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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Mechanism of Airway Hyperactivity

• Decrease in baseline airway caliber
• Alterations in bronchial smooth muscle
  (hypertrophy, hyperplasia)
• Increased number of mast cells
• Increased synthesis of mediators
• Lowered receptor threshold
• Damage to airway epithelial cells
• Alterations in ANS regulation
• Increased parasympathetic activity
• Decreased b adrenergic responsiveness
• Increased a adrenergic responsiveness
• Decreased responsiveness of nonadrenergic
  inhibitory system

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Cholinergic System

• Vagus (Ach) bronchoconstriction
• at rest cholinergic stimulation predominates
• Asthma muscle mass bronchial tone
• Histamines (H1) bronchoconstriction
• Bronchoconstriction requires intracellular Ca

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Adrenergic System

• Weak a adrenergic bronchoconstriction pathway may
  mucous production
• b adrenergic innervation to pulmonary vasculature
• b receptors

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Immunology

• IgE Receptors (basophils, macrophages, mast
  cells, eosinophils, lymphocytes)
• EARLY
• Antigen/Antibody intracellular (Ca/ATP)
• Release of mediators
• Histamine (bronchospasm)
• Eosinophils (chemotactic factor)
• Arachidonic acid (prostaglandins, thromboxanes,
  leukotriens, platelet activating factor)
• SRS - A

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Immunology

• LATE
• Inflammation, edema, bronchoconstriction,
  increased mucus

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Respiratory
Albuterol (Proventil, Ventolin)

• B2 specific bronchodilator
• Reduced potential for cardiac side effects
• Onset within 5 minutes
• Duration 3-8 hours
• 2.5mg/3cc nebulized
• 1.25mg/3cc peds

• Indications
• Asthma
• Exercise Induced bronchospasm
• Bronchitis
• Other obstructive pulmonary diseases

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Respiratory
Albuterol Cont.

• Contraindications
• Known hypersensitivity

Precautions

• May cause paradoxical bronchoconstriction.
• Use cautiously in patients with cardiac disease
  (monitor vitals closely.
• Palpitations, anxiety, nausea, and dizziness.

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Respiratory
Ipratropium Bromide (Atrovent)

• Synthetic parasympatholytic
• Inhibits vagally mediated response
• Does not produce clinically significant changes
  in pulse rate or blood pressure
• ATROPINE
• 500 mcg/2.5cc (mix w/ Albuterol)
• 250 mcg/2.5cc peds (mix w/ Albuterol)

• Indications
• Maintenance bronchodilator for COPD
• Concomitant use with b agonist for acute
  bronchospasm

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Respiratory
Atrovent (Cont.)

• Contraindications
• Hypersensitivity to the drug, Atropine or
  derivatives.

Precautions

• Use cautiously in patients with soy allergy.
• Not appropriate as single agent for treatment of
  bronchospasm.
• Narrow angle glaucoma

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Respiratory
Methylprednisolone (Solu-Medrol)

• Anti-inflammatory action
• Enhance effect of b adrenergic drugs on AMP
  production
• Indicated for chronic treatment
• Contraindicated as primary treatment
• 125mg IV bolus
• 2mg/kg peds

• Indications
• Bronchial asthma
• Reversible bronchospasm

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Cellular Metabolism

• Cyclic AMP inhibits bronchoconstriction
• Binds intracellular Ca to cell membrane
• Adenylate Cyclase (enzyme) Cyclic AMP

ATP
adenyl cyclase
AMP
cAMP
phosphodiesterase
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Respiratory
Methylprednisolone (Cont.)

• Contraindications
• Known hypersensitivity

Precautions

• Paradoxical bronchoconstriction.
• Use cautiously in patients with cardiac disease
  (monitor vitals closely.
• Palpitations, anxiety, nausea, headache, and
  dizziness.
• Epinephrine like side effects.

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Respiratory
Racemic Epinephrine (AsthmaHaler, AsthmaNefrin,
microNefrin, Vaponefrin)

• Onset 1-5 minutes
• Duration 1-3 hours
• Reduces subglottic edema
• 0.5cc/kg for child 20-40kg (0.25cc/kg lt20kg)

• Indications
• Croup
• Post intubation stridor

Precautions

• Similar to Epi.
• Re-occurrence of subglottic edema

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Respiratory
Epinephrine (Adrenaline, Ana-Kit, EpiPen,
Sus-phrine)

• Has b1, b2 , and a activity
• Effect on b receptors more profound
• Onset (inhaled) 1-5 minutes, IV 1-2 min.
• Duration 1-3 hours (inhaled)
• Histamine antagonist
• 2-10mcg/min IV infusion
• 0.1mcg/kg/min peds

• Indications
• Severe bronchial asthma in peds
• Anaphylaxis

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Respiratory
Epinephrine (Cont.)

• Contraindications
• Wheezing due to pulmonary edema or embolism.

Precautions

• Can precipitate angina and MI.
• Use cautiously in patients with cardiac disease
  (monitor vitals closely). Should be given IV
  drip.
• Palpitations, anxiety, nausea, headache, and
  dizziness.
• CVA, hyperthyroidism, and hypertension.

