Overview of Prehospital Pharmacology

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Overview of Pre-hospital Pharmacology

• Lynn K. Wittwer, MD, MPD
• Clark County EMS

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Prehospital Pharmacology

• Cyanide Poisoning
• Rapid Sequence Induction
• Controlled Medications (NEW STUFF)
• Antipsychotic (NEW STUFF)
• Antiemetic (NEW STUFF)
• Antihistamine
• Narcotic Antagonist
• Miscellaneous
• Recent Cardiovascular Agents
• Quiz

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Cyanide Poisoning

• Disrupts metabolism by inhibiting metal
  containing enzymes, most notably, cytochrome
  oxidase.
• Cytochrome A3 catalyzes O2 H2O
• Blocks ability of mitochondria to use O2
• O2 saturation may be normal
• Poisoning can occur through percutaneous
  absorption and inhalation.
• Degree of symptoms depends on severity of
  exposure.

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Cyanide Poisoning

• Antidote
• Nitrites and Sodium Thiosulfate

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Cyanide Poisoning
Amyl Nitrite

• Temporizing agent for reversal of cyanide
  toxicity
• Has same effect on vascular smooth muscle as
  other nitrates.
• 1 amp crushed under nose or in O2 mask. 15 sec on
  15 sec off.

• Indications
• Significant Cyanide Poisoning
• pt. comatose, bradycardic and known cyanide
  exposure.

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Cyanide Poisoning
Amyl Nitrite (Cont.)

• Contraindications
• None in the setting of acute cyanide toxicity.

Precautions

• May cause profound hypotension.
• Stop administration prior to Sodium Thiosulfate.
• Not administered to the patient improving on
  their own.
• Adequate oxygenation is imperative especially
  with smoke inhalation.

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Cyanide Poisoning
Sodium Thiosulfate

• Stimulates detoxification by accelerating
  rhodanese reaction.
• Should be administered slow IV push.
• 12. 5 gm IV bolus
• ? Peds 250 mg/kg.

• Indications
• Significant Cyanide Poisoning
• pt. comatose, bradycardic and known cyanide
  exposure.

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Cyanide Poisoning
Sodium Thiosulfate (Cont.)

• Contraindications
• None in the setting of acute cyanide toxicity.

Precautions

• Do not mix cyanide in jello and give to your
  friends.
• Not administered to the patient improving on
  their own.
• Adequate oxygenation is imperative especially
  with smoke inhalation.

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Rapid Sequence Induction
Neuromuscular Junction

• ACh binds to post synaptic receptors causing
  depolarization Contraction of muscle
• ACh removed by acetylcholinesterase and by
  diffusion . Relaxation of muscle

Dailey The Airway Emergency Management
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Dailey The Airway Emergency Management
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Rapid Sequence Induction
Succinylcholine (Anectine)

• Short acting depolarizing agent that combines w/
  cholinergic receptors
• Has no effect on consciousness, pain, or
  cerebration
• Can cause vagal stimulation and ? intraocular
  pressure.
• Negative inotrope and chronotrope
• Pronounced w/ repeat doses and in children
• 1.5 mg/kg IV bolus
• pretreat with Lidocaine, Atropine, Versed prn

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Rapid Sequence Induction
Succinylcholine (Cont.)

• Indications
• Facilitate intubation w/ failed prior attempt

• Contraindications
• Primarily any condition preventing
  ventilation/intubation

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Rapid Sequence Induction
Succinylcholine (Cont.)
Precautions

• Hyperkalemia/Renal failure.
• Glaucoma.
• Transient hyperthermia.
• Pseudocholinesterase deficiency
• Not to be used in multiple doses as a long-term
  agent
• Missing the tube may lead to personal injury

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Rapid Sequence Induction
Vecuronium (Norcuron)

• Non-depolarizing, competitive neuromuscular
  blocker
• Has no effect on consciousness, pain, or
  cerebration
• -Sedate appropriately w/ Valium
• Duration of action 25-40 minutes.
• 0.1 mg/kg IV bolus

• Indications (all of the following apply)
• 1. Successful intubation
• 2. Pt. Beginning to arouse
• 3. Risk of losing patent airway
• 4. Extended transport time

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Rapid Sequence Induction
Vecuronium (Cont.)

