Term
| Pharmacokinetics of Chloramphenicol |
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Definition
Oral or Parenteral use;
Widely distributed and reaches CSF, making it useful for some forms of meningitis and brain abscesses;
Metabolized in liver to inactive glucuronide conjugate & excreted in urine;
Doses need to be adjusted for hepatic failure but NOT renal failure;
Premies and newborns have decreased liver metabolic function & doses should be lower than adult dose |
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Term
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Definition
prevents protein synthesis by reversibly binding to 50-S subunit of bacterial ribosome;
resistance caused by bacterial production of acetyltransferase which acetylates drug and prevents binding to 50-S subunit of ribosome |
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Term
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Definition
use should be limited to infections in which benefits of drug outweight risks of potential toxicities;
NOT a first line agent, used for life-threatening bacterial meningitis or rickettsial infections;
Targets:
most gram (+) bacteria (except MRSA), gram (-) bacteria (N. meningitidis, H. influenzae), excellent activity against anaerobes (B. fragilis), and Rickettsiae |
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Term
| Clinical uses of Chloramphenicol |
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Definition
alternative therapy for life-threatening bacterial meningitis caused by N. meningitidis, H. influenzae, and Strep. pneumoniae in pts w/ severe ALLERGY to penicillins & cephalosporins;
brain abscess (w/ penicillin);
Rickettsial dxs (Rocky mountain spotted fever, etc) - tetracyclines preferred but this drug may be preferred in pregnancy and w/ young children |
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Term
| Side Effects/Toxicities of Chloramphenicol |
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Definition
| bone marrow toxicity (reversible bone marrow suppression, aplastic anemia [life-threatening, but very rare]), Gray Baby Syndrome - occurs 2-9 days after therapy: vomiting, rapid respiration, abdominal distention, cyanosis |
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Term
| Pharmacokinetics of Tetracyclines (tetracycline, doxycycline, minocycline, tigecycline) |
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Definition
variable GI absorption, greater in absence of food --> Do not take 1-2 hrs before going to bed or lying down, take standing up with a glass of water (risk of esophageal ulceration);
Binds to Ca & to multivalent cations in antacids --> decreases oral absorption --> don't administer w/ dairy products OR antacids;
Widely distributed EXCEPT to CSF --> NOT used for bacterial meningitis;
Crossese placenta & found in breast milk;
Excreted by kidney & excreted into bile and reabsorbedy by enterohepatic circulation; |
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Term
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Definition
preferred parenteral tetracycline;
excreted by non-renal mechanisms and DOES NOT accumulate with renal failure;
Preferred tetracycline for treating Lyme Disease, Rickettsial infections |
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Term
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Definition
broad-spectrum bacteriostatic agents that inhibit protein synthesis;
inhibits protein synthesis by binding to 30-S bacterial ribosome subunit;
Resistance:
increased efflux by active transport pump (Tet[AE] efflux pump in gram (-) bacteria results in resistance to all 3 drugs);
Tek(K) efflux pump expressed by Staph. works only one drug in family |
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Term
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Definition
NOT drug of choice for gram (+) infections - LOTS of resistance;
DRUGS OF CHOICE for Borrelia burdorferi (spirochete, Lyme Dx), Rickettsia (Rocky Mountain spotted fever), Mycoplasma pneumoniae, Chlamydial infections |
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Term
| Clinical Uses of Tetracylines |
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Definition
DRUG OF CHOICE for Lyme Dx (Borrelia burgdorferi);
DRUG OF CHOICE for Rickettsiae (Rocky Mountain spotted fever);
DRUG OF CHOICE (w/ erythromycin) for Mycoplasma pneumonia;
Chlamydial infections;
Acne;
Gastric & Duodenal Ulcers due to H. pylori;
Periodontitis |
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Term
| Side Effects/Toxicities of Tetracyclines |
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Definition
GI - nausea, vomiting, diarrhea, anorexia, epigastric burning --> reduce by giving w/ food;
Superinfection --> C. difficile;
Bones & teeth discoloration, enamel deformities --> DO NOT give to pregnant pts or children < 8 yrs old;
