Opium Alkaloids
Indications: Insomnia; Pain; Pain, severe; Sedation
DESCRIPTION:
Hydrochlorides of opium alkaloids, a narcotic analgesic, is a sterile injectable preparation for intramuscular and subcutaneous administration. It contains all the alkaloids of opium in a highly purified form free from inert matter and in approximately the same proportions as they occur in nature.
Hydrochlorides of opium alkaloids is a yellowish-gray powder which is freely soluble in water. The approximate composition of Pantopon is as follows: anhydrous morphine -- 50 percent, and bases of secondary opium alkaloids -- 29.9 to 34.2 percent. One part of Pantopon is equivalent to five parts of opium.
One ml of Pantopon contains 20 mg hydrochlorides of opium alkaloids compounded with 6% alcohol, 136 mg glycerin, 0.2% parabens (methyl and propyl) as preservatives, and either acetic acid, sodium hydroxide, or both, as necessary to adjust pH to approximately 3.3.
CLINICAL PHARMACOLOGY:
The action of Pantopon is essentially that of opium. Pantopon, therefore, exhibits not only the action of morphine but also the actions of codeine, papaverine and other alkaloids present in opium. The other alkaloids in opium alkaloids enhance the sedative and analgesic effects of morphine and tend to minimize its undesirable side effects. Pharmacokinetic data on opium alkaloids are not available; however, data are available on morphine, the major component of opium alkaloids.
Morphine acts as an agonist interacting with stereo-specific receptors in the brain and other tissues; the receptor sites are distributed throughout the CNS and are present in highest concentrations in the limbic system, thalamus, striatum, hypothalamus, midbrain and spinal cord. Morphine is well absorbed after subcutaneous and intramuscular administration. When therapeutic concentrations of morphine are present in plasma, approximately one-third of the drug is protein bound. Unbound morphine accumulates in parenchyma tissues (such as lung, liver, kidney and spleen) and skeletal muscle; however, 24 hours following the last dose, concentrations of the drug in these tissues are quite low.
The half-life of morphine in plasma is about 2.5 to 3 hours in young adults; in older patients, the half-life may be more prolonged. The major metabolic pathway for the drug is conjugation with glucuronic acid and the major route of elimination is through glomerular filtration. Ninety percent of the total excretion takes place during the first 24 hours after administration, although traces of the drug are detectable in the urine for well over 48 hours. About 7 to 10% of administered morphine eventually appears in the feces.
INDICATIONS AND USAGE:
Opium alkaloids is indicated in conditions in which the analgesic, sedative-hypnotic or narcotic effect of an opiate is needed. It is recommended for the relief of severe pain in place of morphine.
CONTRAINDICATIONS:
Opium alkaloids is contraindicated in patients with a known hypersensitivity to this drug or to other opiates.
WARNINGS:
Drug Dependence: Opium alkaloids may be habit forming. Opium alkaloids can produce drug dependence of the morphine type and has the potential for being abused. Psychological and physical dependence and tolerance may develop upon repeated administration of opium alkaloids; it should be prescribed and administered with the same degree of caution appropriate to the use of morphine.
Intravenous Use: Opium alkaloids should not be administered intravenously. Rapid intravenous injection of narcotic analgesics increases the incidence of adverse reactions; severe respiratory depression, apnea, hypotension, peripheral circulatory collapse and cardiac arrest have occurred.
Interaction with Other Central Nervous System Depressants: Opium alkaloids should be used with great caution and in reduced dosage in patients who are concurrently receiving other narcotic analgesics, general anesthetics, tranquilizers (including phenothiazines), sedative-hypnotics (including barbiturates), tricyclic antidepressants, MAO inhibitors and other CNS depressants, including alcohol. Respiratory depression, hypotension and profound sedation or coma may result.
Hypotensive Effects: The administration of opium alkaloids may result in severe hypotension in the postoperative patient or in any individual whose ability to maintain blood pressure has been compromised by a depleted blood volume or by the administration of drugs, such as phenothiazines or certain anesthetics.
Head Injury: The respiratory depressant effects of opium alkaloids may be markedly exaggerated in the presence of head injury or other intracranial lesions. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries. In such patients opium alkaloids must be used with extreme caution and only if its use is deemed essential.
