MEDICAL CONSEQUENCES OF ALCOHOL AND DRUG USE DISORDERS

SLIDE 1. Today we are going to talk about medical complications related to heavy alcohol or drug use and related disorders. The talk will focus on health consequences of alcohol abuse or dependence as an example, and then we will have a brief overview of medical problems associated with specific drugs of abuse.

 

SLIDE 2. But before we start, I want to thank the Alcohol Medical Scholars Program for their support for the preparation of this lecture. Briefly, this is a group of physicians and other healthcare professionals from several medical schools around the country that have come together to develop initiatives and tools to promote optimal education in medical schools for the identification and care of people with alcohol dependence and other substance use disorders. You may visit the AMSP anytime at www.alcoholmedicalscholars.org

 

SLIDE 3. As an overview, the medical consequences related to substance use disorders can be split into three major categories of potential problems – acute effects, the complications associated with chronic heavy use, and health problems regarding withdrawal from a substance.

 

SLIDE 4. Before we discuss these three categories, I would like to start with a few brief words about the scope of the problem of alcohol abuse and dependence; that is, what kind of disorder are we talking about when we talk about alcoholism.

First of all, there are approximately ____ students in this classroom, and if you look around, know that ___ of you (15%, 1/7) roughly will develop alcohol abuse or dependence. So we are talking about a very common illness that affects more people than does diabetes, lung cancer, breast cancer, heart attacks, and is about as common as hypertension is in the general population.

In addition to this relatively high prevalence, alcoholism causes a great amount of morbidity and mortality. First, up to 40% of all general hospital admissions in the U.S. are related to alcohol or drug problems in some way. So the next time you see a patient with an upper GI bleed in the hospital, for example, wonder whether heavy alcohol use has played a role.

Also, alcoholics are twice as likely to be seen by their primary care provider than nonalcoholics, so there is a particular need for you as young physicians-in-training to recognize sequelae of alcoholism in this arena in order to better identify an alcohol dependent person. In fact, a recent study found that physicians are actually not very good at recognizing alcoholics in the outpatient setting (there’s a link to the news story on the web site).

And if alcoholics aren’t recognized and appropriately treated, or even if they are identified but maintain a severe course with few substantial abstinence periods, these people will die – alcoholism is a lethal illness. Over 100,000 people die per year of alcohol or drug related causes in the U.S., and chronic alcoholics will lose roughly 15 years off their average life span.

And here’s what will kill you: accidents (MVAs, overdose), acts of violence (suicide, homicide), and today’s subject, major medical illnesses (like esophageal varices, cancers, heart failure/MIs, cirrhosis).

 

SLIDE 5. Let’s start with the brain. CNS effects can be broadly categorized into motor, behavioral, and cognitive. Motor impairment, along with the significant errors in judgment and disinhibition that are seen with acute intoxication, are the major factors that contribute to drunk-driving accidents. These behavioral effects also play an important role in suicidal and homicidal acts that occur frequently when people are intoxicated, and are associated with other at-risk sexual behaviors related to contracting STDs.

In addition, many people, alcoholic or not, including medical students, use alcohol to help them sleep at night. While this may be effective to help people fall asleep, alcohol’s effects on sleep architecture are horrendous, and usually results in fitful, restless sleep and subsequent feelings of daytime sleepiness because of the poor quality of sleep attained.

[ANECDOTE: As an aside, I remember on my first day of medical school, a very famous psychiatrist, Dr. George Valliant, lectured to us and offered two pearls of wisdom:

1 – Marry someone who will take of you, because you’ll be taking care of people for the rest of you life

2 – Don’t ever take a substance to fall asleep or stay awake

I can tell you that I’ve made good on the first, and almost made good on the second, but nevertheless, a very important thing to remember as you are starting your careers in a very physically demanding profession.]

Back to acute effects of alcohol use – certainly, you may know of friends or may even have experienced some GI effects of consuming large amounts of alcohol, say for instance, in college – that is, nausea, vomiting etc.

And another important consideration in acute intoxication is the potential for alcohol poisoning in overdose, and subsequent respiratory arrest.

 

SLIDE 6. Now that we have covered acute problems associated with alcohol use, we’ll move on to the consequences of long-term heavy drinking.

 

SLIDE 7. Again we return to the central nervous system. Chronic heavy alcohol use has many CNS effects. So the next time you have a patient in your office with numbness or tingling in her extremities (i.e., a peripheral neuropathy), consider alcohol dependence in the differential diagnosis along with the usual suspects like diabetes, HIV, primary neurological conditions, and toxic/metabolic causes.

