CLINICAL TOXICOLOGY STUDY GUIDE Approach to the Comatose Pt ABCDs: Airway, Breathing, Circulation, Disability Differential of AMS o Alcohols,

s, Arrythmias, Acid/Base disturbances o Electrolytes o Insulin o Opiates o Uremia o Trauma o Infection o Poisoning o Seizure Initial Management of Poisoning and OD ABCs Intentional vs. Accidental ingestion: if intentional, history may not be reliable Common antidotes o Opiates-Naloxone o Benzos-Flumazanil o Tylenol-NAC o OPs-Atropine, Pralidoxime o Fe-Defoxerime o Pb-DMSA o MetHgb-methylene blue o Ethylene glycol, MethanolFomepizole o INH-Pyridoxine (B6) o Digoxin-Digibind, Digifab o Cyanide-Na-nitrite, Na-thiosulfate Uppers: increase RR, HR, BP, SWEATING Anticholinergics: benadryl, OTC sleeping meds o HOT as a hare o RED as a beet o BLIND as a bat o DRY as a bone o MAD as a hatter o Increased HR o Urinary retention o NO SWEATING Delayed symptoms may be due to formation of toxic metabolites, such as tylenol DUMBELS: cholinergics, nerve agents, OPs o Diarrhea o Urination o Miosis o Bronchospasm o Emesis o Lacrimation o Salivation SLUMPEDhagma o Salicilates o Lactica Acidosis o Uremia

o Methanol o (Paraldehyde) o Ethylene Glycol o DKA Best specimen for tox screenurine. Serum levels not helpful unless its for something youd normally check for (coumadin, etc) A negative tox screen does NOT r/o toxic ingestion You are legally obligated to treat the patient whether they want you to or not! GI Decontamination and Enhanced Elimination GID must be done during pre-absorptive phase, while toxin is still in stomach. Gastric lavage position: left lateral, head down to move stomach contents into greater curvature. Contraindications to gastric lavage: loss of protective airway functions, hydrocarbon ingestion, risk of GI hemorrhage. Timing is importantsome characteristics of poison may extend effective time of GID such as sustained release drugs, inhibition of gastric emptying, forms concretions in stomach, or recent ingestion of fatty meal. Syrup of Ipecac- an OTC emetic that activates chemoreceptors in small intestine to activate vagus nerve and produce vomitingrarely recommended today. SOI is cardiotoxic when used chronically Activated Charcoal- Adsorbs poison, must physically contact poison to de-activate it. Time sensitive, does not work on some substances (alcohol, metal, hydrocarbons, inorganics), and depends on quantity given and surface area. Risks same as with GID. WBI: experimental, only used for certain ingestions MDAC: repeated administration of AC. Multiple doses given orally to increase elimination of SOME substances, classically Phenobarbital. Urine Alkalinization: for toxins excreted renally. Urine pH needs to be at least 7.5 enhances excretion of weak acids such as salicylates Hemodialysis is an option for small molecules that are water soluble and dont bind to proteins. Management of Acetominophen Toxicity Acetominophen reaches peak plasma levels in 4h Pharmacokinetics-several pathways in liver: sulfonation, glucuronidationwhen these pathways get full, 3-5% is converted to the toxic metabolite NADQI by the C-P450 MFO system Excreted by the kidneys

