Usuari:Trollramsac/proves: diferència entre les revisions

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Ceftriaxone was patented in 1978, and approved for medical use in 1982.<ref name=Fis2006>{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin | name-list-format = vanc |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=495 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA495 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]], the safest and most effective medicines needed in a [[health system]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2016/>

 

[[Image:Цефтриаксон.JPG|thumb|A vial of ceftriaxone, manufactured and sold in Russia]]

 

In combination with doxycycline or azithromycin, ceftriaxone is recommended by the United States [[Centers for Disease Control and Prevention]] (CDC) for the treatment of gonorrhea. By itself, it is not recommended due to the potential for resistance development.<ref>{{cite journal | title = Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 61 | issue = 31 | pages = 590–4 | date = August 2012 | pmid = 22874837 | doi = | url = https://www.cdc.gov/mmwr/pdf/wk/mm6131.pdf | author1 = Centers for Disease Control Prevention (CDC) }}</ref>

 

Like other third-generation cephalosporins, ceftriaxone is active against ''[[Citrobacter]]'' spp., ''[[Serratia marcescens]]'', and beta-lactamase-producing strains of ''[[Haemophilus]]'' and ''[[Neisseria]]''.<ref name=":12" /> However, unlike [[ceftazidime]] and [[cefoperazone]], ceftriaxone does not have useful activity against ''[[Pseudomonas aeruginosa]]''.<ref name=":12" /> It is generally not active against ''[[Enterobacter]]'' species, and its use should be avoided in the treatment of ''Enterobacter'' infections, even if the isolate appears susceptible, because of the emergence of resistance.<ref name=":12" /> Some organisms, such as ''Citrobacter, Providencia'', and ''Serratia'', have the ability to become resistant through the development of cephalosporinases (these enzymes hydrolyze cephalosporins and render them inactive).<ref name=":12" />

 

Ceftriaxone is available for administration via the intramuscular or the intravenous routes.<ref name=":232"/> Diluents containing calcium should not be used to reconstitute ceftriaxone and it must not be administered in intravenous lines containing other calcium-containing solutions, as a ceftriaxone-calcium precipitate could form.<ref name=":232"/>

 

 

 

Ceftriaxone is pregnancy category B.<ref name=":232"/><ref name="Drugs.com pregnancy" /> It has not been observed to cause birth defects in animal studies, but a lack of well-controlled studies done in pregnant women exists.<ref name=":232"/>

 

 

Low concentrations of ceftriaxone are excreted in breast milk that are "not expected to cause adverse effects in breastfed infants."<ref>{{Cite web|title = TOXNET|url = http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+57|website = toxnet.nlm.nih.gov|access-date = 2015-11-04|url-status = dead|archive-url = https://web.archive.org/web/20170908213423/https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed%253A%2540term+%2540DOCNO+57|archive-date = 2017-09-08}}</ref>{{Failed verification|date=May 2020}} The manufacturer recommends that caution be exercised when administering ceftriaxone to women who breastfeed.<ref name=":232"/>

 

[[Hyperbilirubinemia|Hyperbilirubinemic]] [[neonates]] are contraindicated for the use of ceftriaxone.<ref name=":232"/> It can compete with [[bilirubin]] and displace it from binding to [[Human serum albumin|albumin]], increasing the risk of bilirubin [[encephalopathy]].<ref name=":232"/>

 

According to the package insert, clinical studies did not

show differences in efficacy and safety of ceftriaxone in geriatrics compared to younger patients but "greater sensitivity of some older individuals cannot be ruled out."<ref name=":232"/>

 

 

Although generally well tolerated, the most common adverse reactions associated with ceftriaxone are changes in white blood cell counts, local reactions at site of administration, rash, and diarrhea.<ref name=":02" />

