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Role of the Primary Care Physician in Problems of Substance Abuse
Michael F. Weaver, MD;
Margaret A. E. Jarvis, MD;
Sidney H. Schnoll, MD, PhD
Arch Intern Med. 1999;159:913-924.
ABSTRACT
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Patients with substance abuse problems are common in general medical practice and include people of all ages and socioeconomic groups. Initial diagnosis and treatment of addiction problems are often done by the primary care practitioner before referral to a specialist. This article provides information to help in recognition of addiction, guidelines for treatment of intoxication and withdrawal of various drugs of abuse (such as opioids, sedative-hypnotics, stimulants, hallucinogens, and volatile inhalants), and techniques for brief intervention as well as long-term care of substance-abusing patients. The physician can be a powerful influence for getting the patient to accept treatment, especially when the physician is empathic without being judgmental. Addiction is a chronic disorder with remissions and relapses like any other chronic disease, so exacerbations should not be seen as failures but as time to intensify treatment. Patients with substance abuse problems can be frustrating to treat, but it can also be a rewarding experience when a physician helps a substance-abusing patient return to normal and productive functioning in society.
INTRODUCTION
It is virtually impossible to avoid chemically dependent patients in the modern practice of medicine. Drug abusers include people of all ages, sexes, and ethnic and socioeconomic groups. All generalists and specialists will encounter patients with chemical dependency. Twenty-five percent to 40% of hospital admissions are related to substance abuse and its sequelae, and 10% to 16% of outpatients seen in a general medicine practice are suffering from problems related to addiction.1
The long-term treatment of chemical dependency can be a difficult, frustrating, but rewarding process. There are specialists, both physicians and nonphysicians, who make this area their practice and in many communities referral to a specialist is part of appropriate care. In the current practice of medicine, the primary care physician plays an increasingly important part in the care of the chemically dependent patient, regardless of the referral. The primary care physician may be the first health care professional to be aware of the disorder, or of a relapse, and refer the patient to treatment. As a trusted guardian of the patient's well-being, the primary care physician's concern that the patient stay in remission from drug use is a powerful motivator. At times, the primary care physician will be asked to provide withdrawal or other medical treatment for addiction, particularly in communities where specialized physicians are not available or there are limited resources for specialized treatment.
Because of the large number of substance-abusing patients who present themselves for medical care, physicians must be familiar with the signs and symptoms of abuse to make the diagnosis and provide therapies for acute intoxication and withdrawal along with resources for long-term treatment. This article describes methods for recognition and treatment of acute and chronic drug problems (caused by using opioids, alcohol, other sedative-hypnotics, stimulants, and hallucinogens) as well as issues related to brief intervention and long-term treatment of addiction.
RECOGNIZING THE DRUG ABUSER
It is always easiest to recognize the problem of drug abuse when a patient presents with the request to discontinue using drugs. When this occurs, the physician should be prepared to seize this opportunity and initiate treatment or refer the patient to an appropriate treatment program. Since addiction is a common problem, each patient should be screened for it just as he/she is screened for diabetes mellitus or hypertension. Both physician and patient will feel more comfortable if this screening is part of the physician's routine examination. A simple screening tool for problems of alcohol use is the CAGE questionnaire, which has been modified for screening for drug use and is known as the CAGE-AID questionnaire2: C, Have you ever tried to cut down on your alcohol or drug use? A, Do you get annoyed when people comment about your drinking or drug use? G, Do you feel guilty about things you have done while drinking or using drugs? E, Do you need an eye-opener to get started in the morning?
The more affirmative responses, the more likely that the person answering is chemically dependent.3
A clue to chemical dependency is a sudden change in a patient's behavior. This may be evident from meetings with the patient or reported by family members or employers. Sudden loss of a job or frequent job changes for no apparent reason are often a consequence of drug abuse. Unexplained financial or family problems can also be a result of drug abuse.
