Brands, Medical Use, Clinical Data
Drug Category
- Narcotics
- Analgesics, Opioid
Dosage Forms
Brands / Synonyms
Dea No. 9648; LAAM; Levacetilmetadol [Inn-Spanish]; Levacetylmethadol; Levacetylmethadolum [Inn-Latin]; Levo-Alphacetylmethadol; Levo-Methadyl Acetate; Levomethadyl; Levomethadyl Acetate [Usan]; Methadyl Acetate; Nor-Laam; Orlaam
Indications
LAAM is indicated for the treatment and management of opiate dependence. It is sometimes used to treat severe pain in terminal patients.
Pharmacology
LAAM is a synthetic synthetic opioid analgesic with multiple actions quantitatively similar to those as morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, LAAM is more active and more toxic than morphine. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The LAAM abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.
Mechanism of Action
Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. LAAM effectively opens calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist), resulting in hyperpolarization and reduced neuronal excitability.
Absorption
LAAM is rapidly absorbed from an oral solution.
Toxicity
Signs of overdose include apnea, circulatory collapse, pulmonary edema, cardiac arrest, and death.
Biotrnasformation / Drug Metabolism
LAAM undergoes extensive first-pass metabolism to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These metabolites are more potent than the parent drug.
Contraindications
ORLAAM is contraindicated in patients with known or suspected QT prolongation
(QTc interval greater than 430 [male] or 450 [female] ms). This would include patients with congenital long QT
syndrome, or conditions which may lead to QT prolongation such as: 1) clinically significant bradycardia (less than
50 bpm), 2) any clinically significant cardiac disease, 3) treatment with Class I and Class III anti-arrhythmics, 4)
treatment with monoamine oxidase inhibitors (MAOI's), 5) concomitant treatment with other drug products known to
prolong the QT interval, and 6) electrolyte imbalance, in particular hypokalemia and hypomagnesemia. ORLAAM is
contraindicated in patients with known hypersensitivity to LAAM.
Drug Interactions
Not Available
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