 Potential Liver Damage occurs: o Adults: > 150 mg/kg in acute dose o Adults: >7.5 g in 24 h chronically (may be easy to do if on multiple meds) o Children <10 years: >200 mg/kg children are more resistant to toxicity Toxicity is confirmed if a 4 hour level of 150 mcg/mL is found, and this should be treated! Treat with mucomyst of acetadose: Remember NAC loading dose is 140 mg/kg PO, maintenance at 70 mg/kg PO. o Mucomyst: PO, take q4h X 72 h, may cause nausea and vomiting o Acetadose is IV form, taken over 20 h o Do NOT discontinue the NAC early!! Toxic metabolite may persist even though acetaminophen levels nondetectable on screen. Also, late NAC is still beneficial. Stages of intoxication o Stage 130 minutes to 4 h: pt may appear normal, may have some nausea and vomiting o 224 to 48 h: liver enzymes may become abnormal, renal function deteriorates o 33 to 5 days: Nausea and vomiting reappear with a vengeance, symptoms of hepatic necrosis present (jaundice, coag deficits, renal failure) o Stage 44 days to 2 weeks: either resolution or death occurs Salicylate Toxicity Many products contain ASA, so it is easy to multi-dose on them Pharmacokinetics: H+ + Sal- HS. In an acidic environment, non-ionized forms persist, which can diffuse across CNS. o CNS levels coorelate with mortality o Try and make pt alkalotic to drive equation towards the ionized form which wont diffuse across CNS membranes Pts who OD on ASA will have an increased rate and depth of breathing, producing a compensatory respiratory alkalosis. Do NOT intubate these patients because you will take away their only means of compensating for the hagma that the ASA produced. Pathophysiology of ASA: interferes with Krebs cycle to stop production of ATP, resulting in oxidation of lipids and fats for energyketone productionheat production & hyperthermia.

Salicylate toxicity: hyperthermia, hagma, ketosis, and non-cardiogenic pulmonary edemaARDS o It is very rare to have a lifethreatening bleed in acute ASA tox How to assess severity based on ingested doseneed to know pts weight and how much ASA they took o 15 mg/kg is therapeutic o <150 mg/kg can be reached with no toxicity o 150-300 mg/kg produces mild toxicity (beginning to get hagma) o 300-500 mg/kg is severely toxic o >500 mg/kg is potentially lethal ABG in ASA tox: Respiratory Alkalosis + Metabolic Acidosis. The only other condition that produces this picture is sepsis, but in sepsis you will have very elevated lactic acid. In ASA tox, LA levels are nL to slightly increased. Treatment of acute ASA Tox: o AC for GI decontamination o Repeat AC: 50-100 g PO loading dose, followed by 20-60 g q4-6 h o Treat dehydrationmaintain UO at 2-3 ml/kg/h with D5LR or D5NS. o Remember to CORRECT K+ DEPLETION before you proceed with any other treatment o After K+ is corrected, then can try to alkalinze urine to enhance excretion o Do NOT give PO Bicarb because too much is absorbed in gut, can give Bicarb IV TCA OD Main concern is QRS widening and cardiac arrhythmia. Manage with AC and EKG. Pharmacokinetics: involves activity and effectiveness of P450, which is genetically controlled. Other meds, slower rate of metabolism in elderly can also affect the pharmacokinetics. Cardiovascular toxicity: get an EKG and look at the QRSthis is the most important step in management o QRS <100, 30% risk of seizure o QRS > 160, 50% risk of lethal arrhythmia If QRS is >100, can manage with IV Bicarb. Effectiveness is due to the Na load, not the alkalotic effects. Na loading with Esmolol is the best treatment for tachyarrhythmia! o When treating with Bicarb, pH needs to be between 7.45 and 7.55 to ensure that there is enough Na+ loading

