Usage
- Ethylmorphine is prescribed for the treatment of whooping cough and occasionally for mild to moderate pain and dry cough.
- Pharmacological Classification: Opioid analgesic, Antitussive.
- Mechanism of Action: Ethylmorphine acts primarily as an agonist at mu-opioid receptors in the central nervous system, similarly to codeine and morphine. This leads to decreased pain perception and suppression of the cough reflex. It also interacts with kappa and delta opioid receptors to a lesser extent. It is metabolized to morphine in the liver via CYP2D6 which is thought to contribute to its analgesic effect.
Alternate Names
- Dionine
- Ethomorphine
- Ethylmorphine Hydrochloride
- Codethyline (in combination with codeine)
How It Works
- Pharmacodynamics: Ethylmorphine binds to mu-opioid receptors in the brain, spinal cord, and other tissues, inhibiting pain signal transmission and reducing the cough reflex.
- Pharmacokinetics: Ethylmorphine is administered orally and is rapidly absorbed from the gastrointestinal tract. It is metabolized in the liver primarily by CYP2D6 to morphine, which contributes to its analgesic effect. Ultra-rapid metabolizers of CYP2D6 are at risk for opioid toxicity, even with typical doses. Ethylmorphine is excreted primarily in the urine.
- Mode of Action: Binds to mu-opioid receptors, inhibiting adenylate cyclase and decreasing intracellular cAMP, which leads to hyperpolarization of neurons and reduced neuronal excitability. This inhibits pain transmission and cough reflex.
- Elimination Pathways: Primarily renal excretion; hepatic metabolism via CYP2D6.
Dosage
Standard Dosage
Adults:
- 5-10 mL (12.5-25 mg ethylmorphine) three to four times daily.
- Maximum daily dose: Should not exceed recommendations from other similar products which range from 45-120 mg per day.
Children:
- Not recommended for children under 2 years old.
- 2-5 years: 1-2.5 mL (2.5–6.25 mg ethylmorphine) three times daily.
- 6-10 years: 2.5 mL (6.25 mg ethylmorphine) three times daily.
- 11-12 years: 3.5 mL (8.75 mg ethylmorphine) three times daily.
- 13-17 years (over 40 kg): 5 mL (12.5 mg ethylmorphine) three to four times daily.
- Pediatric Safety Considerations: Use with extreme caution in children due to the risk of respiratory depression. Avoid use in children younger than two years. Not recommended for children under 12 years in some jurisdictions. Not recommended for use in children aged 12 to 18 years with compromised respiratory function.
Special Cases:
- Elderly Patients: Reduce dosage due to potential for impaired hepatic or renal function.
- Patients with Renal Impairment: Administer with caution; dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Administer with caution; dose adjustment may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with respiratory conditions (e.g., asthma, COPD), obstructive sleep apnea, neuromuscular diseases, severe heart or lung conditions, and those with a history of substance abuse.
Clinical Use Cases
Ethylmorphine’s clinical use is primarily limited to whooping cough. Its use in other clinical settings, such as those below, is not supported by current guidelines and practice:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
- Reduce dosage in elderly patients and those with renal or hepatic impairment.
- Ultra-rapid metabolizers of CYP2D6 should avoid ethylmorphine due to increased risk of morphine toxicity.
Side Effects
Common Side Effects
- Constipation
- Nausea
- Vomiting
- Dizziness
- Drowsiness
- Confusion
- Dry mouth
- Headache
Rare but Serious Side Effects
- Respiratory depression
- Hypotension
- Hallucinations
- Seizures (especially in children)
- Anaphylactic reactions
Long-Term Effects
- Dependence and addiction with prolonged use
Adverse Drug Reactions (ADR)
- Respiratory depression, requiring urgent intervention.
- Severe hypotension and circulatory failure.
Contraindications
- Hypersensitivity to ethylmorphine or other opioids.
- Respiratory depression.
- Acute or severe bronchial asthma.
- Obstructive sleep apnea.
- Ultra-rapid metabolizers of CYP2D6.
- Children under 2 years old (in some jurisdictions under 8 years).
- Patients scheduled for tonsillectomy or adenoidectomy.