In addition, chronic alcohol use can cause gait disturbances associated with cerebellar damage and memory problems of a variety of sorts.

A word about Wernicke-Korsakoff’s syndrome – very few alcoholics ever get this – I’ve seen probably 5 cases in my career thus far. The primary pathophysiology is thiamine deficiency due to malabsorption in the GI tract in alcoholics, leading to degeneration of the mamillary bodies of the limbic system and other brain structures (dorsomedial nucleus of thalamus and periventricular grey matter). These individuals have a remarkable presentation of confusion, nystagmus, and some paralysis of ocular muscles, and if not corrected (with thiamine administration) can progress to permanent severe short term memory loss and confabulation. But remember, this is a very rare condition.

 

SLIDE 8. A wide variety of GI problems are related to chronic heavy alcohol use, including peptic ulcer disease, gastritis, varices, Mallory-Weiss tears, malabsorption (as discussed above) and gastric cancers. Of singular importance is the synergistic effect on GI cancers when alcoholics also are nicotine dependent, which the majority (up to 80%) are.

Liver complications range from fatty liver, which occurs several hours after ingesting just a few drinks, to alcoholic hepatitis (i.e., damaged hepatocytes causing elevations in lever enzymes AST/ALT), to cirrhosis or hepatocellular cancer. However, it should be noted that cirrhosis, that is, significant hepatocyte damage and resultant sclerosis, occurs in a minority of alcoholics – only about 15%.

Lastly, pancreatitis and pancreatic cancer are commonly associated with alcoholism, and a source of marked alcohol-related morbidity and mortality.

Thus, the next time a patient presents to you with abdominal pain, look at all the alcohol-related phenomena that can be possible etiologies up and down the GI system. Always include these conditions in the differential diagnosis.

In addition to effects on the GI system, chronic heavy alcohol use impacts the cardiovascular system. Alcoholics have an increased likelihood of having hypertension, strokes, and cardiomyopathy (alcohol is toxic to heart muscle). However, CM is difficult to detect until it is at a fairly advanced stage, but nevertheless, in patients complaining of chest pain symptoms, consider alcoholism as a potential cause.

 

SLIDE 9. Now, we’ve talked about alcohol’s effect on a number of organ systems, but keep in mind that alcohol can also greatly affect the reproductive system. This goes for women as well as for men. So the next time one of your patients complains of impotence or impaired sexual desire or arousal, don’t just prescribe Viagra and expect to see a happy and grateful patient the next week. Ask about problems with alcohol and other substances in your history. In addition, testicular atrophy can result from heavy alcohol use as well.

 

SLIDE 10. And briefly, know that alcohol affects just about every other organ system, from causing a macrocytic anemia, to myopathies. [ANECDOTE: A professor once told me that alcohol is toxic to everything in the body except for maybe the eyes and the kidneys, which pretty well spans the gamut of organ systems that alcohol can impact.]

 

SLIDE 11. Before we proceed, I wanted to talk a little bit about some strategies to detect a potential problem with alcohol (or drugs) in your patients in your office or in the hospital. First and foremost, TAKE A HISTORY – ASK about life problems (e.g. family/marital, job, accidents, legal – DUIs), and transition into nonthreatening, nonjudgmental questions about alcohol, drug and nicotine use. While the issue of detection of substance problems is a whole lecture unto itself, this is just a reminder that the best diagnosis is obtained through taking a history, and then doing a physical exam.

In addition, some blood tests for state markers of heavy drinking can be useful if you are suspicious of alcohol related problems. GGT has good sensitivity and specificity (around 70-80% sensitive and specific), and generally is the first of the liver enzymes to elevate with heavy drinking (i.e., 6-12 drinks/day for several weeks).

Besides GGT, the CDT (carbohydrate deficient transferrin) test is a more expensive alternative for detecting high levels of drinking, and it is about as sensitive and specific as the GGT .

Reflecting alcohol’s effect on red blood cells, MCV (mean corpuscular volume), a measure of how big the RBCs are, also increases with heavy drinking.

The other liver enzymes are not very helpful if you are suspicious of alcohol dependence, since they only elevate when hepatocytes are damaged, which usually is at a fairly advanced stage of alcoholism. Nevertheless, suspect alcohol related causes in patients with high AST and ALT.

Lastly, a urine toxicology screen is useful in detecting acute intoxication with alcohol or drugs, but in the case of alcohol, only relevant if the patient has ingested alcohol in the last 6-8 hours or so.

