Exam 1- Cushman Lec 4- Clindamycin and Tetracycline Flashcards
What is the moa of clindamycin?
Similar to macrolides
-inhibits protein synthesis by binding to 50S ribosome
What is the clinical use of clindamycin?
Aerobic Gram + cocci (staph and strept)
Anaerobic Gram - bacilli (bacterioides and fusobacterium)
-bone infections
-acne
-vaginosis
-lung abscesses
-anaerobic lung and pleural space infections
-MRSA
-AIDS patients with encephalitis caused by Toxoplasma gondii
What are the drug limiting side effects of clindamycin?
Pseudomembranous Colitis
**potentially lethal
-involves overgrowth of Cdiff that produces toxins
Diarrhea
How is clindamycin metabolized?
By cytochrome P450 enzymes in the liver
-metabolized to sulfoxide and the N-demethylated derivative
***metabolites are pharmacologically inactive
Where is clindamycin absorbed?
90% from GI tract
How does clindamycin distribute in the body?
Widely distributed
-penetrates the CNS
How is clindamycin excreted?
Mainly in the urine and bile
*dosage adjustments required in hepatic failure, this can lead to accumulation of drug
How do we treat Pseudomembranous colitis caused by clindamycin?
Metronidazole or Vancomycin
What important chemical property do tetracyclines have?
Chelation
-able to form stable chelates with polyvalent metal ions
*note that these can form if drug is taken with calcium-containing food/products
What are the consequences of tetracyclines forming chelates?
-Chelates formed with calcium are not absorbed from the GI tract
-Note that tetracyclines chelate with calcium during teeth formation and will cause brown/gray coloring
–do not give to kids 8 or younger, or pregnant women after month 4
What is the preferred route of administration of tetracyclines?
Oral
How does epimerization affect tetracycline activity?
The epitetracycline product formed is inactive
*This is how old preparatins can lose half of their potency
At what pH is epimerization most active?
pH 4
How does epimerization in the solid state compare to the solution state?
Epimerization is slow in the solid state and rapid in solutions of pH 4
How does dehydration affect the activity of tetracyclines?
-Discolored, old tetracyclines should be thrown out
-The product of dehydration 4-epianhydrotetracycline is inactive as an antibiotic but toxic to the kidneys
-This can produce a Fanconi-like syndrome
(failure of the reabsorption mechanism in the proximal convoluted tubules) that can be fatal
Which tetracyclines lack a C-6 hydroxyl group and therefore cannot be dehydrated or cause Fanconi-like syndromes?
Minocycline
Doxycycline
Tigecycline
What is the MOA of tetracyclines?
Bind the 30S ribosomal subunit and inhibit bacterial protein synthesis
-done by blocking the attachment of the tRNA to the A site of the ribosome
-results in termination of peptide chain growth
(inhibit the codon-anticodon interaction)
How are tetracyclines able to have selective toxicity for the bacteria and not the host?
-They can inhibit protein synthesis in the host but are less likely to reach the concentration needed for toxicity
–this is because eukaryotic cells do not have tetracycline uptake mechanisms
What is the therapeutic use of tetracyclines?
Broad-spectrum
Most common use: acne
Treatment of choice for: chlamydia, Rickettsia, brucellosis, spirochetal infections (Lyme disease and syphilis)
What is the main benefit to using tetracycline itself and not the other drugs in the class?
It is generic and inexpensive
Food and milk lower the oral absorption of tetracycline by how much?
50%
Why is demeclocycline more stable to hydration?
It has a secondary hydroxyl group at C-6 instead of the tertiary hydroxyl group
-this results in slower dehydration because the secondary cation intermediate from demeclocycline is less stable (higher energy) than the tertiary cation intermediate from tetracycline
What unique toxicities does minocycline have?
Vestibular toxicities (vertigo, ataxia, nausea)
Which tetracycline is considered the tetracycline of choice by many physicians and why?
Doxycycline
-does not undergo dehydration
-fewer GI symptoms
-absorption only lowered by 20% with food/milk
-long half life permits once daily dosing
What two tetracyclines can cause fetal harm if given while breastfeeding/pregnant?
Sarecycline
Omadacycline
