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. Cocaines 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 cocaine, depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the cocaine user may experience dysphoria, or a "crash" after the initial high. The principal actions of cocaine 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. Cocaine 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. Cocaine-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 cocaine use, thereby promoting thrombosis. Cocaine 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, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors. Management
There is no specific antidote for cocaine.
U.S. National Library of Medicine. "Sacituzumab govitecan". ADC Review. "Sacituzumab govitecan". National Cancer Institute. Clinical trial number NCT01631552 for "Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers" at ClinicalTrials.gov
Clinical trial number NCT02574455 for "ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT)" at ClinicalTrials.gov
Clinical trial number NCT03547973 for "Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer" at ClinicalTrials.gov
Sacituzumab govitecan at the US National Library of Medicine Medical Subject Headings (MeSH)