Benzylpenicillin: Difference between revisions

{{Short description|Antibiotic medication}}

{{Use dmy dates|date=September 2020}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Drugbox

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| verifiedrevid = 396298574

| image = Benzylpenicillin.svg

| width = 250

| image2 = Benzylpenicillin-anion-from-xtal-3D-bs-17.png

| width2 =

| caption2=Ball and stick model.<ref>{{cite journal | vauthors = Dexter DD, van der Veen JM | title = Conformations of penicillin G: crystal structure of procaine penicillin G monohydrate and a refinement of the structure of potassium penicillin G | journal = Journal of the Chemical Society, Perkin Transactions 1 | volume = 3 | issue = 3 | pages = 185–190 | year = 1978 | pmid = 565366 | doi = 10.1039/p19780000185 }}</ref> Legend:<br />Blue=[[nitrogen]]; red=[[oxygen]]; yellow=[[sulfur]]<br />grey=[[carbon]] and carbon bonds; white=[[hydrogen]].

<!--Clinical data-->

| tradename = Pfizerpen, other

| Drugs.com = {{drugs.com|international|Benzylpenicillin}}

| MedlinePlus = a685013

| pregnancy_AU = A

| legal_status = Rx-only

| routes_of_administration = [[Intravenous therapy]], [[intramuscular injection]]

<!--Pharmacokinetic data-->

| bioavailability = 30% oral <ref>{{cite book | vauthors = Yip DW, Gerriets V | chapter = Penicillin | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK554560 | title = StatPearls |publisher=StatPearls Publishing |access-date=7 December 2023 |date=2023|pmid=32119447 }}</ref>

| protein_bound = 60%

| metabolism = [[Liver]]

| elimination_half-life = 30&nbsp;min

| excretion = [[Kidney]]

<!--Identifiers-->

| IUPHAR_ligand = 4796

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 61-33-6

| CAS_supplemental = (free acid)<br/>{{CAS|69-57-8}} (sodium salt)

| ATC_prefix = J01

| ATC_suffix = CE01

| ATC_supplemental = {{ATC|S01|AA14}} {{ATCvet|J51|CE01}}

| PubChem = 5904

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01053

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = D02336

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 18208

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 29

| synonyms = Penicillin G potassium,<ref name=Pro2016/> penicillin G sodium

<!--Chemical data-->

| IUPAC_name = (2''S'',5''R'',6''R'')-3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

| C = 16 | H = 18 | N = 2 | O = 4 | S = 1

| charge =

| SMILES = CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)Cc3ccccc3)C(=O)O)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

<!-- Definition and medical uses -->

'''Benzylpenicillin''', also known as '''penicillin G''' ('''PenG'''<ref>{{Cite book|title=Immunology for Pharmacy|url=https://www.sciencedirect.com/book/9780323069472/immunology-for-pharmacy|isbn=978-0-323-06947-2|publisher=Mosby|chapter=Immunogenicity and Antigenicity| vauthors = Flaherty DK |year=2012 |quote=Natural penicillin (PenG), penicillinase-resistant penicillin (methicillin), extended-spectrum penicillin (amoxicillin), and broad-spectrum penicillin (carbenicillin) all have the same core β-lactam ring, which is essential for antimicrobial activity.}}</ref>) or '''BENPEN''',<ref>{{Cite web|title= Australian Product Information – BENPEN | work = Seqirus Pty Ltd |url=https://labeling.seqirus.com/PI/AU/Benpen/EN/Benpen-Product-Information.pdf }}</ref> is an [[antibiotic]] used to treat a number of [[Pathogenic bacteria|bacterial]] [[infection]]s.<ref name=WHO2008/> This includes [[pneumonia]], [[Streptococcal pharyngitis|strep throat]], [[syphilis]], [[necrotizing enterocolitis]], [[diphtheria]], [[gas gangrene]], [[leptospirosis]], [[cellulitis]], and [[tetanus]].<ref name=WHO2008/> It is not a first-line agent for [[Pneumococcal infection|pneumococcal]] [[meningitis]].<ref name=WHO2008/> Due to benzylpenicillin's limited [[bioavailability]] for oral medications, it is generally taken as an injection in the form of a sodium, potassium, benzathine, or procaine salt.<ref name="Castle_2007">{{cite book | vauthors = Castle SS | chapter = Penicillin G | title = xPharm: The Comprehensive Pharmacology Reference | veditors = Enna SJ, Bylund DB | publisher = Elsevier | location = New York | date = 2007 | pages = 1–6 }}</ref> Benzylpenicillin is given by [[intravenously|injection into a vein]] or [[intramuscular|muscle]].<ref name=Pro2016>{{cite web|title=Penicillin G Injection - FDA prescribing information, side effects and uses|url=https://www.drugs.com/pro/penicillin-g-injection.html|website=www.drugs.com|access-date=10 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220230501/https://www.drugs.com/pro/penicillin-g-injection.html|archive-date=20 December 2016}}</ref> Two long-acting forms [[benzathine benzylpenicillin]] and [[procaine benzylpenicillin]] are available for use by [[Intramuscular injection|injection into a muscle]] only.<ref name=WHO2008/>