 SSRIsserotonin syndrome produced in severe ODs o Usually occurs when pt is also taking an MAOI and/or Ltryptophan o AMS, hyperthermia, tachycardia, unstable BP, rhabdomyolysis, lactic acidosis. These pts need to be treated in MICU with aggressive fluid management and treatment for hyperthermia. Heavy Metal Toxicity Arsenic: Arsine gas is the most toxic form. Excretion occurs renally, but arsenic gets concentrated in hair, nails, and skin within 2 weeks of exposure. May cause Mees-Aldrich lines on fingernails. Treat with chelation therapyDMSA. Seafood can cause extreme arsenic levels. o Is toxic b/c it inhibits enzyme activity by binding to SH groups and uncoupling ox phos o Pts who have arsenic tox will have garlic breath, vomiting, and diarrhea. They may have such bad diarrhea that they stool themselves to death and get hypotensive. o 1-2 weeks after exposure, they can get a peripheral neuropathy o Remember blackfoot & that chronic small doses are more effective if you want to poison someone Mercuryclassic triad of chronic exposure is gingivitis & salivation, tremor, and neuropsychiatric changes. Treat with DMSA. Elemental Hg is essentially non-toxic if ingested. o Do NOT use AC for mercury tox. o 24 h urine catch specimens are helpful. Levels >300 mcg/L associated with symptoms. Leadusually seen in inner-city children. Has a long half-life: 32 years in bone and 7 years in kidney. Clinical manifestations are nonspecific, but suspect it in a kid with behavior or personality changes. May also see foot-drop. Treat with chelation with Succimer. Radiation Injury DNA is the primary target for cell damage from ionizing radiation Acute radiation syndrome o Develops after total body irradiation o May occur from internal or external radiation

Components are: hematopoeitic (1-2 Gy), GI (2-6 Gy), and Neurologic (6-8 Gy) Phases of ARS o Prodromal: minutes to hours postexposure. N/V, anorexia, diarrhea, cognitive impairment o Latent: days to weeks. Will see bone marrow depletion Lymphocyte levels drop 1st o Illness: overt illness developspneumonia, severe leucopenia, sepsis, etc. Treatment o Prussian blue for Radiogardase Ion Exchange o Chelation agents: Ca-DTPA and Zn-DTPA o KI to block uptake of radioactive I by the thyroid. o Decontamination procedure: remove clothing, wash pt with soap and water95% effective o Medical-Legal aspects of EtOH Short term memory loss occurs at BAC of 0.05% CNS depression and psychomotor impairment are proportional to blood level BAC is correlated to dose and Ideal Body Weight (Ht more impt than wt) Can decrease glycogenolysis and interfere with gluconeogenesis to decrease blood sugar Know legal aspects of drinking (DWI with standardized field sobriety test, passive alcohol sensors, whole blood concentrations) Herbal Meds in Toxicology Herbs are considered a dietary substance, therefore are not subject to regulation by the FDA. No treatment claims are made for herbals, but structure-function claims are acceptablemust apply and get approval for these. Common herbs and uses (did not include the obvious ones) o Feverfew-migraine prophylaxis o Saw palmetto-BPH o Ginger-motion sickness Herbal products have a lot of variability based on the solvent used to extract the drug from the plant part USP certification: provides some level of safety, but says nothing about a drugs effectiveness. Certification is totally voluntary, must provide ingredients and quantities. Drug must dissolve effectively and be free of harmful contaminants.

 Drug interactions with Herbalsex) St Johns Wort. Interactions due to enhanced CYP-3A and P-Gp transporter o Reduces cyclosporine levels o Reduces dig levels o Causes serotonin syndrome with SSRIs o Decreases OCP effectiveness, decreases protease inhibitor effectiveness Aristolochic acid is associated with nephrotoxicity and urothelial Ca. This was found when lots of people in Belgium took herbs to lose weight and developed renal failure. It turns out that the drugs they took had Aristolochia in them instead of S. tetrandra. Drugs of Abuse Cocaine Blocks reuptake of NE and DA Leads to excess stimulation centrally and peripherallyHYPERTHERMIAseizures o Also blocks fast Na channelscardiac arrhythmias Benzoylecgonine is the metabolite tested for on tox screenthere is nothing that causes a false + for cocaine Treatment: give benzos til they stop struggling. Can give diltiazem to prevent coronary artery ischemia, but avoid pure Bblockers Heroin Heroin is more potent than morphine, works at MU receptor Naloxone antagonizes the MU receptor Synthetic and semi-synthetic opiates (hydrocodone, oxydocodone) do not show up on routine tox screen Some opiates (meperidine, tramadol, propoxyphene) can cause seizures Amphetamines Ecstasy (MDMA) depletes serotenergic supply in the brain with chronic usedepression GHB Toxodrome of GHB: deep coma with OD, loss of protective airway reflex, hypothermia, hypoventilation, bradycardia. Awakening associated with emergence phenomenapt may be wild, throwing up, and aspirate Treatment is supportive with focus on good airway control GHB coma never lasts more than 5 hrs PCP Some cough/cold solutions can give false + for PCP on tox screen Rotary nystagmus

