Objective 6

To describe basic pharmacological treatments for nicotine, alcohol, and other drugs.


The following discussion of Pharmacotherapy is reproduced with permission from the proceedings of the Josiah Macy, Jr. Foundation sponsored conference on Training about Alcohol and Substance Abuse for All Primary Care Physicians.

 


Physicians should be skilled in the pharmacological treatment of nicotine, alcohol and drug dependence. This includes the management of drug withdrawal, post-withdrawal abstinence syndromes, drug maintenance, and co-morbid conditions.

Alcohol or Drug Withdrawal
The primary drugs that usually require acute pharmacological interventions to treat withdrawal symptoms include tobacco, alcohol, sedatives, stimulants, and opioids. Other mood-altering drugs such as cannabinoids, PCP, hallucinogens, inhalants, and anabolic steroids are not usually associated with withdrawal symptoms that require medication. Some patients who use these drugs may benefit from pharmacotherapy after cessation of drug use.

A number of principles underlie the management of tobacco, alcohol, and drug withdrawal. Early pharmacological treatment can reduce the frequency and magnitude of drug withdrawal complications. Most patients identified in a primary care setting can be safely detoxed in an outpatient setting. Patients who develop the clinical picture of drug withdrawal need a comprehensive medical assessment, including a blood alcohol level and urine drug screen. Supportive, empathic care is an essential component of acute withdrawal management. Pharmacological treatment is only one component of a comprehensive treatment plan and should never be used as the sole treatment modality.

Symptoms of tobacco withdrawal can be managed using nicotine replacement patches with minimal side effects. Cessation rates are higher when patches are used in combination with other methods. Alcohol and sedative withdrawal can be life-threatening and is associated with seizures, psychosis, delirium, and violent behavior. Other serious complications include aspiration pneumonia, respiratory arrest, and cardiovascular collapse. High doses of a cross-tolerant drug such as a benzodiazepine is the drug of choice for treating such withdrawal. Loading doses administered orally is the preferred treatment method.

No one certain medication will block the effects of withdrawal from cocaine or other stimulants. Specific symptoms, such as agitation, paranoia, and nausea, should be treated with medications directed at these symptoms. Severe paranoia and suicide attempts should be anticipated and appropriate safety measures instituted. Treatment of opioid withdrawal depends on the drug used and the severity of symptoms. Patients on low doses of oral narcotics can be safely withdrawn in a few days on an outpatient basis. Persons on higher doses of narcotics can usually be tapered off their primary drug in less than 10 days. Symptoms can be treated with a number of medications directed at specific findings. For example, clonidine will block many of the adrenergic signs. Individuals on methadone maintenance programs may require a three-to-six month detoxification plan in order to avoid severe withdrawal and relapse. Newborn infants of women on methadone can be safely withdrawn with Phenobarbital.
 

Post-Withdrawal Craving and Abstinence Syndromes
Pharmacological intervention may help reduce the high rate of relapse associated with tobacco, alcohol, and other drug dependence. While the physiological and psychological responses to abstinence are not well understood, craving appears to be distinct from other problems such as sleep disorder, mood changes, anxiety, and memory lapses, that occur in the post-withdrawal period. In contrast to these chronic effects, abstinence-induced craving is short-lived and frequently occurs in response to cues or environmental stimuli associated with previous use. Medications currently used to treat this problem include nicotine replacement for tobacco cessation and Naltrexone for alcohol cravings.
 

Drug Maintenance
Drug agonists or cross-tolerant drugs are often used in opioid-dependent patients in an attempt to substitute a less harmful drug for the primary drug. The primary example of this technique is the use of methadone for narcotic addiction. The rationale for drug maintenance is based on the clinical observation that many addicts are unable to stay drug free. Clinicians assume that these individuals have irreversible changes in their central nervous system, and/or mental health disorders that do not respond to abstinence-based methods.

The only commonly used drug maintenance program in the U.S. is for opioid dependence. For a physician to be able to place a patient on methadone maintenance, the patient must have been opioid dependent for at least the last year. Recently, the requirements have become less stringent and primarily are left to the discretion of a physician with a program license. Physicians currently are not licensed to prescribe methadone for maintenance except through a licensed methadone treatment program.

While benzodiazepines continue to be used for their agonist properties, they have not been shown to help alcoholics or addicts, with the exception of these with severe anxiety disorders. While no specific cocaine agonists have been discovered, several drugs may be helpful as cocaine replacements to reduce craving. These include dopaminergic drugs such as bromocriptine.
 

