1. 
   

   What are the most commonly abused stimulants?

   
   
2. 
   

   How are the acute cardiovascular complications of stimulants managed?

   
   
3. 
   

   How are the acute psychiatric complications of stimulants managed?

   
   
4. 
   

   What are the other medical sequelae of abused stimulants?

   
   
5. 
   

   What factors should be considered when discharging a patient with complications of stimulants?

What Are the Most Commonly Abused Stimulants?

Cocaine is a naturally occurring plant alkaloid found in the leaves of the coca bush, Erythroxylon coca. Cocaine for illicit use comes in two major forms, the base and the salt. Cocaine base or “crack” is smoked, while cocaine salt or powder cocaine is snorted intranasally or dissolved for intravenous injection. Amphetamine and methamphetamine are synthetic stimulants that are typically abused by the oral or intravenous route. “Ice” is crystallized methamphetamine that can be smoked or used intranasally. “Ecstasy” or MDMA is 3,4-methylenedioxymethamphetamine, and it is usually abused by the oral route. MDMA has both hallucinogenic and stimulant properties. Over-the-counter stimulants include ephedrine, phenylephrine, and pseudoephedrine. Two additional plant-derived stimulants that may be encountered in clinical settings include ephedra or “ma-huang” (from the dried branches of Ephedraceae species) and khat (prepared from the Catha edulis plant) (Table 235-1).

Prescription stimulants include methylphenidate, methamphetamine, dextroamphetamine, mazindol, phenmetrazine, and phentermine. Prescribed stimulants may be used therapeutically for multiple conditions, including attention deficit disorder, narcolepsy, fatigue in multiple sclerosis, and refractory depression, as well as in palliative care. When prescribed stimulants such as methylphenidate or dextroamphetamine are abused by patients who have valid prescriptions for them, clinicians may see unintended side effects such as elevation in resting heart rate or other cardiovascular complications; this may be a clue to the prescriber that unauthorized dose escalation is occurring.

Stimulants increase catecholamine neurotransmitter activity, leading to acute medical and psychological effects. Some stimulants, like cocaine, work via blockade of presynaptic neurotransmitter reuptake pumps. Other stimulants, such as amphetamines, cause presynaptic release of catecholamines. Medical effects result from overstimulation of the sympathetic nervous system leading to peripheral vasoconstriction, increased heart rate, lowered seizure threshold, and other adverse effects. Psychological effects result from stimulation of corticomesolimbic dopamine circuits in the brain, leading to desired effects (increased energy and alertness, euphoria, decreased appetite and need for sleep) as well as negative effects, including anxiety, grandiosity, impaired judgment, psychosis (paranoid delusions and hallucinations) and addiction.

Nicotine and caffeine are mild stimulants that are in widespread use. Nicotine acts at the nicotinic acetylcholine receptor and causes the release of acetylcholine (ACh), dopamine, norepinephrine, serotonin, gamma-aminobutyric acid (GABA), and glutamate. Nicotine has complex physical and psychological effects that are dose related. Physical effects include acute increases in blood pressure, heart rate, and cardiac output and cutaneous vasoconstriction (at low doses); ganglionic stimulation and adrenal catecholamine release (at high doses); and hypotension and bradycardia (at extremely high doses). On a psychological level, nicotine can cause both stimulation (when smoked under conditions of fatigue) and relaxation (when smoked under conditions of anxiety)—these effects make nicotine strongly reinforcing. Caffeine is a nonselective A1 and A2A adenosine receptor antagonist and acts by modulating dopamine and glutamate. While dietary doses of caffeine are generally safe and well tolerated, very high doses of caffeine may cause clinically significant negative physiologic and psychologic effects, including tolerance and withdrawal, features of a substance dependence syndrome, or discrete psychiatric disorders (eg, caffeine intoxication, caffeine-induced anxiety disorder).

About 44% of the world’s users of cocaine reside in North America, where its use has been stable for the last decade. Cocaine is the second most widely used illicit drug in the United States, after marijuana. According to the 2006 National Survey on Drug Use and Health (NSDUH), the lifetime prevalence of cocaine use is 35.3 million Americans (14%), whereas the past-month prevalence is 2.4 million individuals (1%). The lifetime prevalence of noncocaine stimulant use is 20.1 million Americans (8%), whereas the past-month prevalence is 1.2 million individuals (0.5%). Cocaine abuse or dependence occurs at a rate of 1.7 million individuals (0.7%) annually, while noncocaine stimulant abuse or dependence affects 400,000 individuals (0.2%) annually.

Cocaine is the drug most often associated with visits to hospital emergency departments (450,000 visits annually, or 31% of all drug-related visits), while methamphetamine is associated with 109,000 visits annually, or 7.5% of visits. Cocaine is associated with high mortality and has been implicated in 39% of all drug misuse deaths investigated by medical examiners.

Polysubstance abuse is the norm for stimulant users. Patients diagnosed with one substance use disorder (SUD) will often have another. Cigarette smokers or binge alcohol drinkers are each ten times more likely to use cocaine than nonsmokers or moderate drinkers. Almost one-quarter of those who use MDMA also meet the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for another SUD, especially nicotine, alcohol, or marijuana.

Caffeine is the most widely used mood-altering drug in the world. In the United States alone, 87% of children and adults regularly consume caffeine in foods and beverages.

Around the world, 57% of men and 10% of women smoke tobacco products, primarily cigarettes. In the United States, about 21% of the adult population smokes. However, among individuals with severe mental illness, about 70–90% are smokers.

Stimulant intoxication includes physical changes, many of which can be severe and acute, including fulminant hyperthermia, seizures, rhabdomyolysis, acute renal failure, hypertension, and increased myocardial oxygen consumption. Stimulant intoxication may also include severe behavioral effects, including aggression, hypervigilance, acute psychotic reactions, and suicidal ideation. These acute complications of abused stimulants are due to increased sympathomimetic effects and activation of dopamine circuits (Table 235-2).