Ritodrine Explained

Ritodrine, sold under the brand name Yutopar, is a tocolytic drug used to stop premature labor.[1] [2] This drug has been removed from the US market, according to FDA Orange Book. It was available in oral tablets or as an injection and was typically used as the hydrochloride salt.

The drug acts as a selective β2-adrenergic receptor agonist.[3]

It was first approved for medical use in the United States in 1984.

Medical uses

Ridodrine is used to treat preterm labor.

Contraindications

Possible contraindications of ritodrine include type 2 diabetes, high blood pressure, and migraines.

Side effects

Most side effects of β2-adrenergic receptor agonists result from their concurrent β1-adrenergic receptor agonistic activity, and include increase in heart rate, rise in systolic blood pressure, decrease in diastolic blood pressure, chest pain secondary to myocardial infarction, and arrhythmia. β-Adrenergic receptor agonists may also cause fluid retention secondary to decrease in water clearance, which when added to the tachycardia and increased myocardial work, may result in heart failure. In addition, they increase gluconeogenesis in the liver and muscle resulting in hyperglycemia, which increases insulin requirements in diabetic patients. The passage of β-adrenergic receptor agonists through the placenta does occur and may be responsible for fetal tachycardia, as well as hypoglycemia or hyperglycemia at birth. It has also been associated with postpartum bleeding.

Ritodrine has been reported rarely to cause serious side effects including rhabdomyolysis, hepatotoxicity, leukopenia, pulmonary edema, and psychiatric symptoms, among others.[4] [5] [6] [7] [8]

Pharmacology

Pharmacodynamics

Ritodrine is a short-acting β2-adrenoreceptor agonist — a class of medication used for smooth muscle relaxation (other similar drugs are used in asthma or other pulmonary diseases such as salbutamol (albuterol)). Since ritodrine has a bulky N-substituent, it has high β2-adrenergic receptor selectivity. Also, the 4-hydroxy group on the benzene ring is important for activity as it is needed to form hydrogen bonds. Since the drug is β2-selective, it is used for premature labor.[9]

Pharmacokinetics

The 4-hydroxy group of ritodrine makes it susceptible to metabolism by catechol-O-methyl transferase (COMT).

Chemistry

Ritodrine, also known as 4-hydroxy-β-hydroxy-N-(4-hydroxyphenylethyl)amphetamine or as N-(4-hydroxyphenylethyl)-4-hydroxynorephedrine, is a substituted phenethylamine and amphetamine derivative.[10] [11] [12]

The experimental log P of ritodrine is 2.4 and its predicted ranges from 1.53 to 2.3.

History

Ritodrine was first approved for medical use in the United States in 1984.[13]

Society and culture

Names

Ritodrine is the generic name of the drug and its,,, and .[14] [15] In the case of the hydrochloride salt, its generic name is ritodrine hydrochloride and this is its and . It is also known by its developmental code name DU-21220. The drug has been sold under brand names including Pre-Par, Utopar, and Yutopar, among others.

See also

Notes and References

  1. Yaju Y, Nakayama T . Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm labour: a systematic review . Pharmacoepidemiol Drug Saf . 15 . 11 . 813–822 . November 2006 . 16981213 . 10.1002/pds.1317 .
  2. Li X, Zhang Y, Shi Z . Ritodrine in the treatment of preterm labour: a meta-analysis . The Indian Journal of Medical Research . 121 . 2 . 120–7 . February 2005 . 15756046 . 2008-10-05 . 2019-08-25 . https://web.archive.org/web/20190825003349/https://www.icmr.nic.in/ijmr/2005/February/0207.pdf . dead .
  3. Mangrella M, Torella M, Russo F, Rossi F, Piucci B, Cantoni V . [Pharmacology of ritodrine] . Italian . Minerva Ginecol . 51 . 6 . 233–244 . June 1999 . 10479875 .
  4. Sun L, Tang M, Peng M, Xu P, Wang Y . Ritodrine-induced rhabdomyolysis and psychiatric symptoms: a case report and literature review . BMC Pregnancy Childbirth . 23 . 1 . 11 . January 2023 . 36611175 . 9824990 . 10.1186/s12884-022-05299-2 . free .
  5. Ceriani R, Borroni G, Bissoli F . Ritodrine-related liver injury. Case reports and review of the literature . Ital J Gastroenterol Hepatol . 30 . 3 . 315–317 . June 1998 . 9759604 .
  6. Wu CD, Chao AS, Cheng PJ, Soong YK . Ritodrine-induced leukopenia: a case report and literature review . Changgeng Yi Xue Za Zhi . 19 . 4 . 388–391 . December 1996 . 9041773 .
  7. Castro Fernández M, Romero Gómez M, Grande Santamaría L, Caballero Manzano M . [Acute hepatitis due to ritodrine] . Spanish . Med Clin (Barc) . 113 . 6 . 239 . September 1999 . 10472614 .
  8. Alper M, Cohen WR . Pulmonary edema associated with ritodrine and dexamethasone treatment of threatened premature labor. A case report . J Reprod Med . 28 . 5 . 349–352 . May 1983 . 6152991 .
  9. http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html Medicinal Chemistry of Adrenergics and Cholinergics
  10. Web site: Ritodrine . PubChem . 30 August 2024.
  11. Web site: C17H21NO3 . ChemSpider . 2024-08-30 . 2024-08-30.
  12. Web site: Ritodrine: Uses, Interactions, Mechanism of Action . DrugBank Online . 31 December 1984 . 30 August 2024.
  13. Book: Kleemann A, Kutscher B . Ullmann's Pharmaceuticals . Wiley . 2022 . 978-3-527-80733-8 . 30 August 2024 . 4-PA9.
  14. Book: Schweizerischer Apotheker-Verein . Index Nominum 2000: International Drug Directory . Medpharm Scientific Publishers . 2000 . 978-3-88763-075-1 . 30 August 2024 . 923.
  15. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms . Springer Netherlands . 1999 . 978-0-7514-0499-9 . 30 August 2024 . 249.