Acetaminophen
Peak concentration usually within 4 hours post ingestion
Metabolized first by hepatic glucuronidation/sulfation then after saturation, toxicity develops
from formation of intermediate N-acetyl-p-benzoquinonimine (NAPQ1) by the CYP450 system
NAPQ1 is detoxified by glutathione
NAPQ1 is DIRECTLY toxic to kidney and liver
Hepatic Zone 3 (centrilobular) is first/most affected by toxicity
Toxicity produced at 7.5g in adults or 150 mg/kg in children
Phase 1 – Nonspecific symptoms, N/V, malaise, fatigue
Phase 2 – Begins at 24 hrs. Increased AST. RUQ pain
Phase 3 – Begins at 72 hrs. Hepatic encephalopathy, coag defects, jaundice, renal failure
Phase 4 – Begins at day 4. Recovery phase if damage was reversed. If not, death.
Rumack Nomogram is applied at 4-24 hours
If time unknown, treat if: AST elevated regardless of APAP level or at any elevated APAP >10
If [APAP] <50 at 1-4 hrs, then no risk of toxicity
Perform gastric emptying if: <1 hr post ingestion or ER formula or coingestion of GI delaying
agents
Activated charcoal if: <4 hrs post ingestion
140 mg/kg ORAL loading dose NAC
After 4 hours 70 mg/kg ORAL Q4H X17 doses (over 72 hours)
Give IV NAC 150 mg/kg loading dose followed by 50 mg/kg over 4 hrs followed by 6.25
mg/kg/hr X 16 hrs or use same dosing schedule as oral
Start NAC within 8 hours after ingestion but can start up to 24 hours after ingestion
Hydrofluoric Acid
Exposure to aluminum brighteners or rust removers (oil refiners, beer brewing, dental labs,
sandstone cleaning)
Fluoride ion interferes with calcium metabolism and Ca-dependent processes by combining with
Ca and Mg
Causes liquefactive necrosis of soft tissues (other acids cause coagulative necrosis)
Inhibits Na-K ATPase which causes erythrocytes to release K causing HyperK
Inhibits acetylcholinesterase causing acetylcholine excess (N/V, diarrhea, ab pain, weakness)
Burns: concentrations <20% cause delayed pain, 20-50% pain at 1-8 hrs, >50% immediate pain
Ingestion lethal dose: 1.5 g or 20 mg/kg
Inhalation: Rarely noncardiogenic pulm edema
Monitor Ca levels Q1H
Tx: Topical 2.5% Ca gluconate gel for minor burns, Infiltrative Ca gluconate or Bier block
technique for >20% [HF] burns, Intra-arterial therapy (radial/ulnar use 10mL of 10% in 40mL
NS; brachial use 20mL of 20% in 80mL NS; infuse over 4 hrs; repeat if not pain free for 4 hrs)
for burns involving >3 digits, Ca gluconate nebulized for inhalation injuries, Drop solution and
irrigation with LR/milk for ocular exposure, Drink water/milk for ingestions is controversial
If topical therapy fails (no improvement after 30 minutes), use infiltrative therapy
Alkali Ingestions
NaHydroxide, NaHypochlorite (bleach), Ammonia (Oven/drain/toilet bowl cleaners,
disinfectant, dishwasher detergent, hair dyes, batteries)
Each rise in pH of 1 represents a 10-fold increase in [OH]
“Strength” refers to willingness of alkali parent compound to dissociate in aqueous solution
Titratable Alkaline Reserve (TAR) – measure of resistance of a solution to changes in pH
As TAR increases, causticity increases
Causes liquefaction necrosis
Absence of oral burns does not rule out esophageal injury
First and most common site of injury is squamous epithelium of esophagus
Incidence of squamous cell carcinoma increases 20-40X
Esophageal strictures are common complications
Tx: water/milk, endoscopy within 4-24 hrs except in asymptomatic accidental cases (prior to 4
hours underestimates burns and after 24 hrs risks perforation), steroids for second degree burns,
prophylactic ampicillin for pts receiving steroids, perform esophageal stricture dilation after
week 2, resume enteric feeds ASAP
Do not give acid to neutralize as this causes greater thermal heat during neutralization reaction
Antipsychotics
Block dopamine receptors
Low potency (chlorpromazine-thorazine, fluphenazine, hydroxyzine, prochlorperazinecompazine, promethazine-phenergan, thioridazine, mesoridazine)
Block D2 receptors in mesolimbic system
Most sedating due to anticholinergic effects
Most likely to cause tardive dyskinesia/EPS bc blocks D2 in nigrostriatal
High potency (Droperidol, haloperidol, thiothixene, trifluoperazine)
Atypical (Clozapine, olanzapine-zyprexa, quetiapine-seroquel, risperidone, ziprasidone-geodon,
aripiprazole)
Block D2 and serotonin 2A
Also treat negative symptoms
NMS and cardiotoxicity least likely in this group
Acute EPS: dystonia, akathisia, parkinsonism (caused by D2 blockade in nigrostriatal and
reduced by muscarinic receptor antagonism)
Tx: Benadryl, benztropine, benzos (continue Benadryl/benztropine X48hrs)
Delayed EPS: tardive dyskinesia, tardive dystonia (caused by upregulation of D2 receptors)
NMS caused by neuroregulatory dysfxn 2/2 D2 receptor blockade in substantia
nigra/hypothalamus (develops within first 2 weeks of starting drug)
Rigidity, fever, diaphoresis, AMS, tachycardia, leukocytosis, rhabdo
Tx: Cool, hydrate, benzos, paralytics, bromocriptine/amantadine/dantrolene controversial
Phenothiazines (chlorpromazine) possess quinidine-like effects (QT prolongation) – thioridazine,
mesoridazine have greatest risk
Butyrophenones (Haldol) prolong cardiac repolarization causing Torsades
Clozapine – agranulocytosis, seizures, diabetes
Olanzapine – diabetes, agranulocytosis
Acute OD: sedation, pupils any size, orthostatic hypotension, MC rhythm is sinus tach
Ethylene Glycol
Antifreeze – sweet taste
Peak concentration at 1-4 hrs post ingestion
Metabolized to glycoaldehyde via ADH then to glycolic/glyoxilic/oxalic acid via ALDH
These require NAD conversion to NADH. Altered ratio causes increased lactate.
