VA Class:CN101

AHFS Class:

• Opioid Agonists 28:08.08

Generic Name(s):

• Opium Alkaloids Hydrochlorides, Concentrated

• Powdered Opium

Associated Monographs

• Opiate Agonists General Statement

Opium, the air-dried milky exudate obtained by incising the unripe capsules of Papaver somniferum Linné or its variety album De Candolle, Opium contains several alkaloids, including not less than 9.5% anhydrous morphine and small amounts of codeine and papaverine.

Combination preparations containing powdered opium and belladonna extract in rectal suppository form are used for the relief of moderate to severe pain associated with ureteral spasm that is not responsive to non-opiate analgesics or for other conditions in which the analgesic, sedative, and antispasmodic effects of the combination may be useful such as when pain and smooth-muscle spasm are present concurrently.

Opium is used in the preparation of powdered opium and opium extract. Powdered opium is used in the preparation of paregoric, opium tincture, Dover's powder (ipecac and opium powder—a component of several cold preparations containing 10% ipecac, 10% powdered opium, and 80% lactose), and in combination product rectal suppositories. Paregoric is used in the preparation of Brown mixture (a component of cough and expectorant preparations containing 0.6 mL of paregoric, 0.6 mL of glycyrrhiza fluidextract, 1.2 mg of antimony potassium tartrate, 0.6 mL of glycerin, 0.15 mL of alcohol, and purified water to make 5 mL).

With the exception of rectal suppositories containing powdered opium, opium preparations are rarely used for analgesia. Paregoric and opium tincture are used principally as antidiarrhea agents; paregoric and opium tincture have also been used to treat opiate withdrawal in neonates born to addicted mothers.

For uses of paregoric and opium tincture, see Opium Preparations 56:08.

Administration

Combination preparations containing powdered opium in suppository form are administered rectally.

Dosage

Opium preparations should be given at the lowest effective dosage and for the shortest duration of therapy consistent with the treatment goals of the patient. Reduced dosage is indicated in debilitated patients and in very young or very old patients. If concomitant therapy with other CNS depressants is required, the lowest effective dosages and shortest possible duration of concomitant therapy should be used.

The usual adult rectal dosage of combination preparations containing powdered opium is one suppository once or twice daily, or as directed by a physician; prior to rectal insertion, the finger and suppository should be moistened.

Opium preparations share the toxic potentials of the opiate agonists, and the usual precautions of opiate agonist therapy should be observed. (See Cautions in the Opiate Agonists General Statement 28:08.08.) When preparations containing opium in combination with other drugs are administered, the cautions applicable to each ingredient should be borne in mind.

Pharmacology

Clinical evidence indicates that the analgesic activity of opium preparations results from their morphine content. Relatively small doses, which do not produce significant analgesia, are effective in controlling diarrhea. The papaverine content of the mixed alkaloids is too small to have demonstrable spasmolytic activity.

Pharmacokinetics

Absorption

Following oral administration, morphine is variably absorbed from the GI tract. The drug is rapidly metabolized following oral administration, however, and plasma concentrations of unconjugated morphine are lower than those achieved after parenteral administration. Following parenteral administration of concentrated opium alkaloids hydrochlorides (no longer commercially available in the US), activity is similar to that of parenterally administered morphine; peak analgesia occurs within 50-90 minutes following subcutaneous injection and 30-60 minutes after IM injection. Analgesia may be maintained for up to 7 hours. Following rectal administration, opium in suppository form has an onset of action of 15-30 minutes and analgesia is maintained for 3-5 hours.

Elimination

Like the other opiate agonists, opium preparations are metabolized in the liver. Morphine undergoes conjugation with glucuronic acid at the 3-hydroxyl group. Secondary conjugation may also occur at the 6-hydroxyl group to form the 3,6-diglucuronide. Morphine is excreted in the urine mainly as morphine-3-glucuronide and smaller amounts of morphine-3,6-diglucuronide and unchanged drug. Approximately 75% of a dose of morphine is excreted in the urine within 48 hours.

Chemistry

Opium is the air-dried milky exudate obtained by incising the unripe capsules of Papaver somniferum Linné or its variety album De Candolle. Opium contains several alkaloids, including not less than 9.5% anhydrous morphine and small amounts of codeine and papaverine.

Powdered opium is opium dried at a temperature not exceeding 70°C and reduced to a very fine powder. Powdered opium contains 10-10.5% anhydrous morphine and may have diluents added. Powdered opium occurs as a light brown or moderately yellowish-brown powder.

Opium extract is a concentrated preparation of opium containing 20% anhydrous morphine.

Additional Information

For further information on the chemistry, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, drug interactions, and dosage and administration of opium preparations, see the Opiate Agonists General Statement 28:08.08. For information on opium tincture and paregoric, see Opium Preparations 56:08.