Hydromorphone resembles morphine both structurally and pharmacologically. Like other narcotic analgesics, hydromorphone exerts its principal pharmacological effects on the central nervous system and gastrointestinal tract. Its primary action of therapeutic value is analgesia. The analgesic effects of hydromorphone are due to its central action; however, the precise mechanism of action of hydromorphone and other opiates is not known, although it is believed to relate to the existence of opiate receptors in the central nervous system. Hydromorphone, like other narcotic analgesics, appears to increase the patient’s tolerance for pain and to decrease the perception of suffering, although the presence of the pain itself may still be recognized.

In addition to analgesia, narcotics commonly produce such CNS effects as drowsiness, alterations in mood and mental clouding. Hydromorphone is reported to produce analgesia with less sedation than morphine. This may be an advantage in the postoperative period, since the patient with a less-clouded sensorium is better able to cooperate in early ambulation procedures. Likewise, cancer patients can be relieved of pain yet remain sufficiently alert to function within the scope of their underlying physical disorder. Narcotic analgesics also depress various respiratory centers, depress the cough reflex, constrict the pupils, elevate cerebrospinal fluid pressure, produce transient hyperglycemia and enhance parasympathetic activity.

Narcotic analgesics may cause nausea and vomiting by stimulating the chemoreceptor trigger zone (CTZ); however, they also depress the vomiting center, so that subsequent doses are unlikely to produce vomiting. Nausea and vomiting are significantly more common in ambulatory than in recumbent patients. Narcotic analgesics, including hydromorphone, increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. The resultant prolongation in gastrointestinal transit time is responsible for hydromorphone’s constipating effect. Because narcotics may increase biliary tract pressure, some patients with biliary colic may experience worsening rather than relief of pain.

While narcotics generally increase the tone of urinary tract smooth muscle, the net effect tends to be variable, in some cases producing urinary urgency, in others, difficulty in urination. Narcotics have also been reported to cause antidiuretic hormone (ADH) to be released, thereby reducing urine output.

In therapeutic dosage, opiates do not usually exert major effects on the cardiovascular system. However, some patients exhibit a propensity to develop orthostatic hypotension and fainting. Rapid intravenous injection is more likely to precipitate a fall in blood pressure than are intramuscular or subcutaneous injections.

Narcotic analgesics cause histamine release, which appears to be responsible for wheals or urticaria sometimes seen at the site of injection. Histamine release may also produce dilation of cutaneous blood vessels, with resultant flushing of the face and neck, pruritus and sweating.

Hydromorphone is well absorbed after parenteral administration.

After intramuscular administration, hydromorphone has a slightly more rapid onset and slightly shorter duration of analgesia than morphine. The major pathway of hydromorphone metabolism is conjugation with glucuronic acid in the liver; hydromorphone glucuronide is excreted primarily in the urine.