Liver metabolizes 80%
t1/2 – 3 to 9 hrs
If EtOH > 100, ADH sites are saturated causing decreased rate of EG metabolism
Clinical: inebriation, hypocalcemia, ARF, AG met acidosis (2/2 increased glyColate)
Stage 1 Neuro: 0-12 hrs, inebriation, no EtOH odor, N/V, AMS, cereb edema
Stage 2 Cardiopulm: 12-24 hrs, tachy, HTN, compens hypervent, ARDS, most deaths
Stage 3 Renal: 24-72 hrs, oliguria, flank pain, ARF, BM suppression
ARF is generally reversible
Indications for tx with antidote: Level >20 mg/dL or h/o drinking EG in combo with osmol gap
>10 or clinical suspicion + two: art pH <7.3, bicarb <20, osmol gap >10, urine oxalate crystals
Tx:
Lavage if <1 hr post exposure
Charcoal if mixed ingestion
Labs – CBC, BMP, Mg, Ca, Osmol, EtOH, Volatile alcohols, Lactate, UA with microsco
Continue antidote until EG nondetectable or <20 AND pt asymptomatic w/ normal pH
Fomepizole preferred over EtOH (15 mg/kg then 10 mg/kg Q12HX4 doses then 15
mg/kg Q12H until EG<20 and pt asymptomatic with normal pH)
EtOH only if hypersensitive to fomepizole
HD if: severe met acidosis (pH <7.3) unresponsive to therapy, ARF, EG >50 mg/dL
Bicarb if pH <7.3
If seizing, benzos/phenytoin (consider Ca for hypoCa)
Endogenous half life of glycolic acid – 10 hrs
Endogenous elimination rate – 1.08 mmol/L/h
HD half life of glycolic acid – 2.5 hrs
HD elimination rate – 170 ml/min
[glycolic acid] correlates with AG but not pH or bicarb
Methanol
Colorless, Positive alcohol odor
Solvent, windshield wiping fluid, gas line antifreeze, moonshine, model airplane fuel, perfumes
Ingested, inhaled, dermal
Peak concentrations in 30-60 minutes
Metabolized to formaldehyde via ADH then to formic acid via ALDH then formic acid to
H20/CO2 via folate dependent enzyme
Zero order kinetics 10 mg/dL/hr
Formic acid binds to cytochrome oxidase in mitochondria (similar to CO, cyanide, H sulfide)
FA targets optic disc myelin sheath
Damages bilateral basal ganglia/putamen
Clinical: blurred/color vision, “snow-field” vision, blindness, central scotoma, inebriation, ab
pain, ARF 2/2 myoglobinuria, pancreatitis, AG met acidosis
Blindness is generally permanent
Ethanol co-ingestion delays symptoms. Has 10X greater affinity for ADH
EtOH >100 mg/dL is protective
Osm gap present early but decreases. Vice versa for AG.