• Contraindications
• Pt not intubated (I.e. not indicated for
  restraint)
• Initial induction agent

Precautions

• Profound effects in pt. w/ myasthenia gravis.
• Blockade may be prolonged in renal failure.
• Infants lt 1 yr. more sensitive.

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Controlled Medications
Midazolam (Versed)

• Short-acting benzodiazepine CNS depressant
• Bind to specific benzodiazepine receptor sites
• -BZ1 sleep
• -BZ2 memory, motor, sensory, cognitive
• Potentiates other CNS depressants.
• 3-4 times more potent than Diazepam
• Onset of sedative effect 15 min after IM
  administration. IV effects may be seen in 2 min.
• 2.5-10 mg IV/IM (larger dose may be needed for
  sz)
• ? Peds 0.1mg/kg (double if given IM)

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Controlled Medications
Midazolam (Cont.)

• Indications
• -Seizures
• -Sedation prior to pacing, cardioversion, RSI.
• -Sedation in cocaine toxicity

• Contraindications
• -Acute narrow angle glaucoma

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Controlled Medications
Midazolam (Cont.)
Precautions

• Prepare to manage respiratory depression
• Seizure may recur esp. w/ long transport
• Hypotension is uncommon
• Elderly and debilitated patients require lower
  doses
• Will cause short term memory impairment.

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Controlled Medications
Morphine Sulfate

• Narcotic Opiod analgesic
• Bind to Opiod receptors to cause analgesia,
  euphoria, sedation, and respiratory/physical
  depression
• Stimulates emetic chemoreceptors.
• Peripheral vasodilitation and inhibition of
  baroreceptors.
• Histamine release is common
• 2-20 mg IV
• ? Peds 0.1-0.2 mg/kg

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Controlled Medications
Morphine Sulfate (Cont.)

• Indications
• -Chest pain
• -CHF/PE.
• -Musculoskeletal pain

• Contraindications
• -Known allergy

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Controlled Medications
Morphine Sulfate (Cont.)
Precautions

• Prepare to manage hypotension and respiratory
  depression
• -use w/ caution in COPD and Asthma
• Inhibits peristalsis
• Rapid injection increases incidence of adverse
  reactions
• May obscure diagnosis of acute abdominal
  conditions
• Patients can develop tolerance w/ continuous
  therapy

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Antipsychotic
Haloperidol (Haldol)

• Butyrophenone neuroleptic tranquilizer
• Has antiemetic properties
• Produces mild alpha adrenergic blockade
  (Hypotension).
• May have CV side effects including QT
  prolongation and Torsades.
• May reduce seizure threshold (actually IN the
  book).
• 2.5-5 mg IV/IM Max 10 mg
• ? Peds 0.1 mg/kg

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Antipsychotic
Haloperidol (Cont.)

• Indications
• -Sedation to facilitate restraint of combative
  patient

• Contraindications
• -Known allergy
• -Parkinsons disease
• -No Benadryl available

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Antipsychotic
Haloperidol (Cont.)
Precautions

• Use reduced dose in renal/hepatic impairment and
  elderly.
• Associated w/ irreversible Tardive Dyskinesia
• Can cause hypotension
• EPS -- Restlessness, hyperactivity, anxiety
  common
• -Pre-treat w/ Benadryl 25-50 mg
• Concommitant use w/ CNS depressants lower dose
  of Haldol

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Antiemetic
Promethazine (Phenergan)

• Phenothiazine derivative
• Antihistamine, Antiemetic, sedative and
  anticholinergic effects
• Potentiates other CNS depressants
• If inadvertent arterial injection, will cause
  gangrene.
• Effect 5 min IV and 20 min IM, duration 4-6 hrs.
• 12.5-25 mg IV/IM
• ? Peds 2-12 ½ adult dose IV/IM

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Antiemetic
Promethazine (Cont.)

• Indications
• -Antiemetic
• -Adjunct for pain control (adjust narcotic dose
  accordingly)

• Contraindications
• -Hypersensitivity to Phenergan or Phenothiazines
• -Not to be given SC
• -Intra-arterial

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Antiemetic
Promethazine (Cont.)
Precautions

• Should not be used in pt. less than 2.
• Interactions w/ MAOIs may lead to increased EPS.
• Treat w/ Benadryl
• Can cause hypotension
• Use w/ caution in pts w/ sulfite allergy
  (additive).

