STIMULANT USE AND CARDIOVASCULAR CONSEQUENCES

Arthur Westover, MD, MSCS

UT Southwestern Medical Center

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Classes of drugs

• Stimulants

• Depressants (alcohol, diazepam)

• Opioids (morphine, heroin)

• Hallucinogens (LSD)

• Others (e.g., cannabis, inhalants)

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Stimulant misuse carries risks

• Overdose

– Seizures

– ↑ body temp

– CV events

– Death© AMSP 3

This lecture covers

• Description of stimulants

• Patterns of stimulant use

• Physiological effects of stimulants

• Cardiovascular (CV) effects at high doses

• Possible effects of low/moderate doses

© AMSP 4

This lecture covers

• Description of stimulants

• Patterns of stimulant use

• Physiological effects of stimulants

• Cardiovascular (CV) effects at high doses

• Possible effects of low/moderate doses

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Types of stimulants

• Cocaine

– Powder

– Crystalline (“crack”)

• Amphetamines

– Powder

– Crystalline (“crystal meth”)

– Tablets/capsules

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Stimulants

• Characterized by:

– Euphoria

– ↓ Need for sleep

– ↓ Appetite

– ↑ Focus/attention

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Dangers of stimulant misuse

• ↑ BP

• Grand mal seizures

• ↑ Pulse

• Arrhythmias

• ↑ Body temperature

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This lecture covers

• Description of stimulants

• Patterns of stimulant use

• Physiological effects of stimulants

• Cardiovascular (CV) effects w/ high doses

• Possible effects of low/moderate doses

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Rates of illicit use (US)

• Cocaine (12+yo in 2012)

– ~40 million lifetime

– ~5 million past-year

• Amphetamines

– ~12 million lifetime

– ~1 million past-year

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Increased Rx use in US

• 5 million insured users in 2012

• Stimulant use ↑’d from 2008 to 2012

– Children: ↑ 19%

– Adults: ↑ 53%

– Women 26-34yr: ↑ 85%

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Prescription (Rx) amphetamines

• FDA approved indications

– Attention Deficit Hyperactivity Disorder

– Narcolepsy

– Obesity

• Off-label use

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Attention Deficit Hyperactivity Disorder

• Definition: ↓attention ± hyperactivity→ learning/behavior problems

• Rates of ADHD– Children (≤18yo)

• 5% ♂ taking stimulants• 1.5% ♀

– Adults (18-44yo)• 5% ♂ meet ADHD criteria, 3% ♀• A lower percentage are treated

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ADHD Treatment

• Stimulants first-line:

– Methylphenidate (Ritalin) 20mg 3x/day

– Amphetamine (Adderall) 15mg 2x/day

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Narcolepsy

• Definition:

– Sudden disabling daytime sleepiness

– Fast onset dream sleep

• Rate: 1 in 2000 persons

• Treatment: daytime naps and medications

– Methylphenidate (Ritalin) 20mg 2x/day

– Amphetamine (Adderall) 20mg 2x/day

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Obesity• Definition: Body Mass Index ≥ 30

• Rate: > 1/3rd US adults

• Treatment with stimulants :

– Dextroamphetamine (Dexedrine)

– Methamphetamine (Desoxyn)

– Benzphetamine (Didrex)

• Uncommon:

– ↓ Weight only seen first 3 weeks and returns

– Safer options (example: orlistat [Xenical])

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Off-label use• Likely frequent; anecdotal evidence

• Example conditions:

– Depressive symptoms

– Dementia

– Stroke recovery

– “Neuroenhancement” (↑ cognition?)

