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Category: Medical

Topic: Pharmacology

Level: Paramedic

Next Unit: Sedative and Hypnotic Drugs

15 minute read


Cocaine, methamphetamine, and prescribed pharmaceutical stimulants all have similar mechanisms of action and risks, with addiction to, and toxicity of, them leading to similar clinical manifestations. (The most common stimulant is, of course, caffeine.)


Prescription Stimulants

The category of stimulants is a very large category of drugs, and these are used to increase alertness, attention, and dopamine levels in the brain. Thus, they affect the dopaminergic and noradrenergic systems, causing the release of catecholamines from storage sites at the central nervous system synapses. Prescription stimulants are used to increase the level of dopamine slowly over time in an attempt to mimic normal function.

Stimulant drugs include:

  • methylphenidate and
  • amphetamines (dextroamphetamine and mixed dextroamphetamine-amphetamine salts).

Stimulant drugs generally are the first-line treatment for uncomplicated ADHD. They are also useful for such conditions as narcolepsy, chronic fatigue syndrome, and to augment the treatment for major depressive disorder and late-life unipolar treatment-resistant major depression.

Stimulants are available in

  • short-,
  • intermediate-, and
  • long-acting formulations.

Stimulants are controlled substances and require a schedule II prescription. With elevations of dopamine--called the "reward" neurotransmitter--they create a risk for addiction in susceptible individuals and so are part of a social problem that involves drug diversion and illicit sale and trade.


Stimulant Street Drugs

Stimulant street drugs and their abuse pose a greater danger than prescription drugs since their use already involves risky behavior medically and legally.

There is a sociological ebb-and-flow between prescription drug abuse and illicit drug abuse. When one increases, it's at the expense of the other in prevalence. For example, with the recent opioid crisis which brought about strict control of prescriptions and the closing of "pill mills," the use of heroin increased. 

COCAINE: blocks the dopamine transporter (reuptake) and increases dopaminergic activity in critical brain regions.

Cocaine toxicity produces end-organ toxicity in virtually every organ system in the body, primarily through its hemodynamic effects, centrally mediated via the sympathetic nervous system. Among its more important toxic effects are:

  • hypertension,
  • chest pain (although MI is uncommon),
  • arterial vasoconstriction (e.g., coronary arteries and end-organs),
  • thrombus formation,
  • psychomotor agitation (neurologic effects can range from agitation to seizures to intracranial hemorrhage),
  • severe hyperthermia,
  • dyspnea (from pneumothorax, pulmonary infarction, or other pulmonary injury), and
  • ischemic bowel leading to bowel death.

Mortality can be as high as 33% when hyperthermia develops in the setting of cocaine intoxication.

Benzoylecgonine (BE) is the major urinary metabolite of cocaine, used in drug screens. Cocaine is rapidly metabolized and detectable in blood and urine for only a few hours, but BE can be detected in the urine for several days following intermittent use and up to 10 days or more after heavy use.

METHAMPHETAMINE: blocks the dopamine transporter and stimulates the pre-synaptic release of dopamine.

It is readily absorbed via oral, pulmonary, nasal, intramuscular, intravenous, rectal, and vaginal routes. Methamphetamine may be synthesized via simple reactions using readily available chemicals and over-the-counter cold medicines, such as ephedrine and pseudoephedrine. Although diversion of prescription medications is a source of some illicit methamphetamine, the majority of recreational methamphetamine is manufactured specifically for illicit use.

Illegal methamphetamine synthesis carries a significant risk of explosion or toxic exposure and is responsible for exposing many children to profoundly toxic products. 

Call to Action: SAFETY FIRST!

In the field, you may be called to attend burns from explosions as frequently as methamphetamine toxicity. Entering such a scene requires a "safety first" mindset, because of danger from further explosion or exposure (use proper PPE).

Methamphetamine-Related Signs and Symptoms: a host of respiratory, cardiac, vascular, otolaryngologic, neurologic, integumentary, psychiatric, infectious, traumatic, and dental maladies. Among the most frequent findings are:

  • agitation,
  • tachycardia,
  • hypertension, and
  • psychosis.

Portends Badly: in severe intoxication, prognostic factors for mortality (bad omens for doom) include:

  • hypertension,
  • tachycardia,
  • coma,
  • shock,
  • body temperature >39°C (hyperthermia),
  • acute renal failure,
  • metabolic acidosis, and
  • hyperkalemia (serum potassium 5.6 to 8.5 mmol/L).

Call to Action: SAFETY FIRST!

Without provocation, amphetamine-intoxicated patients can abruptly develop severe agitation and manifest extreme violence, placing themselves, their caretakers, and other patients at risk of major injury. Again, "safety first." The clinician should anticipate clinical deterioration and cardiac arrest in any wildly agitated patient, particularly those requiring physical restraints to maintain patient safety.

SYNTHETIC CATHINONES: Cathinones are amphetamine analogs.

Abuse of synthetic cathinones (bath salts) began when these drugs were initially marketed as “bath salts” or “plant food” to avoid controlled-substance restrictions. The mechanism of action of cathinones is similar to that of methamphetamine:

  • blocks the reuptake of dopamine, norepinephrine, and serotonin, as well as
  • stimulates the release of dopamine.

Since cathinones are amphetamine analogs, toxicity, signs and symptoms, and management are the same as for amphetamines.


Management of Stimulant Intoxication

Management for stimulant use disorder depends on the severity, from counseling to intensive outpatient therapy to cognitive behavioral therapy, motivational interviewing, and combinations of medication and psychosocial interventions

In the field, you will be exposed to acute situations involving stimulant toxicity, notably amphetamine and cocaine intoxication.

  • Control of violent behavior is of critical importance, and immediate treatment with IV or IM benzodiazepines is indicated.
  • Severe hypertension, particularly if sedatives fail to lower the BP, may require treatment with vasodilators (not beta-blockers, which are contraindicated because the maintenance of cardiac output depends upon sympathetic drive).
  • Hyperthermia is best controlled by eliminating excessive muscle activity. For those who break through benzodiazepines, paralysis/sedation/intubation may be life-saving.
  • For cardiovascular effects, recommendations include oxygen and reduction of sympathetic stimulation via benzodiazepines.

It is important to rule out hypoglycemia and hypoxia as the causes of psychomotor agitation.

Needless to say, rapid transport to an appropriate facility is indicated, along with support/maintenance of ABC (airway, breathing, circulation), oxygen, and IV access. In cases involving methamphetamine manufacture, exposure to profoundly toxic substances should be avoided with the proper PPE.