Substance Abuse

Question 1

What is the site of action of amphetamine?

Answer 1

The neurotransmitters norepinephrine, epinephrine, and serotonin are stored within cytoplasmic vesicles of presynaptic adrenergic neurons. These neurotransmitters are released into the synapse with nerve depolarization. Once in the synapse, the neurotransmitters bind to postsynaptic receptors and elicit neurochemical responses. Thereafter, they diffuse away from the postsynaptic receptor and are quickly degraded or undergo cellular reuptake and replaced into vesicles.
*Methamphetamine lacks direct adrenergic effects, but is instead an indirect neurotransmitter. Methamphetamine is incorporated into cytoplasmic vesicles where it displaces epinephrine, norepinephrine, dopamine, and serotonin into the cytosol. As cytosolic concentrations rise, neurotransmitters diffuse out of the neuron and into the synapse where they activate postsynaptic receptors. Methamphetamine also inactivates neurotransmitter reuptake transporter systems.

> The result of these two processes is a surge of adrenergic stimulation>Stimulated alpha- and beta-adrenergic receptors produce hypertension, tachycardia, hyperthermia, and vasospasm. Serotonergic activation contributes to alterations in mood as well as deranged responses to hunger and thirst. Dopamine receptor stimulation affects drug-craving and drug-seeking behavior, and psychiatric symptoms.

Question 2

What is the presentation of meth intoxication?

Answer 2

— Patients with methamphetamine intoxication range from the virtually asymptomatic to those in sympathomimetic crisis with seizures, metabolic acidosis, and imminent cardiovascular collapse. Agitation, tachycardia, and psychosis are among the most frequent findings identified on presentation to the emergency department (ED) [14,15]. Life-threatening intoxication is characterized by hypertension, tachycardia, severely agitated delirium, hyperthermia, metabolic acidosis, and seizures. Prognostic factors for mortality include: coma, shock, body temperature >39ºC, acute renal failure, metabolic acidosis, and hyperkalemia (K 5.6 to 8.5 mmol/L) [16].

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• Cardiac ischemia, myocardial infarction, and cardiomyopathy have been identified in acute and chronic users. Retrospective, observational studies of methamphetamine-exposed patients report that a substantial minority show signs of acute coronary syndrome

> *Severe methamphetamine intoxication is associated with sudden cardiovascular collapse, particularly in agitated patients who are physically restrained to prevent injury to themselves and others, including law enforcement and clinicians. Severe agitation often presages cardiac arrest, which can occur with frightening rapidity, and has been observed after only a few minutes’ struggle.
*Cardiovascular collapse is postulated to arise from a combination of neurotransmitter depletion, metabolic acidosis, and dehydration

Valvular dysfunction may be related to the serotonergic effects of methamphetamine, while aortic dissection and rupture are more likely due to its vasospastic and hypertensive effects. Injection drug use increases the risk of infectious sequelae, such as bacterial endocarditis.

Question 3

What are some of the additional physical findings in acute meth intoxication RE:
>skin
>mouth
>lungs
>GI
>neurologic
>psych

Answer 3

> skin popping: SQ and IM Injection drug use may produce cellulitis, abscesses, and track marks. *Protracted methamphetamine abuse is associated with formication (“crank bugs,” a feeling that ants are crawling on the skin), and many methamphetamine abusers suffer multiple small skin excoriations from unremitting picking

> Extensive tooth decay (“meth-mouth”) is common in chronic methamphetamine abuse due to bruxism, decreased saliva production, and poor dental hygiene

> . Illicit methamphetamine may contain pulmonary irritants that are directly toxic to the lung. Methamphetamine has been implicated in acute pulmonary edema [26], pulmonary hypertension [27,28], and, if smoked, thermal injury. Other pulmonary complications include: pneumothorax, pneumomediastinum, pneumonia, acute lung injury, and pulmonary hemorrhage. Similar injuries have been seen after inhalation of heroin and smoked cocaine (crack)
– Methamphetamine can induce vomiting and diarrhea due to sympathomimetic stimulatory effects. Severe abdominal pain out of proportion to physical examination findings suggests methamphetamine-associated bowel ischemia [30], particularly in the setting of body packing and stuffing. Rectal exposure to methamphetamine occurs in cases of transport for distribution (ie, body packing) and rectal administration (“booty bumping”

> Choreiform movement disorders are a relatively common finding in acute methamphetamine intoxication, and arise from derangements in dopaminergic neurotransmission [32]. Focal neurologic deficits may represent central nervous system ischemia, infarction, or hemorrhage. Seizures are associated with severe intoxication, typically within 24 hours of methamphetamine use. They are usually self-limited and brief.

> Acute methamphetamine use can induce agitated delirium and paranoia. Binge or chronic methamphetamine use is strongly associated with a variety of psychiatric symptoms, including paranoia and psychosis, but delusions, homicidal and suicidal ideation, mood disturbance, anxiety, and hallucinations also occur [35]. Suicidality, homicidality, psychosis, and abnormal behavior and movements are commonly seen in binge as well as chronic users. Psychiatric symptoms are often the chief complaint of patients presenting to the emergency or acute care setting.