What are the primary concerns and treatment approaches for a patient with a methamphetamine overdose, presenting with symptoms such as agitation, aggression, confusion, seizures, and cardiovascular instability, including hypertension, tachycardia, or arrhythmias?

Pathophysiology of Methamphetamine Overdose

Core Pathophysiologic Mechanisms

Methamphetamine overdose produces life-threatening toxicity through excessive catecholamine release and reuptake blockade, creating a sustained hyperadrenergic state that simultaneously damages multiple organ systems through direct cellular toxicity, coronary vasospasm, and extreme metabolic demand. 1

Catecholamine-Mediated Toxicity

• Methamphetamine simultaneously stimulates the release and blocks the reuptake of dopamine and norepinephrine, creating catecholamine excess that drives the clinical syndrome 1
• This hyperadrenergic state increases myocardial contractility, heart rate, and blood pressure, dramatically elevating myocardial oxygen demand while simultaneously reducing supply through coronary vasoconstriction 1
• The excessive beta-adrenergic stimulation causes direct myocyte damage independent of ischemia, likely through oxidative stress and mitochondrial dysfunction 1

Cardiovascular Pathophysiology

• Methamphetamine exerts direct vasoconstrictor effects on coronary arteries, producing coronary vasospasm that can cause myocardial ischemia and infarction even in patients with normal coronary anatomy 1
• The drug reduces coronary sinus blood flow and decreases myocardial perfusion, creating repetitive ischemic insults 1
• Methamphetamine increases platelet aggregability, promoting thrombosis formation that can precipitate acute coronary syndromes 1
• Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death 2
• Takotsubo cardiomyopathy may develop as a manifestation of catecholamine excess 2

Central Nervous System Effects

• CNS toxicity manifests as psychomotor agitation, confusion, and hallucinations 2
• Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur 2
• The drug is a strong central nervous system stimulant that causes euphoria, alertness, and psychiatric complications 3, 4

Metabolic and Systemic Complications

• Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop 2
• The hyperthermia results from increased metabolic heat production combined with impaired heat dissipation 5
• Rhabdomyolysis leads to myoglobin-induced renal failure if untreated 5

Cardiovascular Manifestations in Overdose

• Tachyarrhythmias and hypertension or hypotension characterize the cardiovascular effects 2
• Chronic use results in accelerated atherosclerosis through endothelial dysfunction, increased platelet aggregation, and chronic hypertension 1
• Methamphetamine is twice as toxic as amphetamine with clinical effects similar to cocaine 3

Critical Pathophysiologic Principle

The fundamental mechanism underlying methamphetamine toxicity is unopposed alpha-adrenergic stimulation when beta-receptors are blocked, which worsens coronary vasospasm and can precipitate myocardial infarction 6, 1. This explains why beta-blockers are absolutely contraindicated in acute methamphetamine intoxication 5, 6.