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Erythromycin
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| Systematic (IUPAC) name | |
| 6-(4-dimethylamino-3-hydroxy- 6-methyl-oxan-2-yl)oxy- 14-ethyl-7,12,13-trihydroxy-
4-(5-hydroxy-4-methoxy-4,6-dimethyl- oxan-2-yl)oxy-3,5,7,9,11,13-hexamethyl- 1-oxacyclotetradecane-2,10-dione |
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| Identifiers | |
| CAS number | |
| ATC code | J01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C37H67NO13 |
| Mol. mass | 733. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 93 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 100% |
| Protein binding | 90% |
| Metabolism | liver (under 5% excreted unchanged) |
| Half life | 1. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 5 hours |
| Excretion | bile |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | oral, iv, im |
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people that have an allergy to penicillins. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. For a topic outline on this subject see List of basic Australia topics. A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Intramuscular injection is the injection of a substance directly into a Muscle. The macrolides are a group of drugs (typically Antibiotics) whose activity stems from the presence of a macrolide ring, a large macrocyclic In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections Allergy is a disorder of the Immune system often also referred to as Atopy. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and Legionellosis. Mycoplasma is a Genus of bacteria which lack a Cell wall. Without a cell wall they are unaffected by many common Antibiotics such Legionellosis is an Infectious disease caused by Bacteria belonging to the Genus Legionella. It is also used to treat outbreaks of chlamydia, syphilis, acne, and gonorrhea. Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. Acne vulgaris (commonly called acne) is a Skin disease caused by changes in the Pilosebaceous units (skin structures consisting of a Hair follicle Gonorrhea (also gonorrhoea) caused by the bacteria Neisseria gonorrhoeae, is a common Sexually transmitted disease. In structure, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desoamine), making it a compound very difficult to produce via synthetic methods. lactone is a cyclic Ester in Organic chemistry. It is the condensation product of an Alcohol group and a Carboxylic acid
Erythromycin is produced from a strain of the actinomycete Saccharopolyspora erythraea, formerly known as Streptomyces erythraeus. Actinobacteria or actinomycetes are a group of Gram-positive bacteria with high G+C ratio.
Contents |
History
Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly and Company ( is a global Pharmaceutical company and one of the world's largest corporations Year 1949 ( MCMXLIX) was a Common year starting on Saturday (link will display the full calendar of the Gregorian calendar. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate Erythromycin from the metabolic products of a strain of Streptomyces erythreus (designation changed to "Saccharopolyspora erythraea") found in the samples.
Lilly filed for patent protection of the compound and U. S. patent 2,653,899 was granted in 1953. The product was launched commercially in 1952 under the brand name Ilosone (after the Philippine region of Iloilo where it was originally collected from). Year 1952 ( MCMLII) was a Leap year starting on Tuesday (link will display full calendar of the Gregorian calendar. The Philippines ( Filipino: Pilipinas, officially known as the Republic of the Philippines (fil ''Republika ng Pilipinas'' RP Iloilo is a province of the Philippines located in the Western Visayas region. Erythromycin was formerly also called Ilotycin.
In 1981, Nobel laureate (1965 in chemistry) and Professor of Chemistry at Harvard University (Cambridge, MA) Robert B. Woodward, along with a large number of members from his research group, posthumously reported the first stereocontrolled asymmetric chemical synthesis of Erythromycin A. Cambridge Massachusetts is a City in the Greater Boston area of Massachusetts, United States. Robert Burns Woodward ( April 10 1917 &ndash July 8 1979) was an American organic chemist.
The antiobiotic clarithromycin was invented by scientists at the Japanese drug company Taisho Pharmaceutical in the 1970s as a result of their efforts to overcome the acid instability of erythromycin. Clarithromycin is a Macrolide Antibiotic used to treat Pharyngitis, Tonsillitis, acute maxillary Sinusitis, acute bacterial exacerbation ( is a Japanese Pharmaceutical company based in Tokyo. History Taisho was established in 1912 to produce over-the-counter drugs.
Available Forms
Erythromycin is available in enteric-coated tablets, slow-release capsules, oral suspensions, ophthalmic solutions, ointments, gels, and injections.
Brand names include Robimycin, E-Mycin, E. E. S. Granules, E. E. S. -200, E. E. S. -400, E. E. S. -400 Filmtab, Erymax, Ery-Tab, Eryc, Erypar, EryPed, Eryped 200, Eryped 400, Erythrocin Stearate Filmtab, Erythrocot, E-Base, Erythroped, Ilosone, MY-E, Pediamycin, Zineryt, Abboticin, Abboticin-ES, Erycin, PCE Dispertab, Stiemycine and Acnasol.
Mechanism of action
Erythromycin may possess bacteriocidal activity, particularly at higher concentrations[1]. A bactericide or bacteriocide is a substance that kills bacteria and preferably nothing else The mechanism is not fully elucidated however. By binding to the 50S subunit of the bacterial 70S rRNA complex, protein synthesis and subsequently structure/function processes critical for life or replication are inhibited[2]. Note Sometimes the ' 50s is used as shorthand for the 1950s, the 1850s, or other such decades in various centuries Events and Trends Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells. Erythromycin interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex. Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Without this translocation, the A site remains occupied and thus the addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is inhibited. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino This interferes with the production of functionally useful proteins and is therefore the basis of antimicrobial action.
