Clindamycin/Tetracycline Flashcards
What is Clindamycin synthesized from?
Lincomycin, a naturally occurring antibiotic
What do I add to Lincomycin to make Clindamycin?
Triphenylphosphine, chlorine in acetonitrile
Mechanism of change between Lincomycin to Clindamycin?
Inversion of configuration
Why is Lincomycin no longer used?
Toxicity
What is Clindamycin similar to mechanically?
Erythromycin (macrolide antibiotics)
How does Clindamycin work?
Inhibits protein synthesis (binds to part of 50S ribosomal subunit)
How does Clinda and Erythro interact?
Clinda binds to same site as Erythro
What is the result of the interaction between Clinda and Erythro?
Antagonism and cross resistance
What is Clinda most effective against?
Aerobic Gram + cocci
Anaerobic Gram - bacilli
Examples of Aerobic Gram + cocci?
Staph and Strep
Examples of Anaerobic Gram - bacilli?
Bacteroides and Fusobacterium
Best systematic use of Clinda?
Bone infection with Staph aureus
Best topical use of Clinda?
Severe Acne
What drug did Clinda replace in treating lung abscesses, anaerobic lung, and pleural space infections?
Penicillin
How do you treat Toxoplasma gondii encephalitis?
Clinda IV with pyrimethamine and leucovorin
What limits the use of Clinda to infections where it is clearly the superior agent?
Pseudomembranous colitis and diarrhea
How can Clinda be delivered?
Oral, IV, Topical foams/solutions
What metabolizes Clinda?
CYP 450 enzymes in liver
Activity of Clinda after metabolism by CYP 450?
Inactive
How much of the Clinda dose is absorbed in the GI tract?
90%
Where is Clina distributed?
CNS
Where is Clinda and metabolites excreted?
Bile and urine
What is elimination half life of Clinda?
1.5-5 hours
Potentially lethal condition caused by Clinda?
Pseudomembranous colitis
What causes the Pseudomembranous colitis?
Clostridium difficile toxin
How do you treat C. Dif?
Metronidazole or Vancomycin
What produces Tetracycline?
Streptomyces bacteria
What is Chelation?
Process of removing heavy metals from blood
Tetracycline forms stable chelates with what metals?
Ca, Al, Cu, and Mg
Problem with tetracycline chelates?
Insoluble, not absorbed in GI tract
Preferred administration route of Tetracycline?
Oral
Risk of tetracycline with children and tooth formation?
Can permanently stain teeth brown or gray.
Pain associated with injection of Tetracycline caused by?
Formation of insoluble calcium complexes
What do injectable formulations of tetra contain to reduce pain?
EDTA
Epimerization causes what to Tetra?
Inactivates and reduces potency
When is Epimerization of Tetra most rapid?
Acidic solutions of pH 4
What does dehydration do to Tetra?
Inactives and makes toxic
Fanconi syndrome?
Failure of reabsorption in proximal convoluted tubules
What makes Tetra completely safe from potential for toxicity due to dehydration?
Lack of C-6 hydroxyl group
Where do tetracyclines bind on ribosome?
30S ribosomal subunit
What do tetracyclines inhibit?
Bacterial protein synthesis
How do tetras inhibit protein synthesis?
Block tRNA attachment to A site of ribosome stopping the peptide growth chain
Does tetra overlap with erythromycin binding sites like Clinda does?
No
Why does tetra not inhibit host protein synthesis?
We don’t have tetra uptake mechanism
How many binding sites are there on ribosome subunit for Tetra?
6
Which binding site has highest occupancy for Tetra?
Tet1
At what pH are tetra inactivated into lactone?
8.5 or above
Most common use of Tetra?
Acne
Food and milk do what to oral absorption of Tetra?
Lower by 50%
Difference between tetracycline and demeclocycline?
Secondary C-6 hydroxyl as opposed to tertiary
Significance of secondary hydroxyl instead of tertiary?
Dehydrates more slowly so less toxicity
Food and milk do what to oral absorption of Demeclocycline?
Lower absorption by 50%
What is Minocycline synthesized from?
Demeclocycline
Does Minocycline have a C-6 hydroxyl group?
No
Oral bioavailability of Minocycline?
90-100%
Food or milk effect on Minocycline absorption?
Lowers by 20%
Minocycline toxicities associated with what?
Vestibular system
Oxytetracycline produced by what?
Strep Rimosis
What is the most hydrophillic tetracycline?
Oxytetracycline
What is oral bioavilabilty of Oxytetracycline?
60%
Effect of food/milk on absorption of Oxytetracycline?
Lowered by 50%
What is doxycycline synthesized from?
Oxytetracycline
Why is doxy considered the tetracycline of choice by many?
No potential for dehydration related toxicity AND produces fewer GI problems
Oral bioavialabilty for Doxy?
90-100%
Food/milk effect on Doxy?
Absorption reduced 20%
Half life of Doxy?
18-22 hours (one a day dosing)
What is Chloramphenicol obtained from?
Strep venezuelae
Why has use of Chloramphenicol waned?
Toxicities
When would one use Chloramphenicol?
Benefits outweigh risks
How does Chloramphenicol work?
Binds to 50S ribosomal subunit and inhibits peptide bond formation
Where does Chloramphenicol bind on Ribosome?
Near site where Clinda and Erythro bind
What does Chloramphenicol competitively work against?
Clinda and Erythro
Main use of Chloramphenicol?
Ointment or eye drops to treat bacterial conjunctivitis
What is chloramphenicol sodium succinate?
Prodrug hydrolyzed to chloramphenicol in liver
Chloramphenicol sodium succinate used for?
Bacterial meningitis, typhoid fever, rickettsial infections, or intraocular infections
Where can chloramphenicol go in the body?
Everywhere due to lipid solubility
What causes resistance to chloramphenicol?
1) Reduced membrane permeability
2) Mutation of 50S ribosome subunit
3) Elaboration of chloramphenicol acetyltransferase
What is the most serious toxicity of Chloramphenicol?
Aplastic anemia
Highest risk of aplastic anemia with chloramphenicol due to?
Oral, lowest risk eye drops
What causes bone marrow suppression in Chloramphenicol toxicity?
Impairment of mitochondrial function from protein synthesis inhibition
What cancer risk is increased with Chloramphenicol?
Childhood Leukemia
What is Chloramphenicol metabolized to?
Inactive glucuronide
Why should neonates never be given chloramphenicol?
They cannot metabolize it
