Cocaine Use Disorder

Cocaine use disorder is a substance use disorder defined by pathologic consumption of the recreational drug cocaine. Cocaine is an indirect sympathomimetic Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs that blocks the reuptake of dopamine, serotonin, and norepinephrine from the synaptic cleft. This process causes stimulant effects on the body and mind such as euphoria, increased energy, irritability, psychosis, decreased appetite, and weight loss. Cocaine overdose can cause death secondary to cardiac arrhythmia, myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, seizure, or respiratory depression. Prognosis is poor as there is no approved pharmacological treatment, but psychosocial interventions have been associated with improved outcome.

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Definition and Epidemiology

Definition

Cocaine use disorder is defined as the chronic (> 12 months) maladaptive use of the recreational drug cocaine. 

  • Intoxication: 
    • Heightened sense of arousal, alertness, as well as euphoria for a brief period of time
    • May cause end-organ toxicity in multiple organ systems 
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Leads to physical (nausea, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, chills, body aches) and/or psychological symptoms (cravings or perceived need to use the substance)
  • Tolerance: 
    • The need to increase the dose of the substance to achieve the desired effect (diminished effect if using the same amount of the substance)

Epidemiology

  • Prevalence in the United States: 
    • Approximately 2.2 million regular users of cocaine 
    • Of those, 1 million individuals meet criteria for cocaine use disorder.  
  • Limited medical use (used to be administered as a local anaesthetic); most cocaine use is recreational
  • Frequently misused as a performance-enhancing drug
  • Cocaine is involved in an estimated 40% of recreational drug-related ED visits, higher than cannabis and any opioid.

Pharmacology

Types of cocaine

  • Cocaine hydrochloride salt:  
    • Water-soluble formulation 
    • Can be ingested orally, intranasally, or intravenously
  • Freebase cocaine (“crack”):
    • Heat-stable formulation that can be smoked
    • Very rapid onset of action 
    • Extremely addictive

Pharmacodynamics

  • Cocaine is an indirect sympathomimetic Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs → blocks the reuptake of dopamine, epinephrine, and norepinephrine from the synaptic cleft
  • Increased norepinephrine stimulates:
    • α1– and α2-adrenergic receptors 
    • β1– and β2-adrenergic receptors
  • Most important effects on the body: 
    • Transient sense of euphoria, mental alertness, decreased hunger 
    • Increase in norepinephrine →  potent vasoconstrictor → may lead to severe hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, stroke 
    • Direct cardiac toxicity of cocaine → tachycardia, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, coronary spasms

Clinical Presentation

Cocaine intoxication

  • General: 
    • Weight loss
    • Chills and sweating
  • CNS: 
    • Euphoria
    • Increased self-esteem
    • Dilated pupils 
    • Stimulant-induced psychotic disorder
    • Loss of inhibitions
    • Increased libido
  • Cardiovascular: 
    • ↑ Or ↓ blood pressure
    • Tachycardia or bradycardia
  • GI: 
    • Nausea
    • Loss of appetite
    • Dry mouth

Cocaine withdrawal

  • Patient enters a state of severe depression after intoxication (known as “crash” phase). 
  • Generally not life-threatening; however, patient may develop suicidal ideation
  • General symptoms:
    • Malaise
    • Fatigue
    • Disturbed sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep
    • Anhedonia
    • Irritability with psychomotor agitation or retardation
  • CNS: constricted pupils
  • GI: hunger

Management

Cocaine intoxication

The management of cocaine intoxication depends on the severity of symptoms.

  • Mild-to-moderate agitation and anxiety: 
    • Reassurance
    • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for sedation
  • Severe agitation or psychosis: 
    • Antipsychotics (e.g., haloperidol) and benzodiazepines for sedation
    • Symptomatic support (i.e., control of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and arrhythmias)
    • Treating hyperthermia (ice bath, cooling blanket)
  • Potentially fatal symptoms: 
    • Treat according to protocol for each condition (see “Complications”).
    • Avoid use of beta-blockers for treatment of cocaine-induced myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction!

