Some of these compounds are naturally occurring (opium and its constituents morphine and codeine), whereas the others are semisynthetic or wholly synthetic. Some of these drugs have legitimate uses (e.g., morphine, meperidine), whereas others are solely substances of abuse (e.g., heroin). Most are obtained illegally “on the street” and are used primarily by a young or middle-aged, lower socioeconomic population (although heroin is becoming
“fashionable” among higher social classes currently), whereas others are abused more widely (e.g., Demerol, Dilaudid, and Percodan are commonly abused by professionals). Opioid drugs bind to mu, kappa, delta, and lambda locus coeruleus cell receptors (particularly mu) and inhibit norepinephrine release, producing the “high” of opioid abuse. After several weeks, the mu receptors have adjusted to the excess stimulus, and when the drug is stopped, the “mu agonist withdrawal syndrome” or norepinephrine hyperactivity of the locus coeruleus begins, producing the withdrawal syndrome. Typical routes of administration are i.v. (heroin, morphine, methadone: “mainlining”), s.c. (heroin, meperidine: “skin popping”), nasally (heroin: “snorting”), orally (methadone, Percodan), and smoked (opium). It is frequently very difficult to determine the daily dose used because (a) the abuser often consciously over- or underestimates the dose, and (b) the amount of active drug in a “bag” bought on the street is uncertain. A bag of heroin may be 95% adulterants (e.g., quinine, mannitol, lactose), although recently the purity of “street” heroin has increased (some bags being more than 50% heroin).

Abuse (OPIOID ABUSE, p. 271, 305.50) and dependency (OPIOID DEPENDENCE, p. 270, 304.00) are common in some populations, and the search for drugs or money for drugs accounts for the majority of the crime in some communities. Some people (fewer than 50%) are able to abuse opioids without becoming dependent (i.e., without progressing to tolerance or withdrawal or both), and they often use them recreationally without addiction. Those persons who become dependent represent a high-risk group. Recognize that we currently seem to be in a heroin epidemic similar to the “crack” epidemic of a decade ago: inexpensive, high-quality heroin is readily available and seems targeted at youth (e.g., heroin use has doubled among 8th graders over the past decade).

Always carefully evaluate hospitalized addicts medically. Recognize that the analgesic properties of opioids may obscure acute medical problems. After several weeks of use, addicts lose the rush and are left with chronic anxiety and dysphoria; still the craving and hope for euphoria is so strong, and withdrawal so unpleasant, that they continue to abuse. The majority of addicts “grow out of” their habit over the years (or die); thus relatively few old abusers are alive.

Treatment of the opioid addict usually means treatment of the acute episodes (e.g., intoxication and withdrawal; see later). “Cure” of the addiction does occur in some well-motivated patients [and is particularly possible in new, young (e.g., teen) addicts], yet most addicts continue their abuse over many years. The three major forms of maintenance treatment (all with controversial results) are as follows:

The two major features of illicit opioid use that bring patients to medical attention are intoxication (and overdosage) and withdrawal.

OPIOID INTOXICATION (p. 271, 292.89). It develops rapidly after an i.v. dose (1 to 5 minutes). The time course of intoxication varies with the drug used (Table 17.1). The abstinence syndrome begins after this period in the dependent patient. It is because of these kinetics that many heroin addicts “shoot up” 3 to 4×/day, or more.

Intoxication symptoms are similar for most narcotics.

Psychological symptoms: A “rush” immediately follows i.v. administration (described as a “whole-body orgasm” with the focus in the abdomen). This is accompanied by euphoria and a sense of well-being or dysphoria (usually anxiety and fear), a drowsiness and “nodding off,” apathy, psychomotor retardation, and difficulty concentrating.

Physical symptoms: Miosis (pupillary constriction), slurred speech, respiratory depression, hypotension, hypothermia, bradycardia, constipation, and nausea and vomiting. Skin ulcers are common with meperidine injection. Seizures may occur in the patient tolerant to meperidine.