Tx:
No GI decontamination
Fomepizole (dosing as above) or ethanol if: MeOH >20 or h/o MeOH ingestion and
osmol gap >10 or h/o MeOH + 2 (art pH <7.3, bicarb <20, osmol gap >10)
Continue fomep/etoh until MeOH <20
HD if: severe met acidosis or ARF/lyte disturbance or coma/seizure or MeOH >50 mg/dL
or vision abnormality
Bicarb until pH >7.3
Folinic acid – no trials confirming advantage
Isopropyl alcohol (Isopropanol)
Metabolized to acetone via ADH
Rubbing alcohols, nail polish remover, window cleaner
Cause twice the CNS depression of EtOH
Death is rare
First order kinetics
Ketosis without acidosis
Clinical: inebriation, acetone odor, miosis MC, ab pain, n/v, hypotension rare, tachy, hypotherm
“Pseudo-renal failure” – false elevation of creat with normal BUN due to interference of acetone
by the colorimetric method of creat determination
Tx:
Fomepizole/EtOH NOT indicated
HD if hypotensive or level >400 mg/dL
ASA/NSAIDS
ASA peak therapeutic levels at 2 hrs
Protein bound
Inhibits cytochrome oxidase
Causes uncoupling
Ingestion of <150 mg/kg usually benign
Prehospital care: Activated charcoal. If assisted BVM, hyperventilate
MDAC Q4H until ASA <30 mg/dL
If intubated, maintain PCO2 of 35mmHg
Maintain glucose >90-100 (peripheral demand of glucose increases in OD)
Maintain UOP >2ml/kg/hr
If seizures, benzos
Urine alkalinization: 2 mEq/kg NaHCO3 then infusion (3 amps + D5W at 1.5-2X maintenance)
to keep urine pH >7.5 and until ASA <30 mg/dL or arterial blood pH >7.5
Ensure not hypokalemic because hypoK can cause urinary acidification. Keep K>4.0
HD if: severe CNS symptoms or pulm edema or no improvement with GI decontamination/urine
alkalinization or ARF or ASA >90-100 mg/dL
ASA Clinical: N/V, ab pain, tinnitus, reversible hearing loss, dyspnea, AMS, hyperpyrexia,
tachycardic/pnea, hypotensive, flushing, diaphoresis, petechiae, noncardiogenic pulmonary
edema, cerebral edema
ASA labs: Initial resp alkalosis followed by AG metabolic acidosis, hypoglycemia, Ferric
chloride (FeCl3) test of urine (obtained at least 2 hrs post ingestion), Obtain ASA levels Q2-3H
Nomogram useless
NSAID Clinical: N/V, ab pain, CNS depression, coma, met acidosis, ARF
NSAID tx: supportive, AC, benzos for seizures, HD only if ARF but usually worthless
Chronic ASA has increased risk of mortality, CNS symptoms and risk of Noncardiogenic pulm
edema
Pharmacokinetics and Toxicokinetics
Pharmacokinetics – study of behavior of drugs including absorption, distribution, metabolism,
excretion (ADME)
Pharmacodynamics – relationship of drug concentration to clinical effect
Toxicokinetics – study of ADME of a xenobiotic under circumstances that produce
toxicity/excessive exposure
Xenobiotics – foreign, natural, or synthetic chemicals
Toxicodynamics – relationship of toxic concentrations of xenobiotics to clinical effect
Absorption – process by which a xenobiotic enters the body
rate of absorption (ka)
extent of absorption (F) aka bioavailability
Rate fastest to slowest: inhalation, IV > IM, SC, intranasal, PO > cutaneous, rectal
Fick’s law of passive diffusion: Rate of diffusion = (diffusion constant X surface area X
partition coefficient X change in concentration of drug)/membrane thickness
pH = pKa + log [A-]/[HA]
pH = pKa + log [B]/[BH+]
Presystemic elimination can decrease or increase the bioavailability of a drug
GI tract microbial organisms can metabolize digoxin, OCPs, insulin and can even convert
xenobiotics into poisons (amygdalin into cyanide)
First pass metabolism – when drug goes from intestine into venous system directly to liver,
avoiding systemic circulation
Distribution
Volume of distribution (Vd) = [% pure drug (S) X F X dose (mg)]/time zero (Co)
A large Vd indicates that the xenobiotic resides outside of the plasma compartment and
thus it is unlikely that hemodialysis/hemoperfusion/exchange transfusion would be
effective
High plasma protein binding limits effectiveness of hemodialysis
Albumin binds weak acids (ASA, warfarin, phenytoin)
Alpha1-acid glycoprotein binds weak bases (lidocaine, propranolol)
Elimination – removal of a parent compound from the body
Phase 1 metabolic reactions – (preparative metabolism) introduces polar groups onto
nonpolar xenobiotics via oxidation, reduction, or hydrolysis
Phase 2 metabolic reactions – (synthetic reactions) conjugates polar groups with a
glucuronide, sulfate, acetate, etc. which increases hydrophilicity
In first order metabolism, regardless of the concentration of the xenobiotic, the rate of
decline is constant. –(dC/dt) = (Vmax/Km) X C
In first order, the FRACTION of drug eliminated each hour is the same e.g. 15% of the
total remaining concenctration is eliminated each hour
Half-life - Time necessary for the xenobiotic concentration to be reduced by 50%
Half-life calculations can NOT be determined for zero order kinetics
The time to achieve 95% of steady state concentration in a first-order process is
dependent on the half life and is usually 5 half-lives.
