Cocaine cardiotoxicity

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Cocaine cardiotoxicity
Robertas Badaras Vilnius University, Faculty of
Medicine Clinic of Anaesthesiology and
Intensive Care
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Coca leaf (Erythroxylon coca)

• Cocaine (benzoylmethylecgonine) is derived from
  the leaves of Erythroxylon coca, a shrub
  indigenous to Peru, Bolivia, Mexico, the West
  Indies, and Indonesia
• Coca leaves have been chewed by South American
  Indians for many thousands of years to induce a
  mild and long-lasting euphoria. Coca is believed
  to be a gift from God 

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Lets go to Europe!

• In 1580 Monardes brings coca leaves to Europe
  unlike tobacco, it fails to generate interest or
  use, probably because most coca leaves lost their
  potency during the long voyage

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History of use I

• Spanish physicians reported the first European
  use of coca for medicinal purposes in 1596
• In 1859 Cocaine was first isolated as the active
  ingredient of the Coca plant by Albert Niemann of
  the University of Gottigen
• In 1862 Merck produces 1/4 pound of cocaine
• By 1880, Parke-Davis sold a fluid extract
  containing 0.5 mg/mL of a crude cocaine

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History of use II

• By 1863, a wine fortified with 6 mg of cocaine
  alkaloid extract per ounce was marketed in France

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History of use III

• In 1884, William Stewart Halsted performed the
  first nerve block using cocaine as the
  anesthetic. Subsequently, Halsted became the
  first cocaine-impaired physician on record

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History of use IV

• That same year, Sigmund Freud published the essay
  "Uber Coca," in which he advocated the use of
  cocaine in the treatment of asthma, wasting
  diseases, and syphilis. As with Halsted, Freud
  also fell prey to cocaine dependency

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History of use V

• In 1886 Coca-Cola is first introduced by John
  Pemberton, containing cocaine laced syrup and
  caffeine
• By 1901, Coca-Cola removed Coca from their formula

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History of use VI

• By 1893, occasional reports of fatality were
  associated with cocaine use, and, in 1895, The
  Lancet reported a series of 6 deaths
• By 1909, more than 10 tons of cocaine was being
  imported into the USA each year
• The Harrison Narcotics Act of 1914 banned
  nonprescription use of cocaine-containing products

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Cocaine in USA - use

• Cocaine use in the USA has been reported to be as
  high as 5 million regular users, with as many as
  30 million with a history of past use
• 2001 year
• 5 of inhibitans from 18 till 45 years old used
  cocaine regularly
• Substance Abuse and Mental Health Services
  Administration, 2001

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Cocaine in USA - deaths
Cocaine was the most frequently reported
substance associated with drug-abuse-or-misuse
deaths Medical Examiners/Coroners data for
2003
Regular cocaine use was associated with an
increased likelihood of MI in younger patients.
Approximately 1 of every 4 nonfatal MIs in
persons aged 18 to 45 years was attributable to
frequent cocaine use Qureshi AI, Suri FK,
Guterman LR, et al. Circulation. 2001
According to different sources 0,5-1,5 of all
deaths in US are related to cocaine use
Goldfrank LR et al. Goldfranks toxicologic
Emergencies 2002
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Cocaine in Bulgaria
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Cocaine and athletics I
Former Tour de France winner Marco Pantani (the
Pirate) was found dead in the Italian seaside
resort of Rimini
"The death of Marco Pantani was caused by acute
cocaine intoxication Dr.Giuseppe Fortuni
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Cocaine and athletics II

• When you hear about an athlete dying suddenly
  and the autopsy reports that he had a heart
  attack with multiple dead areas in the heart and
  dilated cardiomyopathy, think of cocaine.
• Keller DJ, Todd GL. International Journal of
  Cardiology, 1994

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Pharmacology

• The primary effect - blockade of norepinephrine
  reuptake secondary - marked release of
  norepinephrine
• Moderate release and reuptake blockade of
  serotonin and dopamine
• Local anesthetic effects are caused by blocking
  the sodium channels
• Fat soluble and freely crosses the blood-brain
  barrier

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Inhibition of reuptake
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Phases of acute cocaine toxicity I

• In fatal cases convulsions and death frequently
  occurring in 2-3 minutes though sometimes in 30
  minutes

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Phases of acute cocaine toxicity II

• Phase I - Early stimulation
• CNS - mydriasis, headache, nausea, vomiting,
  vertigo, nonintentional tremor, preconvulsive
  movements, and pseudohallucinations
• Circulatory - Possible increase in BP, slowed or
  increased pulse rate (possibly with ventricular
  ectopy), and pallor
• Respiratory - Increase in rate and depth
• Temperature - Elevated body temperature
• Behavioral - Euphoria, agitation, restlessness

