Toxicology I, II, & III
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| Most common overdose/Toxicity issues = ? | *analgesics... * cosmetics... * acetominophen alone
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| Management of Acute Poisoning = ? | * Provide supportive care -- Prevent poison absorption -- Antidotes (when available) -- Enhance poison elimination.... * For a vst majority of drugs, there is no specific antidote
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| ABCDE 's of acute poisoning management ? | * Airway -- Breathing -- Circulation -- Disability (neurological stabilization) -- Exposure
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| What Dextrose, Naloxone, or Thiamine or used for ? | * For pts with altered consciousness ... * for hypoglycemia, opiate detox, or alcohol intox.
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| Can provide important clues to narrow a differential diagnosis ? | * Toxidromes or toxic syndromes, that are specific to certain drug agents
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| Big thing about E of the ABCDE's ? | * Don't expose yourself !
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| GI Decontamination methods = ? | * Activated charcoal -- Gastric lavage -- Induced emesis -- Whole bowel irrigation -- Cathartics
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| Enhance Elimination = ? | * Urinary alkalization -- Hemodialysis
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| About helping detox someone = ? | * we only help about 4% of ppl that come in, bc their body is usualy already trying to do it
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| When to use GI Decontamination = ? | * Usually most beneficial:
-- Within 1-2 hr after ingestion
-and- When toxic amount ingested
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| Preferred method for GI decontamination = ? | * Activated Charcoal ( need 1g/per kg of patient) ... * LOTS need to be ingested... * it binds drugs
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| AC does NOT adsorb ? | * CHARCOAL: Caustics & Corrosives -- Heavy Metals -- Alcohols & glycols -- Rapidly absorbed substances -- Cyanide, chlorine -- Other insoluble drugs -- Aliphatic hydrocarbons
(gas, kerosene, liq furniture polish) -- Laxatives
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| Continued... | * * PHAILS: Pesticides, potassium -- Hydrocarbons -- Acids, alkali, alcohols -- Iron, insecticides - Lithium --Solvents
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| When not to us AC ? | * if over 1-2 hrs of exposure or when there is a bowel obstruction, bc these can form charcoal bricklets
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| When to use/not use GASTRIC LAVAGE ? | * Use when AC is not going to work... * DO NOT USE: to remove Strong acids/bases bc of the risk of perforation and not in unconscious pts bc of aspiration risk
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| Emetics - Ipecac use/when not to use = ? | * Use: only in settings of when someone can not make it to the hospital in time..... * DO NOT USE: < 6mths old, if they can't support their airway (bc they will aspirate), biggesst issue is that it can cause CNS effects
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| Potential SEs of Emetics = ? | * Protracted Vomiting (cant stop, is most common SE), Aspiration, Esophageal Tearing
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| Whole bowel irrigation uses = ? | *administer PEG.... * cleans out the GI system... * USE: for drugs that are sustained release drugs
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| Cathartics use = ? | * Use: flushes out the GI system again... *used in AC brickets constipation issue
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| Urinary alkalinization MoA and Use = ? | * changes pH to have faste rurine elim... *Uses: phenobarbital and salicylate poisoning... * SE: Can cause severe acidosis
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| Hemodialysis uses = ? | * Useful for alcohols, salicylates, ethylene glycol, lithium
... * Not useful for drugs with large Vd
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| A note on specific antidotes = ? | * Treat the patient, NOT the poison... * Ex. fix vitals first, then poison
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| Antidote for opiate narcotics = ? | * Naloxone
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| Antidote for benzodiazepine toxicity = ? | * Flumazenil
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| Carbon Monoxide poisoning causes ? | * anemic hypoxia by Hb can’t carry O2 because COHb accumulates and also prevents whatever o2 is on Hb to not be able to be unloaded
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| Some other things it causes = ? | * Myoglobin binding, Cytochrome binding (low Ox phos--> ROS formation), and CO stimulates guanylate cyclase (VD and cuases syncope)
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| CO CxSx = ? | * Brain / CNS (fainting, h/a, confusion, coma) and myocardial injury common and Hyperpnea.... * Hb looks aturated bc CO is bound to Hb, even though it is not O2
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| What happens to to the low 02 ? | * fainting is common... * also see tissue damage due to the accumulation of lactic acid
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| CO TmT = ? | * take out of exposure area, let patient rest, and give 100% O2.... * hyperbaric O2 therapy (fastest since O2 is a compet. antag of CO)
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| Hydrogen Cyanide (CN), where can we get exposure from ? | * Formed when plastics burn...* see mostly in domestic fires (firefighters are common)
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| CN MoA it has on the body ? | * CN- binding to Fe+3 and prevents the Fe2+ state... * can't generate ATP even though lots of O2 is there, cells then create Lactate --> Met. Acidosis
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| What we see in CN poisoning ? | * histotoxic hypoxia - high O2 lvls, but thet can't use it... * So, NO cyanosis, resp distress and high O2 lvls..... * seizures, hyperpnea, gasping, convulsions
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| How CN is eliminated = ? | * Thiosulfate breaks it down to a form to be excreted
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| CN TmT = ? | * must be immediate !!!
