Overview of Pre hospital Pharmacology

Overview of Pre-hospital Pharmacology Lynn K. Wittwer, MD, MPD Clark County EMS 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  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.  Cyanide Poisoning  Antidote – Nitrites and Sodium Thiosulfate Sodium Nitrite Oxyhemoglobin Rhodanase Sodium Thiosulfate Thiocyanate Kidneys Methemoglobin Cyano-methemoglobin CYTOCHROME OXIDASE CN CELL 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. Cyanide Poisoning •Contraindications: Amyl Nitrite (Cont.) -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. 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. 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. Rapid Sequence Induction Neuromuscular Junction   Dailey; The Airway; Emergency Management 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 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 Rapid Sequence Induction Succinylcholine (Cont.) •Indications: -Facilitate intubation w/ failed prior attempt •Contraindications: -Primarily any condition preventing ventilation/intubation Rapid Sequence Induction Succinylcholine Precautions •Hyperkalemia/Renal failure. •Glaucoma. •Transient hyperthermia. •Pseudocholinesterase deficiency •Not to be used in multiple doses as a long-term agent (Cont.) •Missing the tube may lead to personal injury 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 Rapid Sequence Induction Vecuronium •Contraindications: (Cont.) -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 < 1 yr. more sensitive. 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) Controlled Medications Midazolam (Cont.) •Indications -Seizures -Sedation prior to pacing, cardioversion, RSI. -Sedation in cocaine toxicity •Contraindications -Acute narrow angle glaucoma 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. 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 Controlled Medications Morphine Sulfate (Cont.) •Indications -Chest pain -CHF/PE. -Musculoskeletal pain •Contraindications -Known allergy 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 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 Antipsychotic Haloperidol (Cont.) •Indications -Sedation to facilitate restraint of combative patient •Contraindications -Known allergy -Parkinsons disease -No Benadryl available 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 Promethazine •Phenothiazine derivative Antiemetic (Phenergan) •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 Promethazine •Indications Antiemetic (Cont.) -Antiemetic -Adjunct for pain control (adjust narcotic dose accordingly) •Contraindications -Hypersensitivity to Phenergan or Phenothiazines -Not to be given SC -Intra-arterial Promethazine Precautions Antiemetic (Cont.) •Should not be used in pt. less than 2. •Interactions w/ MAOI’s may lead to increased EPS. •Treat w/ Benadryl •Can cause hypotension •Use w/ caution in pt’s w/ sulfite allergy (additive). Diphenhydramine Antihistamine (Benadryl) •Competitive antihistamine @ 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 Diphenhydramine •Contraindications Antihistamine (Benadryl) -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 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 < 6 yr (or < 21 kg) 0.1 mg/kg 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 50% Dextrose in H2O •CNS energy source Miscellaneous (D50/W) •Transports Potassium across cell membrane •25gm IV  Peds 0.5 gm/kg (use D25/W for infant) •Indications -Hypoglycemia (<60 mg/dl) -ALOC -Hyperkalemia 50% Dextrose in H2O •Contraindications Miscellaneous (Cont.) -Diabetic coma Precautions •Increased ICP. •Hypertonic solution •Hypoglycemia may recur. •Take follow-up BGL prior to signing the refusal Miscellaneous Acetaminophen •Analgesic/Antipyretic •Inhibits hypothalamic prostaglandin synthetase •Metabolized by the liver  Peds 20 mg/kg suppository  Remove foil prior to insertion •Indications -Fever > 103 Miscellaneous Acetaminophen •Contraindications -Known hypersensitivity Precautions •Used as directed, rarely causes toxicity Activated Charcoal •Carbon from organic material Miscellaneous (Actidose) -Activated = fine network of pores •Greater surface area increases absorptive properties •50 gm po  Peds 1 gm/kg •Indications -Ingestion Activated Charcoal •Contraindications Miscellaneous (Actidose) -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) 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 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. 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 dc’d Abciximab (Reo Pro) Eptifibatide (Integrilin) Tirofiban (Aggrastat) 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 Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Quinapril, Ramipril, Trandolapril ACE Inhibitors •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 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 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 Acebutolol, Atenolol, Betaxolol, Bisoprolol, Carteolol, Esmolol, Labetalol, Metoprolol, Nadolol, Penbutolol, Pindolol, Propranolol, Sotalol, Timolol BETA Blockers •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 BETA Blockers •Indications •Hypertension •Angina •Cardiac Arrythmias •AMI •Contraindications •CHF/PE •Heart block, high degree •Hypotension •Acute asthma/severe COPD 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. 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 Calcium Channel Blockers •Indications – Agent specific •Hypertension •Angina, vasospastic (Prinzmetals) •Cardiac Arrythmias •AMI •Subarachnoid hemorrhage •Migraine headache •Variety of other ailments 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 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: