Revisiting Pharmacological Principles DANIEL BECKER, DDS MIAMI - - PDF document

Revisiting Pharmacological Principles

DANIEL BECKER, DDS

MIAMI VALLEY HOSPITAL DAYTON, OH

DEBECKER@PREMIERHEALTH.COM

• Comfort Level of Practitioner ?
• EMS Response Times ?
• Dental Board Requirements ?

Drug Kits

 Preparations ?

• Amps
• Vials
• Prefilled Syringes

 Routes ?

• IV
• IM
• SC
• SLI

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.” “Solutions and suspensions are generally less stable but in one report, four outdated samples of atropine solution (three up to 12 years past expiration were all found to contain significant amounts of the drug.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

• r discolored or show signs of precipitation,

particularly injectables, should not be used.” “One study found that EpiPens 3-36 months past their expiration dates contained 84.2- 101.5% of the labeled dose.”

Med Lett Drugs Ther. 2015 Dec 7;57(1483):164-5

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Chest Pain Sedation Reversal Bradycardia/Hypotension Allergy / Asthma Hypertension Stroke

Airways, Suction, Extra Syringes, Stethoscope.

Cardiac Arrest Algorithm

Emergency Kit

Remove Cases

Breathing ? Assess ! Triple Airway: Head Tilt / Chin Lift / Jaw Thrust

YES NO

SpO2 ≥ 95 SpO2 < 95

#1 ↑ Supplemental O2

• Cannula 4-6 L/min
• NRB 6-10 L/min

#2 Assist Ventilation

• BVM 10-15 L/min

 Consider Reversal  Support  Consider Reversal SpO2 ≥ 95 ?  BVM Ventilation AND Reversal !  If No, Add Adjunct: #1 Oral Airway #2 Supraglottic Airway Chest Rise ? Opioid Reversal Naloxone 0.4 mg/ 1 mL x 2 (SLI, IV) BZ Reversal Flumazenil 0.2 mg / 2 mL x 5 (SLI, IV)

Sedation Reversal Algorithm

• 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 !

Reversal Agents

Flumazenil Naloxone Formulation 0.1 mg/mL 0.4 mg/mL Conventional Dose 0.2 mg (2 mL) 0.4 mg (1 mL) Incremental Doses 0.1 mg (1 mL) 0.2 mg (0.5 mL)

Opioids Naloxone Fentanyl Alfentanil Remifentanil Distribution T1/2α (min) 5-8 m 9.2-19 m 9.5-17 m 2.0-3.7 m Elimination T1/2β (hr) 0.5-1.5 h 3.1-6.6 h 1.4-1.5 h 0.17-0.33 h Sedatives Flumazenil Midazolam Diazepam Distribution T1/2α (min) 4-11 m 7-15 m 10-15 m

Data from Miller’s, Barash, et al.

Elimination T1/2β (hr) 0.4-1.4 h 1.7-2.6 h 20-50 h Brain Muscle, Fat

Duration for CNS Effects

 Determined by time at site, not by time in body  Distribution time (T1/2α), not Elimination time (T1/2β)  How many T1/2 Required? (1-4?)

Eliminate Kidney, Liver Distribute & Redistribute Distribute

Becker DE. Emergency Drugs 1

• Rapid reversal may lead to nausea/vomiting.
• Resedation following flumazenil is overstated

and is dose-dependent.

Flumazenil

“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
• f fentanyl or remifentanil.
• Concerns regarding pulmonary edema only when no

local anesthesia present.

Naloxone

“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

• 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

• Bronchospasm may be attributed to asthma, COPD, anaphylaxis
• r aspiration.
• Selective Beta-2 agonists ideal but epinephrine (per anaphylaxis)

also acceptable. Albuterol: Terbutaline: (?)

• Act as muscarinic (M) receptor

antagonists, blocking parasympathetic influences.

Anticholinergics

Presynaptic & Postsynaptic Muscarinic Receptors Subtype Location Subtype Location M1 Presynaptic M3 Glands M2 Heart M4,5 CNS

Anticholinergic Drugs

Drug Adult Dose (IV) Duration CNS

(M4,5)

Heart

(M2)

Secretions

(M3)

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 2011. Glick DB. The Autonomic Nervous System. In: Miller's Anesthesia. 7th edition 2009.

Atropine for Bradycardias

• Acts by blocking vagal influence on

heart

• Effective:
• Sinus bradycardia
• 1st degree AV block
• 2nd degree Mobitz I AV block

 Ineffective for higher degree blocks: Mobitz II and 3rd degree

Becker DE. Emergency Drugs 2

Vasopressors act as adrenergic receptor agonists, mimicking sympathetic influences.