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Cardiac
Atropine

• Parasympatholytic (vagolytic)
• Enhances sinus automaticity and AV conduction
• 0.5mg-1.0mg max 3mg
• 0.02mg/kg peds (min. dose 0.1mg) max 1mg child /
  2mg adolescent.

• Indications
• Symptomatic bradycardia
• Asystole
• Heart block
• Organophosphate poisoning

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Cardiac
Atropine (cont.)

• Contraindications
• Asymptomatic bradycardia

Precautions

• High degree AV blocks.
• Glaucoma.
• May increase myocardial Oxygen demand.

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Cardiac (Antidysrhythmics)
Adenosine (Adenocard)

• Endogenous, present in all cells
• Slows AV nodal conduction
• Prevents AV nodal reentry
• Half life 10 seconds
• 6mg rapid bolus, 12mg x 2 prn
• 0.1mg/kg, 0.2mg/kg prn peds

• Indications
• PSVT
• WCT of uncertain type

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Cardiac (Antidysrhythmics)
Adenosine (Cont.)

• Contraindications
• 2 3 heart block
• Hypersensitivity

Precautions

• Dipyridamole (persantine) potentiates its
  effect.
• Antagonized by methylxanthines.
• May cause transient asystole or other FLBs
  during conversion.

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Cardiac (Antidysrhythmics)
Lidocaine

• Local anesthetic (prevents generation and
  conduction of nerve impulses).
• Antidysrhythmic decreases automaticity and
  attenuates phase 4 depolarization
• May raise the V-fib threshold
• Onset immediate w/ brief duration of action
• Metabolized by the liver
• 1-1.5mg/kg IV bolus followed by 1-4 mg/min
  infusion
• 1mg/kg IV bolus followed by 20-50mcg/kg/min
  infusion for peds

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Cardiac (Antidysrhythmics)
Lidocaine (Cont.)

• Indications
• -Ventricular dysrhythms PVCs, V-tach, V-fib,
  WCT
• -Topical anesthetic pleural decompression,
  facilitate intubation, etc
• -RSI

• Contraindications
• -Heart block
• -WPW
• -Allergy
• -Dysrhythm prophylaxis

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Cardiac (Antidysrhythmics)
Lidocaine (Cont.)
Precautions

• Reduce dose in renal/hepatic impaired, CHF,
  reduced CO, and gt70 yo, .
• CNS depression if gt3mg/kg
• Adverse reactions include seizure, tinnitus,
  euphoria, visual disturbances, agitation, and
  twitching

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Cardiac (Antidysrhythmics)
Bretylium (Bretylol)

• Antidysrhythmic increases fibrillation threshold
• Initially provokes release of norepinephrine then
  prevents reuptake
• 5mg/kg then 10mg/kg prn (max 35mg/kg)

• Indications
• Refractory V-fib/V-tach
• Refractory PVCs

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Cardiac (Antidysrhythmics)
Bretylium (Cont.)

• Contraindications
• -None in the presence of life-threatening
  dysrhythmias

Precautions

• Postural hypotension
• Will cause nausea and vomiting
• May aggravate digitalis toxicity
• Transient hypertension and tachycardia may occur

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Cardiac (Antidysrhythmics)
Magnesium Sulfate

• Cofactor in numerous enzymatic reactions
• CNS depressant decreases amount of ACH at the
  motor end plate.
• Mag deficiency associated w/ dysrhythmias and SCD
• Essential for Na/K ATPase pump
• Will produce vasodilation and hypotension at
  higher doses (also loss of DTRs)
• Mag toxicity can be antagonized w/ Calcium
• Do not mix w/ NaHCO3 or Calcium

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Cardiac (Antidysrhythmics)
Magnesium Sulfate (Cont.)

• Indications
• -V-tach, V-fib 2gm bolus
• -PVCs, TCA OD 2gm/100cc over 5-20min
• -WCT, Status Asthma 2gm/100cc over 4-5min
• -ETOH Sz 2gm/100cc over 20min
• -Ecclamptic Sz 2 gm/100cc over5-10min

• Contraindications
• -Heart block
• -Recent MI (myocardial damage)

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Cardiac (Antidysrhythmics)
Magnesium Sulfate (Cont.)
Precautions

• Use w/ caution in impaired renal function
• Rapid administration can cause flushing,
  sweating, bradycardia, hypotension
• Toxicity hyporeflexive, flaccid paralysis,
  circulatory collapse, and respiratory paralysis

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Cardiac (Antidysrhythmics)
Procainamide (Pronestyl.)

• Class IA antidysrhythmic
• Slows intraventricular conduction
• Inhibits ectopic pacemaker activity
• Has vasodilatory and negative inotropic effects
• May be effective in refractory ventricular ectopy
• 20mg/min max 17mg/kg

• Indications
• -Refractory PVCs, V-tach, V-fib, WCT

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Cardiac (Antidysrhythmics)
Procainamide (Pronestyl.)