Zero order Vmax = -(dC/dt)
In zero order, the AMOUNT of drug eliminated each hour is the same e.g. 150 mg is
eliminated each hour (Phenytoin, Warfarin, Heparin, Ethanol, Aspirin, Theophylline)
t1/2 = 0.693/Ke
Ke = [lnC1 - lnC2]/(t1-t2)
Co = (S x F x dose)/[Vd (L/kg) x Wt (kg)]
2Na + BUN/2.8 +Gluc/18 + EtOH/4.6
Hematologic Consequences of Poisoning
Erythrocytes
Oxidant stress (removal of electrons from molecules) – caused by infection/drugs/food
Removal from protein portion of Hgb causes Heinz body hemolytic anemia
Removal from iron in Hgb causes methemoglobinemia
Removal from porphyrin ring by sulfur causes sulfhemoglobinemia
Hexose monophosphate shunt
Glucose-6-phosphate is converted to 6-phosphogluconate via G6PD with cofactor
NADP+ which becomes NADPH (this maintains glutathione stores needed for
oxidant stress)
Heinz body hemolysis
Oxidation of protein portion of Hgb causes denaturation of Hgb and attachment of
protein to RBC internal cell membrane
Removed by spleen
Causes extravascular hemolysis
Arsine, stibine, gasoline, naphthalene cause massive hemolysis
Methemoglobinemia
Reduced Hgb (ferrous, Fe2+) converted to oxidized Hgb (ferric, Fe3+)
Normally <2%
Produces functional anemia
Shifts oxyhemoglobin curve to left (oxygen unloading becomes more difficult)
>10-15% causes cyanosis
>20% causes CV and CNS signs/symptoms (HA, dyspnea, tachypnea, tachycard)
>40-50% causes lethargy, metabolic acidosis, bradycardia, coma, seizures
>70% causes death
Anemic patients suffers more severe symptoms at lower fractions
Cytochrome-b5 Reductase is responsible for most of MetHgb reduction
NADPH MetHgb Reductase normally is inactive but cofactor methylene blue
accelerates its activity
Many causes: nitroglycerin, benzocaine spray, teething ointments, hemorrhoid
creams, lidocaine, phenazopyridine (Pyridium), dapsone, well water, aniline dyes
Diagnosis: multiple-wave-length co-oximetry, cyanosis with normal arterial
oxygen tension, failure of cyanosis resolution with oxygen, chocolate colored
blood
Pulse ox not reliable (may produce falsely high or low values)
Total Hgb concentration is not affected by presence of MetHgb
Tx: O2, check CBC for hemolysis (hgb, blood smear, Heinz body stain,
haptoglobin)
If asymptomatic, observation
If symptomatic, IV methylene blue 2mg/kg (if no h/o G6PD deficiency)
Side effects of methylene blue: dysuria, SSCP, tachy, HTN, anxiety, green
urine, hemolysis in pts with G6PD deficiency
Cimetidine in dapsone overdose
Riboflavin in congenital MetHgb
Blood/exchange transfusion if refractory to methylene blue
Sulfhemoglobinemia
Sulfur incorporated into porphyrin ring by oxidant stress
SulfHgb persists for the life of the RBC (no conversion back to Hgb)
0.5g/dL causes slate-gray discoloration
Shifts oxyhemoglobin curve to right (reduces affinity of hgb for oxygen)
Diagnose: Co-oximeter, electrophoresis
MCC: phenacetin, sulfonamides, metoclopramide, phenazopyridine, dapsone
Tx: supportive. Methylene blue does NOT work. Transfusion if needed
Leukopenia – colchicine, benzene, metals, podophyllum, valproic acid
Thrombocytopenia – colchicine, arsenic, snake bite
Aquatic Envenomations
Cnidarians (jellyfish, corals, sea anemones)
Envenomate via nematocysts
Venom is dermatonecrotic, cardiotoxic, myotoxic, hemolytic, neurotoxic, hepatotoxic
Most cause dermal effects and very few cause the other systemic effects
Chironex fleckeri (box jellyfish) – causes CV collapse and hemolysis by increasing
intracellular Calcium
Irukandji syndrome – extreme HTN, pulm edema due to Carukia barnesi jellyfish
Tx: Avoid rubbing area (causes nematocyst discharge), vinegar/acetic acid for box,
antivenom for life-threatening Chironex, baking soda/papain for Chrysaora (Chesapeake
Bay)
Stingrays
1-4 spines on dorsum of whiplike tail
Tx: place area in hot water, inject lidocaine around area, xray, wound tract exploration
Scorpionfish (stonefish, lionfish)
Heat labile venom contains hyaluronidase, hemolytic activity, and biogenic amines (NE)
Cardiotoxicity due to verrucotoxin (inhibits Ca channels)
Tx: place area in hot water, inject lidocaine around area, xray, wound tract exploration,
stonefish anti-venom
Catfish
Spines on dorsal and pectoral fins
Hemolytic activity
Heat labile toxin
Tx: place area in hot water, Tdap, Cipro or 1st generation cephalosporin if infection
evident, xray for retained spine
Sea Snakes
Anterior fangs
Neurotoxic venom with neuromuscular blockade
Nephrotoxic directly and 2/2 rhabdo
Tx: admit for 24hrs obs, antivenom for neuro weakness or muscle necrosis
Seabather’s eruption/swimmer’s itch
Due to cnidarian larvae trapped btw swimsuit and body
Tx: topical steroids, antihistamines
Dinoflagellates
Ptychodiscus brevis causes red tides
Destroyed by wind causing airborn toxin
Wheezing, rhinorrhea, lacrimation, sneezing
Treat prophylactically with quinolones or Bactrim in immunocompromised patients with aquatic
wounds in order to avoid Vibrio infections
Insecticides/Cholinesterase Inhibitors/Carbamates/Organophosphate
Parathion, Sarin, Tabun, VX gas, Physostigmine
Cause rise in Ach at muscarinic (heart, lungs) and nicotinic (skeletal muscle) receptors
(Cholinergic Crisis)
“Aging” occurs if oxime is not supplied early enough. After ‘aging’, bond is irreversible.
