Exam 7: Tetracyclines and Macrolides

Question 1

What is the structure of tetracyclines?

Answer 1

4 rings…

Question 2

What shouldn’t you consume with Tetracyclines? Why?

Answer 2

Dairy products or antacids

They bind to Calcium, decreasing their absorption

Question 3

Which Tetracycline is preferred for IV administration? When is it used?

Answer 3

Doxycycline (long-acting Tetracycline)

Used for serious infections and when oral use causes GI upset.

Question 4

What precaution should you take when taking a Tetracycline? Why?

Answer 4

Drink with lots of water, standing up

They are prone to causing esophageal ulceration

Question 5

How are tetracyclines excreted? Exception?

Answer 5

By the kidneys through glomerular filtration
Also in the bile/feces
Doxycycline is excreted mostly non-renal mechanisms (useful for patients with renal failure)

Question 6

Tetracycline Mechanism

Answer 6

Inhibit bacterial protein synthesis by binding to the 30S Ribosomal Subunit, preventing addition of amino acids onto peptide chains
Enter the bacteria via passive diffusion and active transport
STATIC AGENTS

Question 7

Mechanisms of Resistance to Tetracyclines

Answer 7

Efflux pumps spit the drug out of the bacteria (gram negatives and Staph)
Tet(M) ribosomal protection protein in Gram positives
** Tetracyclines are a good marker for MDR because plasmids usually also have resistance genes for Aminoglycosides, Sulfonamides, and Chloramphenicol.

Question 8

Tetracycline Spectrum

Answer 8

Lots of resistance with Gram positives (staph/strep)
Pseudomonas and Enterobacteraceae are resistant.
Anaerobes tened to be resistant
Good against Atypical Bacteria (Spirochetes, Rickettsiae, Mycoplasma pneumo, Chlamydia)

Question 9

Uses of Tetracyclines

Answer 9

Rickettsial (RMSF) Doxycycline
Mycoplasma (atypical pneumonia) Doxycycline
Chlamydia (doxy)
Spirochetes/Lyme disease (doxy)
Periodontitis- useful because they are both antibacterial and are collagenase inhibitors** (doxy/minocycline)
Acne (doxy/tetra/minocycline)

Question 10

Tetracycline Adverse Effects

Answer 10

GI Upset, make sure to take with food
Superinfection (C diff)
** Can be deposited into growing teeth/bones because they bind to calcium. Cause teeth discoloration/enamel and bone deformities in babies when given to pregnant women.
When used past expiration date, they can cause renal damage
Photosensitivity
Can inhibit ADH and cause a DI-like state (could be used to treat SIADH)

Question 11

Tetracycline Contraindication ** Probably on test

Answer 11

Pregnant women and children under 8 years old

Calcium/tetracycline complexes get deposited into bones/teeth and cause tooth discoloration and bone/enamel deformities

Question 12

Tigecycline

Answer 12

Newer Tetracycline

Used in Skin/intraabdominal infections

Question 13

What is the tissue distribution of macrolides?

Answer 13

Most tissues, but DO NOT enter CSF

Question 14

Macrolide elimination mechanism

Answer 14

Metabolized by p450 system

No need to adjust dose for renal failure

Question 15

How can macrolide absorption be increased?

Answer 15

Enteric coating or esthrization improve oral absorption

Question 16

Macrolide Mechanism

Answer 16

Static usually, can be cidal
Bind to 50S subunit and prevent movement of polypeptide chains from the acceptor site to the donor site (block protein synthesis)

Question 17

Macrolide Resistance Mechanism

Answer 17

Modification of the 50S ribosomal subunit by methylase

Also Efflux pumps

Question 18

Erythromycin Spectrum

Answer 18

GAS, some other strep and staph, Corynebacterim

Question 19

Uses of Macrolides

Answer 19

Mycoplasma pneumonia (USE THE MACROLIDE IF THE PATIENT IS PREGNANT, NOT THE TETRACYCLINE*****)
Legionella
Community acquired pneumonia
Non strep pharyngitis (corynebacterium)
Chlamydia
Alternative to beta lactams when bacteria is resistant

Question 20

Adverse Effects of Macrolides

Answer 20

GI Upset due to direct GI motility stimulation (can be used to improve GI motility)

Question 21

Erythromycin Adverse Effect

Answer 21

Can inhibit p450 enzymes, messing with other drugs

Associated with sudden cardiac death when interacting with other medications

Question 22

Clarithromycin/Azithromycin General Features

Answer 22

Newer macrolide
Better oral absorption
Less GI intolerance
Longer half life
Clarithromycin inhibits P450 like erythromycin, but Azithromycin does not.

Question 23

Azithromycin Half life? Why?

Answer 23

3 days (very long)
It concentrates in the tissues and slowly releases over time

Question 24

Uses of Clarithromycin/Azithromycin

Answer 24

Mycobacterium Avium
Very good against H flu, especially Azithromycin
Azithromycin is highly effective against Chlamydia, also Gonorrhea at high doses
Respiratory and skin infections

Question 25

Azithromycin Consideration

Answer 25

May lead to deadly arrhythmias

Highest risk was in patients with preexisting heart problems

Question 26

Telithromycin

Answer 26

New Macrolide
Used for Community Acquired Pneumonia
Inhibits CYP 3A4 can cause liver toxicity

Question 27

How should you treat Gonorrhea?

Answer 27

First line- Ceftriaxone plus Azithromycin or Doxycycline
Second line- Cefixime + Azithromycin or Doxycycline
Make sure you treat for Chlamydia (co-infection is common)

Question 28

How should you treat Chlamydia?

Answer 28

Azithromycin (1 dose) or Doxycycline (7 days)