• Contraindications
• -Heart block
• -Lupus
• -Torsade de pointes

Precautions

• Discontinue administration if QRS widens by 50,
  no ectopy, BP lt90, or max dose
• Administer w/ caution in the face of MI
• Hypotension
• Potential to cause hematologic disorders
  (agranulocytosis, leukopenia)

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Cardiac (Vasopressor)
Dopamine (Intropin)

• Endogenous catecholamine precursor of norepi.
• Stimulates dopaminergic, ?1,and ? receptors
  depending on dose
• -Low cerebral, renal, mesenteric vasodilation
• -Mid inotropy increased CO
• -High ? effect increased SVR
• 5-20mcg/kg titrate

• Indications
• -Non-hypovolemic shock

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Cardiac (Vasopressor)
Dopamine (Intropin)

• Contraindications
• -Hypovolemia
• -Uncorrected tachydysrhythmias
• -Pheochromocytoma

Precautions

• May induce or exacerbate dysrhythms
• Will cause nausea and vomiting
• Tissue necrosis if extravasation occurs
• reduce dose if patient taking MOIs

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Cardiac (Sympathomimetic)
Epinephrine (Adrenaline, Ana-Kit, EpiPen,
Sus-phrine)

• Has b1, b2 , and a activity (inotrope and
  chronotrope)
• Effect on b receptors more profound
• Onset IV 1-2 min.
• Increases blood sugar and glycogenolysis
• Histamine antagonist
• 1-5 mg IV infusion (cardiac arrest)
• 0.01-0.2 mg/kg peds

• Indications
• Cardiac Arrest

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Cardiac (Sympathomimetic)
Epinephrine (Cont.)

• Contraindications
• None in cardiac arrest

Precautions

• High doses in patients with underlying
  cardiovascular disease can exacerbate hypoxic
  encephalopathy post resuscitation.

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Cardiac (Sympathomimetic)
Isoproterenol (Isuprel)

• Synthetic sympathomimetic
• Nearly pure ? activity (inotrope/chronotrope)
• Markedly increases myocardial O2 demand
• Not as effective as pacing
• Also used to treat bronchospasm (nebulized)
• 2-10mcg/min
• 0.1-1mcg/kg/min peds

• Indications
• Symptomatic bradycardia refractory to Atropine

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Cardiac (Sympathomimetic)
Isoproterenol (Isuprel)

• Contraindications
• -Tachydysrhythms
• -Cardiogenic Shock

Precautions

• chronotrope may induce dysrhythmias.
• Digitalis toxicity
• Patients with underlying ischemic heart disease
• May paradoxically worsen heart block (AV nodal
  disease)

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Cardiac (Vasodilator)
Furosemide (Lasix)

• Loop diuretic/venodilator
• Inhibits reabsorption of sodium and chloride
• Onset IV diuresis 10 min.
• 40-80mg IV
• 1mg/kg peds

• Indications
• Pulmonary Edema
• CHF
• Hypertensive Crisis

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Cardiac (Vasodilator)
Furosemide (Cont.)

• Contraindications
• -Anuria
• -Severe electrolyte depletion

Precautions

• Increase dose if patient already taking Lasix.
• Electrolyte imbalance/Dehydration
• Hypotension
• May induce allergic reaction in patients
  sensitive to sulfonamides

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Cardiac (Vasodilator)
Nitroglycerine (Nitrogard, Nitropaste,
Nitrostat.)

• Relaxes vascular smooth muscle via stimulation of
  cyclic GMP
• VIAGRA
• Reduces preload and afterload.
• Decreases myocardial O2 demand
• Reduces pulmonary vascular resistance
• Patient can develop tolerance
• 0.4mg SL spray/tablet x 2 prn or 2 in. paste

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Cardiac (Vasodilator)
Nitroglycerine (Cont.)

• Indications
• -Chest pain
• -CHF/Pulmonary edema
• -Hypertensive crisis

• Contraindications
• -Increased ICP

Precautions

• Headache common
• Hypotension

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Cardiac (Buffer)
Sodium Bicarbonate

• Alkalinizing agent buffers excess H ion
  concentration, raises blood Ph, reverses
  acidosis.
• Produces left shift of oxyhemoglobin dissociation
  curve.
• 1mEq/kg

• Indications
• -Acidemia during cardiac arrest and near drowning
  (after adequate airway/ventilation has been
  addressed)
• -Urine alkalinization (TCA OD, salicylates,
  lithium)

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Cardiac
Sodium Bicarbonate (Cont.)

• Contraindications
• -None during cardiac arrest

Precautions

• Will precipitate when mixed w/ calcium
• Can lead to metabolic alkalosis
• Adverse effects include hypernatremia and
  hyperosmolality.

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Cardiac (Other)
Aspirin

• Analgesic, antipyretic, antirheumatic, and
  anti-inflamatory.
• Prevents platelet aggregation
• 160mg chewed

• Indications
• -Cardiac chest pain

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

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Cardiac (Other)
Aspirin (Cont.)
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.