Tetracyclines and Glycyclines

Tetracycline Pharmacokinetics - Distribution

- Excellent Tissue Penetration (lung, soft tissue, bone) - Some CNS penetration but not for meningitis (because bacteriostatic, not cidal) - Readily crosses placenta and into breast milk

Tigecycline

- First drug in a quasi-class called glycylcyclines - Derivative of minocycline - IV only

Tetracycline Pharmacokinetics - Absorption

- Food, milk and divalent ions decrease absorption (more so with tetracycline) - Bioavailability Tetracycline 60-80% Doxycycline 90-100% Minocycline 90-100%

Tetracycline MOA

- Protein synthesis inhibitor (reversible binding at the 30s ribosomal subunit)

Tetracycline Pharmacokinetics - Elimination

- Tetracycline: 1. Minimal hepatic metabolism 2. 60% unchanged in the urine (good for UTIs) 3. Significant bile/fecal elimination - Doxycycline: 1. 50% hepatic metabolism 2. 20-30% in urine (only very suseptible bacteria if want to use this for a UTI) 3. Remainder bile/fecal elimination - Minocycline 1. More than 50% hepatic elimination 2. 10% in urine 3. Remainder in bile/feces

Tetracycline Pharmacokinetics - Half-Life

- Tetracylcine: About 6 hours (must be given 4 times a day) - Doxycycline: 15-24 hours - Minocycline: 11-22 hours

Drug Interactions with Tetracyclines

1. Antacids (Ca and Mg containing) 2. Calcium Supplements 3. Iron suppements. They are all chelate forming

Tygecycline Therapeutic Uses

1. Complicated skin and skin structure infections 2. Intra abdominal infections 3. Good for community acquirred pneumoniae not caused by pseudomonas but too expensive to use for that purpose

Adverse Effects of Tetracyclines

1. GI (worse with tetracycline) 2. Photosensitivity 3. Hepatitis (rare) 4. Hypersensitivity (uncommon) 5. Tooth discoloration (with children under 8) 6. Antianabolic effects (inhibit incorporation of amino acids into proteins... muscle wasting)

Contraindications with Tetracyclines

1. Pregnancy D Category because it causes the inhibition of bone growth in fetus. Should not be used in pregnant or breastfeeding women. 2. Should not be used in children under 8. It will deposit in newly forming bone and teeth.

Therapeutic Uses of Tetracyclines

1. Rickettsial Infections (Rocky Mountain Spotted Fever) -- Ticks Doxycycline is the best 2. Lyme Disease -- Ticks spread borrelia burgdorferi 3. Acne (minocycline) 4. Acute exacerbations of chronic bronchitis

Tigecycline Pharmacokinetics

Absorption & Distribution: Good tissue penetration, with slow release from tissues. CSF penetration not known. Metabolism: Half Life is 36 hours but twice a day because N/V is associated with peak concentrations so it's better to be right below. Excretion: Biliary elimination - Most tetracycline resistance mechanisms do not affect tigecycline

Tetracycline Mechanisms of Resistance

Efflux pumps mostly with tetracycline

Tetracycline Spectrum of Activity

Good 1. Atypicals 2. Rickettsia 3. Spirochetes 4. Plasmodium (malaria) Moderate 1. Staph (MSSA & MRSA) 2. S. pneumoniae

Tigecycline Spectrum of Activity

Gram Positive 1. S. aureus (including MRSA) 2. Enterococcus species 3. S. pneumoniae Gram Negative 1. Enterobacteriacae 2. Acinetobacter species Good Anaerobic Coverage NO PSEUDOMONAS

Tigecycline MOA

Inhibits protein synthesis by binding to 30S ribosomal subunit

Adverse Effects of Tigecycline

nausea and vomiting.