Renal Damage (outdated & degraded drug);
Sensitivity to light;
Inhibit actions of ADH (vasopressin) --> diabetes insipidus-like state, SIADH; |
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Term
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Definition
tetracycline that is available for parenteral administration and is eliminated by NON-RENAL mechanisms and dosing adjustments are NOT necessary for pts w/ renal failure;
NOT effectively pumped out by Tet(AE) or Tet(K) efflux pumps --> useful in some tetracycline-resistant bacteria;
Uses:
skin & skin structure infections & intra-abdominal infections |
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Term
| erithromycin (base, stearate, estolate, ethylsuccinate, lactobionate) |
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Definition
poor oral absorption;
esters were created to increase oral absorption & increase acid stability;
also available for IV administration;
widely distributed in body EXCEPT for brain & CSF;
excreted unchanged in bile & metabolized by hepatic CYP3A enzymes;
Dose adjustment NOT necessary in RENAL failure but should be AVOIDED w/ Liver dx; |
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Term
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Definition
bacteriostatic by reversible binding to 50-S ribosomal subunit --> inhibits protein synthesis;
50-S binding site for chloramphenicol is CLOSE to this drug's binding site --> ANTAGONISTIC action if both administered at same time;
Resistance:
modification of binding site on 50-S ribosomal subunit by METHYLASE which alters binding site & prevents drug from binding; |
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Term
| Spectrum of ACtivity for Erythromycin |
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Definition
Gram (+) bacteria: Group A Strep., penicillin-susceptible Strep. pneumoniae, Staph. aureus, Corynebacterium;
Gram (-): Moraxalla, Neisseria, Campylobacter;
RESISTANCE: H. influenzae, Enterobacteriacea (E.coli, Klebsiella, Enterobacter);
NOT good against Anaerobic agents (B. fragalis) |
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Term
| Clinical Uses of Erythromycin |
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Definition
DRUG OF CHOICE for mycoplasma pneumonia;
Also used for:
Legionella pneumophila, Nonstrep pharyngitis;
Chlamydial infections - in pregnancy, FIRST LINE AGENT for chlamydial urogenital infections;
Alternative agent used to treat Staph, Strep, and Pneumococci infections in pts allergic to penicllins;
Prevents bacterial endocarditis w/ dental procedures & prophylaxis of rheumatic fever |
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Term
| Side Effects/Toxicities of Erythromycin |
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Definition
GI upset - anorexia, vomiting, diarrhea;
*Can be used to INCREASE GASTRIC EMTPYING - prokinetic agent*
Liver toxicity - cholestatic hepatitis (fever, jaundice, decreased liver fcn);
Cardiac arrhythmia, QT prolongation, ventricular tachycardia;
Inhibits CYP450 3A enzymes --> increases serum levels of drugs metabolized by liver (theophylline, anticoagulants, antihistamine [terfenadine, astemizole]) |
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Term
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Definition
macrolide w/ chemical alteration that makes it more acid stable & demonstrates better oral absorption;
Longer half-life than other drugs in class (6 hrs - BID dosing);
More active against Mycobacterium avium (infection in AIDS pts);
Better activity against H. influenzae than erithromycin;
Clinical Uses:
pharyngitis/tonsillitis, sinusitis, bronchitis, community-acquired pneumonia (CAP), uncomplicated skin infections, prevention & treatment of Mycobacterium avium complex (MAC) |
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Term
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Definition
macrolide that is more acid stable and exhibits better oral absorption vs other drugs in class;
Penetrates most tissues very well (except CNS) --> tissue conc. 10-100x higher than plasma conc. --> drug is slowly released from tissue stores & elimination half-life is 3 days;
DO NOT USE TO TREAT Bacteremia/Sepsis;
NOT extensively metabolized;
Uses:
SINGLE DOSE - uncomplicated genital chlamydial infections (as effective as 7-day doxycycline tx);
MOST active against H. influenzae;
slightly LESS effective against Staph. and Strep infections;
DOES NOT inactivate or induce CYP450 enzymes; |
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Term
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Definition
newest macrolide on market;
used to tx bacterial respiratory infections --> community acquired pneumonia (CAP);
able to be effective against macrolide-resistant bacteria;
Potent inhibitor of CYP3A4 --> severe liver toxicity!!! |
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