Ketamine There is no tox screen for ketamine Toxic plants Most commonly reported Pepperirritates skin, lungs if breathed in. No effective treatment Peace LilyCalcium oxalate crystals cause intense pain when eaten or when it gets on skin. Cold therapy most effective o Other plants with oxalate crystals: Philodendron, Dumbcane Holly2-3 berries are non-toxic, may get CNS and resp. depression with large amts Pokeweedquick onset gastroenteritis Rubber treecontact dermatitis from the sap Poison Ivytransmission is by sap transfer. Urushiol, the toxic moiety, can persist for years. Important to wash it off of clothes as it can spread to other items in laundry and cause rash when wornhot water will wash out the urushiol. Non-toxic plants: Jade, Pointsettia Most Toxic Aconite-persistant activation of Na channels can cause cardiac arrythmias. There is no anti-arrythmic proven to treat the arrhythmia. Castor beaninhibits protein synthesis. Beans must be chewed or crushed in order to be toxic. Can use WBI to get rid of the beans, but there is no antidote for their effects Poison HemlockCNS stimulation, gastritis, resp failure. Will NOT cause seizures (water hemlock will) o Always use benzos as 1st line treatment for toxic seizures Tobaccoif an adult eats 3 whole cigs (60 mg), it is a lethal dose. Toxicityvomiting, tachycardia, SEIZURES. If symptoms are mild, will resolve in about 2 h. Oleanderdig toxicity. Can cause HYPERkalemia. There is an antidoteFab. JIMSON WEED (on test)anticholinergic symptoms, which may last >48 h. 50-100 seeds = 3-6 mg of atropine. Treat with physostigmine. Water hemlockrapid onset GI symptoms, and causes seizures. Very toxic, symptoms occur 15-90 minutes post-ingestion: rhabdo, renal failure, opisthotonos, hemiballismus. There is no antidote. Cyanogenic glycosidesfruit pits. Must crush or chew pit for it to be toxic. Causes a cyanide toxicity, cells cant use O2 so you will get hypoxic. Will not bind to AC Nightshadelate GI contamination, with or without co-existing anticholinergic symptoms Rhododendronazaleasmay cause seizures

Hazmat Review Definition of hazardous materials any substance or material capable of posing an unreasonable risk to health, safety, and property Always approach site from a distance visually inspect from a distance before rushing in Placards are used by DOT to ID hazards in 9 categories (explosives, gases, flammables, etc) MSDS are required for each chemical produced, stored, used and transported in the US. They contain info for safe handling and storage of the chemical. These forms must be in the workplace where chemicals are used! HazMat response Site survey: should be done from a distance, uphill and upwind of the site. Initial assessment and control of site is critical to safety DO NOT: stage too close to an explosive hazard, stage downhill or downwind, enter without proper protection, contact contaminated victim without proper protection, or fail to evacuate areas close to the scene Safety Zones Hot (red) zone: highest degree of contaminationMUST wear appropriate protective equipment to enter. Suit is completely self-contained with its own O2 supplyLevel A equipment. Warm (yellow) zone: limited-access, protective equipment still requiredlevel B equipment, chemical resistant but not impervious (a firefighter in his fire suit is considered to be in level B equipment). This is where victims are decontaminated and initial pt. contact occurs Cold (green) zone: support area, minimal protective equipment required. Restricted to emergency personnel only. Level C equipment consists of hooded chemical resistant suit, air purifying respirator (NOT a supplied air respirator). Level D equipmentwork clothes Snakebite management in Louisiana Venomous vs. non-venomous snakes Pit vipers have a heat seeking pit between the nostril and eye, harmless snakes do not Vipers have elliptical pupils, harmless snakes have round pupils Vipers have fangs, harmless snakes do not Vipers have a single row of plates distal to the anal plate, harmless snakes have double row of plates distal to anal plate Types of venomous snakes in LA Cottonmouth