Certainly, the patient who presents exhibiting toxic behavior is potentially abusing drugs. A history of driving under the influence traffic citations or a blood alcohol concentration higher than 150 mg/dL with the patient still ambulatory is indication of significant tolerance and, therefore, evidence of long-term, high-dose use of alcohol. Any patient 18 years or older with a history of 2 or more nonsports-related traumatic events is considered at high risk for addiction. Another screening tool similar to the CAGE-AID questionnaire used to assess potential for substance abuse problems is the Trauma Test.4 Since your 18th birthday have you: Had any fractures or dislocations of your bones or joints (excluding sports injuries)? Been injured in a traffic accident? Injured your head (excluding sports injuries)? Been in a fight or been assaulted while intoxicated? Been injured while intoxicated? A positive response to 2 or more of these questions indicates a strong potential for addiction.5
Almost all drugs of abuse alter sexual function as well as other behaviors. Although many people believe that drugs will enhance sexual performance, in reality drug use usually decreases it and may even cause impotence or other dysfunctions. Any patient presenting with complaints of sexual dysfunction should be evaluated for possible drug abuse as a contributing cause. There is mounting evidence that drug use is the leading cause of impotence in the United States.6
Chemically dependent individuals frequently develop medical sequelae of drug abuse. Intravenous (IV) drug abuse often causes infections such as endocarditis, hepatitis, and human immunodeficiency virus. Needle marks may be present on the skin from recent injections, or "tracks" may be present over veins from repeated injections. Injection is not always confined to the obvious sites. Many users, in an attempt to hide their drug problems, will inject in the axilla, under the tongue, under the breast, in the legs, and even into the dorsal vein of the penis. Smoking or snorting cocaine and other drugs can cause respiratory problems (pneumomediastinum and decreased alveolar diffusion capacity), atrophy of the nasal mucosa, and perforation of the nasal septum.7
Laboratory findings are often indications that drug abuse is occurring: the mean corpuscular volume is elevated during long-term alcohol use, the liver enzymes can be elevated by alcohol use and by hepatitis acquired from sharing needles, and quinine (used to cut heroin for sale "on the street") can cause a widened QRS on an electrocardiogram.8 In all suspected cases, a urine sample should be collected for a drug screen. A urine toxicology screen can be helpful as an indication of recent drug use (past few days) but will not provide evidence of use outside of a small window of time. The best evidence for long-term drug use is a combination of a good history and a urine toxicology screen.
Although many of these signs and symptoms can be caused by other diseases, the differential diagnosis should include drug abuse, and steps should be taken to verify whether the patient is abusing substances. One method is to express to the patient in a nonaccusatory tone the concern that drug abuse is occurring and offer help. Give concrete examples of reasons for considering the substance abuse diagnosis. Many patients will be relieved that they no longer have to hide their problem and that help is available. Others will adamantly deny having a problem. Sometimes patients will need to hear the concerns about drug use several times before they will be able to respond.
A common problem in the differential diagnosis of substance abuse can be the patient who is prescribed addictive drugs on a long-term basis for the treatment of a disease (ie, a chronic pain syndrome). These patients develop neuroadaptation (physical dependence), but do not meet the behavioral criteria for drug dependence.9 Once these patients are stabilized on therapeutic doses of the drugs they need, they spend no more energy in seeking and consuming the drug than a patient with diabetes spends on checking his blood glucose levels and taking insulin. Typically, these are patients who do not end up in crisis any more often than patients with other chronic diseases, who do not "lose" their prescriptions, and do not require increasingly large doses of medication to control their symptoms. Undertreatment can result in pseudoaddiction. In these cases, patients seek more medication to treat a problem that is currently undertreated.10
There are chemically dependent patients addicted to prescription medications. Identification of these patients can be made by watching for requests for increased doses of prescribed abusable drugs or requests for refills more frequently than anticipated. Tolerance develops to almost all drugs of abuse. However, tolerance develops to the euphoric effects of the drugs more rapidly than to the therapeutic effects of the drugs. Therefore, patients abusing drugs desire increasing amounts soon after a therapeutic level of the drug is reached. Anyone can lose a prescription once, but the patient who repeatedly requests new prescriptions may have a substance abuse disorder. Patients who are dependent on prescription medications may get prescriptions from several physicians, so calling the pharmacy may reveal previously unknown drug abuse. Many pharmacists will call physicians to alert them to the problem of prescriptions from several sources.11
Once the diagnosis of substance abuse is made, both acute and long-term treatment is necessary; simple admonitions to stop are sometimes helpful if the diagnosis is made early but in most cases are insufficient. Therapy for substance abuse sometimes begins with withdrawal, or detoxification, but this is merely a first step in overall treatment.
