Download Stimulant Use and Cardiovascular Consequences

STIMULANT USE AND
CARDIOVASCULAR
CONSEQUENCES
Arthur Westover, MD, MSCS
UT Southwestern Medical Center
© AMSP
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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
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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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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
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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
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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
© AMSP
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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
>160 mmHg
≤125 mmHg
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Psaty et al., 2001
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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
Habel et al., JAMA 2011
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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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