Revisiting Pharmacological Principles

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1 Revisiting Pharmacological Principles DANIEL BECKER, DDS MIAMI VALLEY HOSPITAL DAYTON, OH

2 Drug Kits Preparations? Amps Vials Prefilled Syringes IV IM SC SLI Remove Cases Sedation Reversal Cardiac Arrest Algorithm Bradycardia/Hypotension Assess! Breathing? Allergy / Asthma One study found that EpiPens 3-36 months past their expiration dates contained % of the labeled dose. Sedation Reversal Algorithm Emergency Kit Airways, Suction, Extra Syringes, Stethoscope. Med Lett Drugs Ther Dec 7;57(1483):164-5 Solutions and suspensions are generally less stable but in one report, four outdated samples of atropine solution (three up to 12 years past expiration were all found to contain significant amounts of the drug. Drugs in solution that have become cloudy or discolored or show signs of precipitation, particularly injectables, should not be used. Routes? Expiration Dates Many solid drugs stored under reasonable conditions in their original unopened containers retain 90% of their potency for at least 5 years after the expiration date on the label, and sometimes much longer. Comfort Level of Practitioner? EMS Response Times? Dental Board Requirements? Triple Airway: Head Tilt / Chin Lift / Jaw Thrust YES NO Chest Pain Hypertension SpO2 95 Stroke Support Consider Reversal Item# Case Photo Storage Carrier $32.99 / ($46.05 Tax/Shipping) Cannula 4-6 L/min NRB 6-10 L/min #2 Assist Ventilation BVM L/min Consider Reversal The Container Store ( ) BVM Ventilation AND Reversal! Chest Rise? SpO2 95? If No, Add Adjunct: #1 Oral Airway #2 Supraglottic Airway Opioid Reversal www. Containerstore.com 0.4 mg/ 1 ml x 2 (SLI, IV) Duration for CNS Effects Reversal Agents Act as receptor antagonists. When control of airway and ventilation are difficult, or unconsciousness is not intended. Generally eliminate opioid first BUT must consider BZ or Opioid dependence! BZ Reversal Opioids Conventional Dose 0.4 mg/ml 0.4 mg (1 ml) Distribution T1/2α (min) Incremental Doses 0.1 mg (1 ml) 0.2 mg (0.5 ml) Distribution T1/2α (min) Elimination T1/2β (hr) Sedatives Elimination T1/2β (hr) 0.2 mg / 2 ml x 5 (SLI, IV) Brain Distribute Determined by time at site, not Distribute & by time in body Redistribute Distribution time (T1/2α), not Elimination time (T1/2β) How many T1/2 Required? (1-4?) 0.1 mg/ml 0.2 mg (2 ml) SpO2 < 95 #1 Supplemental O2 Muscle, Fat Kidney, Liver Eliminate Fentanyl Alfentanil 5-8 m m m m h h h h Midazolam Diazepam 4-11 m 7-15 m m h h h Remifentanil Data from Miller s, Barash, et al. 1

3 Rapid reversal may lead to nausea/vomiting. Resedation following flumazenil is overstated and is dose-dependent. Resedation is least likely in cases where flumazenil is administered to reverse a low dose of a short-acting benzodiazepine (less than 10 mg midazolam). It is most likely in cases where a large single or cumulative dose of a benzodiazepine has been given in the course of a long procedure along with neuromuscular blocking agents and multiple anesthetic agents. (Facts & Comparisons 2016) Renarcotization not an issue with conventional doses of fentanyl or remifentanil. Concerns regarding pulmonary edema only when no local anesthesia present. Excessive dosage may result in significant reversal of analgesia and increase in blood pressure. Similarly, too rapid reversal may induce nausea, vomiting, sweating or circulatory stress. (Facts & Comparisons 2016) Bronchodilators Anticholinergics Bronchospasm may be attributed to asthma, COPD, anaphylaxis or aspiration. Selective Beta-2 agonists ideal but epinephrine (per anaphylaxis) also acceptable. Albuterol: Terbutaline: (?) Full expiration Activate with full inspiration Hold breath 6-10 sec Repeat 2-4 times SC: 0.25 mg repeat 15-30min If IV (tocolysis): 5 mcg/min x 5 Act as muscarinic (M) receptor antagonists, blocking parasympathetic influences. Presynaptic & Postsynaptic Muscarinic Receptors Subtype Location Subtype Location M 1 Presynaptic M 3 Glands M 2 Heart M 4,5 CNS Anticholinergic Drugs Drug Adult Dose (IV) Duration CNS (M 4,5 ) Heart (M 2 ) Secretions (M 3 ) Atropine 0.5 mg 15-30min Scopolamine 0.3 mg 30-60min +++ 0,+ +++ Glycopyrrolate 0.2 mg 2-4hr Atropine is also available in concentrations of 0.3 and 0.4mg/mL but doses lower than 0.5 mg may be associated with paradoxical vagotonic effects that result in further slowing of heart rate! Brown JH, Laiken N. Muscarinic Receptor Agonists and Antagonists. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th edition Glick DB. The Autonomic Nervous System. In: Miller's Anesthesia. 7th edition Atropine for Bradycardias Acts by blocking vagal influence on heart Effective: Sinus bradycardia 1 st degree AV block 2 nd degree Mobitz I AV block Ineffective for higher degree blocks: Mobitz II and 3 rd degree 2

