20.03.5.1 Morphine

Morphine is readily absorbed from the gastrointestinal tract, the rectal mucosa, the skin, and muscle. Morphine is available in oral, suppository preparations (rectal), subcutaneous, and intramuscular preparations. It is used intravenously for fast action. Morphine can be introduced into the epidural or intrathecal space, from which it penetrates into spinal cord. As the spinal cord is the site of action of morphine, achieving high concentrations in the spinal cords achieves high levels of pain relief.

Morphine undergoes considerable first pass metabolism, such that bioavailability is only about 25% after oral administration. Thus, high doses of morphine have to be give orally, to achieve reasonably plasma levels. A broad range of steady-state plasma concentrations of morphine (16 to 364 ng/ml) is associated with analgesia.

As morphine is metabolised by the liver, in hepatic dysfunction, it may be necessary to decrease the dose of morphine, as bioavailability may be increased. Morphine is metabolised to morphine-6-glucuronide and morphine-3-glucuronide. Morphine-6-glucuronide is an active metabolite. Morphine-6-glucuronide is actually more potent than morphine as an agonist at µ-receptors, and therefore, in causing pain relief. The half-life of morphine is 2 hours, whereas morphine-6-glucuronide has a longer half life, thus, the pain relieving effect of morphine is prolonged, and the prolongation is due to the morphine-6-glucuronide.

Morphine-6-glucuronide is excreted by the kidney. In kidney disease, it may be necessary to decrease the dose of morphine, as there may be accumulation of the morphine-6-glucuronide. Accumulation of morphine-6-glucorinide may lead to excessive respiratory depression.

Because of the respiratory depression, morphine should be used with caution in people with compromised respiratory function. For instance, morphine should be used with caution in subjects with emphysema.

Most of the unwanted effects of morphine are part of, or extensions of, stimulating the µ-receptors, and include excessive respiratory depression, nausea and vomiting, and constipation. Morphine also causes hypotension, due to its ability to cause peripheral vasodilation and inhibiting the baroreceptor reflex. Also, morphine can cause urinary retention.

In high doses, the euphoria with morphine goes, and is replaced by dizziness, mental clouding, and dysphoria. Dysphoria is a feeling of anxiety, depression, and unease. Morphine can also cause pruritis (itchy skin).