Cocaine & C-V Disease

Article: Cardiovascular Complications of Cocaine Use, N Engl J Med, Vol.345, No.5, 8/2/01.

Josh Partnow, MD

Review Article Summary

Overview:

CV events including angina, MI, cardiomyopathy, and sudden death have increased dramatically

30% of all drug-related ER visits

Most commonly used illicit drug among pts seeking care in an ER

Most frequent cause of drug-related deaths reported by medical examiners

Pharm and Mech of Action:

Cocaine is an alkaloid extracted from leaf of coca bush primarily in S America

Available in two forms: hydrochloride salt and free base

Hydrochloride form can be taken PO(chewing), IV(mainlining), intranasally(snorting), decomposes when heated

Well absorbed through all mucous membranes so can take it intranasal, SL, intravaginal, PR and achieve high serum concentrations (all have slower onset, later peak, longer duration than IV)

Free base form has added baking soda to remove hydrochloride making heat stable to smoke, known as crack because of the popping sound it makes when heated

Most addictive and potent form

Cocaine metabolized by liver and excreted in urine

Serum half life of 45-90 min

Only detectable in urine for several hrs, but metabolites for 24-36 hrs, hair for several wks

Local anesthetic inhibits membrane permeability to Na during depolarization, blocking initiation/transmission of electrical impulses

Systemically, blocks presynaptic reuptake of NE/DAà excess of these NT at post synaptic receptor, ie potent sympathomimetic

Cocaine-Related Myocardial Ischemia/Infarction:

Risk of AMI increased by factor 24 during 1hr post cocaine use in those at otherwise low risk

MI is Unrelated to amt ingested, route of administration, freq of use (reported in doses 200-2000mg, by all routes, in habitual/1^st time users)

Chest Pain is most common Sx in cocaine users

14-25% (urban), 7% (suburban) of pts with nontraumatic CP have detectable levels of cocaine metabolites in urine

6% of pts with cocaine-associated CP have positive enzymes for MI

Classic cardiac History and Risk Factors are not very useful in risk stratification

EKG may be abnormal in pts s/p cocaine use in absence of MI

EKG reported abnormal in 56-84% of pts with cocaine-related CP and in 43% of cocaine abusers without MI meet EKG criteria for lysis(ST elev atleast 1mm in 2 or more contiguous leads)

EKG sens 36%, specif 90%, PPV 18%, NPV96%

High failure rate EKG in identifying MI is due in part to high incidence of early repolarization abnorm in young people in general

Serum CPKs not reliable indicator of myocardial injury since they are elevated in half of cocaine abusers without MI(due to rhabdomyolysis)

Troponins are more sens and specif

CV complications of cocaine-related MI: Ventricular Arrhythmias 4-17%, CHF in 5-7%, death in 2%.

Most complications occur in 1^st 12 hrs after presentation to hospital

Pathogenesis of MI:

Multifactorial, increased O2 demand, marked vasoconstriction of coronary art, enhanced platelet aggregation/thrombus formation.

Cocaine increases O2 demand by increasing HR, Systemic BP, LV contractility

Vasoconstricion of epicardial coronary arteries(inappropriate vasoconstriction)

Effects are greatest in diseased vessels, thus pts with CAD are at greater risk for event

Vasoconstriction from alpha agonism, increased endothelin production(potent vasoconstrictor) and decreased production of nitric oxide(potent vasodilator)

Most pts develop CP/MI within 1hr of ingestion due to peak serum concentration, but may occur several hrs later due to metabolites effects of delayed vasoconstriction

Thrombus formation from enhanced platelet activation and aggregation as well as increases concentration of plasminogen-activator inhibitor

Causes endothelial structural abnormalities increasing permeability of LDLs/expression of endothelial adhesion molecules/leukocyte migrationàatherosclerosis

Cocaine induced vasoconstriction of coronary art reversed with phentolamine(alpha antagonist)

Exacerbated by propranolol(B blocker) thus NOT used in cocaine-related CP

Agents of choice: NG, verapamil since they reverse HTN/vasoconstriction caused by cocaine

ASA given to inhibit platelet aggregation

Benzos helpful since they reduce HR and systemic BP

Caution with Lytics due to limited experience, reports of catastrophic complications, difficulty in using standard EKG criteria

Lytics considered only after treatment with O2, ASA, NG, Benzos have failed and PTCA is not available. Use if evidence of Evolving MI persists despite medical therapy. Contraindicated if severe HTN exists 180/110

Recommendation from AHA For Treatment Cocaine induce MI/ischemia

1^st line: O2, ASA, NG, Benzos

2^nd line: Verapamil, Phentolamine, Lytics/PTCA

Avoid: B Blockers

Labatelol(alpha/B blocker) does NOT reverse vasoconstriction of coronary arteries

Cocaine, Cigarettes, and Alcohol:

Many pts using cocaine also smoke cigarettes and drink alcohol simultaneously

Cigarettes also cause increase in HR, BP, and coronary artery vasoconstriction thus greatly exacerbating the ischemia

9 million people in US abuse cocaine and alcohol simultaneously, 2^nd most common combo in pts who die of substance abuse

Ethanol and cocaine together produce metabolite (cocaethylene) in liver that also inhibits reuptake of DA thus acting synergistically

Long term Cocaine causes LVH, systolic dysfxn, dilated cardiomyopathy, reversible profound myocardial depression after binging

Cocaine induce arrhythmias:

Na channel blocker and its enhanced sympathetic stateà can cause or exacerbate arrhythmias especially in presence of ischemia or LVH

May increase ventricular irritability, lower threshold for fibrillation

Na channel blocking characteristics Inhibits generation and conduction of action potential thus Prolonging duration of QRS and QT

Thus acts like a class I anti-arrhythmic agent

Increases intracellular Ca conc

Reduces vagal activity

Tx of arrythmias:

Standard therapy, treat ischemia, correct metabolic abnormalities (electrolytes, hypoxemia, acidosis)

Can give anti-arrhythmics

Several reports of good outcomes with use of NaHCO3 in wide complex tachy, and the use of lidocaine in V tach and V Fib

AVOID class I agents such as quinidine, procainamide, disopyramide since they may worsen QRS and QT and slow metabolism of cocaine and its metabolites

For unknown reason, use of IV cocaine has greater risk for endocarditis than other IV drugs and actually more commonly effects LEFT sided valves.

Aortic dissection and rupture of mycotic and intracerebral aneurysms have been documented