Rx DRUG ABUSE

Presented By: Steven Jones, NREMT-P

OVERDOSE / TOXICOLOGY

Toxicologic Emergencies

• Prescription– β Blockers– Calcium Channel

Blockers– Clonidine– Cardiac Glycosides

(Digitalis)– Benzodiazepines– TCA’s

• Other Substances– Hyperadrenergic

agents– Organophosphates

Prescription Medication Toxicity

• Scope of the problem– Widely available medications– Third most common cause of fatal OD in

pediatric patients– Fifth most common cause of fatal OD in Adult

patients

Beta Blockers

• Therapeutic effect– β1 Cardiac influence– β2 Peripheral influence

• Prescribed for– Hypertension

• Most common Rx

– Angina– Hyperthyroid– Migraine– Glaucoma– SVT

Beta Blockers

• Pharmacology– Lipophilicity– Membrane stabilizing effect

• Selective vs non-selective agents• Propranolol is most common and most

dangerous

Beta Blockers

• Toxic Dose – 2-3 times therapeutic dose

• Signs and Symptoms– Bradyarrhythmia– Hypotension– Decreases LOC– Respiratory depression– Seizure– Ventricular arrhythmia

Beta Blockers

• Pre-hospital Management– Aggressive Airway Management– AMS Protocol– Atropine 0.5mg prn (max 3mg)– Transcutaneous Pacemaker

- Do not delay in symptomatic bradycardia

Beta Blockers

• Pre-hospital Management– Glucagon 1-2 mg IV or IM– Fluid resuscitation 20ml/kg bolus– Pressors (PRN)

• Dopamine 5-20 mcg/kg/min• Epinephrine drip 2 mcg/min

Titrate to response. May need higher than normal dose

Beta Blockers

• Other Management Issues– Treat Dysrhythmias– Pediatric Patient

• Hypoglycemia more common• Seizures more likely than adult

– Consider Heroic Measures• Heroic Measures = Prolonged/Aggressive CPR.

– Cases have been reported of CPR in progress for up to 2 hours with successful outcomes.

Beta Blockers: Case ReportLang et al. Ann Emerg Med 1987, 16(12)

• 17 yo M ingested 8 gm Propranolol• PEA treated with

– Fluid resuscitation, Atropine, Glucagon, pressors and two hours of CPR

• IABP (Intra-Aortic Balloon Pump) placed for 48 hrs• Complete recovery with no neurologic

deficit

Beta Blockers

Summary• Transcutaneous Pacing: useful in drug-induced

symptomatic bradycardia • Drug-induced shock may require high-dose

pressors

Calcium Channel Blocker

• Prescribed for:– Angina– Hypertension– Migraine– SVT

• Mechanism of Action– Blocks entrance of

calcium into cardiac and smooth muscle cells.

Calcium Channel Blocker

• Pharmacology– Negative Inotrope

• Blocks flow of calcium ions through slow channels• Decreased amount of calcium from sarcoplasmic

reticulum– Negative Chronotrope/Dromotrope

• Decrease automaticity in SA node and AV junction– Reduction in PVR

Calcium Channel Blocker

• Agents– Verapamil

• Significant cardiac depressant – Vasodilation– AV slowing

– Diltiazem– Nifedipine– Felodipine– Amlodipine

Calcium Channel Blocker

• Toxicity– Hypotension– Bradycardia– Arrythmias– Respiratory depression– Neurologic disorders

• Seizures etc.

Calcium Channel Blocker

• Pre-hospital Management– Aggressive airway management– AMS Protocol– Atropine 0.5 mg (max 3mg)– Transcutaneous Pacemaker

- Do not delay in symptomatic bradycardia

Calcium Channel Blocker

• Prehospital Management– Calcium Chloride 250-500 mg IV

• (Not CLEMC approved protocol)– Glucagon 1-2mg IV or IM– Fluid resuscitation 20ml/kg bolus

Calcium Channel Blocker

• Other Management Issues– Pressors (PRN)

• Dopamine 5-20 mcg/kg/min• Epinephrine drip 2 mcg/min

Titrate to response. May need higher than normal dose

– Treat Dysrhythmias– Pediatric Patient

• Small doses can be lethal• Seizures more likely than adult

– Consider Heroic Measures

Case Report:* 14 mo boy died 3hrs

after ingesting 10 mg ofProcardia.