 

SLIDE 12. Thus far we’ve discussed how alcohol can affect the body in acute intoxicated states, with chronic heavy drinking, and now let’s move on to the medical consequences associated with alcohol withdrawal.

 

SLIDE 13. Let’s first define what I mean by withdrawal. Withdrawal from a drug is an acute physiological rebound after the body is acutely deprived of a substance that has been taken in high enough levels and over a long enough period of time to develop physiologic dependence.

As a general rule of thumb, a withdrawal syndrome for a particular drug is characterized by symptoms and signs that are opposite to what the acute effects of the drug are.

Thus, for alcohol (a CNS depressant), the withdrawal syndrome consists of tremors, anxiety, autonomic instability (tachycardia, hypertension), and can progress to seizures and/or delirium tremens (DTs). However, only a minority of alcoholics (less than 5%) experience DTs, and it is usually those with other serious medical illnesses. Nevertheless, it is important to recognize symptoms and signs of alcohol withdrawal because it is responsible for a lot of morbidity (hospitalizations, relapses) and mortality that are wholly treatable. This is a whole separate lecture – the detection and treatment of alcohol withdrawal.

Lastly, as an aside, the two other substances that have clinical significant withdrawal syndromes are opioids (e.g., heroin) and stimulants (cocaine and amphetamine), which will discuss later.

 

SLIDE 14. Before we move on to medical problems related to drug use, I want to talk to you about a few other special issues about alcohol and health. The first is drug-drug interactions between alcohol, which is a drug, and other drugs. Let’s talk about some specific examples.

First, when alcohol is taken simultaneously with cocaine, -- this is the second most lethal drug combination -- a third product is formed called cocaethylene, which is longer lasting (half-life 2 hrs vs. 30 minutes for cocaine hydrochloride) and more euphorigenic. This can also impact the cardiovascular system and raise the risk for having a cardiac event (MI or arrhythmia) or stroke. Another example is when alcohol and heroin are combined – both can cause respiratory depression and can synergize to become that much more lethal.

The second category of alcohol-drug interactions is that between alcohol and prescription drugs. For example, say you have a patient who is a female college student with vaginitis who you just began on metronidazole (Flagyl). The combination of alcohol and metronidazole produces an "Antabuse-like" reaction in some patients. Thus, your patient could get violently ill with nausea, vomiting, dizziness/lightheadedness, palpitations. The pharmacodynamic interaction is that medicines like these inhibit aldehyde dehydrogenase, the second step in the major metabolic pathway for ethanol. As a result of this inhibition, high levels of the toxic metabolite acetaldehyde build up and cause the syndrome.

Other important interactions between alcohol and prescription drugs include those with other CNS depressants, for example, benzodiazepines or barbiturates. The problem here is the synergistic adverse effects on the respiratory system to cause respiratory depression. Some may remember that this type of combination – alcohol and barbiturate – was the cocktail ingested by the members of the Heaven’s Gate cult in the mass suicide of a few years ago in San Diego.

The third category of relevant alcohol-drug interactions is that between alcohol and over-the counter medicines like acetaminophen (Tylenol). The alcohol-acetaminophen syndrome can occur at levels of acetaminophen ingestion as low as 7 grams (#14 Extra Strength Tylenol) and probably lower. The result is potential fulminant hepatic failure requiring emergent transplant or death.

[ANECDOTE: As an aside, I had a case once in the ER of a woman who had attempted suicide two days prior with an overdose of alcohol and Vicodin and was seen in the ER that day. The ER physician appropriately did a urine toxicology (which was positive for opiates), but she was cleared medically rather quickly and discharged only to return to the ER 2 days later with AST/ALT levels in the mid 30,000s. The problem was not the combination of alcohol and hydrocodone, but the mixture of alcohol and the acetaminophen portion of the Vicodin that caused acute liver failure – no acetaminophen level was performed in the ER two days prior and the patient nearly died.]

 

SLIDE 15. Another special case regarding alcohol’s adverse effects is its impact on the developing fetus. With as few as three drinks a day, fetal alcohol syndrome can occur. This condition is characterized by a number of deficits including growth retardation, mental retardation and other CNS dysfunction, facial dysmorphism, and cardiac abnormalities. In fact, FAS is the #1 preventable cause of mental retardation.

Here we see an example of a young boy with FAS – notice the distinct facial features. For anyone interested, there’s a book chronicling the life of a child with FAS – it’s called "A Broken Cord" by Michael Dorris, and I would recommend it to all medical students.