An OD (either accidental or intentional) is a medical emergency; these patients may die of respiratory depression and pulmonary edema. Look for needle tracks and pinpoint pupils in the unconscious patient, but recognize that if the patient already has experienced significant CNS anoxia, the pupils may be dilated. Seizures occasionally occur (particularly with meperidine). Treat the OD with intensive medical care (ICU) and the narcotic antagonist naloxone (Narcan). Give 0.4 mg i.v. and repeat ×5 at 3-minute intervals. Expect a rapid response (i.e., clearing in 1 to 2 minutes), and if this does not occur after four doses, suspect another etiology for the coma. If the patient improves, continue monitoring; the patient probably will need additional doses of naloxone because it has a much shorter half-life than heroin and certainly methadone and LAAM. Excessive naloxone may throw
a dependent patient directly from coma into withdrawal; do not be confused. Multiple drugs may have been taken; be alert to the possibility of a more slowly developing coma from a second agent. Of course, get a STAT urine drug screen.

OPIOID WITHDRAWAL (p. 272, 292.0). In spite of its reputation as a dramatic and traumatic withdrawal syndrome, opioid withdrawal is uncomfortable but usually not life-threatening in healthy young adults and is not as dangerous or as difficult to manage as the withdrawal from sedative-hypnotic drugs. Symptoms are similar for each of the narcotics, but the time course varies (dependent partly on the “size of the habit”) (Table 17.2).

Psychological symptoms: Early, often intense drug craving followed by severe anxiety, restlessness, irritability, insomnia, and decreased appetite. In this state, the hospitalized patient is frequently extremely demanding and manipulative.

Physical symptoms: Yawning, diaphoresis, tearing, rhinorrhea, pupillary dilation, piloerection (hard to “fake” so look for it), muscle twitching, and hot flashes. Later nausea and vomiting, fever, hypertension, tachycardia, tachypnea, diarrhea, and abdominal cramps appear. Seizures occur with meperidine withdrawal.

Newborn addicts: Babies born to addicted mothers, including those on methadone maintenance, often experience an abstinence syndrome, including a high-pitched cry, irritability, tremor, fever, decreased food intake, vomiting, yawning, and hyperbilirubinemia.

Be aware that successful withdrawal is only the beginning of the treatment of opiate dependence. Withdraw the opioid gradually by using oral methadone (chosen because of long half-life) to lessen the symptom severity. After a complete history and physical (including urine screen for opioids and other drugs), wait for signs of withdrawal, and then give methadone 10 mg p.o. Establish the stabilization dose over the first 1 to 2 days by adding 5 to 10 mg of methadone on a q.i.d. schedule as the
patient continues to show signs of abstinence (recognize that some patients will vigorously demand more drugs even while they are sedated by their current dose). Once stabilized, give the methadone on a qd or b.i.d. schedule, and reduce the total daily amount by 5 mg/day (or 10% to 20% of the stabilization dose, but more slowly with outpatients). Most withdrawals from heroin addiction take 7 to 10 days; methadone-addiction withdrawals should be done more slowly (e.g., 2 to 3 weeks). An alternate method of opiate withdrawal is to use clonidine (Catapres), which reduces withdrawal symptoms (nausea, vomiting, diarrhea, cramps but not muscle aches, insomnia, or craving) by stimulating the α₂-adrenergic receptors on the locus coeruleus (0.1 mg q4 to 6h until stable to maximum of 1.2 mg/day, and then taper 0.1 to 0.2 mg/day) (5). (Withdraw Talwin from patients by using decreasing doses of Talwin.) Many patients who become free of their drug find the craving irresistible and need to be maintained on methadone to stay “clean.” Naltrexone (ReVia) seems to block the euphoric effects of the opioids (50 mg daily), as it does with alcohol, and can be used in patients taking clonidine who are (temporarily) free of opioids. Given daily or 3 times weekly; it blocks the positive effects of opioids but may produce dysphoria, anxiety, and GI distress initially. Of course, the biggest problem is that the patient still craves the opioid and may become noncompliant with the naltrexone.

If a patient is withdrawing from both opioids and sedative-hypnotics (not uncommon), concentrate on a safe sedative-hypnotic withdrawal by maintaining the patient on the stabilization dose of methadone until the first withdrawal has been completed.