Drug Interactions
- CNS Depressants: (e.g., benzodiazepines, barbiturates, alcohol) – Increased risk of respiratory depression, sedation, coma, and death.
- Opioid Antagonists: (e.g., naloxone) – Reduced efficacy of ethylmorphine.
- CYP2D6 Inhibitors: (e.g., certain antidepressants, antipsychotics) – Increased ethylmorphine levels and toxicity.
- CYP2D6 Inducers: (e.g., rifampicin) – Decreased ethylmorphine levels and efficacy.
- MAOIs: Concomitant use is not recommended.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: There is no established FDA pregnancy safety category for ethylmorphine.
- Fetal Risks: Potential for fetal respiratory depression and neonatal withdrawal syndrome. Use only if clearly necessary and the benefits outweigh the risks. Not recommended after week 20 of pregnancy in some jurisdictions.
- Breastfeeding: Ethylmorphine passes into breast milk. Use only if clearly necessary and if the benefits outweigh the risks. Monitor infant for adverse effects. Not recommended in some jurisdictions.
Drug Profile Summary
- Mechanism of Action: Mu-opioid receptor agonist.
- Side Effects: Constipation, nausea, vomiting, dizziness, drowsiness, confusion, respiratory depression (serious).
- Contraindications: Respiratory depression, asthma, obstructive sleep apnea, ultra-rapid CYP2D6 metabolizers.
- Drug Interactions: CNS depressants, opioid antagonists, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution only if benefits outweigh risks.
- Dosage: Adults: 5-10 mL (12.5-25 mg) TID-QID; Children: Dose based on age/weight (see above).
- Monitoring Parameters: Respiratory rate, blood pressure, oxygen saturation, level of consciousness.
Popular Combinations
- Not commonly used in combination therapies. Historically it has been combined with codeine, for example in the brand codethyline.
Precautions
- General Precautions: Assess respiratory function, history of substance abuse, hepatic and renal function before initiating therapy.
- Specific Populations: Use with extreme caution in elderly patients and children due to risk of respiratory depression. Avoid use in pregnant and breastfeeding women unless absolutely necessary.
- Lifestyle Considerations: Avoid alcohol; may impair ability to drive or operate machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ethylmorphine?
A: Adults: 5-10 mL (12.5-25 mg) three to four times daily. Children: Dosage varies based on age and weight (see detailed dosage section).
Q2: What are the common side effects of Ethylmorphine?
A: Common side effects include constipation, nausea, vomiting, dizziness, drowsiness, confusion, dry mouth, and headache.
Q3: What are the serious side effects of Ethylmorphine?
A: Serious side effects include respiratory depression, hypotension, seizures, and allergic reactions.
Q4: What are the contraindications for Ethylmorphine?
A: Contraindications include hypersensitivity to ethylmorphine or other opioids, respiratory depression, severe asthma, obstructive sleep apnea, and being an ultra-rapid metabolizer of CYP2D6.
Q5: Can Ethylmorphine be used during pregnancy or breastfeeding?
A: Ethylmorphine should be used with extreme caution during pregnancy and breastfeeding only if clearly necessary and the benefits outweigh the risks. Consult the pregnancy and breastfeeding section for more details.
Q6: What are the drug interactions associated with Ethylmorphine?
A: Ethylmorphine interacts with CNS depressants (e.g., benzodiazepines, alcohol), opioid antagonists (e.g., naloxone), and drugs that affect CYP2D6 activity (e.g., certain antidepressants, antipsychotics).
Q7: How does Ethylmorphine work?
A: Ethylmorphine is an opioid agonist that primarily binds to mu-opioid receptors in the CNS, reducing pain perception and suppressing the cough reflex.
Q8: Can Ethylmorphine be used in children?
A: Ethylmorphine use in children should be approached with extreme caution due to the increased risk of respiratory depression. Dosage should be adjusted based on age and weight. It is contraindicated in children younger than two years.
Q9: Is Ethylmorphine addictive?
A: Yes, Ethylmorphine, like other opioids, has the potential for dependence and addiction, especially with prolonged use.
Q10: How should Ethylmorphine be administered?
A: Ethylmorphine is typically administered orally as a solution.
