Morphine

Morphine an alkaloid. Belongs to the group of strong-acting opioids of level III in the WHO staging scheme (classification of pain therapy) and is approved as an analgesic for severe and most severe pain. Its action is mediated through opioid receptors. Morphine is the most important component of opium, the dried, milky sap of the opium poppy (Papaver somniferum), accounting for about 10% of its content. Morphine is subject to narcotic regulations according to the BTMG.

Morphine binds centrally to opioid receptors and has an agonistic effect on them. This prevents the transmission of pain and reduces the patient's perception of pain. The activation of the μ-receptors is in the foreground. Morphine has a lower affinity for κ-receptors (Pacifici GM 2016).

Presynaptically, morphine leads to a decrease in cellular calcium influx via the opioid receptor, G-protein mediated, resulting in hyperpolarization.

Postsynaptically, there is G-protein mediated activation of potassium channels with subsequent potassium efflux. The potassium efflux also leads to hyperpolarization and effective prevention of pain transmission.

Morphine slightly reduces blood pressure and heart rate.

Morphine can be prescribed in the form of tablets, capsules, syrup, suspension, suppositories, drops or as an injection.

After oral administration, the effect sets in after about 30 to 90 minutes and lasts for 4-6 hours. With 20 to 40%, the absolute bioavailability after oral administration is low. Injected intramuscularly, morphine takes effect after 15 to 30 minutes. Intravenously, morphine takes effect within a few minutes. Metabolism occurs in the liver and intestinal epithelium (for oral administration). The major morphine metabolites are morphine-3-glucuronide and morphine-6-glucuronide (Christrup LL 1997). The half-life is 1.7 to 4.5 hours after parenteral administration. Morphine is predominantly excreted renally. In renal insufficiency, the dose must be adjusted (Lee KA et al. 2016).

Morphine may reduce fertility.

Because morphine crosses the placental barrier, the drug should be used in pregnancy only if the benefit to the mother is greater than the risk to the child. After delivery, children should be watched for withdrawal symptoms.

Morphine has mutagenic effects; therefore, patients of procreative and childbearing age should use safe contraception during therapy. Because morphine passes into breast milk, breast-feeding should not occur during therapy.

The dosage of medication with morphine must be individually adapted to the pain situation (Pacifici GM 2016).

Intramuscularly or subcutaneously: adults 10-30 mg, children 0.05-0.1 mg/kg body weight.

Intravenously, adults receive 5-10 mg, children 0.05-0.1 mg/kg body weight.

Epidurally, adults receive 1-4 mg, children 0.05-0.1 mg/kg body weight (diluted in each case).

Intrathecally, adults receive 0.5-1.0 mg, children 0.02 mg/kg body weight (diluted in each case).

The smallest analgesic effective dose should always be administered. The morphine dose should be kept as low as necessary. Single doses in the form of injections can be repeated 4-6 hours if necessary.

Beware of overdose - it is life threatening! The therapy should be phased out, otherwise withdrawal symptoms will occur.

During therapy with morphine, the following side effects are to be expected with varying frequency, depending on the form of administration:

Very common: mood changes (euphoria/dysphoria).

Frequent: headache, dizziness, dullness, increase in agitation, insomnia, alteration in cognitive and sensory performance, vomiting, loss of appetite, dyspepsia, changes in taste, micturition disorders, hyperhidrosisRarely: elevation of pancreatic enzymes, pancreatitis, biliary colic, renal colic, bronchospasm, withdrawal symptoms.

Very rare: Tremor, muscle twitching, seizures, neurological symptoms such as paresis, respiratory inhibition (delayed), dependence, decrease in libido, potency weakness, blurred vision, double vision, eye tremor, intestinal obstruction, abdominal pain, increase in liver enzymes, muscle cramps, muscle rigidity, dyspnea, asthenia, malaise, chills, amenorrhea, dental changes, syndrome of inadequate ADH secretion.

Occasional: alteration of blood pressure and heart rate.

Dermatological UAWs: Extensive lichenoid exanthema has been described under diamorphine (heroin) a semisynthetic morphine derivative. Furthermore, pruritus has been described, especially after intrathecal application (George RB et al. 2009). Epidurally applied morphine seems to be associated with reactivation of HSV in obstetric patients in the postpartum period. An association between HSV reactivation and epidural fentanyl has not been established (Crone LA et al. 1988). Urticaria, urticarial exanthema and peripheral oedema have also been described in isolated cases.

Drug interactions showed with morphine with the following agents:

Anaesthetics, cimetidine, hypnotics, benzodiazepines, antihistamines/antiemetics, neuroleptics, barbiturates, antidepressants, psychotropic drugs, other opioids, Parkinson's drugs, tranquillisers, muscle relaxants, MAO inhibitors, rifampicin.

Alcohol consumption should be avoided during therapy with morphine (enhancement of morphine side effects such as respiratory depression and sedation).

Hypersensitivity to the active substance, ileus, acute abdomen, respiratory depression, severe chronic obstructive pulmonary disease, coagulation disorders and infections in the area of injection.

Special monitoring or dose reduction is required in cases of:

Opioid dependence, impaired consciousness, respiratory dysfunction, cor pulmonale, increased intracranial pressure without ventilation, hypotension, prostatic hyperplasia with residual urine formation, urinary tract obstruction, biliary tract disease, inflammatory bowel disease, pheochromocytoma, pancreatitis, hypothyroidism, seizures/epilepsy.

The psychotropic morphine is abused as an intoxicant and is physically and psychologically addictive, which is why it is subject to narcotics law.

Morphine can alter responsiveness and attention. Especially at the beginning of therapy or when increasing the usual dose, patients should therefore neither actively participate in road traffic nor operate dangerous machinery.

For further details on morphine, see the relevant specialist information.

1. Christrup LL (1997) Morphine metabolites. Acta Anaesthesiol Scand 41:116-122.
2. Crone LA et al (1988) Recurrent herpes simplex virus labialis and the use of epidural morphine in obstetric patients. Anesth Analg 67:318-323.
3. George RB et al. (2009) Serotonin receptor antagonists for the prevention and treatment of pruritus, nausea, and vomiting in women undergoing cesarean delivery with intrathecal morphine: a systematic review and meta-analysis. Anesth Analg 109:174-182.
4. Kolm I et al. (2013) Lichenoid drug eruption following Intravenous Application of Orally Formulated Diamorphine, a Semisynthetic Heroin. Case Rep Dermatol 5:176-180.
5. Lee KA et al (2016) Evidence for Neurotoxicity Due to Morphine or Hydromorphone Use in Renal Impairment: A Systematic Review. J Palliat Med 19:1179-1187.
6. Pacifici GM (2016) Metabolism and pharmacokinetics of morphine in neonates: A review. Clinics (Sao Paulo) 71:474-80.
7. Sverrisdóttir E et al. (2015) A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain. Eur J Pharm Sci 74:45-62.