Orciprenaline/ Metaproterenol

Orciprenaline belongs to the Beta2-Adrenergic Receptor Agonist Pharmacological class.

Orciprenaline is approved for the treatment of asthma, bronchospasm and Chronic Obstructive Pulmonary Disease.

An average of about 40% of Orciprenaline is absorbed after the oral administration. Orciprenaline is rapidly cleared off in the urine in the form of glucuronic acid conjugates. Peak effect of Orciprenaline is observed after 1 hour.

The common side effects associated with Orciprenaline are headache, dizziness, palpitations, nausea, increased heart rates etc.

Orciprenaline is available in the form of Oral Tablets and Oral Syrups.

Orciprenaline is available in India, U.K., U.S., Canada, India, E.U., China, Japan, Australia.

Orciprenaline belonging to the pharmacological class of Beta2-Adrenergic Receptor Agonist, acts as a Bronchodilator therapeutic agent. Through its action on Beta2-adrenergic receptors, Orciprenaline is found to work by activation of adenylate cyclase, the enzyme which is responsible for the production of cellular mediated cAMP. Orciprenaline hence leads to Bronchodilation of the smooth muscles and reverses bronchospasm.

Orciprenaline has a quick onset of action is found to be 30 - 45 minutes, and the duration of action is around 3- 6 hours.

Orciprenaline is available in oral tablets, syrup

Tablet are to be administered as a whole with water/liquid.

Syrups are to be administered as per dosage instructions by the medical practitioner.

Orciprenaline can be used in the treatment of:

• Asthma
• Bronchospasm
• COPD (Chronic Obstructive Pulmonary Disease)

Orciprenaline can help to relieve symptoms of Asthma, Bronchospasm, Chronic Bronchitis, Emphysema and other lung associated conditions.

Orciprenaline is approved for use in the following clinical indications:

• Asthma
• Bronchospasm
• Chronic Bronchitis
• Emphysema
• COPD (Chronic Obstructive Pulmonary Disease)
• Exercise-induced Asthma

For asthma and bronchospasm:

Syrup –Oral Solution Dosage Form:

Adults—Two teaspoonfuls i.e.10 ml, three or four times a day.

Children older than 9 years of age —Two teaspoonfuls i.e.10 mL, three or four times a day.

Children 6 to 9 years of age —One teaspoonful i.e.5 mL , three or four times a day.

Children younger than 6 years of age—Usage and dosage must be determined by the child's doctor.

Tablets- Oral Dosage Form

Adults—About 20 mg three or four times a day.

Children older than 9 years of age —20 mg three or four times a day.

Children 6 to 9 years of age —10 mg three or four times a day.

Children younger than 6 years of age—Usage not recommended.

Tablet: 10mg, 20mg

Syrup: 10ml/5ml

Oral Syrups, Oral tablets

Maintaining health and smoking cessation is a must.

Avoid or restrict or limit the usage of caffeine as it might lead to the risk of nausea, palpitations, nervousness, rapid heartbeat, etc.

Diet containing refined and high energy-dense foods, low fiber, food with a high glycemic index, saturated and trans fat food, red and processed meat, added sugar, salt, preservatives, low antioxidants, and vitamins needs to be restricted.

The dietary restrictions should be individualized as per the patient's requirements.

Orciprenaline maybe contraindicated during the co-administration with the following drugs: Sympathomimetic amines

• Monoamine oxidase inhibitors
• Tricyclic Antidepressants.
• Beta blocking agents
• Hypersensitivity to the ingredients of the medication

Treating physician should closely monitor the patient and keep pharmacovigilance as follows:

• Orciprenaline is not advised to be used on a regular daily basis without appropriate concomitant anti-inflammatory therapy.
• Orciprenaline is not advised to be administered to pregnant women unless the expected benefits outweigh the possible risks to the fetes
• Patients who are suffering from cardiac arrhythmias, recent myocardial infarction, severe organic heart and/or other vascular disorders, myocardial insufficiency, hypertension, hyperthyroidism pheochromocytomas or diabetes mellitus should be taken care of while concomitant administration of Orciprenaline
• Occasionally patients have reported to have developed severe paradoxical airways resistance with repeated excessive use of sympathomimetic inhalation preparations.
• Potentially serious hypokalemia may result from concomitant therapy with b2–agonist therapy, mainly from parenteral and nebulized administration.
• Particular caution has been advised in acute severe asthma as this may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics.

