Clindamycin Flashcards
What is the mechanism of action of clindamycin
inhibits protein synthesis by binding to 50S ribosome at the 23S site (like erythromycin)
What are the main uses of clincamycin
- aerobic gram + cocci (staphylococcus and streptococcus)
- aerobic gram - baccilli (bacteroides and fusbacterium)
- bonin infectiosn
- acne
- MRSA
- lung abcesses and anearerobic lung and pleural space infections
- AIDS encephaitis
What is the main side effect of clindamycin that limits its clinical use
- pseudomomembranous colitis and diarrhea
What is the main metabolic pathway of clindamycine
metabolized by Cyp P450 enzumes in the liver to the sulfoxide and N-demethylated derivative
PK of clindamycine
- 90% absorbed in the GI tract
- penetrates and widley distributed in the CNS
- excreted in the urin and bile
- hepatic failure dosage adjustment
What is the main adverse effects of clindamycin
- diarrhea
- nasea
- vomiting
- pseudomembranous coitis
- contact dermatitis
What is pseudomembranous colitis
- overgrowth of C diff that can cause a range of effects ranging diarrhea to colitis and toxic megacolon
How do tetracyclines bind to heavy metals
chelates
Why shouldnt tetracyclines be administered with foods that are rich in calcium or other heavy metals
chelates make the drugs insoluble in the GI tract
What is the preferred administration of tetracyclines
oral absorption is adequate
Why shouldnt children take tetracycliens during the period of permanent teeth formulations
chelate calcium, resulting in brown teeth
what is epimerization
- hydrogen on the amine bearing carbon atom is acidic resulting in enolization and epirmerization
- epitetracyclinc product is inactive
What is the pH of when the rate of epimerization is most rapid
4
How is epimerization in the solid state
slow
What is tetracycline dehydration
- hydroxyl group at C6 is set up for elimination
- deactivates and turns into 4-epianhydrotetracycline
What is the toxicity of epianhydrotetracycline
can be toxic to the kidneys and can produce fanconi like syndrome
Which tetracyclines do not have the 4-epihandrotetracycline metabolite
minocyclien and doxycyclein
How do tetracyclines cleave under basic solution
at pH of 8.5 or above (lactone is inactive)
What is the mechanism of action of tetracyclines
bind to the 30S subunit aand inhibit bacterial protein synthesis by blocking the A site of the ribosome, resulting in termination of peptide chain growht
What are the main advantages of using tetracycline itself
binds to the small ribosomal subunit in 6 different locations
its generic and inexpensive
What are tetracyclines used for
- acne
- infections caused by chlamydia, rickettsia, spirochetal infections
- anthrax, plague, tularemia, legionnaires disease
Why is demeclocycline more stable to dehydration
has a secondary hydroxyl group at C-6 instead of tertiary hdyroxyl group, dehydrates more slowly due to secondary cation intermediate that is less stable (higher energy)
What are the unique effects of minocycline
vertigo ataxia nausea
Why is doxycycline the tetracycline of choice?
- no potential for 4-epianhydrotetracycline mediated toxicity
- fewer gi symptoms
Why does tigecycline have no potential for 4-epianhydrotetracycline
does not have C-^ hdyroxal group
what are the toxic effects of tigecyclien
- hepatotoxicity, pancreatitis , anaphyalctoid
What is hte MOA of tigecyclien
inhibits protein translation in bacteria by binding to 30S ribosomal subunit and blocking entry of amio-acyl tRNA into the A site of the ribosome
Why shouldnt sarecycline and omadacycline be administered to pregnant women and nursing
can cause fetal harm
