Opioid intoxication

INTRODUCTION  Opioids have analgesic and central nervous system (CNS) depressant effects with the potential to cause euphoria. Morphine is the prototypic opioid. Heroin is a derivative of morphine and is the most commonly abused opiate.

INTRODUCTION Opiate medications are effective in the treatment of acute and chronic pain, as sedatives, and as anesthetic agents. They have the potential to be abused for these effects and the associated feeling of euphoria.

DEFINITIONS The term opioid refers to natural and synthetic substances with morphine-like activity. The term opiate refers to a subclass of opioids consisting of alkaloid compounds extracted from opium, including morphine, codeine, and semisynthetic derivatives of the poppy plant. The term endorphin refers to another subclass of opioids consisting of endogenous peptides that produce pain relief, including enkephalins, dynorphins, and beta-endorphins.

Classification of opioid agents Origin Agent (Brand Name) Comments Natural Codeine AT Morphine - Paregoric Synthetic Diphenoxylate (Lomotil) AD Fentanyl (Sublimaze) Loperamide (Imodium) Meperidine (Demerol) S,1 Methadone (Dolophine) Long-acting Tramadol (Ultram) s Propoxyphene (Darvon)

Origin Agent (Brand Name) Comments Semisinthetic s 2,3 AT Heroin Hydromorphone (Dilaudid) Levorphanol (Levodromoran) Long-acting Buprenorphine (Buprenex) s Pentazocine (Talwin) 2,3 Naloxone (Narcane) Naltrexone (Re Via) Dextromethorphan AT AD: antidiarrheal; AT: antitussive; S: seizures; 1: use cautiously with renal compromise; 2: may cause withdrawal symptoms in opioid-dependent patients; 3: has ceiling for analgesia and respiratory depression.

PHARMACOLOGY The activity of opioids resembles that of the body's endogenous opioid peptides (enkephalins, endorphins, and dynorphins) Three types of receptors have been identified: mu (µ), kappa (k), and delta (δ ); most opioids interact with more than one type. The primary sites of opioid action are the limbic system, thalamus, and hypothalamus.

Classes — Opioids are classified into three groups based upon their actions Morphine-like opioid agonists, including heroin, codeine, meperidine, hydrocodone, diphenoxylate, loperamide, sublimaze, and methadone. Opioid antagonists competitively block receptor activation by occupying opioid receptor sites. Examples include naloxone, nalmefene, and naltrexone. Mixed agonist-antagonists/partial agonists have different effects depending upon the predominance of agonistic or antagonistic activity in the opioid receptor and prior exposure to opiates.

Metabolism Most opioids are metabolized by the liver. Patients with liver disease have impaired metabolism and are at increased risk for toxicity caused by accumulation of active metabolites. Renal dysfunction can lead to toxicity caused by accumulation of active metabolites.

Drug interactions Phenothiazines potentiate their action, by interfering with their metabolism. TCAs increase the bioavailability and plasma level of opioids. Cimetidine may enhance effects through prolonging the duration of action. Antibiotics may increase (erythromycin) or decrease (rifampin) opioid effect.

CLINICAL MANIFESTATIONS The diagnosis is based upon the history and physical examination. Laboratory tests have a limited role because not all opioids are detected on drug screens. The classic findings of opioid toxicity are miosis, respiratory depression, and CNS depression. Other findings, including hyporeflexia, hypothermia, hypotension, or decreased bowel sounds, may be present.

Respiratory Respiratory evaluation should include assessment of ventilation, respiratory rate, cyanosis, hypercarbia, and hypoxia by pulse oximetry or arterial blood gas. Most opioid-related deaths are caused by respiratory depression, which is caused by central and peripheral effects. Respiratory depression may be subtle. The isolated respiratory rate is not a reliable measure of ventilation because a small decrease in tidal volume occurs before the respiratory rate declines. Bronchospasm can occur a few days to 18 months after regular heroin use by inhalation or injection. The dyspnea and wheezing are relieved with standard therapy.

Noncardiogenic pulmonary edema Noncardiogenic pulmonary edema findings include pink, frothy bronchial secretions, cyanosis, and rales in a stuporous or comatose patient with respiratory depression and miotic pupils. The distribution of pulmonary edema on chest radiograph usually is nonuniform . The pathophysiology is not known. Proposed mechanisms include inspiration (negative pressure) against a closed glottis, direct toxicity of the drug, hypoxia, and acidosis secondary to hyperventilation and/or cerebral edema.

Cardiovascular Opiates cause bradycardia and hypotension via the increased parasympathetic activity, decreased sympathetic activity, and release of histamine brought about by their effects on the vasomotor center. The drug-induced bradycardia and increased automaticity can cause arrhythmia, including potentially lethal ventricular tachyarrhythmia.

Neurologic  Mental status can vary from mild sedation to coma and affect from euphoria to dysphoria. Patients typically are stuporous or in a state of coma. Generalized seizures can occur after intravenous fentanyl and sufentanil administration, the prolonged use of meperidine, and large ingestions of propoxyphene, tramadol or pentazocine .

Gastrointestina Opioids cause various gastrointestinal effects. Constipation results from decreased motility and increased sphincter tone in the rectum.

Musculoskeletal   All opioid agonists can produce skeletal muscle rigidity, even at low doses Acute rhabdomyolysis and renal failure may occur with the use of heroin, methadone, and propoxyphene. A Parkinsonian-like syndrome has been associated with some opioid-based designer drugs.

DRUG TESTING False-positive results — The metabolites of some medications and foods are the same as the metabolites of opioids of abuse (eg, acetaminophen with codeine, codeine cough syrup, and poppy seeds). False-negative results — Some synthetic opioids (eg, 3-methyl-fentanyl) do not metabolize to opioids. Opioids are detectable in the urine for only two to four days after use.

MANAGEMENT OF ACUTE TOXICITY  Most of the direct morbidity and mortality related to opiate use occur after acute ingestion and are caused by anaphylaxis, pulmonary edema, acute respiratory acidosis, and aspiration pneumonitis. Immediate management involves airway management and administration of an opioid antagonist.

General considerations  Patients whose respiratory status is compromised should be supported with bag mask ventilation and 100 percent oxygen while the opioid antagonist is administered. Glucose should be administered intravenously if indicated by immediate bed-side glucose testing (<70 mg/dL). Seizures and cardiac dysrhythmias occur rarely and should be managed with standard therapies.

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