Avoid alcohol usage while on Orciprenaline Medication as alcohol can worsen the effects of any underlying disease condition.

Orciprenaline or the components of the drug medication has not been found to be excreted in milk, hence a decision should be made by the treating medical practioner whether to continue and should be only advised if the potential benefits outweigh the risks.

Pregnancy Category C.

There is no well-established data in pregnant patients. Orciprenaline should be administered and used during pregnancy only if the potential benefit outweighs the risks.

No sufficient scientific evidence traceable regarding the use and safety of Orciprenaline in concurrent use with any particular food.

The adverse reactions related to Orciprenaline can be categorized as:

Common

• Fast, pounding, or irregular heartbeat.

Less common

• Trembling or shaking of the hands or feet or legs
• Worsening of asthma

Rare

• Pounding in the ears
• Puffiness of the face and fingers
• Runny nose
• Shivering
• Slow or fast heartbeat
• Sore throat
• Sweating
• Swelling
• Insomnia
• Vomiting
• Blurred vision
• Chest pain
• Chills
• Cough
• Diarrhoea
• Dizziness
• Fainting
• Fever
• Headache
• Increased sweating
• Joint pain
• Loss of appetite
• Muscle aches and pains
• Nausea
• Nervousness

The clinically relevant drug interactions of Orciprenaline is briefly summarized here:

Sympathomimetic Agents: Concomitant use of Orciprenaline Sulphate with other sympathomimetic agents has not recommended since the combined use may lead to adverse cardiovascular effects.

Epinephrine, Monoamine oxidase Inhibitors and Tricyclic Antidepressants: Extreme care must also be exercised in the concomitant use of Orciprenaline with epinephrine, monoamine oxidase inhibitors or tricyclic antidepressants since the action of beta-adrenergic agonists may be enhanced.

Halogenated Hydrocarbons: Inhalation of halogenated hydrocarbon Anaesthetics such as halothane, trichloroethylene and enflurane is said to increase the susceptibility to the deleterious cardiovascular effects of beta-agonists.

The common side effects of Orciprenaline include the following:

• Dizziness
• Fast or pounding heartbeat
• Headache
• Dizziness
• Nausea
• Nervousness
• Sweating
• Tremors
• Vomiting

Pregnancy

There is no well documented experience of clinical studies in pregnant women. Orciprenaline should only be used during pregnancy if the potential benefits outweigh the risks associated to the foetus growth.

Nursing Mothers

It is not known whether Orciprenaline is excreted in human milk. Therefore, Orciprenaline should be used during nursing only if the potential benefits outweigh the potential risks associated with the new born growth.

Pediatric Use

Clinical studies have not been performed on the relationship of age to the effects of Orciprenaline oral solutions and tablets in children younger than 6 years of age, hence safety and efficacy cannot be established.

Geriatric Use

No information is available/established on the relationship of age to the effects of Orciprenaline in geriatric patients.

The physician should be vigilant about the knowledge and treatment pertaining to the identification and treatment of over dosage of molecule Orciprenaline.

The symptoms of over dosage are tachycardia, palpitation, tremor, hypertension, and hypotension, widening of the pulse pressure, anginal pain, arrhythmias, and flushing.

Treatment therapy may include the administration of sedatives, tranquilizers, or, in severe cases, intensive therapy.

Beta-receptor blockers, preferably beta1-selective, are suitably used as specific antidotes. A possible increase in bronchial obstruction must be taken into account and the dose should be adjusted carefully in patients suffering from asthma. It has been found that the beta-blocker propranolol effectively antagonizes the action of Orciprenaline.