4 Action α, β1, β2 Duration 3-5 min Dosage (IV) 1 mg/ml 10 mcg increments or 2-10 mcg/min Ephedrine Phenylephrine α, β1, β2 and Indirect 1-2 hr 15 min 50 mg/ml 10 mg/ml 10 mg increments 0.1 mg increments α Drug Administration Dosage Use Tuberculin Syringe: Ephedrine Phenylephrine 50 mg/ml 10 mg/ml 10 mg increments 0.1 mg increments 0.1 ml = 5 mg 0.1 ml = 1 mg Dilute to 1 ml 0.1mL = 0.1 mg Stroke Volume Epinephrine Ephedrine ~ Mean Arterial Pressure Heart Rate Vasopressors act as adrenergic receptor agonists, mimicking sympathetic influences. Systolic Blood Pressure [ Cardiac Output = HR x SV ] Diastolic Blood Pressure [ Arterial Resistance ] C 2. Contractility (+) Sympathetic (Beta-1) 2 1 HR HR Sympathetic (Beta-1) Parasympathetic (Cholinergic) 1. Preload (+) Pulmonary Circuit Venous Return Venoconstriction Venodilation Phenylephrine ~ SBP B DBP A SBP DBP 3 Cardiac Output (L/Min) A DBP - Beta2 vs Alpha 3. Afterload (DBP) B SBP - Beta1 vs Alpha (veins Arterial Constriction (alpha) Arterial dilation (Beta-2) Negative influence preload + reflex response to afterload) C HR Beta1 vs Reflex to MAP Epinephrine IM 1: Gm / 1000 ml 1000 mg / 1000 ml 1 mg / ml (1000 mcg / ml) Epinephrine IV 1:10,000 1 Gm / 10,000 ml 1000 mg / 10,000 ml 0.1 mg / ml (100 mcg / ml) 0.3 mg (0.3mL) IM for anaphylaxis 1 mg (10 ml) IV for Cardiac Arrest This concentration ONLY for Cardiac Arrest! For Hypotension or severe anaphylaxis MUST dilute! (10 mcg increments or 2-10mcg/min infusion) Use tuberculin syringe Draw 0.1 ml = 100 mcg Dilute to 1 ml 0.1 ml = 10 mcg/min 1 mg (1 ml) in 500 or 250 ml of normal saline or D5W Provides 2 or 4 mcg/ml respectively (1-2 ml/minute) Lieberman P, et al. J Allergy Clin Immunol 2010; 126(3): e1-42. Marx JA, et al. Rosen's Emergency Medicine 8th Ed 2014 Antihypertensives URGENCY if No Symptoms Rarely Require Treatment Address Possible Causes for Sudden Elevation EMERGENCY if Symptoms Headache, Paresthesia, Chest Pain EMS Transport The most sensible approach to the patient in the ED found to have very high blood pressure, without evidence of acute end organ damage, is referral for outpatient management of serious disease that needs to be treated; not urgently, but for life. Focusing on the height of the column of mercury in the sphygmomanometer confers no demonstrable benefit on the patient and risks doing harm. Gallagher EJ. Ann Emerg Med 2003;41: Antihypertensives Nitroglycerin (1 tab Q5min) Venodilation reduces preload Esmolol (20-30mg Q2-3min) Beta-1 Blocker reduces HR and contractility Labetalol (10-20mg Q3-5min) Beta-1, Beta-2 and Alpha Blocker Reduces contractility, venodilation reduces preload and arterial dilation reduces arterial resistance Caution: Beta -2 blockade may produce bronchospasm & epinephrine interaction 3

5 Antidysrhythmics Unstable Patients, i.e., severe hypotension, require cardioversion Stable ACLS Guidelines: Wide Complex or Known VT Narrow Complex Regular (SVT) Irregular (A. Fib/Flutter) Vagal Maneuvers Ca Blockers Beta Blockers Ca Blockers Beta Blockers Digoxin Anticoagulation? Action/Effects Coronary Vasodilation Depresses SA and AV Nodes. and accessory AV Pathways Not reversed by Atropine Side Effects Facial Flushing (18%) Dyspnea (12%) Chest Pain (7%) Bronchospasm in Asthmatics Procainamide Amiodarone Sotalol Lidocaine T1/2 <10 Seconds 6 mg Rapid Bolus. 12 mg Bolus if No Response 3 mg/ml in 2 ml Vials Reduce pain/anxiety Reduces MVO2 Morphine 2.5mg = fentanyl 25 mcg Nitroglycerin Aspirin mg provides complete platelet cyclooxygenase inhibition < 1 Hr Action presystemic within portal system 4 baby asa chew and swallow Opioids Anti-Anginals Drug Esmolol Dosage 6 mg / 12 mg mg Action Depresses SA & AV nodes Blocks Beta-1 Receptors Lidocaine mg/kg Depresses Ventricular Foci Amiodarone 150 mg (10 min.) Depresses Atrial and Ventricular Foci / Alpha & Beta Blocker? Glucose Options Glucagon Facts & Comparisons 2016 Vasodilation (Veins > Arteries) Reduces MVO2 (preload & SBP) 0.4 mg tabs ( 1 tab Q5H x 3) Reasonable Choices 50% Dextrose IV: mg slow IV infusion (1 ml/min) High osmolarity causes venous irritation! Expensive ($ ) Triggers glycogenolysis and therefore ineffective if poor glycogen stores IM: 1 mg (20-30 min) IV: 0.5 mg (10-20 min) Nausea! Drug Facts and Comparisons 2016 Anticonvulsants Midazolam IM versus Lorazepam IV >40 kg - midazolam 10mg lorazepam 4 mg kg midazolam 5 mg lorazepam 2 mg Equivalent safety and efficacy Silbergleit R. et al. NEJM 2012;366(7): Midazolam IM >40 kg 10 mg <40 kg 5 mg Midazolam IV: 2 mg/min increments Tintinalli JE, et al. Tintinalli s Emergency Medicine. 8th ed