Pharmacokinetics
Erythromycin is easily inactivated by gastric acid; therefore, all orally-administered formulations are given as either enteric-coated or more-stable laxatives or esters, such as erythromycin ethylsuccinate. Esters are a class of Chemical compounds and Functional groups Esters consist of an inorganic or organic Acid in which at least Succinic acid ( IUPAC Systematic name: butanedioic acid; historically known as spirit of amber) is a Dicarboxylic acid. Erythromycin is very rapidly absorbed, and diffuses into most tissues and phagocytes. Phagocytes are cells that are found in the blood bone marrow and other tissues of Vertebrates. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where, during active phagocytosis, large concentrations of erythromycin are released.
Metabolism
Most of erythromycin is metabolised by demethylation in the liver. Demethylation is the chemical process resulting in the removal a Methyl group (CH3 from a molecule The liver is a vital organ in the human body and is present in Vertebrates and some other animals Its main elimination route is in the bile, and a small portion in the urine. Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. Erythromycin's elimination half-life is 1. The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 5 hours.
Adverse effects
Erythromycin inhibits the cytochrome P450 system, particularly CYP3A4, which can cause it to affect the metabolism of many different drugs. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains If CYP3A4 substrates, such as simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor), are taken concomitantly with erythromycin, levels of the substrates will increase, often causing adverse effects. Simvastatin ( INN) (ˈsɪmvəstætɨn (marketed under the trade names Zocor, Simvastatin Simlup Simcard and others is a hypolipidemic drug belonging Lovastatin is a member of the drug class of Statins used for lowering Cholesterol ( Hypolipidemic agent) in those with Hypercholesterolemia and Atorvastatin ( INN) (əˌtɔrvəˈstætən (marketed under the name Lipitor, Lipidra Aztor Torvatin Sortis Torvast Torvacard Totalip Tulip Xarator A noted drug interaction involves erythromycin and simvastatin, resulting in increased simvastatin levels and the potential for rhabdomyolysis. Rhabdomyolysis is the rapid breakdown ( Lysis) of Skeletal muscle tissue ( rhabdomyo) due to injury to muscle tissue
Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are fairly common, so erythromycin tends not to be prescribed as a first-line drug. In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Abdominal pain can be one of the Symptoms associated with transient disorders or serious disease Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the However, erythromycin may be useful in treating gastroparesis due to this pro-motility effect. Gastroparesis, also called delayed gastric emptying is a medical condition consisting of a Paresis (partial Paralysis) of the Stomach ("gastro-" Intravenous erythromycin may also be used in endoscopy as an adjunct to clear gastric contents. In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following
More serious side-effects, such as arrhythmia and reversible deafness, are rare. Dysrhythmia redirects here For the American band see Dysrhythmia (band. Allergic reactions, while uncommon, may occur, ranging from urticaria to anaphylaxis. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals Cholestasis, Stevens-Johnson syndrome, and toxic epidermal necrolysis are some other rare side-effects that may occur. In Medicine, cholestasis is a condition where Bile cannot flow from the Liver to the Duodenum. Stevens-Johnson syndrome (SJS is a life-threatening Condition affecting the Skin in which Cell death causes the epidermis to separate from the Toxic epidermal necrolysis (TEN also known as Lyell's syndrome, is a life-threatening dermatological condition that is frequently induced by a reaction to medications
Erythromycin has been shown to increase the probability of pyloric stenosis in children whose mothers took the drug during the late stages of pregnancy or while nursing. Pyloric stenosis (or infantile hypertrophic pyloric stenosis) is a condition that causes severe vomiting in the first few months of life
It can also cause hyperactivity in high doses.
Contraindications
Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia, and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4 (Ray et al 2004). Ventricular tachycardia ( V-tach or VT) is a Tachycardia, or fast heart rhythm that originates in one of the ventricles of the Heart Verapamil (brand names Isoptin, Verelan, Calan, Bosoptin, Covera-HS) is an L-type Calcium channel blocker. Diltiazem is a member of the group of drugs known as Benzothiazepines which are a class of Calcium channel blockers used in the treatment of Hypertension Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism Hence, erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time. In medicine specifically Cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap). Terfenadine is an Antihistamine formerly used for the treatment of allergic conditions Astemizole (marketed under the brand name Hismanal) is a second generation Antihistamine drug which has a long duration of action Cisapride is a Parasympathomimetic which acts as a Serotonin 5-HT4 receptor Agonist. Pimozide (sold as Orap) is an Antipsychotic drug. It was discovered at Janssen Pharmaceutica in 1963.
References
- ^ Katzung PHARMACOLOGY, 9e Section VIII. Chemotherapeutic Drugs Chapter 44. Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins
- ^ Katzung PHARMACOLOGY, 9e Section VIII. Chemotherapeutic Drugs Chapter 44. Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins
- Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes. N Engl J Med 2004;351:1089-96. The New England Journal of Medicine ( N Engl J Med or NEJM) is an English-language Peer-reviewed Medical journal published
- British National Formulary "BNF 49" March 2005.
- Mims C, Dockrell HM, Goering RV, Roitt I, Wakelin D, Zuckerman M. Chapter 33: Attacking the Enemy: Antimicrobial Agents and Chemotherapy: Macrolides. In: Medical Microbiology (3rd Edition). London: Mosby Ltd; 2004. p 489
External links
Dictionary
erythromycin
-noun
- Any of a class of macrolide antibiotics produced by an actinomycete of the genus Streptomyces
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