Diarrhea, diaphoresis
Urination
Miosis
Bradycardia
Bronchosecretions
Emesis
Lacrimation
Lethargy
Salivation
Due to nicotinic activation at NMJ, may see fasciculations followed by weakness
“Intermediate Syndrome” – occurs 24-96 hrs post exposure; follows cholinergic crisis; proximal
muscle weakness, cranial nerve palsies, and progression to resp failure; first symptom is
weakness of neck flexion
Chronic OP exposure – peripheral neuropathies; caused by phosphorylation of lysophospholipase
in nerves; vague distal muscle weakness and pain; atropine/pralidoxime does not help
Diagnosis: Clinical; cholinesterase activity (butyrylcholinesterase, red cell acetylcholinesterase)
Tx:
Atropine – competitive antagonist at muscarinic receptors; start at 1-3mg IV; double dose
Q5 minutes if response to previous dose is inadequate then start gtt; does NOT affect
nicotinic receptors
If CNS antimuscarinic toxicity develops, may use glycopyrrolate or scopolamine
Pralidoxime – need to give within a few hrs so aging of phosphorylated AChE does not
occur; usually does not help in carbamate poisoning but should be given anyway; give
30mg/kg up to 2 g IV then 10mg/kg/h up to 650mg/h
Crotalids
AKA Pit vipers
Triangle heads, elliptical pupils, heat-sensing pits
Crotalus – rattles on tails, diamondback, sidewinders
Sistrurus – rattles on tails, pigmy rattlesnake
Agkistrodon – cottonmouths (water moccasins), copperheads
Venom contains multiple substances such as metalloproteinases, collagenase, hyaluronidase, etc.
Tissue injury
Venom Metalloproteinase (VMP) causes release of TNF alpha
Edema, ecchymosis, lymphangitis, LAD
Myotoxin-a causes increased intracellular Ca causing skeletal muscle necrosis
Coagulopathy
Defibrination (depletion of fibrinogen/fibrin) without DIC
Rarely DIC
Definbrination + thrombocytopenia looks like DIC but does not have microangiopathic
hemolysis or organ infarction
Thrombocytopenia
Cardiovascular toxicity
Hypotension due to third spacing
Neurotoxicity
Rarely weakness and paralysis (Mojave)
Myokymia (timber rattler)
Compartment syndrome if fang penetrates fascia
Tx:
Immobilize
Elevate extremity
NO heat, ice, compression, tourniquet, incision, suction, extraction kits, or electric shock
Obtain CBC, fibrinogen, PT/PTT/INR, CK Q4H X24H
Antivenin (polyvalent from horse) if: rapid progression of swelling, neuromuscular
toxicity, coagulopathy/defibrination/thrombocytopenia, or shock
Monitor for anaphylaxis and serum sickness; skin test prior to administration
CroFab (polyvalent ovine Fab) – replacing Antivenin; no Copperhead venom used in
preparation but may be used in copperhead bites
Smoke Inhalation
Simple asphyxiants – carbon dioxide
Irritant toxins – produce acids, alkalis or ROS; acrolein, ammonia, sulfur dioxide, HCl, chlorine,
nitric oxide, etc.
Chemical asphyxiants – exert effects at extrapulmonary sites; CO, cyanide
Obtain: ABG, carboxyHgb, MetHgb, CXR, co-ox, if lactate >10 then assume cyanide poisoning
Tx: supportive, O2, consider treating CO/cyanide, beta-agonists, No steroids
Cyanide/Hydrogen Sulfide
Cyanide
Smoke inhalation, photo developing, Cassava root, nitroprusside
Apricots, bitter almond, cherry, peach pits contain amygdalin which is converted to
cyanide
Combines with MetHgb to make CyanoMetHgb which is converted to Thiocyanate via
rhodanese
The sulfation of cyanide via rhodanese to thiocyanate is irreversible and is the limiting
factor in cyanide detoxification
Pathophys: Inhibits cytochrome oxidase, carbonic anhydrase, superoxide dismutase
causing a cellular hypoxia and thus despite sufficient oxygen supply, O2 can’t be used
Hyperlactatemia occurs due to failure of aerogic energy metabolism
Acts as potent neurotoxin at most oxygen sensitive areas (basal ganglia, cerebellum)
Directly activates NMDA receptors
Acute exposure: HA, anxiety, agitation, lethargy, seizures, coma, N/V, cherry red skin
Delayed manifestations of acute poisoning: parkinsonism
Chronic exposure:
tobacco amblyopia – loss of visual fxn in smokers (bc lower cyanocobalamin)
tropical ataxia neuropathy – demyelinating disease (cassava consumers)
Leber hereditary optic atrophy – due to rhodanese deficiency
Hypothyroidism – thiocyanate is competitive inhibitor of iodide entry
Tx:
Hydroxycobalamin – central cobalt atom complexes cyanide forming Vit B12; 5g
IV; may turn skin red
Antidote kit (amyl nitrite, sodium nitrite, sodium thiosulfate)
Thiosulfate – donates sulfur atom in rhodanese reaction
Nitrite – generates MetHgb; cyanide has higher affinity for MetHgb than oxidase;
may turn skin blue
Hydrogen sulfide
Leather, roofing asphalt, rayon, coke, oil/gas production, manure, volcanoes, caves
“rotten eggs” odor
Inhibits cytochrome oxidase with higher affinity than cyanide
Clinical: “knocked down”, enclosed space, multiple victims, bradycardia, HA, seizures,
coma, N/V, conjunctivitis, dyspnea, cyanosis, hemoptysis
Tx: Nitrite – MOA similar as in cyanide
No role for thiosulfate or hydroxycobalamin
Cyclic Antidepressants
Inhibit presynaptic reuptake of NE and/or serotonin
May cause refractory hypotension (depletion of NE/epi); don’t use dopamine for tx
Muscarinic competitive antagonists
Causes sinus tachycardia
“D” agents have least anticholinergic affect (doxepin, etc.)