Ceftriaxone may precipitate in bile, causing [[biliary sludge]], [[biliary pseudolithiasis]], and [[gallstone]]s, especially in children. [[Hypoprothrombinemia|Hypoprothrombinaemia]] and bleeding are specific side effects. Haemolysis is reported.<ref name="pmid22272902">{{cite journal | vauthors = Shiffman ML, Keith FB, Moore EW | title = Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility | journal = Gastroenterology | volume = 99 | issue = 6 | pages = 1772–8 | date = December 1990 | pmid = 2227290 | doi = 10.1016/0016-5085(90)90486-K }}</ref><ref>{{cite journal | vauthors = Shrimali JD, Patel HV, Gumber MR, Kute VB, Shah PR, Vanikar AV, Trivedi HL | title = Ceftriaxone induced immune hemolytic anemia with disseminated intravascular coagulation | journal = Indian Journal of Critical Care Medicine | volume = 17 | issue = 6 | pages = 394–5 | date = November 2013 | pmid = 24501497 | pmc = 3902580 | doi = 10.4103/0972-5229.123465 }}</ref><ref>{{cite journal | vauthors = Guleria VS, Sharma N, Amitabh S, Nair V | title = Ceftriaxone-induced hemolysis | journal = Indian Journal of Pharmacology | volume = 45 | issue = 5 | pages = 530–1 | date = Sep–Oct 2013 | pmid = 24130395 | pmc = 3793531 | doi = 10.4103/0253-7613.117758 }}</ref> It has also been reported to cause post kidney failure in children.<ref>{{cite journal | vauthors = Li N, Zhou X, Yuan J, Chen G, Jiang H, Zhang W | s2cid = 2854637 | title = Ceftriaxone and acute renal failure in children | journal = Pediatrics | volume = 133 | issue = 4 | pages = e917-22 | date = April 2014 | pmid = 24664092 | doi = 10.1542/peds.2013-2103 }}</ref> Like other antibiotics, ceftriaxone use can result in [[Clostridium difficile colitis|''Clostridium difficile'']]-associated diarrhea ranging from mild diarrhea to fatal colitis.<ref name=":02" />

 

 

Ceftriaxone should not be used in those with an allergy to ceftriaxone or any component of the formulation. Although there is negligible cross-reactivity between penicillins and third-generation cephalosporins,<ref name="Katzung 2009 783–7842" /><ref>{{Cite web|title = The Use of Cephalosporins in Penicillin-allergic Patients|url = http://www.medscape.com/viewarticle/764042|website = www.medscape.com|access-date = 2015-11-10|url-status = live|archive-url = https://web.archive.org/web/20151114135258/http://www.medscape.com/viewarticle/764042|archive-date = 2015-11-14}}</ref> caution should still be used when using ceftriaxone in penicillin-sensitive patients.<ref name=":02">{{Cite web|url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050585s061lbl.pdf|title = Rocephin Prescribing Information|access-date = November 1, 2015|publisher = Roche|url-status = live|archive-url = https://web.archive.org/web/20160304055415/http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050585s061lbl.pdf|archive-date = March 4, 2016}}</ref> Caution should be used in people who have had previous severe penicillin allergies.<ref name=":02" /> It should not be used in hyperbilirubinemic neonates, particularly those who are premature because ceftriaxone is reported to displace bilirubin from albumin binding sites, potentially causing bilirubin encephalopathy. Concomitant use with intravenous calcium-containing solutions/products in neonates (≤28 days) is contraindicated <ref>{{cite web|url = http://healthcare.utah.edu/pharmacy/alerts/243.htm|title = FDA Updates warning on Ceftriaxone-Calcium injection|url-status = live|archive-url = https://web.archive.org/web/20091128093447/http://healthcare.utah.edu/pharmacy/alerts/243.htm|archive-date = 2009-11-28}}</ref> even if administered through different infusion lines due to rare fatal cases of calcium-ceftriaxone precipitations in neonatal lungs and kidneys.<ref name=":02" /><ref>{{cite journal | vauthors = Bradley JS, Wassel RT, Lee L, Nambiar S | title = Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events | journal = Pediatrics | volume = 123 | issue = 4 | pages = e609-13 | date = April 2009 | pmid = 19289450 | doi = 10.1542/peds.2008-3080 }}</ref>

 

 