Clonidine

• Prescribed for – Hypertension– Withdrawal syndrome– Migraine– ADHD– Tourette’s syndrome

• Mechanism– α adrenergic agonist

Case Report:* 3 yo boy dies after application of multiple clonidine transdermal patches (mistaking them for Band-Aids)

Hum Tox 1993;35:345

Clonidine

• Toxic Effects– Cardiovascular

• Bradycardia• Hypotension (Initial

hypertension)• Arrhythmias

– Neurologic• Miosis• Respiratory Depression• Seizures• Coma

• Signs/symptoms– Mimics

Barbiturate/Opiate OD• Withdrawal

– Sx seen after chronic use.

Clonidine• Treatment

– ALS management symptomatic• Airway, seizures, respiratory depression

– Atropine 0.5mg (max 3mg)– Transcutaneous Pacemaker

- Do not delay in symptomatic bradycardia

– Pressors (PRN)• Dopamine 5-20 mcg/kg/min• Epinephrine drip 2 mcg/min

Clonidine

• Narcan– May be useful for respiratory depression or

coma• Induction of Emesis

– Not indicated due to probability for rapid CNS depression

Digoxin

• Prescribed for– CHF

• Improves cardiac output– A-fib

• Mechanism– Cardiac glycoside– Inhibition of Na+/K+ ATPase (sodium-potassium pump)

• Allows increase in calcium to activate contractile proteins (actin/myosin)

– Increased myocardial contractility

Naturally Occurring Cardiac GlycosidesFoxglove (Digitalis purpurea)

Lily of the valley (Convallaria majalis)

Oleander (Nerium oleander)

Red squill (Urginea maritima)

Yellow oleander (Thevetia peruviana)

Digoxin

• Toxicity– Dysrhythmias

• PVC’s• Slow A-fib, PAT w/ block• Bradycardia, V-fib, V-tach

– Hypotension– Hyperkalemia (Renal insufficiency is a risk factor)– CNS

• Delirium, hallucinations, lethargy, agitation• Ocular disturbances

Digitalis Effect• The digitalis effect or “dig dip” is a unique finding on a 12-lead EKG.

– shortened QT interval– characteristic down-sloping ST depression, reverse tick appearance

Digoxin

• Treatment– Basic management (ABC’s etc.)– Electrolyte disturbances

• Hyperkalemia• NEVER give Calcium

– Atropine/Pacemaker– Manage dysrhythmias

Other Prescriptive Medications

Overdose/Toxidromes

Case Presentation

• 30-year-old woman, unconscious• Boyfriend calls EMS and reports recent

anxiety and stress• Empty bottles of Ativan (lorazepam) and

bourbon whiskey found

Case PresentationPrimary ABCD Survey• Airway: open; saliva accumulating; gurgling;

smell of alcoholic beverage on breath • Breathing: respiration = 8/min; sonorous;

decreased gag reflex• Circulation: BP = 80/50 mm Hg; sinus

tachycardia 130 bpm

What is your treatment for this patient?

Case Presentation

Secondary ABCD Survey• Airway: clearly needs intubation performed• Breathing: ETT placement confirmed 2 ways• Circulation:

– 2 large-bore IVs, begin fluid challenge• Develop differential diagnosis; note major findings:

– LOC, RR, and BP– HR– Not consistent with benzodiazepine OD!

Benzodiazepine

• Treatment for Overdose– Supportive ABC’s– AMS Protocol

• Treatment of BZD OD, Critical Points• Hemodynamic compromise unexpected in BZD

OD; when observed search for another cause

Case Presentation• 42 yo female resident of a van under the Kemah

bridge. • Teenage children moved to Phoenix to be with

father. • Boyfriend recently jailed for Narcotic trafficking• Took complete bottle of anti-depressant• Found by fisherman unconscious barely breathing

What is your initial Management?