Pharmacodynamics

Orciprenaline which is also known as metaproterenol, a synthetic amine, is structurally and pharmacologically similar to Isoproterenol. Orciprenaline is used widely exclusively as a bronchodilator. The pharmacological effects of beta-adrenergic agonist drugs, such as Orciprenaline, occurs by the stimulation through beta-adrenergic receptors of intracellular adenyl cyclase which is an enzyme which catalyses the conversion of adenosine triphosphate (ATP) to cyclic- 3',5'- adenosine monophosphate (c-AMP). An increased cAMP level leads to the relaxation of bronchial smooth muscles and in turn, inhibits the release of inflammatory mediators from mast cells that are involved in promoting immediate hypersensitivity.

Pharmacokinetics

• Absorption

Excretion studies in humans during the oral administration of labelled compounds have demonstrated that an average of about 40% of the drug is absorbed.

• Metabolism and Excretion

The drug is excreted primarily in urine as glucuronic acid conjugates. Animal studies such as in rats, rabbits and monkeys have also demonstrated good absorption as evidenced by recovery of substantial amounts of Orciprenaline in the urine and the major metabolite in animals is also the form of the drug conjugate. The concentration of radioactivity in blood plasma was determined in rabbits which were followed by intravenous administration of radiolabelled orciprenaline sulfate. Radioactivity was found to be decreased in two phases of different velocities. During the first phase, the decrease was found to be linear on the semi-logarithmic scale with a half-life of about 40 minutes. This may represent tissue penetration. The second phase was considerably slower and a half-life of approximately 15 hours was observed.

There are some clinical studies of the drug Orciprenaline mentioned below:

1. Comparative study of isoproterenol and metaproterenol sulfate. Canad Med Assoc J 1968;99: 585.
2. Clinical statistical evaluation of the bronchodilatory activity
3. Alupent in measured dose manual aerosol compared with conventional aerosolization of the same drug. Much Med Wschr Ed Esp 1966; 108: 517.
4. Holmes TH, Morgan B. A comparative clinical trial of metaproterenol and
5. isoproterenol bronchodilator aerosols. Clin Pharmacol Ther 1968; 9: 615.
6. Ieda M. Long–term therapy with Alotecâ. The Treatment 1965; 18: 696.
7. Kimura M, Ogihara M: Stimulation
8. by transforming growth factor-alpha of
9. DNA synthesis and proliferation of adult rat hepatocytes in primary cultures: modulation by alpha- and beta-adrenoceptor agonists. J
10. Pharmacol
11. Exp Ther. 1999 Oct;291(1):171-80.
12. Gelmont DM, Balmes JR, Yee A: Hypokalemia induced by inhaled bronchodilators. Chest. 1988 Oct;94(4):763-6.
13. Fitch KD: The use of anti-asthmatic drugs. Do they affect sports performance? Sports Med. 1986 Mar-Apr;3(2):136-50.
14. Singh H, Linas S: Beta 2-adrenergic function in cultured rat proximal tubule epithelial cells. Am J Physiol. 1996 Jul;271(1 Pt 2): F71-7.
15. Ishikawa S, Cherniak RM. The effect of nebulized bronchodilators on airflow resistance in chronic airway obstruction. Am Rev Resp Dis 1969; 99: 703.
16. Kennedy MCS. A new bronchodilator drug: Alupentâ (TH 152). Brit J Clin Pract 1963; 17:
17. Kennedy MCS, Jackson SLO. Oral sympathomimetic amines in treatment of asthma. BritMed J 1963; 5371: 1506.
18. Kessler F. Clinical trial of metaproterenol aerosol in bronchial asthma. Ann Allergy 1964; 22:

1. https://reference.medscape.com/drug/metaproterenol-343439#10
2. https://www.drugs.com/cons/alti-orciprenaline.html
3. https://www.rxwiki.com/orciprenaline
4. https://www.researchgate.net/publication/17696891_Treatment_of_Premature_Labour_with_Orciprenaline
5. https://pubmed.ncbi.nlm.nih.gov/6145456/
6. https://go.drugbank.com/drugs/DB00816
7. https://www.medbroadcast.com/drug/getdrug/orciprenaline
8. https://pubchem.ncbi.nlm.nih.gov/compound/Metaproterenol#section=NORMAN-Suspect-List-Exchange-Classification
9. https://www.aapharma.ca/downloads/en/PIL/2016/Orciprenaline-PM.pdf