Amitriptyline has most anticholinergic affect
Alpha1 antagonists
Postural hypotension
Cardiac sodium channel blockade
Slow the recovery from inactivation of the fast sodium channel
Slows phase 0 depolarization
Causes prolonged QRS which can lead to wide-complex tachycardia
Right bundle is affected more due to longer refractory period; causes RBBB pattern
R-R’ in aVR
Rarely causes Brugada pattern
Histamine antagonists
Agitation, delerium
Peak concentrations 2-8 hrs post ingestion
Rapidly absorbed so get very sick very fast
If asymptomatic/mild symptoms and normal EKG, okay to have psych eval after 6 hours
Low blood pH increases the amount of free drug (serves as basis for alkalinization therapy)
TCAs are weakly basic so when pH low, they become more ionized which is the state that binds
to Na channels
NaHCO2 also provides Na which acts competitively at Na Channel Site
Tx:
If QRS > 100 or R-R’ in aVR >3mm, bicarb at 1-2 mEq/kg boluses
If pH <7.35, give bicarb until pH 7.45-7.55
Mildly hyperventilate if intubated
If refractory to bicarb, give lidocaine
Last ditch with ECMO or intralipid
Agents causing Na Channel blockade:
TCA
Carbamazepine
Cocaine
Cyclobenzaprine
Propoxyphene
First generation phenothiazine AP (thioridazine causes DELAYED dysrhythmias)
Quinidine/quinine/hydroxycholorquine
Propafenone
Mushrooms/Plants
Cyclopeptide-containing groups
Amanita phalloides (death cap) pic 1
Amanita virosa (destroying angel) pic 2
Galerina spp. Pic 3
Lepiota helveola pic 4
Phallotoxin – GI symptoms in initial phase
Amatoxin – Inhibits RNA polymerase II
preventing transcription
Phase I – 6-12 hrs PI, gastroenteritis
Phase II – 12-24 hrs PI, transient improvement
Phase III – 1-6 days PI, hepatic failure
Mgmt (controversial): Thioctic acid, high dose PCN?, cimetidine, AC absorbs toxin,
silymarin/silybin (inhibits hepatic uptake of amatoxin)
Monomethylhydrazine-containing groups
Gyromitra esculenta (false morel) – looks like brain
Gyromitrin toxin – undergoes hydrolysis to acetylaldehyde and
monomethylhydrazine which inhibits conversion of pyridoxine
Onset 6-12 hrs
N/V, HA, Seizures, hepatorenal failure
Mortality 40%
Mgmt: pyridoxine 25mg/kg IV
Muscarine-containing groups
Clitocybe dealbata (the Sweater) pic 1
Clitocybe clavipes pic 2
Clitocybe illudens (Jack O’Lantern) 3
Inocybe spp.
Causes peripheral cholinergic syndrome (no CNS symptoms bc doesn’t cross BBB)
Onset 0.5-2 hrs
Coprine toxins
Coprinus spp, includes atramentarius (Inky Cap)
Amino acid metabolized to L-aminocyclopropanol which blocks aldehyde dehydrogenase
Disulfiram type reaction if ingested with EtOH
Muscimol-containing groups
Amanita muscaria, pic 1
Amanita pantherina, pic 2
Ibotenic acid decarboxylated to muscimol
Inhibitor of GABA receptor
Euphoria, hallucinations, ataxia, dream-filled sleep
Severe ingestions with fever, confusion, myoclonus, mydriasis, sz, coma
Lasts 6 hrs
Mgmt: benzos
Hallucinogenic groups
Psilocybe spp
Gymnopilus spectabilis
Psathyrella foenisecii
Psilocybin/psilocin indoles similar to LSD
Hallucinations, ataxia, sz, hyperkinesis
Onset 0.5-3 hrs
Mgmt: benzos
LBM’s
Chlorphyllum molybdites (green parasol), esculentum
GI distress in 0.5-3 hrs
Orelline-containing groups
Cortinarius rainierensis, found in Northwest
Bipyridal compounds (orelline and orellanine) similar to paraquat/diquat
Renal tubular injury
Symptoms delayed 24 hrs
Initial gastritis, HA, chills, anorexia then oliguric renal failure in days/weeks
Allenic norleucine (breaks rule of early vs late symptoms)
Amanita smithiana, found in Northwest
Renal tubular/interstitial injury similar to Cortinarius
Acute GI 30min-12hr
Renal failure days
Rhabdomyolysis
Tricholoma equestre (man on horseback)
Unidentified toxin causes myopathy
Nutmeg
Nut from evergreen tree Myristica fragans
Toxin: myristicin located in the SEED
MAOI
Metabolized to MMDA
N/V, hallucination, hyperthermia, HTN, Tachy
Morning Glory Seeds – Contain LSD
Pennyroyal oil
Volatile oil from Mentha pulegium and Hedeoma pulegoides
Toxin: pulegone
Direct hepatotoxin
Bronchial epithelial cell
Neurotoxin
Mgmt: consider NAC
Chamomile tea
Tea brewed from chamomile flower
Anaphylaxis
Jimsom Weed
Contain hyocyamine, scopolamine, atropine
Anticholinergic poisoning
Pyrrolizidine alkaloids
Found in herbal teas
Heliotropium (pic), Senecio, Crotalaria
Hepatic venoocclusive disease, Hepatomegaly, Hepatic Carcinoma
Khat
Catha edulis
Cathine and cathionine
Stimulant effect btw caffeine and amphetamine
Chew leaves and stems
Absinthe
Liquor from wormwood (Artemisisa absinthium)
Psychosis, hallucinations, intellectual deterioration
Dieffenbachia (Dumbcane)
Contains Ca oxalate spear-like crystals packaged into raphides
Forceful ejection of crystals into mucous membrane
Histamine response
Poinsettia (Euphorbia pulcherrima)
Minimal GI symptoms
Not a significant toxin
Holly (Ilex spp.)
