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Morphine

Morphine Morphine
Morphine Morphine

Morphine is a narcotic analgesic and it is available for administration as hydrochloride or sulfate salt in all dosage forms. It is a strong analgesic used primarily for the relief of severe pain. 

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Introduction

Morphine is a narcotic analgesic and it is available for administration as hydrochloride or sulfate salt in all dosage forms. It is a strong analgesic used primarily for the relief of severe pain. Higher doses are useful for preoperative sedation and as a supplement to anesthesia. Morphine is also used for analgesia during labor. The effect on uterine contractions depends on the stage of labor when morphine is administered. Morphine is a drug of choice for pain associated with myocardial infarction.

Pharmacological Class: Opioid analgesic

Indications

  • Acute and chronic pain
  • Acute pulmonary edema
  • All forms of epilepsy
  • Cancer pain
  • Dyspnoea in palliative care
  • Myocardial infarction
  • Post-operative pain

Pharmachologic action

The precise mechanism of the analgesic action of morphine is unknown. However, specific central nervous system (CNS) opiate receptors have been identified and likely play a role in the expression of analgesic effects. Morphine first acts on the µ-opioid receptors. The mechanism of respiratory depression caused by opioids involve a reduction in the responsiveness of the brain stem respiratory centers to increase in carbon dioxide tension and to electrical stimulation. It has been shown that morphine binds to and inhibits gamma-aminobutyric acid (GABA) inhibitory interneurons. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.

Dosage

  • Adult dose for patients who are not opioid tolerant: 15 mg orally every 12 hours
  • Adult dose for patients who are opioid tolerant: 60 mg orally per day
  • Pediatric dose: 0.2 to 0.4 mg/kg orally every 4 hours
  • Neonatal dose: 0.2 to 0.4 mg/kg orally every 4 hours

Pharmacokinetics

Oral absorption of morphine is found to be 37.5%. Volume of distribution is found to be 2.75 l/kg and plasma protein binding is 30%. Presystemic metabolism is noted as 58% and metabolism occurs extensively by liver. Renal excretion accounts for 4% and plasma half life is 3 hours. 

Contraindications

  • In patients with significant respiratory depression
  • In acute or severe bronchial asthma
  • In patients with known or suspected paralytic ileus
  • In patients with hypersensitivity (e.g., anaphylaxis) to morphine

Drug interaction

  • Morphine may increase the anesthetic or sedative effects of propofol
  • The concomitant use of morphine sulfate extended-release tablets with other
  •  depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death
  • Mixed agonist/antagonist (i.e. pentazocine, nalbuphine, and butorphanol) and partial agonist (buprenorphine) analgesics may reduce the analgesic effect of morphine sulfate extended-release tablets or precipitate withdrawal symptoms
  • Morphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and cause respiratory depression

Side effects

Common (affecting between 1 in10 to 1 in 100)

  • Dizziness
  • Drowsiness
  • Nausea
  • Vomiting
  • Stomach pain and cramps
  • Diarrhea
  • Loss of appetite
  • Weight loss
  • Dry mouth
  • Sweating

Uncommon (affecting 1 in 100 to 1 in 1000)

  • Blue or purple color of the skin
  • Fast or slow heartbeat
  • Seizures
  • Extreme drowsiness
  • Fainting
  • Chest pain
  • Fever
  • Hives

Very rare (affecting less than 1 in 10,000)

  • Slow, shallow, or irregular breathing
  • Sleepiness
  • Loss of consciousness
  • Limp muscles
  • Cold and clammy skin
  • Small pupils
  • Slow heartbeat

Precautions

  • Morphine should be used with caution in patients with CNS depression, convulsive disorder, ulcerative colitis, fever, recent gastrointestinal (GI) surgery, bradyarrhythmias, supraventricular tachycardia and pulmonary diseases
  • Caution should be taken while driving or alertness requiring tasks, as it may produce drowsiness.
  • Morphine may cause constipation. Patients should change their diet or use other medications to prevent or treat constipation while you are taking morphine.

Clinical evidence

  • Oral morphine, in either immediate release or sustained release form remains the analgesic of choice for moderate or severe cancer pain. The recent study has reported morphine to be an effective analgesic. Pain relief did not differ between MSR (morphine sustained release) and MIR (morphine immediate release). Sustained release versions of morphine were effective for 12 or 24 hour dosing depending on the formulation.1
  • Morphine Sulfate Controlled release (MSC) is an effective oral opioid analgesic that allows an increased dose interval without increased side effects or decreased potency. It can improve the quality of life of cancer patients by allowing them to be maintained without frequent dosing or parenteral medication. Twenty-six patients with inadequately controlled cancer-related pain were examined in an open, but controlled study, using oral morphine sulfate. Of 18 patients who completed the study, all achieved satisfactory levels of analgesia on morphine sulfate, 7 at q8h and 11 at q12h dosing intervals. All patients reported better analgesia while taking morphine sulfate compared to previous regimen.2

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