ACUTE OPIOID INTOXICATION
Table 1 describes the clinical findings of acute opioid intoxication.
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Table 1. Acute Opioid Poisoning*
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Immediate therapy for acute opioid intoxication includes first assuring an adequate airway and stabilizing respiration and cardiac status. Intravenous naloxone is presently the drug of choice in the treatment of opioid overdose because it is a relatively pure antagonist; it has also been shown to be effective in treating overdoses with propoxyphene and the mixed agonist-antagonist opioids, eg, pentazocine, nalbuphine, and butorphanol.
If an opioid overdose is suspected, 1.2 mg (3.0 mL) of naloxone should be administered IV. If there is no response to the initial dose of naloxone within 1 or 2 minutes, a second or third dose may be administered. If there is no improvement in the patient's condition after 3 IV doses of naloxone, it can be assumed that the patient has not taken an opioid overdose, since the majority of patients who have taken opioids respond after 1 or 2 doses of naloxone.
In treating opioid intoxication with naloxone, it is important to remember that the duration of action of naloxone IV is 1 or 2 hours—whereas the duration of action of most opioids is 3 to 6 hours, and that of methadone is 24 to 36 hours. Because of this, the patient who has initially responded to naloxone may lapse into coma again unless carefully monitored. Patients who have received naloxone should be monitored for vomiting. Suction should be readily available to reduce the chance of aspiration.
The patient who has responded favorably should be monitored for level of consciousness, respirations, pulse, and blood pressure at least every 15 minutes. If the patient appears to be losing consciousness, additional naloxone should be administered. An alternative form of therapy is to administer naloxone by IV drip. Add 4 mg of naloxone to a liter of 5% dextrose solution, and titrate the dose to deliver the amount of naloxone per hour necessary to maintain the desired level of consciousness.
The patient with acute opioid intoxication should be observed for at least 24 hours before being released from the hospital. Plans for long-term management of the drug problem should be made as well; psychiatric consultation is frequently indicated.
LONG-TERM USE OF OPIOIDS
Because of the development of tolerance, patients who are long-term users of opioids are unlikely to manifest symptoms of acute intoxication unless they have ingested an unusually large dose. Tolerance does not develop to the miotic effects, nor to the constipating and respiratory depressing effects.
Although sudden withdrawal from opioids usually produces physical effects no worse than a bad case of influenza, this form of therapy is not justifiable because of the extreme anxiety produced in opioid users by sudden cessation of the drug. Methadone is used frequently for withdrawal from illicit opioids, but prescribing methadone for withdrawal or long-term treatment of drug dependence requires a special state and federal Drug Enforcement Administration license, and therefore this treatment option may not be available in every situation. Current federal regulations restrict use of methadone for treatment of opioid addiction. It may only be used for chronic addiction by a licensed narcotic treatment program or licensed inpatient hospital detoxification unit. Methadone may be used by a private practice physician for temporary maintenance or detoxification when an addicted patient is admitted to a hospital for an illness other than opioid addiction. It may also be used by a private practitioner in an outpatient setting when administered daily for a maximum of 3 days while a patient awaits admission into a licensed methadone treatment program. However, methadone can be prescribed on an outpatient basis for treatment of pain outside of a licensed narcotic treatment program. A Drug Enforcement Administration license to prescribe schedule 2 medications is required.
When choosing a medication for withdrawal from any physical dependence-inducing drug, there are several considerations. For opioids, there are many different drugs with different potencies and different durations of action (Table 2). The effects of short-acting medications can be controlled precisely, but require frequent assessment and dosage adjustment. Patients may experience some severe withdrawal symptoms toward the ends of dosing periods. Short-acting medications are most appropriately used in intensive care units or in other situations where the patient's condition is likely to change rapidly and the patient can be closely monitored. Long-acting medications are more convenient for medical and nursing staff, produce less severe withdrawal symptoms themselves (if any symptoms are seen), but the withdrawal symptoms may last for long periods. These medications are most appropriately used when the patient is medically stable (other than the opioid withdrawal).
