Overview of Prehospital Pharmacology

Overview of Pre-hospital Pharmacology Lynn K. Wittwer, MD, MPD Clark County EMS 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 Cholinergic System  Vagus (Ach) – Asthma bronchoconstriction bronchial tone – at rest cholinergic stimulation predominates muscle mass  Histamines (H1) bronchoconstriction  Bronchoconstriction requires intracellular Ca Adrenergic System  Weak a adrenergic bronchoconstriction pathway may mucous production b adrenergic innervation to pulmonary  vasculature  b receptors 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 Immunology LATE  Inflammation, edema, bronchoconstriction, increased mucus 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 Respiratory Albuterol •Contraindications: -Known hypersensitivity Cont. Precautions •May cause paradoxical bronchoconstriction. •Use cautiously in patients with cardiac disease (monitor vitals closely. •Palpitations, anxiety, nausea, and dizziness. 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 Respiratory •Contraindications: Atrovent (Cont.) -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 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 Cellular Metabolism Cyclic AMP inhibits bronchoconstriction –Binds intracellular Ca to cell membrane Cyclic AMP adenyl cyclase Adenylate Cyclase (enzyme) ATP AMP phosphodiesterase cAMP 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. 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 <20kg) •Indications: -Croup -Post intubation stridor Precautions •Similar to Epi. •Re-occurrence of subglottic edema 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 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. 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 Cardiac Atropine (cont.) •Contraindications -Asymptomatic bradycardia Precautions •High degree AV blocks. •Glaucoma. •May increase myocardial Oxygen demand. 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 Cardiac •Contraindications (Antidysrhythmics) Adenosine (Cont.) -2° & 3° heart block -Hypersensitivity Precautions •Dipyridamole (persantine) potentiates it’s effect. •Antagonized by methylxanthines. •May cause transient asystole or other FLB’s during conversion. 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 Cardiac •Indications (Antidysrhythmics) Lidocaine (Cont.) -Ventricular dysrhythms; PVC’s, V-tach, V-fib, WCT -Topical anesthetic; pleural decompression, facilitate intubation, etc -RSI •Contraindications -Heart block -WPW -Allergy -Dysrhythm prophylaxis Cardiac Precautions (Antidysrhythmics) Lidocaine (Cont.) •Reduce dose in renal/hepatic impaired, CHF, reduced CO, and >70 yo, . •CNS depression if >3mg/kg •Adverse reactions include seizure, tinnitus, euphoria, visual disturbances, agitation, and twitching 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 PVC’s Cardiac •Contraindications (Antidysrhythmics) Bretylium (Cont.) -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 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 DTR’s) •Mag toxicity can be antagonized w/ Calcium •Do not mix w/ NaHCO3 or Calcium Cardiac •Indications -V-tach, V-fib; -PVC’s, TCA OD; -ETOH Sz; (Antidysrhythmics) Magnesium Sulfate (Cont.) 2gm bolus 2gm/100cc over 5-20min 2gm/100cc over 20min -WCT, Status Asthma; 2gm/100cc over 4-5min -Ecclamptic Sz; •Contraindications -Heart block 2 gm/100cc over5-10min -Recent MI (myocardial damage) Cardiac Precautions (Antidysrhythmics) Magnesium Sulfate (Cont.) •Use w/ caution in impaired renal function •Rapid administration can cause; flushing, sweating, bradycardia, hypotension •Toxicity; hyporeflexive, flaccid paralysis, circulatory collapse, and respiratory paralysis 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 PVC’s, V-tach, V-fib, WCT Cardiac •Contraindications -Heart block -Lupus (Antidysrhythmics) Procainamide (Pronestyl.) -Torsade de pointes Precautions •Discontinue administration if; QRS widens by 50%, no ectopy, BP <90, or max dose •Administer w/ caution in the face of MI •Hypotension •Potential to cause hematologic disorders (agranulocytosis, leukopenia) Cardiac (Vasopressor) Dopamine (Intropin) •Endogenous catecholamine; precursor of norepi. •Stimulates dopaminergic, b1,and a receptors depending on dose: -Low; cerebral, renal, mesenteric vasodilation -Mid; +inotropy; increased CO -High; a effect; increased SVR •5-20mcg/kg titrate •Indications -Non-hypovolemic shock Cardiac •Contraindications (Vasopressor) Dopamine (Intropin) -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 MOI’s 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 Cardiac (Sympathomimetic) Epinephrine (Cont.) •Contraindications: -None in cardiac arrest Precautions •High doses in patients with underlying cardiovascular disease can exacerbate hypoxic encephalopathy post resuscitation. Cardiac (Sympathomimetic) Isoproterenol (Isuprel) •Synthetic sympathomimetic •Nearly pure b 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 Cardiac •Contraindications (Sympathomimetic) Isoproterenol (Isuprel) -Tachydysrhythms -Cardiogenic Shock Precautions •+chronotrope; may induce dysrhythmias. •Digitalis toxicity •Patients with underlying ischemic heart disease •May paradoxically worsen heart block (AV nodal disease) Cardiac •Loop diuretic/venodilator (Vasodilator) Furosemide (Lasix) •Inhibits reabsorption of sodium and chloride •Onset IV diuresis 10 min. •40-80mg IV 1mg/kg peds •Indications: -Pulmonary Edema -CHF -Hypertensive Crisis Cardiac •Contraindications -Anuria (Vasodilator) Furosemide (Cont.) -Severe electrolyte depletion Precautions •Increase dose if patient already taking Lasix. •Electrolyte imbalance/Dehydration •Hypotension •May induce allergic reaction in patients sensitive to sulfonamides 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 Cardiac •Indications (Vasodilator) •Contraindications Nitroglycerine (Cont.) -Chest pain -CHF/Pulmonary edema -Hypertensive crisis -Increased ICP Precautions •Headache common •Hypotension 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) 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. Cardiac •Prevents platelet aggregation •160mg chewed •Indications -Cardiac chest pain •Contraindications -Active bleeding ulcer -Known allergy -Sinusitis/Asthma (Other) Aspirin •Analgesic, antipyretic, antirheumatic, and antiinflamatory. Cardiac Precautions (Other) Aspirin (Cont.) •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.