-- Sodium nitrite (IV) followed by sodium thiosulfate (IV)
-- Plus positive pressure oxygen
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| Nitrite MoA = ? | * promotes formation of methemoglobin (metHb, Fe+3) to detoxify cyanide to cyanmethemoglobin
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| Thiosulfate MoA = ? | * facilitates enzyme-catalyzed conversion of cyanide to less-toxic thiocyanate
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| Can also use to treat CN = ? | * Hydroxycobalamin (IV) - Forms harmless vitamin B12a cyanocobalamin
(eliminated in urine)..... * Works both within the intravascular space and within the cells
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| Organophosphate Pesticides basics = ? | * Poisoning is common … but death is rare
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| Organophosphate Pesticides MoA = ? | * Potent acetylcholinesterase inhibitors (lots of Ach builds up).... * SLUDGE/BBB or DUMBBBELS (symptom mnemonics)
.... * Muscarinic, nicotinic, and CNS effects (fasiculations, paralysis, increase in tears/urine/defication, and bradycardia)
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| Organophosphate Pesticides big SE = ? | * May produce delayed neurotoxicity with sensory and motor disturbances of limbs
...... * No effective treatment
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| TmT for the Acute Exposure = ? | * Respiratory support and decontamination quickly..... * Atropine
= To block muscarinic effects ... * Pralidoxime (2-PAM) = Reactivates acetylcholine esterase
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| Carbamate Pesticides = ? | * Poisoning is common … but death is rare again.... * same effects as organophosphates, but effects less severe … because carbamoylation is rapidly reversible ..... * TmT = Atropine (No PAM, bc it makes it worse)
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| Herbicide - Paraquat = ? | * A specific pulmonary toxicant.... * Toxicity is rare, and DEATH is likely in this one.... * if not reversed, will kill you.... * MoA= ROS in lungs damage everything
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| After oral exposure = ? | * GI irritation, then Respiratory distress (hemorrhagic pulmonary edema and fatal pulmonary fibrosis)
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| TmT = ? | * No specific antidote... * need to act quickly or it will kill you.... * use AC or Fullers Earth.... * NO emesis removal bc Concentrated solutions are corrosive
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| Warfarin overdose tmt = ? | * lg amounts of Vitamin K
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| Methyl bromide = ? | * Fumigant used to kill insects in the seed industry... * Major toxicity is on CNS
.... * TmT = symptomatic issues only
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| Strychnine = ? | * Competitive antagonist of glycine (an inhibitory molecule, so get no inhibition) .... * Causes powerful & uncontrollable muscle contractions.... * See Opisthotonus = Spasm where head & heels arch backward in extreme hyperextension
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| Strychnine death and TmT = ? | * Death due to respiratory paralysis
..... * Must treat immediately..... * TmT = Support respiration with diazepam
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| PETROLEUM HYDROCARBONS = ? | * Gas, Kerosene, turpentine, etc…
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| What we see Cx? | * CNS depression and issues in lungs from aspiration (Chemical pneumonitis)
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| What we clinicians see ? | * we see Oral ingestion over inhalation from kids getting in to it.... * it is usu Charcoal lighter fluid
..... * Death is RARE
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| TmT = ? | * No specific antidote ..... * DO NOT lavage or produce emetic effects (cause aspiration issues)
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| Halogenated and aromatic hydrocarbons basics = ? | * Different from Pet. Hydrocarbons... * are Systemic toxicity, and readily absorbed (GI and RESP.)
