Products and production
Morphine drops are an aqueous dropping solution of morphine hydrochloride, usually in concentration 1% or 2%, maximum 4%. The concentration refers to the salt; the effective amount of morphine base is less. The drug is subject to strict control as an anesthetic and is available only on prescription. The morphine drops of Streuli Pharma AG are registered as medicinal products with Swissmedic (Morphini hydrochloridum Streuli, drops). However, pharmacies also traditionally produce the drops themselves as an extemporaneous preparation. A common prescription is found in the Formularium Helveticum, but in practice other and modified prescriptions are also used. Morphine solutions and suspensions (Oramorph, retarded: MST Continus) based on morphine sulfate are also approved, but from our point of view they do not belong to morphine drops in the strict sense.
Structure and properties
Morphine hydrochloride (C17H20ClNO3 – 3 H2O, Mr = 375.8 g/mol) is the hydrochloride and trihydrate of morphine. It is also known as morphini hydrochloridum PhEur or morphini hydrochloridum trihydricum. Morphine hydrochloride exists as a white crystalline powder, as colorless silk-like needles, or as cube-shaped masses and, unlike morphine base, is soluble in water. Morphine occurs naturally in opium from opium poppies and has a strong bitter taste.
Effects
Morphine (ATC N02AA01) is analgesic. It has cough-irritant, constipating, sedative, respiratory depressant, antidiuretic, miotic, multiple psychotropic, and emetic properties. Morphine is an agonist at opioid receptors with high affinity at the µ-receptor and weak affinity at the κ-receptor.
Indications
Morphine drops are used according to the WHO staging scheme for the treatment of moderate to severe acute and persistent pain, i.e., when non-opioid analgesics (e.g., acetaminophen) or weak opioids (e.g., codeine) are insufficiently effective.
Dosage
According to the drug label. Bioavailability varies widely interindividually due to high first-pass metabolism. Therefore, the dose is adjusted on an individual basis. The solution is usually administered by counting the drops. Intake with sufficient liquid is recommended; intake is independent of meals. The solution is intensely bitter and can be mixed with syrup or other beverages if necessary (exception: black tea, tannins). Due to the short half-life of morphine of about 2-4 hours, frequent application is necessary. The WHO recommends regular intake “by the clock” for chronic pain, i.e., the drug should be administered on a fixed schedule rather than as needed, unless other opioids such as fentanyl patches are also prescribed. Morphine-containing medications should be discontinued gradually when changes in pain management occur to avoid withdrawal symptoms.
Contraindications
Morphine drops are contraindicated in hypersensitivity. Full and comprehensive precautions, as well as other contraindications that include, in particular, impaired respiratory function, and risk of epileptic seizures, can be found in the drug label.
Interactions
Morphine is primarily conjugated in the liver by UGT2B7 to morphine-3-glucuronide and morphine-6-glucuronide and demethylated to normorphine. Morphine-6-glucuronide is an active metabolite. Centrally depressant drugs, such as sedatives, sleeping pills, antidepressants, neuroleptics, or alcohol, may potentiate the adverse effects of morphine and result in respiratory depression, sedation, low blood pressure, or coma. Anticholinergic agents may potentiate the anticholinergic side effects of morphine (constipation, dry mouth, urinary disturbances, confusion in the elderly). Other interactions are possible with opioid antagonists, cimetidine (controversial, only in rats? ), muscle relaxants, MAO inhibitors, ritonavir, and rifampicin, among others.
Adverse effects
Possible adverse effects include mood changes, sleep disturbances, hallucinations, respiratory depression, fatigue, drowsiness, dizziness, sweating, visual disturbances, miosis (small pupils), convulsions, low blood pressure, indigestion, dry mouth, nausea, constipation opioids and constipation, smooth muscle spasms, psychological and physical dependence, histamine release, skin flushing, itching, and hypersensitivity reactions. Overdose manifests as respiratory depression, low blood pressure, and coma.