Cocaine withdrawal

  • Mild-to-moderate use: Symptoms resolve within 72 hours.
  • Heavy, chronic use: Symptoms last for 1–2 weeks.
  • Treatment is supportive. 
  • Hospitalization:
    • Not generally indicated for detoxification from cocaine 
    • Indicated in patients with severe psychiatric symptoms

Cocaine use disorder

  • There is no Food and Drug Administration (FDA)-approved pharmacotherapy for cocaine dependence. 
  • However, some medications have proven to be helpful:
    • Bupropion
    • Cholinergic medications: galantamine
    • Gabanergic medications: vigabatrin and topiramate
  • Physicians should try to build a rapport with patients to treat underlying mood disorders or personality disorders.
  • Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy and psychological interventions: 
    • Contingency management
    • Relapse prevention
    • Narcotics Anonymous (NA)

Complications

Cardiovascular complications

  • Myocardial infarction: 
    • Due to severe coronary vasoconstriction → ischemic damage
    • Giving beta-blockers in this case is contraindicated!  
  • Arrhythmias
  • Aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a "false lumen." Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection
  • Heart failure
  • Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension

Neurologic complications

  • Psychomotor agitation through release of excitatory amino acids and neurotransmitters in the CNS
  • Hyperthermia: Body is unable to dissipate the heat produced from constant agitation due to peripheral vasoconstriction. 
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures 
  • Ischemic and hemorrhagic strokes 
  • Respiratory depression

Nasal septal perforation

  • Vasoconstriction in nasal septum arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries
  • Nasal septal perforation in chronic use (due to ischemic necrosis and severe vasoconstriction)

Effects on pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care

  • Effect on mother: increases risk of abruptio placentae ( placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity is either completely or partially detached prior to birth)
  • Fetal effects: 
    • Increased fetal morbidity and mortality
    • Fetal cortical cystic lesions
    • Intrauterine growth restriction → low birth weight 
    • Preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth

Differential Diagnosis

  • Amphetamine use disorder Amphetamine use disorder Amphetamine use disorder (AUD) is a condition characterized by pathologic use of psychostimulants. Amphetamines produce their effect by increasing the release and blocking the reuptake of neurotransmitters (dopamine, norepinephrine, serotonin). Medically, they are used for the treatment of ADHD and narcolepsy. Amphetamine Use Disorder: Amphetamines are stimulant drugs, producing their effect by increasing the release and blocking the reuptake of neurotransmitters (dopamine, norepinephrine, serotonin). Amphetamines are used for treating ADHD, narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy, and obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, but are often abused for their stimulating effects. Intoxication results in effects similar to those of cocaine: euphoria, pupillary dilation, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin excoriation, paranoia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Withdrawal symptoms include increased appetite, severe depression, fatigue, and vivid dreams. Amphetamines and cocaine are often consumed together. 
  • Hallucinogen intoxication: Hallucinogens are substances that cause perceptual distortions (visual or auditory). Examples include LSD (lysergic acid diethylamide), ketamine, and dextromethorphan. Hallucinogens are used for their psychedelic effects, which temporarily lead to an altered state of consciousness. Similar to cocaine intoxication, hallucinogen intoxications produce nausea, vomiting, and mild sympathomimetic Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs effects (e.g., tachycardia, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, mydriasis, hyperthermia, and diaphoresis). Hallucinogens do not result in dependence or withdrawal symptoms.
    Inhalant intoxication: the abuse of inhalant substances such as glue, paint, or lighter fluid. In order to reach euphoric effects, patients administer inhalers through the mouth (commonly known as “huffing”) or sniff substances through the nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose. The effect lasts only for several minutes. Signs of acute intoxication include transient euphoria up to loss of consciousness. Inhalants result in CNS inhibition and cardiac arrhythmia. Treatment is supportive, and sedative drugs should be avoided as they tend to worsen intoxication.

References

  1. Ganti L, Kaufman M, Blitzstein S. (2016). First Aid for the Psychiatry Clerkship, 4th ed. New York: McGraw-Hill Education. Substance-related and addictive disorders (chapter 7, p. 80, 87).
  2. Le T, Bhusan V, Sochat M, et al. (Eds.) (2019). First Aid for the USMLE Step 1, 29th ed. (p. 242, 558).
  3. Gorelick D. (2017). Cocaine use disorder in adults: Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis. UpToDate. Retrieved February 21, 2021, from https://www.uptodate.com/contents/cocaine-use-disorder-in-adults-epidemiology-pharmacology-clinical-manifestations-medical-consequences-and-diagnosis
  4. Kampman K. (2021). Pharmacotherapy for stimulant use disorders in adults. UpToDate. Retrieved February 21, 2021, from https://www.uptodate.com/contents/pharmacotherapy-for-stimulant-use-disorders-in-adults
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  6. Sadock BJ, Sadock VA, Ruiz P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 20, Substance use and addictive disorders, pages 671-680. Philadelphia, PA: Lippincott Williams and Wilkins.
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