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| Halogenated and Aromatic Hydrocarbons = ? | * C: Camphor
--- H: Halogenated hydrocarbons (trichloroeth-ane, -ylene)
--- A: Aromatic hydrocarbons (benzene, toluene, xylene)
--- M: Metal additives (arsenic, mercury)
--- P: Pesticide additives (organophosphates)
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| Lead (Pb) basics = ? | * Acute poisoning seldom a problem
.... * Chronic exposure = Long t½ of Pb enables slow accumulation to toxic concentrations
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| Lead and kids = ? | * CNS of children tend to be more sensitive to Pb because it can cross BBB
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| Inorganic Lead, where we get it ? | * Absorption is SLOW.... * get from Eating paint chips (pica)(ORAL) or from Industrial (refineries, manufacturers)(INHALATION)
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| Inorganic Lead goes to where ? | * Initially binds to hemoglobin in RBCs, remainder goes to soft tissues..... * Later = redistributes to bone (95%), teeth, and hair (Can see on X-Ray bc of this)
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| Inorganic CxSx in kids = ? | * CNS issues = Lead encephalopathy
..... * May cause lowered IQ and behavioral problems
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| In Adults = ? | * GI toxicity = Lead Colic (constipation and abdom. pain)..... * Gingival lead lines (Lead-Sulfate) when lead binds (black lines on gums and teeth)
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| Overall, what are some Inorganic Lead CxSx = ? | * CNS, Gingival Lead Lines, Lead Palsy, WRIST DROP, Hyperuricemia with gout, and Hematological toxicity
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| Lead and Heme issues = ? | * Inhibits heme formation
..... * inhibits delta-aminolevulinic acid dehydratase and inhibits ferrochelatase (puts Fe in Heme)
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| Anemia we see = ? | * Anemia (hypochromic microcytic)
... * also see basophilic stippling
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| Lead poisoning - Diagnosis = ? | * Blood lead level (BLL) = most useful for screening and diagnosis...... *Urinary ALA levels and Zinc-protoporphyrin in RBCs (both from the Two Nz that are inhibited)
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| Organic Lead Poisoning basics = ? | * Well absorbed … even through skin (lipophillic)
.... * see rapidly progressive CNS symptoms (without the anemia or basophilic stippling bc no effect on Heme)
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| Lead poisoning – TREATMENT = ? | * Remove Exposure.... * Chelation therapy with EDTA and BAL with severe or encephalopathy.... * In Kids = Succimer
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| Inorganic Arsenic where we see it and issues it causes = ? | * coal and pressure treated wood.... * absorbed in lungs/GI tract... * deposits in Hair and Nails
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| Big SEs of ACUTE = ? | * projectile vomiting and rice water stool or bloody stool.... * get fluid loss and that can cause hypovolemic shock
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| Chronic Arsenic Poisoning SEs = ? | *less GI issues.... * garlic odor on breath and perspiration.... * Sensorimotor Peripheral Neuropathy = pin/needle sensation in stocking/glove distribution..... * Hyperpigmentation = palms & soles
Hyperkeratosis = white lines in nails (Mee’s lines)
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| Inorganic Arsenic Poisoning TmT = ? | * empty stomach.... * Chelation therapy = -- Dimercaprol (BAL)
-- Penicillamine
-- Succimer (children)
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| Organic (rapidly absorbed) Arsenicals = ? | * poisonings are rare ..... * Arsine gas poisoning - industrial setting... * Produces rapid severe hemolysis --> extensive hemolytic anemia ... * Renal Failure.... * FATAL if not treated
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| Organic Arsenicals TmT = ? | * Nothing really works.... * supportive care and transfusions if severe
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| Mercury affects = ? | * KIDNEYS and CNS
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| Acute Mercury Poisoning CxSx = ? | * get from Mercury Vapor inhalation..... * Triad of: Neuropsychiatric disorders -- Tremors
-- Gingivostomatitis
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| Acute TmT = ? | * Chelation with succimer (preferred)
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| Chronic Mercury Poisoning CxSx = ? | * Triad... * Erethism (Mad Hatter Syndrome) pathological shyness with explosive anger
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| Inorganic Mercury CxSx and TmT = ? | * Corrosive properties = ashen-gray mucous membranes (burns places) ...... * TmT = Succimer (preferred) (NO lavage or emesis)
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| Inorganic Chronic Mercury Poisoning CxSx and TmT = ? | * Acrodynia (pink disease) = Erythema of extremities – legs, hands, fingers..... * CNS CNS CNS issues..... * TmT = nothing, only supportive
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| Iron poisoning and CxSx = ? | * Acute = in young kids who eat brightly colored tablets that look like candy.... * CxSx: GI damage (necrotizing gastroenteritis), If patient survives 6 hrs … apparent recovery in 12 – 24 hrs, followed by death (phases)
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| Iron TmT = ? | * Empty Stomach (lavage or emesis) and X-Ray to see pill number in GI.... * Chelator: Deferoxamine (only Fe uses this drug)
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| **Chelating Agents** | .
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| Ethylene diamine tetraacetic acid (EDTA) MoA and uses = ? | * Give with Ca, bc can cause severe hypocalcemia w/o Ca+.... * Lead displaces Ca on EDTA... * USE: LEAD Poisoning Only
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| Dimercaprol (BAL) uses = ? | * Arsenic, Mercury or Lead poisoning
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| Succimer uses = ? | * Orally effective..... * Approved for use in children..... * USES: Lead, Arsenic or Mercury poisoning
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| Penicillamine uses = ? | * Wilsons Disease.... * RA.... * Lead and Mercury (Not approved for Pb and Mercury though)
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| Deferoxamine uses = ? | * Iron Poisoning specific drug
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