Case PresentationPrimary ABCD Survey• Not in full cardiac arrest• Multiple episodes of nonsustained VT occur• One shock converts episode of sustained VTSecondary ABCD Survey• Needs intubation and hyperventilation• Oxygen, IV, monitor, fluid challenge• Continuous grand mal seizures begin

What is the cause of her toxicity?

Tricyclic Antidepressant

• Anticholinergic effects– Hyperthermia, blurred vision, flushed skin,

hallucinations, tachycardia, status seizures• Quinidine-like effects

– Negative inotrope, prolonged QT, ventricular arrhythmias (eg, torsades de pointes)

• α-Adrenergic blockade effects– Hypotension

• CNS effects– Seizures, coma

Tricyclic Antidepressant

• Clinical Features of Toxicity– Mild-Moderate

• Drowsiness, lethargy• Hypertension, tachycardia

– Severe• Seizures• Hypotension• Arrythmias• Coma

Rapid progression of toxic symptoms:

characteristic of TCAs

Tricyclic Antidepressant

• Pre-hospital Management– Aggressive airway management– Fluid challenge– NaHCO3 (sodium bicarbonate)1 mEq/kg IV

• Tachycardia, widened QRS, seizures– MgSO4 (magnesium sulfate) 2gm slow IV

• Wide QRS or Torsades– May need high dose vasopressors for refractory

hypotension

Tricyclic Antidepressant

• Treatment Goal• Systemic alkalinization (achieve and sustain)

– Bicarbonate: superior to hyperventilation– Complications: indicative of severe toxicity

• Marked conduction disorders (QRS >120 ms)• Marked tachycardia/bradycardia• Ventricular arrhythmias• Significant hypotension• Seizures or coma

Typical Dysrhythm

Tricyclic Antidepressant

Tricyclic Antidepressant

“Twisting (spindle) about the Points” (node)

“Spindle-node” pattern “Spindle”

“Node” (“point”)

Torsades Tangent

Interesting thought…

Tricyclic Antidepressant

• Torsades - Polymorphic V-tach– Drugs that induce torsades

• YES: terfenadine (Seldane), astemizole (Hismanal)

• NO: loratadine (Claritin), cetirizine (Zyrtec), or fexofenadine (Allegra)

• Erythromycin, Class IA and III antiarrhythmics, TCA, phenothiazines, pentamidine, cisapride

– Symptoms of torsades• Dizziness, syncope, palpitations, sudden death

Tricyclic Antidepressant

• Risk factors– High levels of torsades-inducing drugs are caused by

• Excessive exposure (iatrogenic or intentional) • Drug-induced impaired elimination• Hepatic failure

–K, Mg, heart disease, congenital long-QT syndrome

Tricyclic Antidepressant

• Treatment of drug induced Torsades– Correct K, Mg– Overdrive pacing

• Transcutaneous Pacing– Antiarrhythmics

• Magnesium or lidocaine?

Tricyclic Antidepressant

• Typical EKG Effects of TCA– Prolonged QT/QRS– Bundle Branch blocks– AV block– Ventricular arrhythmia– PEA

Tricyclic Antidepressant

• Summary– Alkalinize severe cases—bicarbonate is best antidote! – Use high-dose pressors when necessary– Stop TCA seizures with bicarbonate, BZDs– If cardiac arrest occurs, perform prolonged CPR:

• Buys time for drug to dissipate• Good neurologic outcome possible• Good heart; good conduction system

Case Presentation

• 35 you male c/o crushing chest pain, pt. states he has been partying for 3 days

• Pt appears quite agitated, diaphoretic, speaks in 4-5 word sentences

• HR = 140 bpm, BP = 160/120 mm/Hg, RR = 30/min, T = 102.2°F

What is your initial management for this patient?

Case Presentation

• Primary ABCD SurveyABCD: clear

• Secondary ABCD SurveyA: No intubation requiredB: Oxygen givenC: IV fluids, monitor, cool him downD: Develop a differential diagnosis; decontaminate,

define toxidrome, drug-specific therapy

What is your differential diagnosis?

