Pathology of Drug Abuse

Pathology of Drug Abuse

Smoking

Smoking leads to the greatest number of problems of any drug in use in the world today. Smoking contributes to more than 400,000 deaths each year in the United States. These deaths are mainly the result of increased numbers of lung cancers as well as increased numbers of cases of atherosclerotic heart disease and emphysema of the lung. Smoking increases the risk for cancers of the bladder, pancreas, kidney, and cervix. There is an increased risk for gastritis and gastric ulceration in persons who smoke. Cataracts of the crystalline lens of the eye occur with increased frequency in smokers.

Young women who are pregnant and who smoke put their fetuses at increased risk for decreased birth weight, premature birth, and perinatal mortality. The risk for spontaneous abortion is increased with maternal smoking. Fetal deaths late in gestation are increased 50% in mothers who smoke more than 3 cigarettes per day.

1. Normal lung, gross.
2. Small cell anaplastic (oat cell) carcinoma of lung, gross.
3. Squamous cell carcinoma of lung, gross.
4. Emphysema, centrilobular type, gross.
5. Emphysema, representing a late 20th century version of "The Masque of the Red Death" in Edgar Allen Poe's short story.
6. Composite photograph with a narrowed coronary artery at the left and a markedly narrowed coronary artery at the right, microscopic.
7. Pelvis of kidney, urothelial carcinoma, gross.
8. Acute gastric ulcerations, gross.
9. Hyaline membrane disease in the lung of a premature neonate, microscopic.

Alcoholism

The abuse of alcohol contributes to many deaths per year in the United States. One of the most common drug overdoses leading to death is ingestion of a large amount of alcohol. Chronic alcoholism leads to liver disease. Liver disease can be manifested as fatty change. Excessive alcohol ingestion for many years can lead to micronodular cirrhosis. A cirrhotic liver leads to portal hypertension and the complication of bleeding esophageal varices with massive, life-threatening gastrointestinal hemorrhage. There is also an increased risk for hepatocellular carcinoma arising in a cirrhotic liver. In the brain, alcoholism can lead to Wernicke's disease.

1. Normal liver, gross.
2. Fatty change of liver, microscopic.
3. Micronodular cirrhosis of liver, gross.
4. Micronodular cirrhosis of liver, microscopic.
5. Hepatocellular carcinoma, liver with micronodular cirrhosis, gross.
6. Esophageal varices, gross.
7. Wernicke's disease, hemorrhages in the mammillary bodies, gross.

Intravenous Drug Abuse

Many drugs can be injected intravenously. The drugs themselves may have the major effect of impairment of mental function, but the route of administration can have serious complications. Injection of drugs with needles that are not sterile leads to the potential for a wide variety of infections. Such infections include: human immunodeficiency virus (the causative agent for AIDS), viral hepatitis (particularly hepatitis B and C), and bacterial infections.

Persons with a history of intravenous drug abuse also are more likely to have tuberculosis of the lungs. The drug heroin can produce a nephropathy in the kidney that resembles focal segmental glomerulosclerosis. In addition, a "talc granulomatosis" can occur because many injected drugs have been adulterated with an inert substance (such as talcum powder) to "cut" or dilute the amount of drug.

1. Normal aortic valve compared with infective endocarditis, gross.
2. Surface of the brain with acute meningitis, gross.
3. Viral hepatitis of the liver, gross.
4. Viral hepatitis of the liver, microscopic.
5. Macronodular cirrhosis of the liver, gross.
6. Mycobacterium tuberculosis, lung, cavitary disease, gross.
7. Glomerulus of kidney demonstrating focal scarring with heroin nephropathy, microscopic.
8. Talc granulomatosis of the liver, gross.
9. Talc granulomatosis of the lungs, polarized light, microscopic.

Oxycodone

Oxycodone, best known by the trade name OxyContin®, is a controlled release form of opioid analgesic prescribed to treat moderate to severe pain of constant and prolonged duration. Persons abusing this medication risk addiction and death, particularly if oxycodone is used in association with other drugs. Abusers may progress to usage by intravenous injection and to usage of other opiates or drugs of abuse.
Cocaine

Cocaine can exert a variety of effects. The major acute effects producing pathologic conditions result from the increased circulating catecholamine levels with cocaine use. These increased catecholamines can produce vasoconstriction. The lesions can include acute hemorrhages and infarction in the brain. Ischemic changes in the heart from small artery narrowing and sclerosis lead to contraction band necrosis of the myocardium and possible sudden death. Combining cocaine use with ethanol use can compound the myocardial damage. Pregnant mothers who use cocaine can affect their fetuses from abnormalities of placental function leading to low birth weight babies or an increased risk for placental abruption. Maternal cocaine use increases the risk for spontaneous abortion.

Persons with cocaine intoxication (not necessarily related to the drug level) may develop a state of iatrogenic psychosis (cocaine psychosis) with "excited delerium" in which they are markedly agitated and combative and develop hyperthermia, often of a severe degree (to 106 F). Organ damage can accompany this state of excited delerium and may include rhabdomyolysis of muscle, hepatotoxicity, and renal failure. Disseminated intravascular coagulation (DIC), hypotension, and sudden death are additional complications.