Copperhead Eastern Diamondback Rattlesnake (these probably arent in LA anymore) Canebrake rattlesnake First Aid for Snakebites Put victim at rest Reassurance Attempt to ID snake (but dont catch it if you cannot!) Watch for untoward rxns Record edema progression q15 minutes Transport to nearest medical facility DO NOT: Do incision and suction Immerse in ice Put on a tourniquet THE MOST IMPORTANT THING IS TO GET THE VICTIM TO A HOSPITAL ASAP Grading of evenomation Minimal: swelling confined to area of bite (within 8 cm circumference) at 30-60 minutes, no paresthesias or fasciculations, minor pain only, no ecchymoses or blebs, no abnormal lab findings Moderate: progressively enlarging after 90 minutes, may have perioral paresthesias and minimal lab abnormalities. The swelling is progressive of the extremity. Severe: systemic signs and symptoms (hypotension, LOC), marked lab abnormalities, rapid progression of local findings OR progression despite treatment for moderate evenomation. Wyeth crotalid antivenom Polyvalent horse serum that contained IgGs and caused serum sickness CroFab Ovine derived, mixed monospecific crotalid antivenom. Consists of highly purified venom-specific Fab fragments, minimal serum sickness reported Venom of the Mojave, Western diamondback, Eastern diamondback, and water moccasin injected into sheeppurified Abs collected Is expensive ($900/vial), but limits local tissue destruction and is not likely to cause anaphylactic rxns. Coral snake identification Red on Black=friendly Jack Red on Yellow=Kill a fellow Elapid evenomation (coral snakes) This venom is neurotoxic and all pts should be observed for at least 6 hours for sings of respiratory depression! Organophosphate Physiology Remember DUMBELSsee above

 Parasympathetic NS: presynaptic release of Achpostsynaptic release of Achmuscles, causes muscarinic symptoms Sympathetic and Somatic NS works through NorE and Epi to cause nicotinic symptoms Acetylcholine Esterase is an enzyme that quickly inactivates Ach in the NMJ, without AchE there would be no way to control effects of Ach (sweating, drooling, diarrhea, etc) Ach release at the motor end plate causes muscle fibers to contractif there is no AchE to deactivate the Ach at the muscle fiber, the muscle will stay contracted which makes it get fatigued and causes fasiculations, and eventually paralysis. ORGANOPHOSPHATES act by DE-ACTIVATING Ach Esterase o The goal of treatment is to get the OP off of the AchE so it can be active again. If the OP stays attached to the AchE for too long (aging, it becomes permanently attached and the AchE is destroyed and cannot be re-used. It takes a long time to make new AchEabout 1-2% increase in stores per day. Atropine is a competitive antagonist of muscarinic effectsmay have to use very large amounts in OP poisoning o Atropine binds to the postsynaptic neuron receptors and

prevents Ach from binding. BUT, there are NO ATROPINE RECEPTORS on the muscle fibers, so atropine WILL NOT PREVENT FASICULATIONS! Pralidoxime (2-PAM) reverses the phosphorylation of cholinesterase enzyme by the OP, it has to be given to get the OP off of the AchE before it ages too long and gets stuck. It is most effective when given within 24 hours of exposure, and works synergistically with atropine. 2-PAM causes the OP to release from the AchE so the AchE can be re-used. o It takes at least 30% of your normal AchE levels just to breathe on your own, so it is important that these are recycled and dont have to be made from scratch! Diagnostic studies to help confirm OP tox? o RBC cholinesterase, plasma cholinesterase. These are difficult to interpret without baseline levels, so anyone who works around OPs needs to get pre-employment levels drawn.