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Phases of acute cocaine toxicity III

• Phase II - Advanced stimulation
• CNS - encephalopathy, generalized seizures,
  status epilepticus, decreased responsiveness to
  all stimuli
• Circulatory - hypertension tachycardia and
  ventricular dysrhythmias (possible), hypotension
  peripheral cyanosis
• Respiratory - tachypnea, dyspnea, gasping, and
  irregular breathing pattern
• Temperature - severe hyperthermia (possible)

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Phases of acute cocaine toxicity IV

• Phase III - Premorbid state
• CNS - Coma, areflexia, pupils fixed and dilated,
  loss of vital support functions
• Circulatory - circulatory failure and cardiac
  arrest (VF or asystole)
• Respiratory - respiratory failure, pulmonary
  edema, agonal respirations, and paralysis of
  respiration

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Interaction with another substance of abuse

• 30-60 of individuals who take cocaine combine it
  with alcohol. It results in the formation of a
  third active compound - cocaethylene. Its
  toxicity is greater - the addition of alcohol to
  cocaine increases the risk of sudden death
  25-fold
• Many of the physiologic effects of nicotine are
  identical to those of cocaine, which suggests
  that simultaneous use of cocaine and tobacco may
  enhance coronary vasospasm

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Cocaine cardiotoxicity

• The effect of cocaine on cardiac muscle and
  coronary vessels remains poorly understood
• emedicine 2006

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Possible Mechanisms of Cardiovascular
Complications of Cocaine
Cocaine
Membrane stabilization
Adrenergic Effects
Platelet aggregation
Direct Toxicity
Coronary Spasm
Myiocarditis, Focal Necrosis, Contraction Band
Necrosis
? Myocardial O2 Demand
Coronary Thrombosis
Arrhytmias
Cardiomiopathy
Myocardial Infarction
Myocardial Ishaemia
Adapted from Isner JM, Choski SK. Curr Probl
Cardiol 1991
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Acute cocaine effects
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Cocaines influence on myocard I

• Increasing levels of plasma plasminogen activator
  enhances clot formation
• Increases the production of the endothelin, and
  simultaneously decreases the production of
  nitrous oxide
• Cocaine may exert a direct vasoconstrictive
  effect by increasing the influx of calcium across
  endothelial cell membranes. These factors may
  produce coronary artery spasm

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Cocaines influence on myocard II

• Cocaine potentiates platelet thromboxane
  production
• Decreases protein C and antithrombin III
  production, as well as the production and release
  of prostacyclin

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Cocaine effects on coronary arteries
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Cardiac Dysrhythmias and Conduction Disturbances
reported with Cocaine use

• Sinus tachycardia
• Sinus bradycardia
• Supraventricular tachycardia
• Bundle branch block
• Complete heart block

• Accelerated idioventricular rhytm
• Ventricular tachycardia
• Ventricular fibrilation
• Asystole
• Torsade de pointes

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Cocaine induced Dysrhythmias

• Direct toxicity - foci of myocarditis, microfocal
  fibrosis, and contraction band necrosis
• Increases in catecholamine levels
• Quinidine-like direct cardiotoxic effects,
  causing intraventricular conduction delays,
  depolarization of the cardiac membrane, extra
  systoles, and tachycardia
• Reduces vagal activity which potentiates
  cocaines sympathomimetic effects

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Endocarditis

• Increased risk of bacterial endocarditis. The
  greater risk factor than the use of other drugs
• elevation of the heart rate and arterial pressure
• immunosuppressive effects of cocaine
• adulterans
• The endocarditis associated with cocaine abuse
  more often involves the left-sided cardiac valves

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Aortic dissection

• Probably results from the increase in systemic
  arterial pressure induced by cocaine

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Diagnosis

• The accurate identification of patients with
  cocaine related MI may be difficult for at least
  two reasons
• The ECG may be abnormal in 56 to 84 patients
  with chest pain after cocaine use, even in the
  absence of MI As many as 43 of cocaine abusers
  without MI meet the ECG criterion for the
  initiation of reperfusion therapy (STsegment
  elevation of at least 0.1 mV in two or more
  contiguous leads)
• The serum CK concentrations are not a reliable
  indicator of myocardial injury, since they are
  elevated in about half of cocaine users.
  Accordingly, serum troponin concentrations should
  be measured

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Recommendations of the AHA for the treatment of
Cocaine related Myocardial ishaemia or Infarction

• First-line agents
• Oxygen
• Aspirin
• Nitroglycerin
• Benzodiazepines
• Second-line agents
• Verapamil
• Phentolamin
• Thrombolytic agent or primary angioplasty (after
  arteriography)
• Agents to be avoided
• Propranolol

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Chronic cocaine effects