1. Massive intracerebral hemorrhage associated with cocaine use, gross.
2. Cerebral infarction, gross.
3. Heart with myocardial contraction band necrosis, microscopic.
4. Heart with peripheral coronary artery sclerosis, microscopic.
5. Abruptio placenta with large recent blood clot compressing the parenchyma, gross.

Methamphetamine

Methampetamine is a stimulant drug with inotropic effects upon the cardiovascular system. Methamphetamine is metabolized to amphetamine, which is also a stimulant. The heart may have such stress placed upon it that there are ischemic changes to the myocardial fibers. The myocardial effects are made worse by concomitant ethanol use.

1. Heart with ischemic changes, microscopic.

GHB

Gamma-hydroxybutyrate (GHB) is a metabolite of the neurotransmitter gamma aminobutyric acid (GABA) and also functions as a neurotransmitter by affecting the dopaminergic system. GHB may also potentiate the effects of endogenous or exogenous opiates. GHB was introduced into the U.S. in 1990 as a purported stimulant to muscle growth during sleep, but it was soon banned because of problems with overdose and adverse reactions. Moreover, GHB is no longer used as an anesthetic agent because of the risks. The effects of GHB can be potentiated by alcohol and by benzodiazepines. The ingestion of GHB results in drowsiness and dizziness with the feeling of a "high" within 10 to 20 minutes and lasting up to 4 hours. There are a multitude of adverse effects that can occur within 15 minutes to an hour, including: headache, nausea, vomiting, hallucinations, loss of peripheral vision, nystagmus, hypoventilation, cardiac dysrhythmias, seizures, and short-term coma. These findings generally subside in 2 hours to 4 days. It is difficult to predict how much GHB will produce an overdose. Withdrawl from GHB can have an onset in 12 hours and last up to 12 days. In rare instances, deaths have occurred from these adverse effects.

Ecstasy

The methylene-dioxy derivatives of amphetamine and methamphetamine are "designer drugs" that generically are termed "ecstasy" and include 3,4-methylenedioxy-methamphetamine (MDMA), also known as "Adam," 3,4-methylenedioxy-ethylamphetamine (MDEA), also known as "Eve," and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), also known as "Methyl-J" or "Eden." A "designer drug" is a compound that is chemically altered from the form of a controlled substance in order to produce special effects and to bypass legal regulations. MDMA and similar compounds are "entactogens" that act upon dopaminergic and serotonergic pathways in the brain to give users a felling of euphoria, energy, and a desire to socialize. These immediate effects last approximately 3 to 6 hours.

The adverse effects of ecstasy use may include hyperthermia, liver toxicity, and neuropsychiatric effects. Severe dehydration leading to excessive fluid intake and water intoxication. There can be memory deficits, confusion, depression, and sleep problems even weeks after taking this drug. Long term use may be accompanied by long-lasting brain damage and memory impairment.

A syndrome including hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, hepatic failure, and renal failure has been reported with MDMA use, findings similar to the excited delirium of cocaine use. In addition persons using MDMA may develop acute fulminant hepatitis with liver failure, and possible death, that can occur days to weeks following drug use.

Anabolic-Androgenic Steroids

The use of anabolic-androgenic steroids (AAS) has increased substantially over the past 3 decades. These drugs are used mainly for their effect of increasing muscle mass for the desired goal of increasing athletic performance and enhancing physical appearance. However, such drugs do not increase the level of skill in performance and cardiovascular function--the major enhancers to most sports-related activities.

There are many adverse effects to AAS use. In men these include: testicular atrophy, decreased testosterone production, gynecomastia, baldness, hypertension, fluid retention, tendon injuries, nosebleeds, more frequent colds, and sleep disorders. In women, the adverse effects reported include: decreased breast size, fluid retention, hypertension, and sleep disorders. Physical changes such as testicular atrophy and gynecomastia in men, or breast atrophy in women, are often not reversible even after stopping the drugs. Adolescents taking AAS may have diminished bone growth and shorter stature. AAS may produce cholestatic jaundice; they reduce the level of HDL cholesterol to promote atherogenesis. The major psychiatric effects of AAS use include increased aggression and major mood disorders including depression and mania. Such adverse effects could significantly impact athletic performance negatively and decrease sexual function. In short, anabolic steroids can prevent the very things that they are supposed to enhance.

The most serious complication of AAS use is an increased risk for heart disease and sudden death. Anabolic steroids decrease HDL cholesterol and increase cardiac size. Myocardial fibrosis can occur, similar to cardiomyopathy. Hypertension induced by AAS further increases heart size. These effects may persist even after use of AAS has been stopped, increasing the risk for morbidity and mortality. Anabolic steroids have been shown to enhance the coronary artery response to catecholamines released during periods of stress, and this may play a role in the sudden cardiac deaths reported with their use. Contraction band necrosis, indicative of ischemia, has been observed in such deaths.

1. Heart with hypertrophy, gross.
2. Heart with myocardial contraction band necrosis, trichrome stain, microscopic.
3. Testicular atrophy, gross.
4. Testicular atrophy, microscopic.
5. Gynecomastia, gross.