<!-- Side effects and mechanism -->

Side effects include [[diarrhea]], [[seizures]], and [[Allergy|allergic reaction]]s including [[anaphylaxis]].<ref name=WHO2008/> When used to treat syphilis or Lyme disease a reaction known as [[Jarisch–Herxheimer reaction|Jarisch–Herxheimer]] may occur.<ref name=WHO2008/> It is not recommended in those with a history of [[Penicillin#Side effects|penicillin allergy]].<ref name=WHO2008/> Use during pregnancy is generally safe in the [[penicillin]] and [[Beta-lactam|β-lactam]] class of medications.<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | publisher = World Health Organization | hdl-access=free |pages=98, 105 }}</ref>

<!-- Society and culture -->

Benzylpenicillin is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<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>

==Medical uses==

===Antimicrobial potency===

As an antibiotic, benzylpenicillin is noted to possess effectiveness mainly against [[gram-positive bacteria|gram-positive]] organisms. Some [[gram-negative bacteria|gram-negative]] organisms such as ''[[Neisseria gonorrhoeae]]'' and ''[[Leptospira weilii]]'' are also reported to be susceptible to benzylpenicillin.<ref>{{cite web|url=http://www.toku-e.com/Upload/Products/PDS/20120521008049.pdf|title=Penicillin G|date=2010-10-10|publisher=Toku-E|archive-url=https://web.archive.org/web/20160303205812/http://www.toku-e.com/Upload/Products/PDS/20120521008049.pdf|archive-date=2016-03-03|access-date=2012-06-11}}</ref>

== Adverse effects ==

Adverse effects can include hypersensitivity reactions including urticaria, fever, joint pains, rashes, angioedema, anaphylaxis, serum sickness-like reaction. Rarely central nervous system toxicity including convulsions (especially with high doses or in severe renal impairment), interstitial nephritis, haemolytic anaemia, leucopenia, thrombocytopenia, and coagulation disorders. Also reported diarrhoea (including antibiotic-associated colitis). Benzylpenicillin has relatively low toxicity, except for in the nervous system, in which it is one of the most active drugs among β-lactam agents.<ref name="Castle_2007"/> In addition, benzylpenicillin is an irritant, a health hazard, and an environmental hazard.<ref name="ACS_MW">{{cite web | title = Benzylpenicillin | url = https://www.acs.org/content/acs/en/molecule-of-the-week/archive/b/benzylpenicillin.html | access-date = 9 November 2022 | work = Molecule of the Week | publisher = American Chemical Society }}</ref>

Benzylpenicillin serum concentrations can be monitored either by traditional microbiological assay or by more modern chromatographic techniques. Such measurements can be useful to avoid central nervous system toxicity in any person receiving large doses of the drug on a chronic basis, but they are especially relevant to patients with [[kidney failure]], who may accumulate the drug due to reduced urinary excretion rates.<ref name="Fossieck_1974">{{cite journal | vauthors = Fossieck Jr B, Parker RH | title = Neurotoxicity during intravenous infusion of penicillin. A review | journal = Journal of Clinical Pharmacology | volume = 14 | issue = 10 | pages = 504–12 | date = October 1974 | pmid = 4610013 | doi = 10.1002/j.1552-4604.1974.tb01364.x| s2cid = 40884225 }}</ref><ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1195–1196 }}</ref>