Epinephrine Ephedrine Phenylephrine Action α, β1, β2 α, β1, β2 and Indirect α Duration 3-5 min 1-2 hr 15 min Formulation 1 mg/mL 50 mg/mL 10 mg/mL Dosage (IV) 10 mcg increments or 2-10 mcg/min 10 mg increments 0.1 mg increments

Mean Arterial Pressure

Diastolic Blood Pressure [ Arterial Resistance ] Systolic Blood Pressure [ Cardiac Output = HR x SV ]

▪Sympathetic (Beta-1) ↑ ▪Parasympathetic (Cholinergic) ↓ Stroke Volume Heart Rate

Pulmonary Circuit

• 1. Preload (+)

▪ Venous Return ▪ Venoconstriction ↑ ▪ Venodilation ↓

• 3. Afterload (DBP)

▪ Arterial Constriction ↑ (alpha) ▪ Arterial dilation ↓ (Beta-2) ▪ Negative influence

• 2. Contractility (+)

▪ Sympathetic (Beta-1)

1 2 3

Phenylephrine ~ Ephedrine ~ HR SBP DBP HR SBP DBP

DBP - Beta2 vs Alpha A A SBP - Beta1 vs Alpha (veins

preload + reflex response to afterload)

B B HR – Beta1 vs Reflex to MAP C C

Cardiac Output (L/Min)

Ephedrine Phenylephrine Formulation 50 mg/mL 10 mg/mL Dosage 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

Use Tuberculin Syringe:

Drug Administration

Epinephrine IM Epinephrine IV 1:1000 1:10,000 1 Gm / 1000 mL 1 Gm / 10,000 mL 1000 mg / 1000 mL 1000 mg / 10,000 mL 1 mg / mL 0.1 mg / mL (1000 mcg / mL) (100 mcg / mL)

This concentration ONLY for Cardiac Arrest !

Lieberman P, et al. J Allergy Clin Immunol 2010; 126(3):477-80. e1-42. Marx JA, et al. Rosen's Emergency Medicine 8th Ed 2014

0.3 mg (0.3mL) IM for anaphylaxis

For Hypotension or severe anaphylaxis MUST dilute ! (10 mcg increments or 2-10mcg/min infusion)

1 mg (10 mL) IV for Cardiac Arrest

• Use tuberculin syringe
• Draw 0.1 mL = 100 mcg
• Dilute to 1 mL
• 0.1 mL = 10 mcg/min
• 1mg (1mL) in 500 or 250mL of

normal saline or D5W

• Provides 2or 4 mcg/mL

respectively (1-2 mL/minute)

• URGENCY if No Symptoms
• Rarely Require Treatment
• Address Possible Causes

for Sudden Elevation

Antihypertensives

“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;41:530-31

• EMERGENCY if Symptoms
• Headache, Paresthesia,

Chest Pain

• EMS Transport

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

* * *

Becker DE. Emergency Drugs 3

Antidysrhythmics

 Ca Blockers  Beta Blockers  Digoxin  Anticoagulation ?  Vagal Maneuvers  Adenosine  Ca Blockers  Beta Blockers  Procainamide  Amiodarone  Sotalol  Lidocaine

Stable

Narrow Complex Regular (SVT) Irregular (A. Fib/Flutter) Wide Complex

• r Known VT

Unstable Patients, i.e., severe hypotension, require cardioversion ACLS Guidelines:

Reasonable Choices

Drug Dosage Action Adenosine 6 mg / 12 mg Depresses SA & AV nodes Esmolol 20-30 mg Blocks Beta-1 Receptors Lidocaine 0.5-1 mg/kg Depresses Ventricular Foci Amiodarone 150 mg (10 min.) Depresses Atrial and Ventricular Foci / Alpha & Beta Blocker

?

Adenosine

• 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
• T1/2 <10 Seconds
• 6 mg Rapid Bolus.
• 12 mg Bolus if No

Response

• 3 mg/mL in 2 mL Vials

Facts & Comparisons 2016

Glucose Options

• Expensive ($150-200)
• Triggers glycogenolysis and therefore

ineffective if poor glycogen stores

• IM: 1 mg (20-30 min)
• IV: 0.5 mg (10-20 min) Nausea!
• IV: 25-50 mg slow IV

infusion (1 mL/min)

• High osmolarity causes

venous irritation!

Drug Facts and Comparisons 2016

50% Dextrose Glucagon

• Vasodilation (Veins > Arteries)
• Reduces MVO2 (preload & SBP)
• 0.4 mg tabs ( 1 tab Q5H x 3)
• 160-300mg provides complete

platelet cyclooxygenase inhibition < 1 Hr

• Action presystemic within portal

system

• 4 baby asa chew and swallow
• Reduce pain/anxiety
• Reduces MVO2
• Morphine 2.5mg = fentanyl 25 mcg

Nitroglycerin Aspirin Opioids

Anti-Anginals

Anticonvulsants

• Midazolam IM versus Lorazepam IV
• >40 kg - midazolam 10mg lorazepam 4 mg
• 13-40 kg – midazolam 5 mg lorazepam 2 mg
• Equivalent safety and efficacy

Silbergleit R. et al. NEJM 2012;366(7): 591-600. Tintinalli JE, et al. Tintinalli’s Emergency Medicine. 8th ed. 2016

• Midazolam IM
• >40 kg – 10 mg
• <40 kg – 5 mg
• Midazolam IV: 2 mg/min increments

Becker DE. Emergency Drugs 4