Contains polyphenols, triterpens, saponins
Mild GI symptoms
Mistletoe (Phoradendron spp.)
Phoradendron flavescens (Christmas Mistletoe in US)
Viscum album in Europe
Viscum is cardiotoxin (bradycardia, neg inotrope)
Inhibits protein synthesis at 60S ribosomal unit
All parts of plant are poisonous
Jequirty pea/Rosary pea (Abrus precatorius)
Used in jewelry as bead
Contains toxalbumin abrin
A&B protein chains with disulfide linkage
B chain binds to cell surface glycoproteins allowing entry
A chain inhibits ribosomal protein synthesis
Bean must be chewed to be toxic
Sz, CNS depression, cerebral edema, dysrhythmias
Castor bean (Ricinus communis)
Contains toxalbumin ricine (similar to abrin)
Seeds must be chewed
Severe GE, hemorrhagic gastritis
Rhubarb (Rheum rhaponticum)
Leaves contain oxalates
GI symptoms
Solanacea (Nightshade)
Potatoes (Solanum tuberosum)
Nightshade or European bittersweet (Solanum dulcamara) pic 1
Jerusalem cherry (Solanum pseudocapsicam) pic 2
Horse Nettle or wild tomatoe (Solanum carolinense)
Solanine – glycoalkaloid removed by boiling; in buds/stems/shoots
N/V, diarrhea, HA, hallucinations, blurred vision
Pokeweed (Phytolacca Americana)
Mistaken for horseradish
Phytolacca: GI irritant
Mitogens: lymphocytosis
N/V, diarrhea, blurred vision, diaphoresis, weak, Sz, dysrrythmias
Colchicine containing plants
Autumn crocus (Colchium autumnale) pic 1
Glory Lilly (Glorisosa superba) pic 2
Highest concentration in bulb
Antimitotic, binds to tubulin
GI then multi-system organ failure with NCPE
Cyanogenic plants
Prunus spp (apricots, bitter almond, peach, apple, wild cherry) – amygdalin in seeds
Hydrangea – in leaves/buds
Elderberry
Cassava – in tubers not properly prepared (pic)
Amygdalin and linamarin or lotaustralin
Enzymatic breakdown releasing cyanide
Peppers (capsicum)
Capsaicin
Laryngospasm
Mucosal irritant
Releases neuropeptide substance p
Ackee fruit
Unripe fruit contains hypoglycine
Similar to Reye Syndrome
Hypoglycemia, fatty infiltration of liver, n/v, ams
Plants cultivated for flowers
Foxglove (digitalis) pic 1
Monkshood, wolfbane (aconitum napellus) pic 2
Aconitum toxin
Paresthesias of throat
Nausea, salivation, hypotension, dysrhythmias
Lantana
Lantadene toxin
Photosensitization
Children poisoned from green berries unripe
GI, CNS depression; cholestatic jaundice in livestock
Rhododendron spp
Toxin: diterpenic polyalcohols (grayanotoxin, asebotoxin, rhodojaponin)
Acts as cardiac glycoside, hypotensive, bradycardic, n/v, blurred vision
Yew
Toxicity from leaves or chewed seed; berries nontoxic
Christmas decoration
Taxine A&B inhibit Na and Ca currents
Oleander
Toxin cardiac glycoside
All plant parts are toxic
Mayapple (Podophyllum peltatum)
DNA strand uncoupler
GI symptoms
Peripheral neuropathy
Sz, coma, fever, ileus, ARF, BM suppression
Tree tobacco (Nicotiana spp)
Nicotine
SLUDGE symptoms
NMB
Deadly nightshade (Atropa belladonna)
Toxin hyocyamine
Anticholinergic syndrome
Poison hemlock (Conium maculatum)
Toxin conium
Similar to nicotine
Buckthorn
Unidentified neurotoxin
Similar to Guillain Barre
Water hemlock (wild carrot, false parsley)
All parts toxic
CNS stimulant, Sz
Strychnine
Used as rodenticide
Competitive inhibition of glycine at post-synaptic motor neuron receptor in spinal cord
“Awake seizures”
Cardioactive steroids
Digoxin (Foxglove, Oleander, Lily of the Valley, Red Squill, Dogbane; Toad Bufo species)
Steroid core with attached lactone ring and sugar group
Sugar group confers more water solubility enhancing entry into cells
Increase contractility, positive inotrope by increasing cytosolic Ca during systole
Dig inhibits Na-K ATPase
This inhibits Na extrusion and increases intracellular Na thereby decreasing
transmembrane gradient.
Since Na-Ca antiporter derives power from the gradient, Ca extrusion from the cell is
decreased.