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Table 2. Equivalent Doses of Opioids
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A problem with substituting methadone or another narcotic for illicit opioids is how to determine what dose of methadone is approximately equivalent to the dose of opioid being used by the patient. Although there is no clear-cut evidence that the severity of withdrawal symptoms is related to the amount of opioid being used, the method described in Table 3 has been used extensively to titrate methadone for opioid withdrawal, without producing oversedation or severe discomfort to the patient during withdrawal. It is better to err on the side of estimating a dose that is a bit too large rather than too small.
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Table 3. Sample Methadone Dosage Calculation Chart
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After 24 hours, the total dose of methadone or other opioid that has been administered to the patient is computed. This dose of methadone is approximately equivalent to the dose of opioid the individual was taking. After being stabilized on the appropriate dose of methadone, the patient can be withdrawn by gradually reducing the dose. Reduce the total daily intake by approximately 10% per day, maintaining the dosing frequency as long as possible. By reducing the frequency (increasing the interval between doses) at which the drug is given, the patient goes into withdrawal repeatedly, making the process uncomfortable and difficult, especially with short-acting narcotics like morphine, meperidine, and hydromorphone. Once a withdrawal schedule is determined, it should not be altered unless the patient shows objective signs of worsening. Some treatment centers subscribe to blind treatments in which patients are never told their dosage. In some cases, this can help allay anxiety the patient might have as the dose is decreased.
Clonidine, an alpha2-agonist, has been shown to be effective in reducing withdrawal symptoms in patients on low doses of opioids.12 Doses as high as 1.2 mg/d in divided doses have been used. Clonidine can be used in conjunction with methadone when the methadone dose is below 15 mg. It is important to monitor the blood pressure for hypotension and then to gradually taper the patient off of the clonidine to avoid a hypertensive rebound. Clonidine has also been used in conjunction with naloxone as part of a protocol for rapid opioid detoxification to help ameliorate the severity of symptoms from naloxone-induced opioid withdrawal syndrome.13
A method for ultrashort opioid detoxification has been recently developed in which the substance-abusing patient is anesthetized during the initial induction of withdrawal by large doses of naloxone.14-16 Patients who undergo this regimen are anesthetized, then intubated and mechanically ventilated. They are then given a large bolus of naloxone to precipitate acute opioid withdrawal while unconscious. The patient is given a diuretic to enhance excretion of the opioid. After awakening from anesthesia, patients will experience mild withdrawal symptoms for about 6 days compared with similar withdrawal symptoms on a 20-day methadone taper. Ultrashort detoxification can reduce the length of withdrawal symptoms, but patients must be in good health to be able to tolerate general anesthesia and the physiological stress of rapid induction of acute withdrawal by naloxone. This type of withdrawal is not commonly available since it requires specific personnel who are knowledgeable about anesthesia as well as substance abuse and the patients require intensive monitoring.
Frequently, patients receiving methadone require analgesic medications for coexisting medical problems. In most cases, attempts should be made to control the pain through the use of nonnarcotic analgesics. If this is not possible, the dose of methadone that the patient is receiving should be used as a baseline, and additional narcotic analgesics should be added in standard therapeutic doses to control the pain. It is important to remember that neither pentazocine (Talwin), nalbuphine (Nubain), nor butorphanol (Stadol) should be administered to any patient taking pure agonists such as methadone because these drugs have antagonist properties and can precipitate an immediate withdrawal.
ACUTE SEDATIVE-HYPNOTIC INTOXICATION
The clinical features of acute sedative-hypnotic intoxication are presented in Table 4.
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Table 4. Sedative-Hypnotic Intoxication*
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The patient who has taken an overdose of sedative-hypnotics should be treated initially like any other patient with drug intoxication: provide an adequate airway and ventilation and maintain the cardiovascular system. In a patient who has taken the drug orally, once these initial measures have been carried out, activated charcoal should be administered. This prevents absorption of the drug into the system and also prevents the drug or active metabolites from being absorbed through enterohepatic recirculation. Laxatives may be used to induce catharsis.
If barbiturates are the cause of the overdose, administer a sufficient amount of IV sodium bicarbonate to alkalinize the patient's urine.17 The dose of bicarbonate will vary depending on the patient's metabolic state. This alkalinization increases the rate of excretion of barbiturates; the urine pH should be monitored and kept at about 7.5. Depending on the gravity of the patient's condition, dialysis may be required.
