Protein Synthesis Inhibitors (Tetracyclines)

Match each tetracycline with its unique feature.

- Doxycycline → Lyme disease, Chlamydia, RMSF, malaria prophylaxis

- Minocycline → Vertigo, tinnitus, concentrates in tears and saliva

- Tetracycline → Empty stomach; expired drug can cause nephrotoxicity

- Demeclocycline → Off-label SIADH

- Tigecycline → Boxed warning for increased mortality

- Eravacycline → More potent than tigecycline

- Omadacycline → Oral; active against some resistant strains

How do human and bacterial ribosomal subunits differ?

-Humans: 40S and 60S

-Bacteria: 30S and 50S

Why can protein synthesis inhibitors selectively target bacteria?

Bacteria have different ribosomal subunits than humans, allowing bacterial protein synthesis to be targeted without damaging human ribosomes.

What is the basic structural feature of tetracyclines?

They contain four fused rings.

What is the mechanism of action of tetracyclines?

-Bind reversibly to the bacterial 30S ribosomal subunit

-Prevent incoming charged tRNA from binding at the A site

-Inhibit protein synthesis

Are tetracyclines bacteriostatic or bactericidal?

They are bacteriostatic because they prevent bacterial growth and division. At high doses, they may be bactericidal.

Why must tetracyclines penetrate and accumulate inside bacterial cells?

Their 30S ribosomal target is inside the bacterial cytoplasm.

How can impaired intracellular accumulation cause tetracycline resistance?

A bacterial mutation can prevent the drug from entering and accumulating in the cytoplasm.

What additional tetracycline resistance mechanism was noted in the PowerPoint?

Efflux pumps; resistance is common.

Which traditional tetracyclines were emphasized in lecture?

-Tetracycline

-Doxycycline

-Minocycline

What is the general coverage of traditional tetracyclines?

-Gram-positive organisms

-Some gram-negative organisms

-Atypical organisms

-No meaningful anaerobic coverage

Which two organisms do tetracyclines NOT cover?

-Pseudomonas

-Group A Streptococcus

Which gram-positive organisms may be covered by tetracyclines?

-Staphylococcus aureus

-MRSA in some skin and soft tissue infections

-Penicillin-sensitive Streptococcus pneumoniae

Why should a culture guide tetracycline use for MRSA skin infections?

MRSA is sometimes susceptible to tetracyclines, but not always.

Which gram-negative organisms are listed under tetracycline coverage?

-Haemophilus influenzae

-Pasteurella

-Vibrio cholerae

-Brucella species

Which atypical or other organisms are covered by tetracyclines?

-Chlamydia

-Mycoplasma

-Legionella

-Rickettsia

-Nocardia

-Plasmodium

What are doxycycline's major claim-to-fame infections emphasized by the professor?

-Lyme disease

-Chlamydia

-Rocky Mountain spotted fever

What is the drug of choice for Lyme disease?

Doxycycline.

What organism causes Lyme disease?

Borrelia burgdorferi.

Which sexually transmitted infection is treated with doxycycline, and for how long?

Chlamydia; the PowerPoint lists a 7-day regimen.

For which rickettsial infection is doxycycline a drug of choice?

Rocky Mountain spotted fever.

What other infections or uses are listed for tetracyclines?

-Anthrax

-Tularemia

-Leptospirosis

-Plasmodium falciparum malaria prophylaxis

-Community-acquired pneumonia

-Acne

-Staphylococcal skin and soft tissue infections

What unique distribution feature is associated with minocycline?

It concentrates in tears and saliva.

Which tetracycline is especially associated with vestibular reactions?

Minocycline.

What vestibular reactions can minocycline cause?

-Tinnitus: ringing in the ears

-Vertigo: a swirling or spinning sensation

How is tetracycline best taken for absorption?

-On an empty stomach

-Take it about 2 hours before multivalent cations when possible

Which substances can bind tetracyclines and reduce their absorption?

-Calcium

-Magnesium

-Aluminum

-Iron

-Dairy products

Why must tetracycline be separated from dairy, antacids, and mineral supplements?

It binds multivalent cations, preventing absorption and potentially causing treatment failure.

Is the multivalent-cation interaction equally important for all tetracyclines?

No. It is most important with tetracycline and less important with doxycycline or minocycline.

Where are tetracyclines distributed?

They are widely distributed, including into urine, prostate, and CSF.

What happens to tetracyclines in the liver and bile?

All are concentrated in the liver and excreted into the bile.

Why do longer-acting tetracyclines have better tissue penetration?

They have enhanced lipid solubility.

How are tetracyclines eliminated?

They are metabolized in the liver and excreted in urine and feces.

Which tetracycline does NOT require renal dose adjustment?

Doxycycline.

Which newer tetracyclines are considered broad-spectrum?

-Tigecycline: IV

-Eravacycline: IV

-Omadacycline: oral

How does the spectrum of newer broad-spectrum tetracyclines differ from traditional tetracyclines?

-Newer agents: gram-positive, gram-negative, anaerobic, and atypical coverage

-Traditional agents: no meaningful anaerobic coverage

What resistant organisms may be covered by newer broad-spectrum tetracyclines?

-Coagulase-negative Staphylococcus

-MSSA and MRSA

-Vancomycin-intermediate and vancomycin-resistant Staphylococcus

-Enterococci and VRE

-Acinetobacter

What atypical or other organisms may be covered by newer broad-spectrum tetracyclines?

-Rickettsia

-Chlamydia

-Legionella

-Mycobacteria

What are the approved indications listed for newer broad-spectrum tetracyclines?

-Skin infections

-Intra-abdominal infections, except omadacycline

-Community-acquired pneumonia

Why should newer broad-spectrum tetracyclines not be used for primary bacteremia?

They do not achieve high enough concentrations in the bloodstream.

For which infections should newer broad-spectrum tetracyclines NOT be used?

-Urinary tract infections

-Primary bacteremia

What boxed warning is associated with tigecycline?

Increased risk of all-cause mortality.

What key feature distinguishes eravacycline?

It is an IV broad-spectrum tetracycline thought to be more potent than tigecycline.

What key features distinguish omadacycline?

-Available orally

-Take on an empty stomach

-Some tetracycline-resistant strains may remain sensitive

Why are tetracyclines contraindicated during pregnancy, nursing, and early childhood?

They bind calcium in newly forming bone and teeth, causing bone deposition and potentially permanent tooth discoloration.

Which patients should generally not receive tetracyclines?

-Pregnant patients

-Nursing mothers

-Children younger than about 8-9 years

-Patients with a tetracycline allergy

What common adverse effects occur with tetracyclines?

-Nausea

-Vomiting

-Diarrhea

-Clostridioides difficile infection

-Photosensitivity

How should patients be counseled about tetracycline-related photosensitivity?

Avoid excess sun exposure, cover up, and use sunscreen because severe sunburn can occur easily.

Why should expired tetracycline be discarded?

It breaks down into toxic metabolites that can cause nephrotoxicity.

What are the two major counseling points emphasized for a patient taking tetracycline?

-Avoid excess sun exposure because of photosensitivity

-Separate the drug from dairy, antacids, iron, and other multivalent-cation supplements