This enhances the Ca-induced Ca release from the SR during systole
Dig decreases rate of depolarization/conduction through the SA/AV nodes
Occurs via vagally mediated parasympathetic tone and by depression of myocardium
Reflected on EKG by a decrease in ventricular response rate to suprajunctional rhythms
and by PR prolongation.
EKG shows QT shortening and ST/T forces opposite in direction to major QRS force
(scooping of ST segment)
Hypokalmeia enhances effects of digoxin by inhibiting Na-K ATPase activity (decreased
competitive inhibition between dig and K at the ATPase)
Manifestations of toxicity:
Acute: N/V, ab pain, lethargy, confusion, weakness
Chronic: anhedonia, loss of appetite, weakness, AMS, seizures rarely, amblyopia,
scotomata, photophobia, yellow halos around lights
Hyperkalemia – better prognosticator than dig level or EKG changes (keep <5.0)
First cardiac sign is usually extopic vent rhythm
Bidirectional ventricular tachycardia is diagnostic
Indications for DSFab
Any dig related life threatening dysrhythmia
K >5
Serum dig concentration >15ng/mL at any time or >10 6hrs post ingestion
Acute ingestion of 10 mg in adults
Acute ingestion of 4 mg in children
Chronic elevation of serum dig concentration associated with AMS, dysrhythmias, GI
Number of vials = (SDC X pt weight)/100 = (mg ingested x bioavail 0.8)/0.5mg per vial
Carbon Monoxide
Most Serious complication - delayed neurological sequelae occurs in up to 50%
Binds to Hgb at affinity 200-250 X oxygen
Causes left shift (decrease in 2,3-BPG)
Binds to mitochondrial cytochrome oxidase which causes ischemic reperfusion injury in brain
Leads to delayed lipid peroxidation of neurons
Only 10-15% of total body CO is extravascular, bound to myoglobin
Acute exposure: headache, N/V, dizziness, chest pain, dysrhythmias, ataxia, cherry red skin
Early resp alkalosis due to compensation of decreased O2 carry capacity then met acidosis due to
lactate
COHb normal 0-5%
COHb smokers 6-10%
Measure with co-oximeter
COHb is misinterpreted as oxyHb on most pulse oximeters
Measure lactate
EKG if chest pain
MGMT: 100% oxygen with positive pressure mask/ET (decreases half-life from 5 hrs on RA to
1 hr)
HBO decreases half life to 20 minutes (but also decreases lipid peroxidation in pts who have lost
consciousness)
Use HBO in: syncope (LOC), coma, Sz, AMS, COHb >25%, abnl cerebellar fxn, age >36,
prolonged >24hr exposure, fetal distress in pregnancy
Use HBO within 6-24 hrs post-exposure (within 6 is better)
CCB/BB toxicity
Inhibit flow of Ca through L-type voltage sensitive channels but via different mechanisms
Ca flux is necessary for pacemaker activity, AV conduction, myo contraction, insulin secretion,
vasc tone
Stimulation of beta1 receptors on myocytes causes increased intracellular cAMP which causes an
increase of Ca flow through L-type channel. Increased intracellular Ca causes Ca release from
SR causing contraction of muscle.
Dihydropyridines (nifedipine) are potent vasodilators with little effect on heart
Non-dihydropyridines (verapamil, diltiazem) effect both heart and vascular tone
In BB with membrane stabilizing activity (labetalol, carvediolol, acebutolol, propranolol) may
see increased QRS and seizures
See hyperglycemia, hyperlactatemia
Mgmt:
Ca – more specific for CCB but give for both; give lots
CaCl – 13 mEq Ca; 0.6ml/kg then infuse
CaGluconate – 4 mEq Ca; 1.8 ml/kg then infuse
Glucagon – Stimulates adenyl cyclase which increases cAMP; 5-10 mg IV then infuse
Side effects: N/V, diarrhea
PDE inhibitor (milrinone) – used in Europe
Epi/NE
High dose insulin if poor heart contractility bc helps with glucose utilization by heart
(view with U/S) – 1U/kg bolus then 1U/kg/hr up to 10U/kg/hr; Tolerate K to 2.5 bc
whole body K is WNL
Lithium
Element number 3
Mood stabilizer; used in bipolar disorder
Eliminated unchanged; no metabolism
Renally excreted
Li >2 is high
Chronic OD: usually due to adding new drug, dehydration; mental slowing, tremor,
ataxia, Sz, heart block, serotonin syndrome, Nephrogenic DI
Acute OD: Vomiting, clonus, AMS, Decreased anion gap if very elevated
Mgmt: normal saline, HD if: AMS, coma, sz, acute level >4, chronic level >2
Lead
Element number 82
Used in saudering, fish weights, paint, bullets, cheap jewelry
Usually seen as FB ingestion or “ethnic” red food dyes
Usually chronic toxicity
Acts like Ca and Fe bc it’s divalent
Tremor, ab pain, HTN, encephalopathic, constipation, “Saturnine” gout, multiple myelom
If >5, then elevated
Inteferes with heme synthesis
Mgmt: MVT with Ca and Fe for competitive antagonist
If FB, consider EGD for retrieval
Fiber diet
Xray
Chelation if: >40
Succimer preferred, 17 day course
BAL (made with peanut oil)
EDTA (may cause hypoCa)