Term
| What is the core structure of tetracyclines? |
|
Definition
Four fused 6-membered rings (tetra-cyclin). |
|
|
Term
| What structural modification to tetracycline yields tigecyline? |
|
Definition
Glycoamino complex.
[image]
|
|
|
Term
| How do tetracyclines (and tigecycline) work? |
|
Definition
They inhibit protein synthesis by binding to th 30S bacterial ribosomal subunit.
Note: Tigecycline binds more strongly |
|
|
Term
| Tetracyclines used to be considered broad-spectrum antibiotics. What changed? |
|
Definition
Widespread resistance limits their use. |
|
|
Term
| Are tetracyclines (and tigecylcine) bactericidal or bacteriostatic? |
|
Definition
|
|
Term
| What are mechanisms of resistance to tetracyclines? |
|
Definition
1. EFFLUX (main mechanism): Both Gram+ and Gram- can synthesize large amounts of efflux proteins.
2. Ribosomal Protection Proteins: Bacteria can produce proteins that bind to the ribosome, causing a conformational change so that tetracyclines can no longer bind.
3. Decreased penetration across bacterial membrane.
Tigecycline is less susceptible to resistance; tet-resistant organisms are susceptible to tigecycline. |
|
|
Term
| How are tetracyclines administered and absorbed? What about tigecycline? |
|
Definition
Tetracyclines are administered orally, with variable absorption. Absorption is impaired by di- and trivalent cations, e.g. Ca2+ (don't take with milk), Mg2+, Al3+ (component of antacids).
Tigecycline is administered by IV. |
|
|
Term
| How is tetracycline distributed in the body? |
|
Definition
Sequestered in tissues, usually liver. This means Vd can be bigger than body water. Concentration in CSF is low. |
|
|
Term
| How are tetracyclines metabolized and eliminated? |
|
Definition
Tetracyclines are concentrated in the liver.
Primary elimination route varies:
-- Doxycycline and minocycline ("domino") eliminated hepatically. Use these for renal failure patients.
-- Demeclocycline and tetracycline eliminated renally.
Note: t1/2 of doxycycline (16hrs) is twice as long as t1/2 of tetracycline (8hrs), which makes doxycycline very popular. |
|
|
Term
| What are some adverse effects of all tetracyclines? Specific tetracyclines? |
|
Definition
1. GI irritation
2. Efects on calcifying tissues (tetracyclines bind Ca2+)
-- Inhibit bone growth in utero (contraindicated in pregnant women, children <8yo)
-- Discoloration of teeth
3. Hepatotoxicity (especially in pregnant women)
4. Decreased efficacy of oral contraceptives
5. Can lead to superinfections by broadly killing off flora
*6. Democlo- and doxycycline can lead to photosensitivity
("phoDosensiDivity")
*7. Minocyclin can lead to dizziness |
|
|
Term
| What are two reasons tetracycline is contraindicated in pregnant women? |
|
Definition
1. Inhibition of fetal bone growth
2. Increased susceptibility to hepatotoxicity in both mother and fetus |
|
|
Term
| Who may not take tetracyclines due to its effect on calcifying tissues? |
|
Definition
Pregnant women and children under 8yo. |
|
|
Term
| What are some adverse effects of tigecycline? |
|
Definition
Fever
GI irritation
Hypertension
Hepatotoxicity
Hematologic
Alphbetical: FGHHH |
|
|
Term
| What are tetracyclines used for? |
|
Definition
Since broad spectrum activity has been largely compromised by resistance, tetracyclines are good for intracellular organisms lacking a cell wall.
-- Rickettsiae
-- Chlamydiae
-- Borreliae (Lyme disease) |
|
|
Term
| What are differences between tetracyclines and tigecycline? |
|
Definition
Administration: tetracyclines are given orally, tigecycline by IV
Efficacy: tigecyline binds better to 30S subunit AND evades resistance mechanisms
Clinical uses: Tetracyclines have some broad spectrum activity (diminished due to resistance) and are effective against organisms that lack a cell wall. Tigecycline is reserved for complex skin and intra-abdominal infections and drug-resistant organisms.
Adverse Effects: Lots for tetracyclines, few for tigecylcine
|
|
|
Term
| What is tigecycline used for? |
|
Definition
Used for complex skin or intra-abdominal infections and drug-resistant organisms. Not a first-line therapy. (This is good stuff - we don't want to breed resistance to it!) |
|
|
