Other known mechanisms of cardiotoxicity, include cocaine’s blockage of sodium channels and a subsequent increase in calcium flux and a vasoconstrictor response . Ischemia is suggested as the main mechanism of acute damage responsible for various clinical presentations . While smoking crack or sniffing cocaine, there is a vast accumulation of the drug in the heart affecting myocardial tissue directly . Cocaine crosses the blood–brain-barrier perhaps better than other psychoactive chemicals and may even induce its breakdown 17,18.
Medical Definition
As nitric oxide/glyceraldehyde-3-phosphate dehydrogenase pathway mediates cocaine induced autophagy, glyceraldehyde-3-phosphate dehydrogenase can be tested for use (see clinical trials in Parkinson’s disease 48,94). Here too, it is helpful to briefly review prevention and treatment recommendations separately for acute vascular events. Cocaine use promotes vascular disease, while also influencing the course of disease management, and therapy. The prevailing low socio-economic status, limited awareness of health issues, lack of sleep, and poor nutrition, could further hasten vascular disease 43,44. Literature that characterizes atherosclerosis in the carotid arteries in asymptomatic cocaine users is scarce.
Browse Nearby Words
Treatment for cocaine-induced acute vascular events may be similar to indications in patients with traditional risk-factors, with few exceptions. Additionally, genetic factors leading to variability in reaction to cocaine can enhance hemodynamic responsiveness, incidence of coronary vasoconstriction, and vascular damage . In addition to cocaine-specific effects, there are secondary harms resulting from synergetic effects between multiple environmental, psychosocial and behavioral factors comprising the addiction phenomenology that could in turn enhance potential vascular damage. Additional in vivo examinations are clearly required to solidify knowledge concerning early vascular disease detection in CUD, especially, the assessment of carotid plaque composition for determining risk profiles and predicting future clinical events in CUD.
Review Date 10/9/2024
Indeed, silent disease progression is particularly pronounced in CUD who remain asymptomatic until they reach the emergency room with acute events 8,24,73. Atherosclerosis, however, develops during prolonged periods of chronic cocaine use and in its early stages usually does not create symptoms or signs. Given the known vascular toxicity cocaine induces 13,23, further compounded by cigarette smoking and alcohol comorbidity 32,73,96 and interacting with the progressing age of the crack generation 97,98, there is a public health imperative to identify presymptomatic markers of vascular impairments in CUD. Chronic treatments for CUD with cardiovascular problems include antiplatelet and antithrombin agents, statins and diuretics. For example, enhanced supportive care and use of benzodiazepines and phentolamine for sedation; and avoiding β-blockers, which can lead to severe hyper-tension and coronary vasoconstriction resulting from the interaction of β-blockers with cocaine (for review see Ref. ).
- Atherosclerosis, however, develops during prolonged periods of chronic cocaine use and in its early stages usually does not create symptoms or signs.
- Consequently, cocaine use should be included in protocols and guidelines as a risk factor for cardiovascular, cerebrovascular and other vascular and arterial disease.
- These effects, as well as others (e.g., myocardial edema), may show a cocaine dose-related response .
- Medication to reduce inflammation (e.g., recombinant IL-10, soluble receptor medication such as Etanercept) may be helpful to control cocaine induced inflammatory cascade .
- Finally, and perhaps most importantly, cocaine abstinence or even reduced use promotes reduction in endothelial-1 damage 45,46.
Chest pain 8,13,76 and cerebrovascular events 5,31,63 may occur within minutes to just a few hours from cocaine use. As evident from this review, there is ample data on cocaine-induced endothelial dysfunction, vasoconstriction, and accelerated atherosclerosis. The first line of acute and chronic effects of cocaine on cardiovascular health pmc treatment for cocaine induced sodium channel blockade is alkalization with hypertonic sodium bicarbonate.
Popular in Wordplay
For example, vasoconstriction, a main underlying cause of ischemic strokes, may result from the increased availability of epinephrine, norepinephrine, and serotonin (especially in large and medium-sized brain vessels) in the vasculature due to cocaine blockade of their reuptake 55–57. In addition, cocaine induces disruption of cerebral autoregulation of blood flow (maintaining relatively constant blood flow despite changes in perfusion pressure) and global reduction in cerebral glucose metabolism . In addition to ischemic heart disease , other complications include multiple foci of mid-wall and subepicardial late enhancement in the apical septum and apical lateral wall and coronary vasoconstriction 2,16,23. Cocaine creates an elevated immune system inflammatory state with decreased basal anti-inflammatory markers (e.g., interleukin-10) 42,51, and increased pro-inflammatory cytokines (e.g., tumor necrosis factor alpha, Interleukin 1β) 42,51, all contributing to vascular disease (e.g., endocarditis).
- For example, enhanced supportive care and use of benzodiazepines and phentolamine for sedation; and avoiding β-blockers, which can lead to severe hyper-tension and coronary vasoconstriction resulting from the interaction of β-blockers with cocaine (for review see Ref. ).
- Sympathomimetic effects generate a rise of heart rate, blood pressure and myocardial contractility, which enhance myocardial oxygen demand, whereas myocardial oxygen supply is decreased by coronary vasoconstriction and enhanced thrombosis.
- Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best.
- Cocaine use promotes vascular disease, while also influencing the course of disease management, and therapy.
- It follows a trend of homelessness among the youngest care leavers which campaigners say is growing more acute.
Related word
Acute is also frequently used to describe less troublesome matters, such as keenness of perception («an acute observer» or «an acute sense of smell»), a type of angle (one measuring less than 90 degrees), or the demand for urgent attention («acute danger»). It retains this meaning today, but can also refer to the severity of more general matters, such as «acute embarrassment» or «an acute shortage.» For such a short and simple-looking word, acute has a rather bewildering range of meanings.