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Antihistamine
Diphenhydramine (Benadryl)

• Competitive antihistamine _at_ H1 receptor
• Sedative and anticholinergic side effects
• Antiparkinsons agent.
• Rapid onset of action.
• 25-50 mg IV, IM
• ? Peds 1 mg/kg

• Indications
• -Allergic reaction -- Anaphylaxis
• -EPS
• Prophylactic prior to Haldol administration

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Antihistamine
Diphenhydramine (Benadryl)

• Contraindications
• -Known hypersensitivity
• -Newborn infants

Precautions

• MAO inhibitors will prolong anticholinergic
  effects.
• Sedative effect more pronounced in elderly
• Can cause excitation in young children
• Atropine like side-effects may occur

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Narcotic Antagonist
Naloxone (Narcan)

• Pure narcotic antagonist that competes for the
  same receptor sites
• Rapidly reduces narcotic induced coma and
  respiratory depression
• Onset of action w/in minutes.
• High dose Narcan may also reduce respiratory
  depression due to propoxyphene OD.
• 2 mg IV,SC, IM, SL x 2 prn
• ? Peds lt 6 yr (or lt 21 kg) 0.1 mg/kg

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Narcotic Antagonist
Naloxone (Cont.)

• Indications
• -Reversal of narcotic coma/respiratory depression
• -ALOC unk. etiology

Precautions

• Administration may precipitate withdrawal
  syndrome.
• Repeat doses may be necessary

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Miscellaneous
50 Dextrose in H2O (D50/W)

• CNS energy source
• Transports Potassium across cell membrane
• 25gm IV
• ? Peds 0.5 gm/kg (use D25/W for infant)

• Indications
• -Hypoglycemia (lt60 mg/dl)
• -ALOC
• -Hyperkalemia

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Miscellaneous
50 Dextrose in H2O (Cont.)

• Contraindications
• -Diabetic coma

Precautions

• Increased ICP.
• Hypertonic solution
• Hypoglycemia may recur.
• Take follow-up BGL prior to signing the refusal

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Miscellaneous
Acetaminophen

• Analgesic/Antipyretic
• Inhibits hypothalamic prostaglandin synthetase
• Metabolized by the liver
• ? Peds 20 mg/kg suppository

? Remove foil prior to insertion

• Indications
• -Fever gt 103

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Miscellaneous
Acetaminophen

• Contraindications
• -Known hypersensitivity

Precautions

• Used as directed, rarely causes toxicity

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Miscellaneous
Activated Charcoal (Actidose)

• Carbon from organic material
• -Activated fine network of pores
• Greater surface area increases absorptive
  properties
• 50 gm po
• ? Peds 1 gm/kg

• Indications
• -Ingestion

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Miscellaneous
Activated Charcoal (Actidose)

• Contraindications
• -OD of mineral acids and alkalies

Precautions

• Ineffective in ethanol, methanol, iron salt
  ingestion.
• Pt. must be able to protect own airway
• When mixed w/ sorbitol, GI transport time
  decreased from 25 hrs to 1 hr. ( blackout)

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Antiplatelet Agents
Aspirin

• Analgesic, antipyretic, antirheumatic, and
  anti-inflamatory.
• Inhibits prostaglandin synthesis
• Prevents platelet aggregation
• Thromboxane A2 (prostaglandin derivative
• 160mg chewed

• Indications
• -Cardiac chest pain

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Antiplatelet Agents
Aspirin (Cont.)

• Contraindications
• -Active bleeding ulcer
• -Known allergy
• -Sinusitis/Asthma

Precautions

• Hypersensitivity includes bronchospasm, rhinitis,
  angioedema, urticaria, and/or shock
• Side effects include tinnitus, dizzyness, or
  impaired hearing
• Pharmacologic effect may be decreased if patient
  taking antacids.