Asthma and Other Respiratory Conditions: Opium alkaloids should be used with extreme caution in patients with bronchial asthma, chronic obstructive pulmonary disease or cor pulmonale . Similarly, it should be used with extreme caution in patients having a decreased respiratory reserve or with pre-existing respiratory depression, hypoxia or hypercapnia. In such patients, usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.
PRECAUTIONS:
General: The administration of opium alkaloids or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Opium alkaloids should be administered with caution and the initial dose should be reduced in patients who are elderly or debilitated and in those patients with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, toxic psychosis, and prostatic hypertrophy or urethral stricture.
Information for the Patient: In the unlikely event that opium alkaloids would be administered to ambulatory patients, they should be cautioned that opium alkaloids may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: There have been no studies performed with opium alkaloids to permit an evaluation of its carcinogenic or mutagenic potential. Studies have not been performed to determine the effect of opium alkaloids on fertility and reproduction.
Pregnancy, Teratogenic Effects, Pregnancy Category C: Animal studies have demonstrated the teratogenicity of morphine, the major component of opium alkaloids, in rats, mice and hamsters.
There are no adequate or well-controlled studies of opium alkaloids in either laboratory animals or in pregnant women. It is also not known whether opium alkaloids can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. Opium alkaloids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: It has been reported that morphine is excreted in human milk in microgram amounts. Because of the potential for serious adverse reactions from opium alkaloids in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Safety and effectiveness in children have not been established.
DRUG INTERACTIONS:
See WARNINGS.
ADVERSE REACTIONS:
Note: Included in this listing are adverse reactions which have not been reported with this specific drug; however, the pharmacologic similarities among the narcotics require that each of the reactions be considered with opium alkaloids administration.
Neurologic: Respiratory depression and arrest, pinpoint pupils, visual disturbances, coma, sedation, dizziness, headache, tremors, uncoordinated muscle movements. Inadvertent injection in close proximity to a nerve may result in a sensory-motor paralysis which is usually, though not always, transitory.
Psychiatric: Delirium, euphoria, dysphoria, weakness, agitation, hallucinations.
Cardiovascular: Hypotension, collapse, tachycardia, bradycardia, palpitation.
Dermatologic: Rash, urticaria (local and generalized), pruritus.
Gastrointestinal: Nausea, emesis, constipation, dry mouth, biliary tract spasm.
Genitourinary: Urinary retention.
Miscellaneous: Diaphoresis, flushing, pain at the site of injection, anaphylactoid reactions.
DRUG ABUSE AND DEPENDENCE:
Opium alkaloids is subject to Schedule II control under the Federal Controlled Substances Act of 1970. This drug can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological and physical dependence and tolerance may develop upon repeated administration of opium alkaloids, and consequently the same precautions should be taken in administering the drug as with morphine. A narcotic order is required.
OVERDOSAGE:
Serious overdosage with opium alkaloids is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur. The triad of coma, pinpoint pupils and depressed respiration strongly suggests opioid poisoning.
Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and through the institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride (Narcan), is a specific antidote against respiratory depression resulting from narcotic overdosage or unusual sensitivity to narcotics. An appropriate dose of this antagonist should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation.
An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed if needed.
NOTE: The administration of the usual dose of a narcotic antagonist will precipitate an acute withdrawal syndrome in patients physically dependent on narcotics. The severity of this syndrome will depend on the degree of physical dependence and the dose of the antagonist administered. The use of narcotic antagonists in such patients should be avoided if possible. If a narcotic antagonist must be used in physically dependent patients to treat serious respiratory depression, the antagonist should be administered with extreme care using only one-fifth to one-tenth the usual initial dose.
The intravenous LD50 of opium alkaloids in mice is 96 to 99 mg/kg.
DOSAGE AND ADMINISTRATION:
One-third grain (20 mg) of Pantopon with a morphine content of 1/6 grain (10 mg) is therapeutically equivalent to and is usually administered where 1/4 grain (15 mg) of morphine is indicated.
Usual Adult Dosage: 5 to 20 mg (1/12 to 1/3 grain) approximately every 4 to 5 hours according to the individual needs and severity of pain. Administer only by intramuscular or subcutaneous injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.