<unk>  pharmacodynamics involve multiple complex mechanisms. Although it has a short half-life (~ 1 hour),<unk>  metabolites, which rise in concentrations several hours after<unk>  ingestion, persist in circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction. This drug binds and blocks monoamine (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects.<unk> 's acute effect in the central nervous system is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain). When this effect ceases due to metabolism of<unk> , depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the<unk>  user may experience dysphoria, or a "crash" after the initial high. The principal actions of<unk>  on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand.<unk>  and its metabolites may cause arterial vasoconstriction hours after use. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply.<unk> -induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. Plasminogen activator inhibitor is also increased following<unk>  use, thereby promoting thrombosis.<unk>  acts like a class I antiarrhythmic agent by blocking sodium and potassium channels, in a similar way of local anesthetics such as lidocaine, and interferes with action potential propagation. This Vaughn-Williams class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity,<unk>  targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.
Cocaine intoxication
Hypertensive encephalopathy
Carbamate poisoning
Benzodiazepine overdose
Nicotine withdrawal
Alcohol withdrawal syndrome
Benzodiazepine withdrawal syndrome
Opioid overdose