tetracyclines
Efflux pumps spit the drug out of the bacteria (gram negatives and Staph)
Tet(M) ribosomal protection protein in Gram positives
** Tetracyclines are a good marker for MDR because plasmids usually also have resistance genes for Aminoglycosides, Sulfonamides, and Chloramphenicol.
Tetracycline Spectrum
Lots of resistance with Gram positives (staph/strep)
Pseudomonas and Enterobacteraceae are resistant.
Anaerobes tened to be resistant
Good against Atypical Bacteria (Spirochetes, Rickettsiae, Mycoplasma pneumo, Chlamydia)
Uses of Tetracyclines
Rickettsial (RMSF) Doxycycline
Mycoplasma (atypical pneumonia) Doxycycline
Chlamydia (doxy)
Spirochetes/Lyme disease (doxy)
Periodontitis- useful because they are both antibacterial and are collagenase inhibitors** (doxy/minocycline)
Acne (doxy/tetra/minocycline)
Tetracycline Adverse Effects
GI Upset, make sure to take with food
Superinfection (C diff)
** Can be deposited into growing teeth/bones because they bind to calcium. Cause teeth discoloration/enamel and bone deformities in babies when given to pregnant women.
When used past expiration date, they can cause renal damage
Photosensitivity
Can inhibit ADH and cause a DI-like state (could be used to treat SIADH)
Tetracycline Contraindication ** Probably on test
Pregnant women and children under 8 years old
Calcium/tetracycline complexes get deposited into bones/teeth and cause tooth discoloration and bone/enamel deformities
Tigecycline
Newer Tetracycline
Used in Skin/intraabdominal infections
What is the tissue distribution of macrolides?
Most tissues, but DO NOT enter CSF
Macrolide elimination mechanism
Metabolized by p450 system
No need to adjust dose for renal failure
How can macrolide absorption be increased?
Enteric coating or esthrization improve oral absorption
Macrolide Mechanism
Static usually, can be cidal
Bind to 50S subunit and prevent movement of polypeptide chains from the acceptor site to the donor site (block protein synthesis)
Macrolide Resistance Mechanism
Modification of the 50S ribosomal subunit by methylase
Also Efflux pumps
Erythromycin Spectrum
GAS, some other strep and staph, Corynebacterim
Uses of Macrolides
Mycoplasma pneumonia (USE THE MACROLIDE IF THE PATIENT IS PREGNANT, NOT THE TETRACYCLINE*****)
Legionella
Community acquired pneumonia
Non strep pharyngitis (corynebacterium)
Chlamydia
Alternative to beta lactams when bacteria is resistant
Adverse Effects of Macrolides
GI Upset due to direct GI motility stimulation (can be used to improve GI motility)
Erythromycin Adverse Effect
Can inhibit p450 enzymes, messing with other drugs
Associated with sudden cardiac death when interacting with other medications
Clarithromycin/Azithromycin General Features
Newer macrolide Better oral absorption Less GI intolerance Longer half life Clarithromycin inhibits P450 like erythromycin, but Azithromycin does not.
Azithromycin Half life? Why?
3 days (very long) It concentrates in the tissues and slowly releases over time
Uses of Clarithromycin/Azithromycin
Mycobacterium Avium
Very good against H flu, especially Azithromycin
Azithromycin is highly effective against Chlamydia, also Gonorrhea at high doses
Respiratory and skin infections
Azithromycin Consideration
May lead to deadly arrhythmias
Highest risk was in patients with preexisting heart problems
Telithromycin
New Macrolide
Used for Community Acquired Pneumonia
Inhibits CYP 3A4 can cause liver toxicity
How should you treat Gonorrhea?
First line- Ceftriaxone plus Azithromycin or Doxycycline
Second line- Cefixime + Azithromycin or Doxycycline
Make sure you treat for Chlamydia (co-infection is common)
How should you treat Chlamydia?
Azithromycin (1 dose) or Doxycycline (7 days)