Heart mechanisms adapted from Ref. ; figure based on following references 2,5,6,10,13,15–19,23–44. Despite advances in characterization of addiction, knowledge about the contribution of vascular aging to brain impairments in human CUD is scarce. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Www.merriam-webster.com/dictionary/acute. But rarer and more serious ones include acute gallstone disease, pancreatitis and serious allergic reactions.
American Heritage Dictionary Products
Cocaine’s chronic effects on the vessel (Fig. 1, upper box) 10,23,24 consist of repeated endothelial damage leading to premature and severe atherosclerosis in various organs 10,19. Sympathomimetic effects generate a rise of heart rate, blood pressure and myocardial contractility, which enhance myocardial oxygen demand, whereas myocardial oxygen supply is decreased by coronary vasoconstriction and enhanced thrombosis. This cascade reduces blood flow following cocaine use and can lead to acute organ damage. Additional mechanisms implicated in cocaine induced vasoconstriction include increases in calcium .
Prevention and treatment
Additionally, inflammation and atherosclerosis are substantial potentially lethal vascular effects of cocaine use that have acute and chronic systemic impact 2,4,10,13,16,23,35,37,38,42,50. Particular attention was given to the imaging studies that measured cocaine-induced changes to the human heart, brain, and arteries (Table 1), since these methods are gaining a central role as markers of inflammatory disease. The etiology underlying cocaine’s acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Consequently, cocaine use should be included in protocols and guidelines as a risk factor for cardiovascular, cerebrovascular and other vascular and arterial disease. Multimodality imaging studies could promote the identification of CUD with silent pre-symptomatic atherosclerosis in the brain, heart and arteries 100–104. The major cerebrovascular effects of cocaine consist of ischemic and hemorrhagic (including subarachnoid and intracerebral hemorrhages) strokes 5,13,29–32,59–61 (Fig. 2).
When vessels are stressed, endothelin-1 (a vasoconstrictor protein produced by vascular endothelial cells) is elevated and nitric oxide (a blood vessel dilator) decreases, leading to vasoconstriction 35,36. There is also evidence that the cardiovascular actions of cocaine are mediated in part by dopamine , via central and peripheral mechanisms . However, the accelerated development of vascular disease remains mostly undetected and asymptomatic presentation of vascular pathology in CUD results in silent disease progression. Cocaine-induced damage to the cardiovascular and cerebrovascular systems is widely reported, and is linked with hypertension, tachycardia, ventricular arrhythmias ,myocardial infarction 3,4, stroke 4,5, resulting in severe functional impairments or sudden mortality 6–10.
Cerebral vasospasm is pharmacologically induced via cocaine’s potent sympathomimetic properties and an increase of endothelin-132,34. These mechanisms underlie inadequate myocardial oxygen equilibrium, which may lead to ischemia and manifest as angina or infarction 2,13. Cocaine induces acute cardiotoxicity through multiple pathways (Fig. 1, left box). It was recently demonstrated that cocaine elicits autophagy involving nitric oxide and glyceraldehyde-3-phosphate dehydrogenase signaling cascade .
Stimulation of dopamine cells in the ventral tagmental area increases blood pressure and this effect is antagonized by the dopamine D2 receptor blockers . In addition, cocaine blocks reuptake of catecholamines in the presynaptic neurons in the central and peripheral nervous systems, resulting in increased catecholamines, sympathetic output and stimulation 2,19. At high doses, cocaine is markedly more dangerous than other central nervous system stimulants, including amphetamines , and can cause sudden cardiac death through its effect on sodium channels and local anesthetic actions 13,14,16. Underlying this addiction is CUD’s association with abnormal brain morphology and function involving inefficiencies in circuits that coordinate reward and self-control processes . Furthermore, the phenomenology of CUD consists of repeated drug use leading to tolerance, withdrawal, and compulsive drug-seeking behavior with inability to abstain, despite adverse effects to medical, social and occupational functioning. “Crack-Cocaine” was introduced in the mid-1980s involving a new route of administration, smoking (as opposed to sniffing), which enhances vascular toxicity.
We present the main mechanisms of acute and chronic cocaine-induced toxicity on vessels, brain and heart (Fig. 1) and the common vascular and systemic effects of cocaine use in humans (Fig. 2). Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. Furthermore, chronic cocaine-use reduces capillary flows in brain and may be responsible for cerebrovascular small-vessel ischemic disease (e.g. cocaine-induced leukoaraiosis), possibly involving genetic factors 65,66.
Future directions: urgent need for early detection of a complex disease process in a vulnerable and aging population
Thus, prevention of secondary harms and halting of further disease progression in CUD mandates cessation of cocaine use and cigarette smoking, limitation of alcohol consumption, as well as enhancing healthy life routines (e.g., regular health monitoring, physical activity, sleep, diet, stress management). Finally, and perhaps most importantly, cocaine abstinence or even reduced use promotes reduction in endothelial-1 damage 45,46. Medication to reduce inflammation (e.g., recombinant IL-10, soluble receptor medication such as Etanercept) may be helpful to control cocaine induced inflammatory cascade . The issue is complicated further by the fact that contaminants such as procainamide, quinidine and antihistamines, which are often mixed with the cocaine, may contribute to the effects seen and influence the underlying pathophysiology . Studies in healthy populations reveal association between cognitive deficiencies and atherosclerosis, indicating that there is an inflammatory pathway that reduces the brain’s executive control network efficiency 82–84. Advanced atherosclerosis of intracranial vessels is noted as the cause of cocaine-induced stroke in numerous studies 4,29.