==Manufacture==

Benzylpenicillin is produced by fermentation of ''[[Penicillium chrysogenum]]''.<ref name="ACS_MW"/> The production of benzylpenicillin involves fermentation, recovery and purification of the penicillin.<ref name="Liu_2016">{{cite journal | vauthors = Liu Q, Li Y, Li W, Liang X, Zhang C, Liu H |date=February 2016 |title=Efficient Recovery of Penicillin G by a Hydrophobic Ionic Liquid |journal=ACS Sustainable Chemistry & Engineering |volume=4 |issue=2 |pages=609–615 |doi=10.1021/acssuschemeng.5b00975 }}</ref>

The fermentation process of the production of benzylpenicillin creates the product. The presence of the product in solution inhibits the reaction and reduces the product rate and yield. Thus, in order to obtain the most product and increase the rate of reaction, it is continuously extracted.<ref>{{cite web | vauthors = Barros J | date = 4 January 2016 | url = https://www.acs.org/content/acs/en/pressroom/cutting-edge-chemistry/use-extraction-to-improve-penicillin-g-recovery.html | title = Use Extraction to Improve Penicillin G Recovery | work = Discover Chemistry | publisher = American Chemical Society | access-date = 2019-05-06 | archive-date = 6 May 2019 | archive-url = https://web.archive.org/web/20190506191624/https://www.acs.org/content/acs/en/pressroom/cutting-edge-chemistry/use-extraction-to-improve-penicillin-g-recovery.html | url-status = dead }}</ref> This is done by mixing the mold with either glucose, sucrose, lactose, starch, or dextrin, nitrate, ammonium salt, corn steep liquor, peptone, meat or yeast extract, and small amounts of inorganic salts.<ref>{{cite web |url= https://www.diaion.com/en/application/pharmaceutical/pdf/antibiotics_fermentation_products_small_molecules_apis.pdf | pages = 312–324 |title= Separation and Purification of Pharmaceuticals and Antibiotics | publisher = Mitsubishi Chemical Corporation }}</ref>

The recovery of the benzylpenicillin is the most important part of the production process because it affects the later purification steps if done incorrectly.<ref name="Liu_2016" /> There are several techniques used to recover benzylpenicillin: aqueous two-phase extraction, liquid membrane extraction, microfiltration, and solvent extraction.<ref name="Liu_2016" />

In the purification step, the benzylpenicillin is separated from the extraction solution. This is normally done by using a separation column.<ref>{{cite journal | vauthors = Saino Y, Kobayashi F, Inoue M, Mitsuhashi S | title = Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia | journal = Antimicrobial Agents and Chemotherapy | volume = 22 | issue = 4 | pages = 564–570 | date = October 1982 | pmid = 6983856 | pmc = 183794 | doi = 10.1128/AAC.22.4.564 }}</ref>

==Synonyms==

* Penicillin II (old UK nomenclature for naming penicillins)<ref name="Science1945">{{cite journal | vauthors = Robinson FA | title = Chemistry of penicillin | journal = The Analyst | volume = 72 | issue = 856 | pages = 274–276 | date = July 1947 | pmid = 20259048 | doi = 10.1039/an9477200274 | bibcode = 1947Ana....72..274R }}</ref><ref name="PenG">{{cite web

|url=https://pubchem.ncbi.nlm.nih.gov/compound/Penicillin-g

|title=Penicillin G

|website=PubChem

|publisher=National Center for Biotechnology Information, National Library of Medicine

|access-date=2020-12-26

}}</ref>

* Wonder drug<ref name="ACS_MW"/>

== References ==

{{Reflist}}

{{Cell wall disruptive antibiotics}}

{{Glycine receptor modulators}}

{{Portal bar | Medicine}}

{{Authority control}}

[[Category:Benzyl compounds]]

[[Category:Enantiopure drugs]]

[[Category:Glycine receptor agonists]]

[[Category:Penicillins]]

[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]