Some of the older sedative-hypnotics (eg, glutethimide or ethchlorvynol) are highly lipophilic, and consequently these drugs may be erratically absorbed, highly protein bound, and stored in body fats. Some are metabolized to active substances that have long half-lives. Excretion via bile results in reabsorption through enterohepatic circulation. Because of these effects, blood levels of the drug may fluctuate, causing fluctuations in the level of consciousness.18 Therefore, it is important to keep patients who have taken overdoses of these drugs under observation for several days.
Benzodiazepines are the most commonly prescribed sedative-hypnotics. Short-, intermediate-, and long-acting benzodiazepines are available, and the longer-acting benzodiazepines are often converted by the liver into active metabolites with long half-lives. Although these drugs produce less respiratory depression than barbiturates, the long-acting metabolites often cause intoxication that lasts for several days. Benzodiazepine overdose is most dangerous in combination with other sedative-hypnotics. A benzodiazepine antagonist, flumazenil (Romazicon), is available for the treatment of benzodiazepine intoxication. It must be used with some caution as in some cases it has not completely reversed the respiratory depression, can cause seizures in patients with physical dependence, and in a mixed overdose, could precipitate tricyclic antidepressant–induced arrhythmias covered by the sedative.19 It should be given in the lowest possible dose. The starting dose for treatment of an overdose is 0.2 mg IV over 30 seconds. An interval of at least 30 seconds should pass before trying the next dose at 0.3 mg. Further doses of 0.5 mg may be given every 60 seconds up to a total of 5 mg.20 In patients who are physically dependent on benzodiazepines, repeated doses should be administered slowly. Flumazenil is a short-acting drug so there may be resedation after an initial awakening. This can be treated by repeating doses at 20-minute intervals, if necessary.
LONG-TERM USE OF SEDATIVE-HYPNOTICS
Clinical features of long-term use of sedative-hypnotics are similar to acute features, but may be accompanied by a dementia consisting of loss of memory (recent and remote). The symptoms of sedative-hypnotic withdrawal are listed in Table 5. In addition, generalized seizures may occur, sometimes followed by status epilepticus. As in the case of major alcohol withdrawal (delirium tremens), confusion and psychotic behavior can be a part of any sedative-hypnotic withdrawal.
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Table 5. Sedative-Hypnotic Withdrawal
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It is unusual to see patients who are solely abusing short-acting barbiturates. The majority of sedative-hypnotic abusers take 1 or more benzodiazepines and ethanol, along with barbiturates and other sleeping pills. Since many of the benzodiazepines have long-acting metabolites, the patient may not show signs of withdrawal for 7 to 10 days after stopping all drugs.
Treatment is identical for withdrawal from all sedative-hypnotics, including barbiturates, sleeping pills, benzodiazepines, and alcohol, because all drugs in these categories exhibit cross-dependence. The first step is to objectively determine an approximate level of drug to which the patient is tolerant since patients overestimate or underestimate the amount of drug they have been taking. While, as with opioids, precise instruments for the measurement of tolerance exist, they require nursing or medical staff with sophisticated knowledge of the intoxication and withdrawal symptoms and are time-intensive to administer.21-22 Thus, these precise methods are not practical for use in an emergency department or general practitioner's office. Fortunately, in many cases, it is not necessary to be so precise. Observation in an 8-hour partial hospitalization unit is often sufficient. While any drug causing cross-dependence can be used, a scheme for using phenobarbital follows: an initial dose is given, usually 60 to 90 mg of phenobarbital (Table 6), and the patient is monitored for at least 6 to 8 hours. The withdrawal drug can be repeated hourly or at 2-hour intervals, as indicated by the signs of withdrawal the patient is exhibiting. After 8 hours, an approximation can be made of the total dose the patient will require for a 24-hour period. Again, it is better to err on the side of slightly overmedicating than undermedicating. The dose is tapered starting from that dose. Reducing the dose by 10% of the initial dose each day provides a comfortable taper, especially if the patient is expected to participate in demanding psychological therapy exercises or if the patient has coexisting medical conditions. The taper can be accomplished much more rapidly if these conditions do not exist. The use of a long-acting barbiturate decreases the severity of withdrawal symptoms, and phenobarbital is chosen in preference to other sedatives because it has a longer half-life than diazepam, patients rarely achieve a "high" from phenobarbital as they do from the other drugs, and it is available in multiple dosage forms. The dose of phenobarbital can be given in a constant volume of liquid for each dose so the patient is not aware of the amount being decreased each day ("blind taper"), if this is desirable.