Co-morbid Conditions - Pharmacological Treatment of Health Effects
While treatment of conditions that are associated with alcohol use are beyond the scope of this paper, a few facts should be discussed. First, anxiety and panic disorders are very common in persons using alcohol and other drugs. Sedative drugs should be used with extreme caution because they often increase alcohol and drug use and they have minimal effect on anxiety disorders in this population. Hypnotics do not help for sleep disorders associated with alcohol and drug use because they have mood-elevating effects; even over-the-counter hypnotics can precipitate a relapse. Depression will normally clear with abstinence. If depression continues after a period of sobriety, a course of antidepressants may be indicated. Treatment of medical conditions such as alcohol-associated hypertension should include a period of abstinence to determine the effect of alcohol on the patient's hypertension. Liver transplantation should be considered in persons with alcohol-induced liver failure who have been abstinent for six months.
 

Other Pharmacotherapeutic Agents
The opioid receptor naltrexone is used to block the effects of heroin and other opioids at the level of the mu receptor. There are three primary indications. First, it is used to reverse the effects of opioids in cases of drug overdoses because it can reverse the respiratory effects within seconds of reaching the central nervous system. It may have to be given repeatedly or as an intravenous drip in persons using long acting opioids, such as methadone. The second indication is for relapse prevention following withdrawal from all opioids. It is used as an adjunct to counseling and other treatment. In motivated patients, such as impaired professionals, it can be an effective deterrent.

A third primary indication is to accelerate the process of narcotic withdrawal. It is given in combination with buprenorphine in a controlled treatment setting. It can precipitate severe withdrawal, however, and should be done in consultation with an Addiction Medicine specialist. It may be especially helpful in patients who have failed the normal withdrawal protocols.

Antabuse is a medication used in the post-withdrawal period to reinforce sobriety from alcohol. Daily use of Antabuse may be helpful in reducing relapse rates. Drug interactions, hepatic toxicity, and severe reactions in patients who drink while taking the medication, complicate the clinical usefulness of this metabolic inhibitor.

 


For more information on particular drugs mentioned above go to your search engine (I prefer LYCOS and type in the name of the drug you are interested in. You will usually find a nice list of possible "hits" that will give you lots of useful information on the properties of the drug.

Here is a short list of some drugs that are of current interest in the substance abuse world. Just click on the name to learn more about it.


Study Questions:

  1. Which drug categories are responsive to pharmacological interventions to treat withdrawal symptoms?
  2. What are some of the physical risks a patient may encounter when withdrawing from alcohol or other sedatives?
  3. What is the primary example of using a "less harmful" drug as a substitute for the primary drug of addiction?
  4. What are the three primary indications for the use of Naltrexone?
  5. What are the three issues that complicate the clinical usefulness of Antabuse?
  6. Are the following statements true or false?
    1. Clonidine is the only known agent that will block the effects of withdrawal from cocaine.
    2. Newborn infants of woman on methadone can be safely withdrawn with phenobarbital.
    3. Withdrawal from alcohol addiction is never life-threatening.
    4. Withdrawal from opioid addiction should always be medically managed in a hospital.
    5. When following a patient who is going through withdrawal from heavy cocaine use, suicide attempts should be anticipated.
    6. When treating a heroin addict, the primary care physician should always consider prescribing methadone for maintenance as an adjunct to treatment.
    7. Prescribing sedatives for known alcohol or drug dependent patients is very risky and may actually increase alcohol or other drug use by these patients.
    8. Hypnotics are usually effective in treating sleep disorders for alcohol or other drug dependent patients.
    9. Depression experienced by substance abusers usually clears with abstinence.
    10. Naltrexone seems to work better, as an aid to relapse prevention, in motivated patients such as impaired professionals.
    11. Antabuse (Disulfiram) should not be administered until at least 12 hours have elapsed since the last drink was taken.

In addition to the material presented above be sure to review Charles P. O'Brien's article, A Range of Research-Based Pharmacotherapies for Addiction.


Essay Questions:

  1. After reading Koob and Le Moal's article, Drug Abuse: Hedonic Homeostatic Dysregulation, would you argue that people who become dependent on one or more drugs continue to take the drug to feel good (or better) or because they feel bad? Please explain.

  2. Randolph M. Nesse and Kent C. Berridge, in their article: Psychoactive Drug Use in Evolutionary Perspective, argue that, "There are reasons why people who are not succeeding in the social competition are likely to... take drugs more often, and be less responsive to treatment." What are these reasons and what are the implications for substance abuse prevention?