Toxicology Case Studies: Management of Toxin Induced Cardiovascular Effects

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Toxicology Case Studies Management of Toxin
Induced Cardiovascular Effects

• Toxicology Science of Anecdotes
• very few randomized controlled trials
• level of evidence often poor
• most data
• case reports
• case series (LOE 5)
• animal studies (LOE 6)

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Cocaine AssociatedMyocardial Ischemia
mechanism

• ? myocardial O2 consumption
• coronary artery vasoconstriction /or spasm
• coronary artery thrombosis
• ? platelet activation
• ? platelet aggregation
• potentiate thromboxane production

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Management of Cocaine Associated AMI

• Oxygen (I)
• ASA (IIa)
• nitrates (IIa)
• benzodiazepines (IIa)
• phentolamine (IIb)
• angiography /- PCI
• ß Blockers contraindicated (III)
• thrombolysis contraindicated
• intracoronary?

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Acute Cocaine Reaction

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Cocaine dysrhythmias/ conduction abnormalities

• sinus tachy, SVT
• atrial fib/flutter
• v tach, v fibrillation
• widened QRS
• bundle branch block
• Mechanism
• hyperadrenergic state
• sodium channel blockade

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Management of Acute Cocaine Toxicity

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V Tach and V Fib
associated with cocaine toxicity

• first line drug therapy for cocaine associated VT
  or refractory VF
• sodium bicarbonate (Class IIa, LOE 5)
• lidocaine (Class IIb, LOE 5)
• non-selective ? Blockers (i.e. propranolol) are
  contraindicated (Class III)
• epinephrine should be avoided

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Tricyclic AntidepressantsPharmacologic Actions

• inhibit amine uptake (NE, 5HT)
• Na Channel blockade
• antihistamine
• antimuscarinic
• alpha receptor blockade
• K Channel antagonism
• GABA-A receptor antagonism

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Na channel blockade

• quinidine/ membrane stabilizing
• inhibits Na influx through voltage dependant
  Na channels
• altered depol./repol. and conduction
• impaired contractility
• prolonged phase 0 of action potential
• worsened by
• increased HR
• decreased Na
• acidemia

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Na channel blockade

• EKG changes
• increased PR interval/other conduction delays
• widened QRS
• rightward axis deviation of terminal 40ms
• terminal axis 120-270
• ? RV conduction system more susceptible to Na
  channel blockade

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Other drugs that cause sodium channel blockade

• antihistamines (dimenhydrinate)
• cocaine
• phenothiazines
• class 1A 1C antidysrhythmics
• norpropoxyphene
• beta blockers (propranolol, metoprolol)

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Treatment of TCA Cardiac ToxicitySodium
Channel Blockade

• arterial pH of 7.5-7.55 (IIa, LOE 5)
• hyperventilation
• sodium bicarbonate
• bolus 1-2meq/kg
• continuous IV 2 amps in D5W with 20-40 meq/L
  _at_2-3 cc/kg
• procainamide is contraindicated (Class III, LOE
  8)

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Mechanism alkalinization of blood

• increased protein binding
• treats acidosis
• improves conduction through sodium channels (Na
  vs HCO3)
• indications
• QRSgt 100ms
• hypotension refractory to fluids
• ventricular dysrhythmia
• seizure

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CCB ß blockers Pathophysiology

• ß blockers
• inhibit
• ß1 cardiac
• inotropic
• chronotropic
• ß2
• bronchodilation
• smooth muscle relaxation

• CCBs
• inhibit voltage sensitive channels
• phase 2 of action potential
• SA node
• AV node
• cardiac muscle
• smooth muscle

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Cardiovascular Effects CCBs/ß-blockers

• hypotension/shock
• bradycardia
• heart block
• conduction abnormalities
• asystole
• pulmonary edema (rare)

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Shock in CCB/ ß Blocker Overdose

• crystalloid bolus and infusion
• calcium (IIa)
• glucagon
• catecholamines (high dose) (IIb)
• insulin pump therapy (Indeterminate)
• circulatory assist devices (IIb, LOE 6
• cardiac bypass
• IABP

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Glucagon

• produced by the ? cells of the pancreatic islets
• ? c-AMP by stimulating adenyl cyclase
• does not ? cardiac irritability
• glucagon receptors in the heart
• dose 5-10 mg bolus
• infusion 1-5 mg/h
• onset 1-3 minutes, peak 5-7 min
• adverse effects nv

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CCB/ ß-Blocker Shock

• DKA like state
• prevent adequate myocardial utilization of
  carbohydrates
• ? insulin release from pancreas
• myocardial peripheral insulin resistance
• ? insulin substrate delivery due to ? cardiac
  output

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Insulin-Euglycemia Treatment

• myocardium switches from fatty acid to
  carbohydrate oxidation
• increases lactate oxidation
• eliminates fatty acid oxidation
• promotes carbohydrate oxidation
• associated with ?mechanical performance
  (contractility, LV pressure)
• insulin dose 0.1-1.0 units/kg/hr (av 0.5)
• glucose to maintain euglycemia

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Digitalis mechanism of action

• Inhibits Na-K ATPase pump
• ? intracellular Ca2
• ? intracellular Na
• ? extracellular K
• ? vagal effects
• activation of sympathetic tone

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Cardiac Effects of Digitalis

• negative chronotropism
• positive inotropism
• slows sinus node impulse formation
• enhances intra-atrial conduction
• slowing of conduction velocity (AV node)
• ? rate of spontaneous depolarization
  (ventricles)

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Acute vs Chronic Toxicity

• Chronic
• usually elderly
• heart disease
• digoxin ? or therapeutic
• K normal to low
• noncardiac symptoms prominent
• various dysrhythmias

• Acute
• young, normal heart
• ? digoxin level
• K normal to high
• less noncardiac Sx
• AV conduction blocks more common

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Digoxin toxicity cardiac effects

• Acute
• sinus impulse formation disturbances
• sinus bradycardia
• SA arrest
• SA block
• AV conduction disturbances
• 1AVB
• 2AVB
• 3AVB

• Chronic
• PAT with block
• nonparoxysmal junctional tachycardia
• bidirectional v tach
• AV dissociation
• type 2AVB
• PVCs
• v tach
• v fib

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Indications for DIGIBIND

• Acute Overdose
• bradydysrhythmias unresponsive to atropine
• K gt 5.5 mmol/L
• tachydysrhythmia unresponsive to conservative
  treatment
• Chronic Intoxication
• dysrhythmia unresponsive to conservative
  treatment