Protein synthesis inhibitors - Tetracyclines Flashcards
1
Q
Tetracyclines
A
Bacteriostatic
Target:
- Gram +
- Gram -
Indications:
- Acne, Mycoplasma pneumo, Chlamydia, Rickettsiae, Spirochetes, H. pylorii, Actinomyces, Vanc-resistant enterococci
- NOT = Pseudomonas sp, Proteus, Staph sp., Candida
Mechanism:
- enter cell via passive diffusion or active transport
- bacteria accumulate drug (euks dont)
- Bind reversibly to 30S subunit of prok ribosome at A site, blocking aminoacyl-tRNA binding, preventing addition of AAs
Route of Administration:
- PO
Absorption:
- PO occurs in small intestine
- ~70% absorbed
- impaired by food and divalent metals (chelate Ca, Mg, Fe, Al)
Distribution:
- bind (40-80%) to serum proteins
- widely distributed in body (bones and teeth esp), NOT CSF
Metabolism and Excretion:
- renal and hepatic
- via bile and urine
Toxicities:
- N/V, GI irritation
- modification of gut flora
- give with food (may impede absorption)
- hepatic toxicity (w/ renal failure or high dose)
- outdated drugs can cause aminoaciduria (toxic breakdown product), N, and renal tubular acidosis “Fanconi syndrome”
- Superinfection (due to growth of Proteus, Pseudomonas, Staph, and C diff
- Interfere with oral contraceptives
- photosensitivity
- chelate divalent metals
- tooth discoloration
- impair bone growth in developing fetus
Drug Interactions: ?OCs
Pt considerations:
- Pregnancy Class D
- cross placenta/present in breast milk
- not recommended for use in kids under 8 yo, pregnancy or nursing mothers
- adjust dose for renal impaired
Resistance:
- decrease influx, increase efflux (dont accumulate drug = doesnt work)
- Tet(AE) efflux pump in Gram -
- Tet(K) efflux pump expressed in Staph
- Proteus/Pseudomonas sp. express chromosomal multidrug transporter = resistant
- ribosome protection
- Tet(M) protein in Gram +
- enzymatic inactivation by organism (acetylation)
- cross resistance common due to overuse
2
Q
Doxycycline
A
Bacteriostatic
Broad spectrum
Target:
- Gram +
- Gram -
Indications:
- Acne, Mycoplasma pneumo, Chlamydia, Rickettsiae, Spirochetes, H. pylorii, Actinomyces, Vanc-resistant enterococci, B. anthracis
- NOT = Pseudomonas sp, Proteus, Staph sp., Candida
- certain STDs (alone or in combo with cephalosporins), Rocky Mt, Spooted fever (Rickettsii), Lyme Disease (B. bergdorferi)
Mechanism:
- enter cell via passive diffusion or active transport
- bacteria accumulate drug (euks dont)
- Bind reversibly to 30S subunit of prok ribosome at A site, blocking aminoacyl-tRNA binding, preventing addition of AAs
Route of Administration:
- PO and IV
Absorption:
- PO occurs in small intestine
- ~95-100% absorbed (can be taken with food) (longer half life)
- impaired by food and divalent metals (chelate Ca, Mg, Fe, Al)
Distribution:
- bind (40-80%) to serum proteins
- high lipid solubility
- widely distributed in body (bones and teeth esp), NOT CSF
Metabolism and Excretion:
- LOW renal clearance/eliminated by nonrenal mechanisms (safer for pts with renal problems)
- hepatic metabolisim via bile
Toxicities:
- N/V, GI irritation
- modification of gut flora
- give with food (may impede absorption)
- hepatic toxicity (w/ renal failure or high dose)
- outdated drugs can cause aminoaciduria (toxic breakdown product), N, and renal tubular acidosis “Fanconi syndrome”
- high dose Doxy produces vestibular dysfunction (de to HIgh CNS penetration, more lipid soluble, cross BBB)
- Superinfection (due to growth of Proteus, Pseudomonas, Staph, and C diff
- Interfere with oral contraceptives
- photosensitivity
- chelate divalent metals
- tooth discoloration
- impair bone growth in developing fetus
Drug Interactions: ?OCs
Pt considerations:
- Pregnancy Class D
- cross placenta/present in breast milk
- not recommended for use in kids under 8 yo, pregnancy or nursing mothers
- adjust dose for renal impaired
Resistance:
- decrease influx, increase efflux (dont accumulate drug = doesnt work)
- Tet(AE) efflux pump in Gram -
