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Toxicology I - III

Toxicology I, II, & III

Most common overdose/Toxicity issues = ? *analgesics... * cosmetics... * acetominophen alone
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
ABCDE 's of acute poisoning management ? * Airway -- Breathing -- Circulation -- Disability (neurological stabilization) -- Exposure
What Dextrose, Naloxone, or Thiamine or used for ? * For pts with altered consciousness ... * for hypoglycemia, opiate detox, or alcohol intox.
Can provide important clues to narrow a differential diagnosis ? * Toxidromes or toxic syndromes, that are specific to certain drug agents
Big thing about E of the ABCDE's ? * Don't expose yourself !
GI Decontamination methods = ? * Activated charcoal -- Gastric lavage -- Induced emesis -- Whole bowel irrigation -- Cathartics
Enhance Elimination = ? * Urinary alkalization -- Hemodialysis
About helping detox someone = ? * we only help about 4% of ppl that come in, bc their body is usualy already trying to do it
When to use GI Decontamination = ? * Usually most beneficial: -- Within 1-2 hr after ingestion -and- When toxic amount ingested
Preferred method for GI decontamination = ? * Activated Charcoal ( need 1g/per kg of patient) ... * LOTS need to be ingested... * it binds drugs
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
Continued... * * PHAILS: Pesticides, potassium -- Hydrocarbons -- Acids, alkali, alcohols -- Iron, insecticides - Lithium --Solvents
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
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
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
Potential SEs of Emetics = ? * Protracted Vomiting (cant stop, is most common SE), Aspiration, Esophageal Tearing
Whole bowel irrigation uses = ? *administer PEG.... * cleans out the GI system... * USE: for drugs that are sustained release drugs
Cathartics use = ? * Use: flushes out the GI system again... *used in AC brickets constipation issue
Urinary alkalinization MoA and Use = ? * changes pH to have faste rurine elim... *Uses: phenobarbital and salicylate poisoning... * SE: Can cause severe acidosis
Hemodialysis uses = ? * Useful for alcohols, salicylates, ethylene glycol, lithium ... * Not useful for drugs with large Vd
A note on specific antidotes = ? * Treat the patient, NOT the poison... * Ex. fix vitals first, then poison
Antidote for opiate narcotics = ? * Naloxone
Antidote for benzodiazepine toxicity = ? * Flumazenil
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
Some other things it causes = ? * Myoglobin binding, Cytochrome binding (low Ox phos--> ROS formation), and CO stimulates guanylate cyclase (VD and cuases syncope)
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
What happens to to the low 02 ? * fainting is common... * also see tissue damage due to the accumulation of lactic acid
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)
Hydrogen Cyanide (CN), where can we get exposure from ? * Formed when plastics burn...* see mostly in domestic fires (firefighters are common)
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
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
How CN is eliminated = ? * Thiosulfate breaks it down to a form to be excreted
CN TmT = ? * must be immediate !!! -- Sodium nitrite (IV) followed by sodium thiosulfate (IV) -- Plus positive pressure oxygen
Nitrite MoA = ? * promotes formation of methemoglobin (metHb, Fe+3) to detoxify cyanide to cyanmethemoglobin
Thiosulfate MoA = ? * facilitates enzyme-catalyzed conversion of cyanide to less-toxic thiocyanate
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
Organophosphate Pesticides basics = ? * Poisoning is common … but death is rare
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)
Organophosphate Pesticides big SE = ? * May produce delayed neurotoxicity with sensory and motor disturbances of limbs ...... * No effective treatment
TmT for the Acute Exposure = ? * Respiratory support and decontamination quickly..... * Atropine = To block muscarinic effects ... * Pralidoxime (2-PAM) = Reactivates acetylcholine esterase
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)
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
After oral exposure = ? * GI irritation, then Respiratory distress (hemorrhagic pulmonary edema and fatal pulmonary fibrosis)
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
Warfarin overdose tmt = ? * lg amounts of Vitamin K
Methyl bromide = ? * Fumigant used to kill insects in the seed industry... * Major toxicity is on CNS .... * TmT = symptomatic issues only
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
Strychnine death and TmT = ? * Death due to respiratory paralysis ..... * Must treat immediately..... * TmT = Support respiration with diazepam
PETROLEUM HYDROCARBONS = ? * Gas, Kerosene, turpentine, etc…
What we see Cx? * CNS depression and issues in lungs from aspiration (Chemical pneumonitis)
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
TmT = ? * No specific antidote ..... * DO NOT lavage or produce emetic effects (cause aspiration issues)
Halogenated and aromatic hydrocarbons basics = ? * Different from Pet. Hydrocarbons... * are Systemic toxicity, and readily absorbed (GI and RESP.)
