Erythromycin

• IUPAC: 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- dioxane -2-yl ) oxy -3 ,5,7,9,11,13 - hexamethyl -1 - oxacyclotetradecan - 2 ,10 -dione
• Latin: Erythromycinum

• J01FA01
• D10AF02
• S01AA17

White to yellow, crystalline, odorless solid

Macrolide antibiotic

Inhibition of bacterial protein synthesis

1.209 g/cm3

8.6 to 8.8

• Very low ( decreases with increasing temperature )
• 2.0 g / l at 20 ° C.

1,535

Risk

• 9272 mg · kg -1 ( LD50, rat, oral)
• 4600 mg · kg -1 ( LD50, rat, oral)
• 426 mg · kg -1 ( LD50, mouse, i.v.)
• 2580 mg · kg -1 ( LD50, mouse, oral)
• 3018 mg · kg -1 ( LD50, hamsters, oral)

Template: Infobox chemical / molecular formula search available

Erythromycin is a mixture of structurally very similar compounds, which are formed by bacteria of the genus Streptomyces, especially Streptomyces erythreus. Because of its antibiotic effect Erythromycin is used as a drug.

The main component is the erythromycin A, next come up to 5% erythromycin B and erythromycin C before in lesser amount. Chemically, erythromycin is one of the glycosides, pharmacologically it belongs to the macrolide antibiotics. Erythromycin is used to treat infections with gram- positive bacteria ( streptococci, staphylococci), anaerobic bacteria ( propionibacteria, corynebacteria ) and mycoplasma.

• 5.1 salts and esters
• 5.2 Other derivatives

History

1949 sent the Filipino scientist Abelardo Aguilar soil samples from the province of Iloilo to his employer, the pharmaceutical company Lilly. There, isolated a working group under James M. McGuire erythromycin as a metabolic product of Streptomyces erythreus ( Saccharopolyspora erythraea today ). Marketed since 1952 as Ilosone ® Lilly In 1953, U.S. Patent 2,653,899 for this connection. The total synthesis of erythromycin succeeded Robert B. Woodward and co-workers 1981.

Mechanism of action

Erythromycin inhibits the reaction catalyzed by the elongation factor EF -G operation of translocation during translation. EF -G has the function of a GTPase, thus causing the decay of GTP to GDP Pi The released energy is used to solve the free tRNA molecules from the ribosome, thus enabling its movement. An absence of elongation factor prevents the protein.

Erythromycin is effective against gram- positive bacteria, Gram- negative bacteria against a few ( Bordetella, Legionella, Chlamydia ) and against mycoplasma and some rickettsiae. It is a narrow- spectrum antibiotic.

Clinical information

Areas of application

The spectrum of action of erythromycin is similar to the spectrum of action of some penicillins, resulting in similar applications. Therefore, erythromycin may be used if allergic to β -lactam antibiotics exist or if resistance to prevent their use.

Oral therapy is indicated in infections due to erythromycin -susceptible pathogens infectious diseases of the ear, nose and ear area ( otitis media, sinusitis ), lower respiratory tract (bronchitis, pneumonia), the conjunctiva, at (erysipelas ), diphtheria, severe forms of Acne vulgaris and certain forms of urethritis. If ( more effective ) other antibiotics can not be given, eg penicillin allergy, erythromycin is indicated for the treatment of inflammation of the pharynx ( pharyngitis), or pharyngeal tonsils (tonsillitis ), of scarlet fever or syphilis.

Is not possible with oral erythromycin may be administered parenterally.

Topical Erythromycin comes especially in the therapy of inflammatory acne forms used.

Erythromycin can also be used in motility and emptying disorders of the stomach, when the first-line drugs metoclopramide and domperidone no improvement. The use of erythromycin as a prokinetic agent is done, however, under the conditions of the off- label use. Erythromycin binds already in subantibiotischen doses of the motilin receptor, causing a promoting gastrointestinal peristalsis, relaxation of Pylorusmuskulatur and coordinates motor activities of the stomach and duodenum.

Interactions and side effects

Erythromycin is an inhibitor of cytochrome P450 3A4, 3A5 and 3A7. Thus, the biotransformation of drugs in which this enzyme is involved, such as cyclosporine, diazepam, lidocaine, warfarin and esp. impaired, resulting in drug accumulation and strengthening of main and side effects.

Erythromycin is well tolerated, the most common adverse effects are mild gastrointestinal disturbances. Erythromycin is a strong prokinetic agent, which will accelerate the gastric emptying. Very rarely occur anaphylactic reactions, tinnitus or hearing loss or deafness usually temporary.

Chemical and pharmaceutical information

Together, the erythromycins is a 14 - membered lactone ring without double bonds ( erythronolide structure). This is every second carbon atom, methyl-branched and is glycosidically linked to the C -6 of the amino sugar and desosamine at C- 4 with a neutral sugar ( erythromycin A and B: cladinose, erythromycin C and D: mycarose ).

Erythromycin A is sparingly soluble in water and forms colorless to pale yellow crystals.

The erythromycins are dry stable, but decompose in solution at room temperature gradually. When heated above 60 ° C and in an acidic or alkaline solution of the degradation occurs rapidly.

Pharmacokinetics

Erythromycin is mainly biliary excreted with a half-life of 1.5 to 2.5 hours. Therefore administration in approximately 6- hourly rhythm is displayed.

Salts and esters

Erythromycin is not acid stable, so come for peroral treatment with either enteric-coated dosage forms for use or acid-resistant derivatives of erythromycin in the manufacture of medicines must be used: as the esters of the hydroxy group at C-2 'of the Desoxamins, erythromycin stearate and Erythromycinethylsuccinat and erythromycin estolate, the Dodecylsulfatsalz of Erythromycinpropionats used in tablets, capsules and suspensions. The esters are prodrugs, as the free 2' -OH group of the amino sugar is important for binding.

Water-soluble salts such as Erythromycinlactobionat be used for the preparation of parenteral dosage forms.

Erythromycin as the free base is used in externally applied preparations, eg in alcoholic solutions, gel, cream or ointment base ( eg, for topical treatment of acne).

Other derivatives

Erythromycin is the lead compound of the macrolide antibiotics. By partial synthesis is obtained from erythromycin, the 7-O -methyl- erythromycin ( clarithromycin) and erythromycin 9- { (E)- O-[ (2-methoxyethoxy ) methyl] oxime } ( roxithromycin ).

The ring-substituted azithromycin is different from erythromycin A by expanding the structure of erythronolide a carbon atom between C- 9 and C- 10 carbonyl group is substituted at the C -10 by a methylamino ( azalide ).

Clarithromycin, roxithromycin and azithromycin are also used as drugs.

Trade names

AknedermEry (D), Aknefug -EL (D), Aknemycin solution / ointment ( D), Aknilox (CH), Erios (CH), Eryaknen (D, A, CH), Eryfluid (A), Erythrocin (A), Inderm (D) Infectomycin (D), Meromycin (A), Paediathrocin (D), Sanasepton (D), Stiemycine (D ), numerous generics (D, A, CH)

Aknemycin emulsion / Plus / ointment (D, A, CH), Ecolicin (D), Isotrexin (D, A), Zineryt (D)

Erythrocin vet., Erythrocin, Erythromycinthiocyanat, Erytrotil