Hyperdynamic/Hyperadrenergic Agents

• Cocaine (crack)• Ketamine• Phencyclidine (PCP)• Amphetamine/methamphetamine

(ice, crystal meth)• Ephedrine and derivatives, β2-agonists• Caffeine, nicotine, theophylline• Dextromethorphan• MDMA (Ecstasy)

Hyperdynamic/Hyperadrenergic Agents

• Signs and Symptoms– Tachycardia, ventricular dysrhythms– Hypertension, intracranial bleed, aortic dissection– Hyperthermia– Agitation– Delerium– Cerebral, Myocardial infarction– Angina– Seizures

Hyperdynamic/Hyperadrenergic Agents

• Pre-hospital Management– Airway management

• 100% O2

– Ativan 2.5-5 mg– Lidocaine 1 mg/kg

• Ventricular dysrhythmias– Treat V-fib per protocol

• Limit EPI to 1 mg q 5 min

Hyperdynamic/Hyperadrenergic Agents

• Treatment– Reduce the hyperdynamic state – Monitor/reduce temperature

• Physical cooling– Prevent or treat seizures– Restrain to prevent harm

• Chemical restraints preferred over physical restraints

• Agents: BZDs, Ziprasidone

Hyperdynamic/Hyperadrenergic Agents

• Treatment Summary• Hyperthermia: Active cooling• Seizures: BZDs• Delirium: BZDs, Ziprasidone• Drug-induced acute coronary syndrome: BZDs,

Nitrates, Ziprasidone• ST elevation: Avoid Heparin PTCA preferred over IV Thrombolytics

• BP: BZD, Labetalol

Case Presentation

• 54 yo migrant worker c/o severe abdominal cramps with nausea and vomiting. Pt states he has trying to siphon what he thought was gas for his 72 El Camino from a container on a farm.

• Initial exam reveals– Profusely diaphoretic– Incontinent of bowel/bladder– Pt c/o blurred vision, copious tearing– restlessness

Case Presentation

• Exam Continued– Vitals

• BP 90/60, HR 46, RR 36• Temp 100.6

– Bilateral diffuse wheezes, rales/rhonchi• Differential Dx

– Partial airway obstruction– Acute respiratory syndrome– Heat emergency– Poisoning

Case Presentation

• Differential Dx (cont.)– Organophosphates– Anticholinesterases– Amanita Mushrooms– Betel Nuts– Bethenecol– Carbamates– Pilocarpine

Organophosphates

• Mechanism of Action– Inhibition of Acetylcholinesterase– Acetylcholine produces hyperstimulation of

cholinergic nervous system• Muscarinic Effect

– smooth muscles contract (eg, airway constriction); glands produce mega-secretions

• Nicotinic Effect– skeletal muscles contract (twitching)

Organophosphates

• SLUDGE– Salivation– Lacrimation– Urination– Defecation– Gastrointestinal– Emesis

Organophosphates

Muscarinic EffectsGeneral: sweatingEye: lacrimation, pupils

constricted, blurred visionPulmonary: wheezing, rales,

bronchorrheaGI: salivation, n/v/d, cramps,

tenesmusCV: bradycardia,

hypotensionGU: urinary incontinence

Nicotinic EffectsMuscle: fasciculations,

cramps, weakness, twitchingSympathetic ganglia:

tachycardia, hypertensionCNS: anxiety, restlessness,

confusion, ataxia, coma, seizures, insomnia

Organophosphates• Treatment

– Decontaminate – Scene Safety• MARK1 Kits (be prepared to protect yourself)

– Airway management (ABC’s)– Atropine 2mg q 2-3 min

• Antagonizes muscarinic effect• Dries secretions and relaxes smooth muscle• Administer until secretions stop• Requires huge doses – We don’t carry NEAR

enough! (8mg in 20ml vials)

Organophosphates

• Treatment (cont.)– Ativan 2.5-5 mg to prevent seizure

• Other treatment– Pralidoxime (2-PAM or MARK1)

• Helps reverse nicotinic effect• Removes nerve agent from AChE

• Notify Receiving Facility of Hazardous Material!

• Organophosphate poisonings are Hazardous Materials Incidents.

• Poisoned patients– Secrete Organophosphate from their skin after

prolonged exposure– Exhale phosgene gas as a byproduct of

organophosphate inhalation. • Protect YOURSELF – Protect OTHERS

Organophosphates

Questions?