Ceftriaxone is a third-generation antibiotic from the [[cephalosporin]] family of antibiotics.<ref name=":12"/> It is within the [[β-lactam antibiotic|β-lactam family of antibiotics]]. Ceftriaxone selectively and irreversibly inhibits bacterial cell wall synthesis by binding to transpeptidases, also called transamidases, which are [[Penicillin binding proteins|penicillin-binding proteins]] (PBPs) that catalyze the cross-linking of the [[peptidoglycan]] polymers forming the bacterial cell wall.<ref name=":032">{{Cite book|title = Foye's Principles of Medicinal Chemistry|publisher = Lippincott Williams & Wilkins|year = 2013|isbn = 9781609133450|location = Philadelphia, PA|pages = 1093–1094, 1099–1100|editor-last = Lemke|editor-first = Thomas L.|editor-last2 = Williams|editor-first2 = David A.| name-list-format = vanc |edition = Seventh}}</ref> The peptidoglycan cell wall is made up of pentapeptide units attached to a polysaccharide backbone with alternating units of N-acetylglucosamine and N-acetylmuramic acid.<ref>{{cite journal | vauthors = van Heijenoort J | s2cid = 46066256 | title = Formation of the glycan chains in the synthesis of bacterial peptidoglycan | journal = Glycobiology | volume = 11 | issue = 3 | pages = 25R–36R | date = March 2001 | pmid = 11320055 | doi = 10.1093/glycob/11.3.25r }}</ref><ref name=":3">{{cite journal | vauthors = Scheffers DJ, Pinho MG | title = Bacterial cell wall synthesis: new insights from localization studies | journal = Microbiology and Molecular Biology Reviews | volume = 69 | issue = 4 | pages = 585–607 | date = December 2005 | pmid = 16339737 | pmc = 1306805 | doi = 10.1128/MMBR.69.4.585-607.2005 }}</ref> PBPs act on a terminal D-alanyl-D-alanine moiety on a pentapeptide unit and catalyze the formation of a peptide bond between the penultimate D-alanine and a glycine unit on an adjacent peptidoglycan strand, releasing the terminal D-alanine unit in the process.<ref name=":032"/><ref name=":3" /> The structure of ceftriaxone mimics the D-alanyl-D-alanine moiety, and the PBP attacks the beta-lactam ring in ceftriaxone as if it were its normal D-alanyl-D-alanine substrate.<ref name=":032"/> The [[peptidoglycan]] cross-linking activity of PBPs is a construction and repair mechanism that normally helps to maintain bacterial cell wall integrity, so the inhibition of PBPs leads to damage and destruction of the cell wall and eventually to cell lysis.<ref name=":032"/>

 

 

'''Absorption:''' Ceftriaxone can be administered intravenously and intramuscularly, and the drug is completely absorbed.<ref name=":232"/><ref>{{cite journal | vauthors = Patel IH, Kaplan SA | title = Pharmacokinetic profile of ceftriaxone in man | journal = The American Journal of Medicine | volume = 77 | issue = 4C | pages = 17–25 | date = October 1984 | pmid = 6093513 }}</ref> It is not available orally.<ref>{{Cite book|title = Red Book: Pharmacy's Fundamental Reference|publisher = PDR Network, LLC.|year = 2010|isbn = 9781563637513|location = |pages = |edition = 114th}}</ref><ref>{{Cite web|title = DailyMed – Search Results for ceftriaxone|url = http://dailymed.nlm.nih.gov/dailymed/search.cfm?query=ceftriaxone&searchdb=all&labeltype=all&sortby=rel&audience=professional&page=1&pagesize=100|website = dailymed.nlm.nih.gov|access-date = 2015-11-04|url-status = live|archive-url = https://web.archive.org/web/20160306075340/http://dailymed.nlm.nih.gov/dailymed/search.cfm?query=ceftriaxone&searchdb=all&labeltype=all&sortby=rel&audience=professional&page=1&pagesize=100|archive-date = 2016-03-06}}</ref>

'''Elimination:''' The average elimination half-life in healthy adults is 5.8–8.7 hours.<ref name=":232" /> In people with renal impairment, the average elimination half-life increases to 11.4–15.7 hours.<ref name=":232" />

 

 

Ceftriaxone is commercially available as a white to yellowish-orange crystalline powder for reconstitution.<ref name=":232"/> Reconstituted ceftriaxone injection solutions are light yellow- to amber-colored depending on how long the solution had been reconstituted, the concentration of ceftriaxone in the solution, and the diluent used.<ref name=":232"/> To reduce pain with intramuscular injections, ceftriaxone may be reconstituted with [[lidocaine]].<ref>{{cite journal | vauthors = Schichor A, Bernstein B, Weinerman H, Fitzgerald J, Yordan E, Schechter N | title = Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it reduce the pain of the injection? | journal = Archives of Pediatrics & Adolescent Medicine | volume = 148 | issue = 1 | pages = 72–5 | date = January 1994 | pmid = 8143016 | doi = 10.1001/archpedi.1994.02170010074017 }}</ref>

The ''syn''-configuration of the [[methoxy]][[oxime]] moiety confers resistance to [[Beta lactamase|beta-lactamase]] enzymes produced by many [[Gram-negative bacteria]].<ref name=":032"/> The stability of this configuration results in increased activity of ceftriaxone against otherwise resistant Gram-negative bacteria.<ref name=":032" /> In place of the easily [[Hydrolysis|hydrolyzed]] [[acetyl]] group of cefotaxime, ceftriaxone has a metabolically stable thiotriazinedione moiety.<ref name=":032" />

 

 

Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction.<ref>{{cite journal | vauthors = Knackstedt LA, Melendez RI, Kalivas PW | title = Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking | journal = Biological Psychiatry | volume = 67 | issue = 1 | pages = 81–4 | date = January 2010 | pmid = 19717140 | pmc = 2795043 | doi = 10.1016/j.biopsych.2009.07.018 }}</ref>