Morphine

Introduction

Morphine is an opioid analgesic with agonist activity mainly at  opioid receptors. Morphine is used for the relief of moderate to severe pain, especially that associated with cancer, myocardial infarction and surgery.

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Morphine Syrup	MORP26	DD
Morphine SR Tab 10mg	MORP04	DD
Morphine SR Tab 30mg	MORP05	DD

Mechanism of Action

Pain relief Opioid analgesic

Equivalent doses of opioid analgesics

Analgesic/Route	Dose
Codeine: PO	100 mg
Diamorphine: IM, IV, SC	3 mg
Dihydrocodeine: PO	100 mg
Morphine: PO	10 mg
Morphine: IM, IV, SC	5 mg
Oxycodone: PO	6.6 mg
Tramadol: PO	100 mg

Dosage

Morphine is usually administered as the sulphate. Doses are expressed as the salts. Dosage routes include the oral, subcutaneous, intramuscular, intravenous, intraspinal, and rectal routes.

For pain:

• Oral doses are usually equivalent to 5 to 20mg every 4 hours as syrup, or as immediate-release tablet. With modified-release preparations the 24-hour dose is usually given as a single dose or in 2 divided doses. With all modified-release preparations, additional doses of immediate-release tablet may be needed if breakthrough pain occurs.
• Rectally as suppositories in doses of 10 to 30mg every 4 hours.
• Subcutaneous or intramuscular injection is 10mg every 4 hours but may range from 5 to 20 mg.

For myocardial infarction:

• Intravenous injection of 5 to 10 mg given at a rate of 1 to 2 mg/minute

Doses in children

The following initial doses are recommended by the BNFC according to age; doses should thereafter be adjusted according to response:

By subcutaneous injection:

• Neonates: 100 micrograms/kg every 6 hours
• 1 to 5 months: 100 to 200 micrograms/kg every 6 hours
• 6 months to 1 year: 100 to 200 micrograms/kg every 4 hours
• 2 to 11 years: 200 micrograms/kg every 4 hours
• 12 to 17 years: 2.5 to 10 mg every 4 hours

By intravenous injection over at least 5 minutes:

• Neonates: 50 micrograms/kg every 6 hours
• 1 to 5 months: 100 micrograms/kg every 6 hours
• 6 months to 11 years: 100 micrograms/kg every 4 hours
• 12 to 17 years: 5 mg every 4 hours

By mouth or rectum:

• 1 to 2 months: 50 to 100 micrograms/kg every 4 hours
• 3 to 5 months: 100 to 150 micrograms/kg every 4 hours
• 6 to 11 months: 200 micrograms/kg every 4 hours
• 1 to 11 years: 200 to 300 micrograms/kg every 4 hours
• 12 to 17 years: 5 to 10 mg every 4 hours

For severe chronic pain: 5-10 mg q4h, adjusted if needed.

IV Child dose based on body weight. adjusted if needed.

Palliative care pain management dose: 20-60 mg in divided dose depends on where the patients was on opioid before.

Side Effects

As for Opioid Analgesic in general

The commonest adverse effects are nausea, vomiting, constipation, drowsiness and confusion.

Large doses of opioids produce respiratory depression and hypotension, with circulatory failure and deepening coma. Death may occur from respiratory failure.

Treatment of Adverse Effects

1. Constipation can be treated with laxatives such as senna tables and lactulose.

2. Nausea and vomiting can be alleviated by metoclopramide.

3. Intensive supportive therapy may be required to correct respiratory failure and shock. Naloxone is used for rapid reversal of the severe respiratory depression and coma.

       Euphoria, nausea and vomiting, respiratory depression, constipation and cough suppression.

Pharmacokinetics

Oral bioavailability	Morphine salts are well absorbed from the gastrointestinal tract but have poor oral bioavailability since they undergo extensive first-pass metabolism in the liver and gut. After subcutaneous or intramuscular injection morphine is readily absorbed into the blood.
Onset of action	Morphine is distributed throughout the body but mainly in the kidneys, liver, lungs and spleen, with lower concentrations in the brain and muscles. Morphine crosses the blood-brain barrier less readily than more lipid-soluble opioids such as diamorphine. Morphine diffuses across the placenta and also appear in breast milk and sweat.
Metabolism	Up to 10% of a dose of morphine may be excreted into the faeces. The remainder is excreted in the urine.
Elimination half-life	About 35% is protein bound. Mean plasma elimination half-life is about 2 hours.