 

SLIDE 16. Lastly, I’d like to say a few words about the potential benefits of moderate (i.e., 1-2 drinks/day) daily alcohol use. There is evidence that you are probably familiar with regarding the beneficial cardiovascular effects of low levels of regular alcohol use, for example, a lower incidence of MIs. However, not everyone should be drinking red wine with dinner every night. People with a history of alcohol or drug problems, obviously, and those with family histories of substance use disorders should not be encouraged in this practice. Nevertheless, there are data to suggest that alcohol in moderation can have these and other positive health effects. In addition to an impact on the cardiovascular system, moderate alcohol use has protective effects for gallbladder disease.

 

SLIDE 17. So in summary, using alcohol as an example, major health consequences can result from acute intoxication, chronic use at high levels, and withdrawal, and we’ve now discussed several common examples that you will see in your patients in the clinic and in the hospital.

Alcohol can impact nearly every part of the body, from the brain to the heart to the liver and GI tract, as well as causing sexual problems. In addition, there are dangerous alcohol-drug interactions that should be considered by clinicians. The result is much morbidity and mortality, with alcoholics potentially losing 15 years off their lives with persistent heavy drinking.

 

SLIDE 18. Now I’d like to briefly apply the same principles we’ve learned about alcohol to teach you about the medical consequences of other drugs of abuse, starting with marijuana.

Marijuana affects several organ systems including the brain that results in changes in mood and behavior, impaired muscle coordination, and errors in judgment, all of which combine to increase the risk for MVAs. In fact, in a study of 150 reckless drivers, a full one-third had smoked marijuana prior to the accident.

Other CNS effects include learning impairments, even the day after smoking, as one study of college students showed.

Marijuana also impacts the respiratory system as much if not more than cigarettes, and some studies regarding the immunological system have found that T-cell function is impaired by marijuana use.

Lastly, sexual dysfunction, including impotence in males and lack of sexual desire can be attributed to heavy marijuana use in some people.

 

SLIDE 19. Stimulants (cocaine and amphetamine) have major health consequences, and can be lethal. Of primary concern are their effects on the cardiovascular system, related to causing hypertension, tachycardia, and vasospasm. The final result can be MIs, arrhythmias, or strokes.

An additional concern is that a small percentage of stimulant users take the drug intravenously, which heightens the risk for contracting hepatitis B and HIV, as well as blood-borne infections and bacterial endocarditis.

The stimulants are the second group of drugs that cause a clinically significant withdrawal syndrome, albeit, not lethal. Stimulant withdrawal, going back to our rule-of-thumb, can cause hypersomnia, hyperphagia, mood lability and depressed mood. The course is temporary and usually subsides within a few days after stopping the drug.

 

SLIDE 20. The opioids, the class that heroin and morphine are in, are very dangerous drugs, which can result in death by overdose. Heroin carries the added risk of a clinically significant and very miserable withdrawal syndrome for patients, who often manifest (again, using our rule) nausea/vomiting, diarrhea, body pains and cramps, autonomic instability, nightmares, and marked insomnia.

Other medical consequences include the risks encountered with intravenous use.

 

SLIDE 21. Some other less commonly used drugs can cause serious health problems, and two examples are phencyclidine and the inhalants. First, PCP intoxication can cause an organic brain syndrome characterized by delirium, autonomic instability, affect lability, psychosis, violence, and muscle rigidity.

So the next time you have a young patient in the ER with a delirium, think about PCP intoxication.

In addition, inhalants (substances like toluene, gasoline) are particularly toxic to the central nervous system. Chronic use can result in brain damage, especially of the frontal lobes, peripheral neuropathies, hearing loss, and liver and kidney damage. The neurological effects often are irreversible.

 

SLIDE 22. So, we covered a lot of ground today. Let me just summarize a few of the major points.

First, using alcohol as an example, we have seen that it can cause a variety of serious health problems affecting nearly all organ systems. The adverse physical effects can occur during intoxication (e.g., impaired motor coordination and judgment), chronic heavy use (e.g., various levels of liver problems, but remember, a minority of alcoholics – 15% -- go on to cirrhosis), and in withdrawal states (e.g., tremors and anxiety, but again remember that only a small proportion of alcoholics ever experience classic DTs).

Second, we reviewed some important alcohol-drug interactions (e.g., alcohol and acetaminophen) that you will see cause medical consequences in ER, the outpatient clinic, or on the inpatient wards.

Third, every major category of drugs other than alcohol, from marijuana to inhalants, can have a major impact on the body.