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Antiplatelet Agents
Glycoprotein IIb/IIIa Inhibitors

• GP IIb/IIIa receptor found on platelets
• Fibrinogen ( von Willebrands factor) bind to
  receptor
• Leads to aggregation of platelets
• GP IIb/IIIa Inhibitors prevent platelet
  aggregation
• Effect is reversible once infusion dcd

Abciximab (Reo Pro) Eptifibatide (Integrilin) Tiro
fiban (Aggrastat)
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Antiplatelet Agents
Glycoprotein IIb/IIIa Inhibitors

• Indications
• Acute coronary syndromes W/O ST elevation
• Non Q wave MI
• Pt. undergoing PCI

• Contraindications
• Bleeding disorders
• Recent stroke
• Recent surgery, trauma
• Etc., Etc

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ACE Inhibitors
Benazepril, Captopril, Enalapril, Fosinopril,
Lisinopril, Moexipril, Quinapril, Ramipril,
Trandolapril

• Angiotensin Converting Enzyme Inhibitor
• Suppress Renin-Angiotensin-Aldosterone system
• Inhibit conversion of Angiotensin I to
  Angiotensin II.
• Angiotensin II
• Potent vasoconstrictor
• Stimulates Aldosterone secretion
• Aldosterone Na and H2O retention
• Increase Bradykinin levels (vasodilator)
• Delay progression of Heart Failure and infarct
  expansion
• Improve LV dysfunction post AMI

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ACE Inhibitors

• Indications
• Hypertension
• Heart failure
• Suspected MI
• W/ elevation in anterior (LV) leads
• Clinical signs of AMI w/ LV dysfunction

• Contraindications
• CHF w/ hypotension
• Pregnancy

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ACE Inhibitors
Precautions/Side Effects

• Severe anaphylactoid reactions
• Profound hypotension

Treatment for Overdose

• Treat anaphylaxis per protocol
• Fluid Challenge
• Vasopressors prn
• Naloxone
• May reduce hypotension in Captopril OD, MOI
  unclear

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BETA Blockers
Acebutolol, Atenolol, Betaxolol, Bisoprolol,
Carteolol, Esmolol, Labetalol, Metoprolol,
Nadolol, Penbutolol, Pindolol, Propranolol,
Sotalol, Timolol

• Block catecholamines from binding to
  Beta-adrenergic receptors
• Inhibit chronotropic, inotropic response to
  adrenergic stimulation
• Decrease AV nodal conduction
• Decrease incidence of primary VF
• Beta 2 blockade bronchial constriction

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BETA Blockers

• Indications
• Hypertension
• Angina
• Cardiac Arrythmias
• AMI

• Contraindications
• CHF/PE
• Heart block, high degree
• Hypotension
• Acute asthma/severe COPD

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BETA Blockers
Precautions/Side Effects

• Propranolol can increase serum potassium
• Profound hypotension
• Severe CHF pt. may depend on sympathetic
  stimulation for CO
• May blunt sx of
• Shock
• Hypoglycemia
• Etc.

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Calcium Channel Blockers
Amlodipine, Bepridil, Diltiazem, Felodipine,
Isradipine, Nicardipine, Nifedipine, Nimodipine,
Nisoldipine, Verapamil

• Function of Calcium
• Links motor end plate stimulation and muscle
  contraction
• Involved in the genesis of the action potential
  in cardiac conduction cells
• In general, these agents decrease conductivity
  and muscle tone
• Efficacy in Acute Coronary Syndromes questionable
• May be indicated if BETA blocker not effective

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Calcium Channel Blockers

• Indications Agent specific
• Hypertension
• Angina, vasospastic (Prinzmetals)
• Cardiac Arrythmias
• AMI
• Subarachnoid hemorrhage
• Migraine headache
• Variety of other ailments

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Calcium Channel Blockers

• Contraindications Agent specific
• CHF/PE
• Heart block, high degree
• Hypotension

Precautions/Side Effects

• May be harmful in AMI w/ hypotension
• Side Effects exacerbated when used w/ BETA
  blockers
• Verapamil may lead to heart block
• Nifedipine has been associated with gynecomastia
• Sx and treatment of OD have been well chronicled

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QUIZ

• Cyanide Toxicity can be caused by which two
  routes of exposure?
• How does Sodium Thiosulfate stimulate Cyanide
  detoxification?
• Describe the difference between depolarizing and
  non depolarizing paralytic agents.
• Which patient demographic requires a lower dose
  of Midazolam?
• What are the contraindications to Haldol
  administration?
• After administering Phenergan, your 80 yo patient
  begins to cry inconsolably and become quite
  agitated. What is your treatment?
• Activated Charcoal is ineffective for which types
  of ingestions?
• What are the contraindications to Aspirin
  administration?
• Briefly describe the mechanism of action of
  Glycoprotein Iib/IIIa Inhibitors.
• BETA Blockade may blunt sx of

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THE END