• Risks present

• No clear benefit

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This lecture covers

• Description of stimulants

• Patterns of stimulant use

• Physiological effects of stimulants

• Cardiovascular (CV) effects at high doses

• Possible effects of low/moderate doses

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Endogenous vs. Exogenous

• Endogenous stimulants

– Body produces naturally

– Example: norepinephrine

• Exogenous stimulants

– Chemicals that are ingested

– Examples: cocaine, amphetamine

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Endogenous stimulants

• “Catecholamines”

– Nerve tissue

– Brain

– Adrenal glands

• Exist as neurotransmitters

– Epinephrine (i.e. adrenaline)

– Norepinephrine

– Dopamine

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Physiological effects

• Endogenous: “Fight or flight”

• Exogenous: “Hijack” endogenous

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Fight or flight• Stress response

– ↑ Heart rate

– ↑ Release of glucose (energy)

– ↑ Blood flow to skeletal muscles

– ↓ Blood flow to other parts of body

– ↓ Digestion; dilation of the pupil

– ↓ Salivation → dry mouth

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Hijack endogenous

• Mechanism:

– Direct release of catecholamine

– ↓ Reuptake from space between neurons

• Neuron stuck in stimulated position

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Stimulant intoxication• CNS effects

– Euphoria, ↑wakefulness– ↑ Sex drive– ↓Appetite, ↑ energy

• Peripheral effects– Hand tremor, restlessness– ↑ Muscle tension– ↑ body temperature

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This lecture covers

• Description of stimulants

• Patterns of stimulant use

• Physiological effects of stimulants

• Cardiovascular (CV) effects at high doses

• Possible effects of low/moderate doses

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Cardiovascular dangers• High dose stimulants

– Illicit use– Non-medical use

• Low dose stimulants– Medical use– Prescribed doses

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High dose stimulant CV problems

• Stroke – Ischemic– Hemorrhagic

• Heart attack

• Sudden cardiac death

• Aortic dissection (tearing of the aorta)

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Mechanisms of CV problems• Vasospasm arteries in brain/heart

• ↑ BP → bleeding

• ↑ Oxygen demand

• ↓ Perfusion heart muscle

• ↑ Clots from activation of platelets

• Arrhythmia

• Inflammation arteries brain/heart

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Serious CV events• Cocaine

– 25% non-fatal MI in adults (18-45yo)– 3% sudden death

• Amphetamines– 2% bleeding-related strokes in adults

• Cocaine and Amphetamines– 3% aortic dissections in adults

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Risk of serious CV events

• Cocaine: 7x ↑ non-fatal MI

• Amphet: 3x ↑ hemorrhagic stroke

• Amphet: 3x ↑ aortic dissection

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Mechanisms of low-dose CV dangers

• Blood pressure ↑ 2-4 mm Hg

• Heart rate ↑ 6 beats/min

• QT Prolongation → arrhythmias → death

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BP and CV events

• Linear relationship

• Important on population scale

© AMSP32Psaty et al., 2001

≤125 mmHg

>160 mmHg

CV events & Rx stimulants

• Efficacy RCT too small

• Observational studies:– Children

– Adults

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Studies in children• 20% ↑ risk of CV ER visit

• + ↑ risk sudden death

• Best: NO ↑ risk serious CV events

– Cooper et al., NEJM 2011

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Studies in adults

• 3x ↑ “mini-stroke” (not stroke)

• ~2x ↑ sudden death/ventricular

arrhythmia

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Studies in adults

• Best: no ↑ serious CV events

• ? Selection bias:

– Users healthier

– More educated

• Median use 4 months

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Habel et al., JAMA 2011

Remaining questions

• Other variables (e.g. lifestyle factors)

• High risk populations underrepresented?

– Elderly

– Adults with multiple CV risk factors

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Public health considerations• Baseline rates of serious CV events

– Children: 3/100,000 person-years

– Adults: 220/100,000 person-years

• Doubling risk?– Children: 6/100,000 person-years– Adults: 440/100,000 person-years

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Government regs of Rx stimulants

• 2006 US: avoid use if heart disease

• American Heart Association:

– < age 18

– Careful health history

– Physical exam

• American Academy Pediatrics:

– EKG not mandatory

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Conclusions• Stimulants commonly misused

• Rx stimulants: use increasing

• Dangers associated with misuse

• CV safety: a concern with Rx use

– Children: minimal concern

– Adults: no definite risk; safety signal present

• Caution Rx’ing to high risk CV patients

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