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)
Lead (Pb) basics = ? * Acute poisoning seldom a problem .... * Chronic exposure = Long t½ of Pb enables slow accumulation to toxic concentrations
Lead and kids = ? * CNS of children tend to be more sensitive to Pb because it can cross BBB
Inorganic Lead, where we get it ? * Absorption is SLOW.... * get from Eating paint chips (pica)(ORAL) or from Industrial (refineries, manufacturers)(INHALATION)
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)
Inorganic CxSx in kids = ? * CNS issues = Lead encephalopathy ..... * May cause lowered IQ and behavioral problems
In Adults = ? * GI toxicity = Lead Colic (constipation and abdom. pain)..... * Gingival lead lines (Lead-Sulfate) when lead binds (black lines on gums and teeth)
Overall, what are some Inorganic Lead CxSx = ? * CNS, Gingival Lead Lines, Lead Palsy, WRIST DROP, Hyperuricemia with gout, and Hematological toxicity
Lead and Heme issues = ? * Inhibits heme formation ..... * inhibits delta-aminolevulinic acid dehydratase and inhibits ferrochelatase (puts Fe in Heme)
Anemia we see = ? * Anemia (hypochromic microcytic) ... * also see basophilic stippling
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)
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)
Lead poisoning – TREATMENT = ? * Remove Exposure.... * Chelation therapy with EDTA and BAL with severe or encephalopathy.... * In Kids = Succimer
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
Big SEs of ACUTE = ? * projectile vomiting and rice water stool or bloody stool.... * get fluid loss and that can cause hypovolemic shock
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)
Inorganic Arsenic Poisoning TmT = ? * empty stomach.... * Chelation therapy = -- Dimercaprol (BAL) -- Penicillamine -- Succimer (children)
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
Organic Arsenicals TmT = ? * Nothing really works.... * supportive care and transfusions if severe
Mercury affects = ? * KIDNEYS and CNS
Acute Mercury Poisoning CxSx = ? * get from Mercury Vapor inhalation..... * Triad of: Neuropsychiatric disorders -- Tremors -- Gingivostomatitis
Acute TmT = ? * Chelation with succimer (preferred)
Chronic Mercury Poisoning CxSx = ? * Triad... * Erethism (Mad Hatter Syndrome) pathological shyness with explosive anger
Inorganic Mercury CxSx and TmT = ? * Corrosive properties = ashen-gray mucous membranes (burns places) ...... * TmT = Succimer (preferred) (NO lavage or emesis)
Inorganic Chronic Mercury Poisoning CxSx and TmT = ? * Acrodynia (pink disease) = Erythema of extremities – legs, hands, fingers..... * CNS CNS CNS issues..... * TmT = nothing, only supportive
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)
Iron TmT = ? * Empty Stomach (lavage or emesis) and X-Ray to see pill number in GI.... * Chelator: Deferoxamine (only Fe uses this drug)
**Chelating Agents** .
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
Dimercaprol (BAL) uses = ? * Arsenic, Mercury or Lead poisoning
Succimer uses = ? * Orally effective..... * Approved for use in children..... * USES: Lead, Arsenic or Mercury poisoning
Penicillamine uses = ? * Wilsons Disease.... * RA.... * Lead and Mercury (Not approved for Pb and Mercury though)
Deferoxamine uses = ? * Iron Poisoning specific drug
Created by: thamrick800