====== Cocaine ======

Cocaine, also known as coke, is a strong stimulant mostly used as a recreational [[drug]]. It is commonly snorted, inhaled as smoke, or dissolved and injected into a vein. Mental effects may include loss of contact with reality, an intense feeling of happiness, or agitation.
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Cocaine is extracted from Erythroxylon coca leaves (and other Erythroxylon species) and is thus unrelated to [[opioid]]s. It blocks the re-uptake of [[norepinephrine]] by presynaptic adrenergic nerve terminals. It is available in 2 forms: cocaine hydrochloride (heat-labile and water-soluble, it is usually taken PO, IV, or by nasal insufflation) and the highly purified cocaine alkaloid (free base or crack cocaine, which is heat stable but insoluble in water and is usually smoked).
Peak toxicity occurs 60–90minutes after ingestion (except for “body packers”), 30–60 minutes after snorting, and minutes after IV injection or smoking (freebase or crack)
((Acute Reactions to Drugs of Abuse. Med Letter. 1996; 38:43–46)).

===== Acute pharmacologic effects of cocaine =====

Effects on body systems outside the nervous system include [[tachycardia]], [[acute]] [[myocardial infarction]], [[arrhythmia]]s, rupture of ascending aorta ([[aortic dissection]]), abruptio placenta, [[hyperthermia]], intestinal ischemia, and [[sudden death]].

Acute pharmacologic effects pertinent to the nervous system include:

1. mental status: initial CNS stimulation that first manifests as a sense of well-being and euphoria.
Sometimes dysphoric agitation results, occasionally with [[delirium]]. Stimulation is followed by depression. Paranoia and toxic psychosis may occur with overdosage or chronic use. Addiction may occur

2. pupillary dilatation ([[mydriasis]])

3. hypertension: from adrenergic stimulation.

===== Non-pharmacologic effects related to the nervous system =====

1. pituitary degeneration: from chronic intranasal use

Though cocaine intranasal inhalation always determines nasal mucosal damages, extensive septum perforations, and midline destructions-known as cocaine-induced midline destructive lesions (CIMDL)-affect only a limited fraction of patients. CIMDL is viewed as a cocaine-associated autoimmune phenomenon in which the presence of atypical anti-neutrophil cytoplasmic antibody (ANCA) promotes and/or defines the disease phenotype. A 51-year-old man presented with an intracranial tumor-like lesion by its space-occupying effect. CT also revealed the destruction of the nasal septum and skull base. A diagnosis of CIMDL was made in light of the patient's history as well as findings of the physical and endoscopic examinations, imaging studies, and laboratory testing. There was no evidence of other pathologies. Histopathological results from cerebral biopsy led us to consider the intracranial pathology as an extension of the CIMDL. CIMDL is the result of a necrotizing inflammatory tissue response triggered by cocaine abuse in a subset of predisposed patients. The reported case is the first CIMDL consistent with brain extension mimicking a tumor-like lesion. While the presence of atypical ANCA seems to promote and/or define the disease phenotype, the specific role of these and other circulating autoantibodies needs further investigation
((García-Pérez D, Ruiz-Ortiz M, Panero I, Eiriz C, Moreno LM, García-Reyne A, García A, Martín-Medina P, Salvador-Álvarez E, Hernández-Lain A, Serrano A, Gil-Etayo FJ, Castaño-León AM, Paredes I, Pérez-Núñez Á. Snorting the Brain Away: Cerebral Damage as an Extension of Cocaine-Induced Midline Destructive Lesions. J Neuropathol Exp Neurol. 2020 Nov 4:nlaa097. doi: 10.1093/jnen/nlaa097. Epub ahead of print. PMID: 33146379.)).

2. cerebral vasculitis: less common than with amphetamines

3. seizures: possibly related to the local anesthetic properties of cocaine

4. stroke
((Fessler RD, Esshaki CM, Stankewitz RC, et al. The Neurovascular Complications of Cocaine. Surg Neurol. 1997; 47:339–345)).

a) intracerebral hemorrhage

b) subarachnoid hemorrhage
((Lichtenfeld PJ, Rubin DB, Feldman RS. Subarachnoid Hemorrhage Precipitated by Cocaine Snorting. Arch Neurol. 1984; 41:223–224)),
((Oyesiku NM, Collohan ART, Barrow DL, et al. Cocaine-Induced Aneurysmal Rupture: An Emergent Negative Factor in the Natural History of Intracranial Aneurysms? Neurosurgery. 1993; 32: 518–526)):
possibly as a result of HTN in the presence of aneurysms or AVMs, however, sometimes no lesion is demonstrated on angiography
((Schwartz KA, Cohen JA. Subarachnoid Hemorrhage Precipitated by Cocaine Snorting. Arch Neurol. 1984; 41)).
May possibly be due to cerebral vasculitis

c) [[ischemic stroke]]
((Levine SR, Brust JCM, Futrell N, et al. Cerebrovascular Complications of the Use of the 'Crack' Form of Alkaloidal Cocaine. N Engl J Med. 1990; 323:699–704))
: may result from [[vasoconstriction]] 

d) thrombotic stroke
((Acute Reactions to Drugs of Abuse. Med Letter. 1996; 38:43–46))

e) TIA
((Mody CK, Miller BL, McIntyre HB, et al. Neurologic Complications of Cocaine Abuse. Neurology. 1988; 38:1189–1193))

5. [[anterior spinal artery syndrome]]
((Mody CK, Miller BL, McIntyre HB, et al. Neurologic Complications of Cocaine Abuse. Neurology. 1988; 38:1189–1193))

6. effects of maternal cocaine use on the fetal nervous system include
((Volpe JJ. Effect of Cocaine Use on the Fetus. N Engl J Med. 1992; 327:399–407)): 
[[microcephaly]], disorders of neuronal migration, neuronal differentiation, and myelination, cerebral infarction, subarachnoid and intracerebral hemorrhage, and sudden infant death syndrome (SIDS) in the postnatal period




===== Treatment of toxicity =====

Most cocaine toxicity is too short-lived to be treated. [[Anxiety]], [[agitation]] or [[seizure]]s may be treated with IV [[benzodiazepine]]s, e.g. [[lorazepam]]. Refractory HTN may be treated with [[nicardipine]] or [[phentolamine]] (Regitine®). IV lidocaine used to treat cardiac arrhythmias may cause seizures
((Acute Reactions to Drugs of Abuse. Med Letter. 1996; 38:43–46))

===== References =====