- Proteus/Pseudomonas sp. express chromosomal multidrug transporter = resistant
- ribosome protection
- Tet(M) protein in Gram +
- enzymatic inactivation by organism (acetylation)
- cross resistance common due to overuse
3
Q
Minocycline
A
Target:
- Gram +
- Gram -
Indications:
- Acne, Mycoplasma pneumo, Chlamydia, Rickettsiae, Spirochetes, H. pylorii, Actinomyces, Vanc-resistant enterococci
- Lyme’s Disease, acne
- NOT = Pseudomonas sp, Proteus, Staph sp., Candida
Mechanism:
- enter cell via passive diffusion or active transport
- bacteria accumulate drug (euks dont)
- Bind reversibly to 30S subunit of prok ribosome at A site, blocking aminoacyl-tRNA binding, preventing addition of AAs
Route of Administration:
- PO
Absorption:
- PO occurs in small intestine
- ~95-100% absorbed (can be taken with food) (longer half life)
- impaired by food and divalent metals (chelate Ca, Mg, Fe, Al)
Distribution:
- bind (40-80%) to serum proteins
- high lipid solubility
- widely distributed in body (bones and teeth esp)
- Mino reaches CSF (meningococcal infection), saliva, tears
Metabolism and Excretion:
- low/non-renal clearance so safe for pts with renal impairment
- hepatic metabolism
Toxicities:
- N/V, GI irritation
- modification of gut flora
- give with food (may impede absorption)
- hepatic toxicity (w/ renal failure or high dose)
- outdated drugs can cause aminoaciduria (toxic breakdown product), N, and renal tubular acidosis “Fanconi syndrome”
- Mino produces vestibular dysfunction due to high CNS penetration (more lipid soluble, crosses BBB)
- Superinfection (due to growth of Proteus, Pseudomonas, Staph, and C diff
- Interfere with oral contraceptives
- photosensitivity
- chelate divalent metals
- tooth discoloration
- impair bone growth in developing fetus
Drug Interactions: ?OCs
Pt considerations:
- Pregnancy Class D
- cross placenta/present in breast milk
- not recommended for use in kids under 8 yo, pregnancy or nursing mothers
- adjust dose for renal impaired
Resistance:
- decrease influx, increase efflux (dont accumulate drug = doesnt work)
- Tet(AE) efflux pump in Gram -
- Proteus/Pseudomonas sp. express chromosomal multidrug transporter = resistant
- ribosome protection
- Tet(M) protein in Gram +
- enzymatic inactivation by organism (acetylation)
- cross resistance common due to overuse
4
Q
Tigecycline
A
NEW DRUG CLASS = GLYCYLCYCLINE
Bacteriostatic
Target:
- Gram +
- Gram -
Indications:
- Acne, Mycoplasma pneumo, Chlamydia, Rickettsiae, Spirochetes, H. pylorii, Actinomyces, Vanc-resistant enterococci
- useful against MDR organisms (MRSA)
- NOT = Pseudomonas sp, Proteus, Staph sp., Candida
Mechanism:
- enter cell via passive diffusion or active transport
- bacteria accumulate drug (euks dont)
- Bind reversibly to 30S subunit of prok ribosome at A site, blocking aminoacyl-tRNA binding, preventing addition of AAs
Route of Administration:
- IV only
Absorption:
- IV only
Distribution:
- bind (40-80%) to serum proteins
- widely distributed in body (bones and teeth esp), NOT CSF
Metabolism and Excretion:
- low/non-renal mechanisms
- hepatic metabolism (safest for pts w/ impaired renal function)
Toxicities:
- outdated drugs can cause aminoaciduria (toxic breakdown product), N, and renal tubular acidosis “Fanconi syndrome”
- Superinfection (due to growth of Proteus, Pseudomonas, Staph, and C diff
- Interfere with oral contraceptives
- photosensitivity
- chelate divalent metals
- tooth discoloration
- impair bone growth in developing fetus
Drug Interactions: ?OCs
Pt considerations:
- Pregnancy Class D
- cross placenta/present in breast milk
- not recommended for use in kids under 8 yo, pregnancy or nursing mothers
- adjust dose for renal impaired
Resistance:
- decrease influx, increase efflux (dont accumulate drug = doesnt work)
- Proteus/Pseudomonas sp. express chromosomal multidrug transporter = resistant (express this efflux pump already)
- enzymatic inactivation by organism (acetylation)
- cross resistance common due to overuse