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Table 6. Sedative-Hypnotic Equivalent Doses*
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If a patient who has been using sedative-hypnotics on a long-term basis presents in advanced withdrawal (ie, elevated vital signs or delirium), it is important to medicate rapidly and in sufficiently large doses so that the withdrawal is suppressed. Medications with rapid onset of action should be used to initiate suppression of severe withdrawal signs and may be given IV for immediate effect. Lorazepam and diazepam are good choices since they have rapid onset when given IV, but they have shorter duration of action than when given orally since first-pass liver metabolism is bypassed. After stabilization with rapidly acting medications, the patient can be switched to an equivalent dose of a long-acting medication such as phenobarbital. As long as the patient is awake, he/she will not undergo significant respiratory depression from the withdrawal medication and, at times, large doses are required (up to 700 mg/d of phenobarbital). Advanced withdrawal from alcohol—delirium tremens—carries a 5% mortality rate23 even when adequately treated. Withdrawal is most safely done in an inpatient setting if the patient has been using high doses of sedative-hypnotics, has a history of withdrawal seizures or delirium tremens, or has concurrent medical illness.
Anticonvulsant agents that do not show cross-dependence with sedative-hypnotics (ie, carbamazepine or valproate) have been used successfully in the treatment of mild sedative-hypnotic withdrawal. They are given at full anticonvulsant doses for several weeks during the withdrawal. These medications have not been studied for use in severe withdrawal and are only appropriate for use with mild withdrawal.24
A prolonged benzodiazepine withdrawal syndrome, or symptom rebound, can be seen particularly following long-term use of benzodiazepines. The insomnia and anxiety that accompany this may last for several months and, while not life-threatening, are sufficiently uncomfortable that they frequently are a trigger for relapse to drug use. A long taper (2-3 months) of the original benzodiazepine is useful in this situation.25
ACUTE STIMULANT INTOXICATION
The clinical findings of acute stimulant intoxication are presented in Table 7. Amphetamine intoxication is the classic example of stimulant intoxication, but cocaine intoxication is seen most commonly today. Abused methamphetamines include dimethoxymethylamphetamine (DOM, or "STP"), methylenedioxyamphetamine (MDA, the "love drug"), and methylenedioxymethamphetamine (MDMA, or "Ecstasy"), which are "designer drugs" with psychoactive properties.
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Table 7. Stimulant Effects*
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In recent years, there has been increased popularity of cocaine, a short-acting local anesthetic with marked stimulant effects. Cocaine is most commonly used by insufflation (snorting), but the drug can be injected IV or made into a free base ("crack") and then smoked, resulting in a rapid attainment of high blood levels and sometimes extreme paranoid behavior. A crack cocaine habit can cost several thousand dollars a week; running out of money is the most common reason patients come in for treatment. The long-term medical sequelae of crack cocaine use include pulmonary dysfunction,7 arrhythmias,26 myocardial infarction,27 cardiomyopathy,28 and paranoia.29 The smokable free-based form of methamphetamine ("ice") has similar effects to crack, but may last 10 times as long.
For acute management, it is important to approach the acutely intoxicated stimulant user in a subdued manner; never speak in a loud voice or move quickly, never approach the patient from behind, and try to avoid touching the patient unless absolutely sure it is safe to do so (which may include the presence of more than 1 strong, trained assistant).
Treatment of acute amphetamine intoxication (assuming no hepatic dysfunction) includes acidification of the urine with ammonium chloride, up to 4 g orally, 4 times daily. Seizures may be treated with diazepam. Haloperidol may also be used in treating the acute psychotic reactions. Since cocaine is such a short-acting drug, treatment of acute intoxication is rarely necessary except in instances of acute psychotic reaction.
LONG-TERM USE OF STIMULANTS
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