Tetracyclines

Question 1

Chemical properties

Answer 1

Tetracyclines interact with polyvalent metal ions and cause formation of stable chelates which cause antibiotic to be inactive

Question 2

What we should tell patients to avoid chelation

Answer 2

Do not administer with foods rich in calcium or milk

Do not take with any heavy metal drugs like Tums as they will inactivate antibiotic (if patient has to take metals should be administered 1-2 hours after tetracycline)

Do not give to children ages 8 or younger as this is the age of teeth development and tetracyclines can cause permanent teeth to be grey/blue color

Should be avoided in pregnancy after 1st trimester or after 4th month of pregnancy

Question 3

Empimerization and Dehydration
what does it cause and why is it bad

Answer 3

Epimerization of the hydrogen on the amine bearing carbon leads to epitetracycline product which is inactive
This can occur in capsules as well as solutions (older capsules can lose half of potency due to this)

Dehydration The tertiary benzylic hydroxyl group at C-6 has an antiperiplanar relationship with the proton at C-5a so it is set up for elimination

discolored old tetracycline samples should be thrown out due to formation of 4-epihydrotetracycline which is inactive and can cause toxicicty to the kidneys

Question 4

Drugs that completely avoid 4-epihydrotetracycline formation
how do they do it?

Answer 4

Minocycline and Doxycycline

Both lack a C-6 hydroxyl group which means dehydration cannot occur and the inactive form of the antibiotic cannot be created

Question 5

What happens under basic conditions

Answer 5

tetracyclines undergo cleavage in pH values of 8.5 or above which produces a lactone product and this product is inactive

Question 6

MOA

Answer 6

Bind to the 30s ribisomal subunit and inhibit bacterial protein synthesis

Question 7

Therapeutic use

Answer 7

Acne
Chlamydia, rickettsia, brucellosis, and spirochetal infections

Question 8

Demeclocycline

Answer 8

Has a secondary hydroxyl group at C-6 which dehydrates more slowly than tetracycline because the secondary is less stable (higher energy)

Food and milk lower oral absorption by 50%

Question 9

Minocycline and Doxycycline

Answer 9

Lack hydroxyl group at C-6 so 4-epianhydrotetracycline toxicity is avoided

both 90-100% oral bioavailaibilty

Absorption is lowered by 20% when taken with food or milk

Minocycline has vestibular toxicities (vertigo, atazia, nausea)

doxycycline has half life of 18-22 hours that permits once daily dosing

Question 10

Tigecycline

Answer 10

A glycylcycline antibiotic derivative of minocycline

Lacks C-6 hydroxyl group

Inhibits protein translation in bacteria by binding to the 30s ribosomal subunit and blocking entry of amino-acyl tRNA molecules

Question 11

Sarecycline

Answer 11

Weight based dosing

most common AE is nausea

not recommended for those pregnant or breast feeding

Do not use with oral retinoids and dose reduction is recommended if patient is on anticoagulant

Question 12

Omadacycline

Answer 12

for treatment of skin infections and community aquired bacterial pneumonia

IV infusion or orally

teratogenic