PDA III Final

• after oral ingestion only
• not useful if drug given IV, SC, transdermal, or inhalation

• corrosives: strong acid or base-->causes additional damage upon vomiting
• unconscious: may inhale vomit into lungs or choke on it
• stimulants: vomiting may induce seizures
• petroleum products with low viscosity: difficult to vomit completely and product may get into lungs (inhalation)

• alkaloid - emetine - given PO
• induces vomiting in 5-20 min in 85% pts

• children 6 mo - 12 yrs: 15 mL
• adults: 30 mL

• take with lots of water to help with vomiting
• if no emesis in 20 min, may repeat dose

local irritant to stomach and simulates CTZ

• a tube inserted into stomach and water, normal saline or one half normal saline is instilled into the stomach
• solution containing poison is withdrawn via the tube
• must be done within 1-2 hrs after ingesting poison and only if pt is stable; can be used in unconscious patients

• large tube inserted into stomach via mouth
• endotracheal tube should also be inserted to prevent aspiration
• pt placed on left side

• first: withdraw as much stomach contents first
• then instill about 150-300 mL of the lavage solution at a time and withdraw
• repeat until the returns are clear (10-12x or 1.5-3.5 L)

• no evidence to demonstrate a clear benefit to clinical outcomes
• procedure not used routinely

• 20cc/kg/hr (about 2 1/hr in adults) of polyethylene glycol/electrolyte solution is given via nasogastric tube
• antiemetic may also be given IV -- most patients can't tolerate much fluid without vomiting
• given until rectal effluents are clear
• messy and time consuming

• sustained release products
• drugs that don't bind activated charcoal
• body packers

• hasten transit time through GI tract
• hyperosmotic solutions of sodium sulfate, magnesium sulfate or sorbitol pull water into the GI tract
• no study or case report shows a positive clinical outcome

• most drugs are absorbed in 30-90 minutes; cathartics take a few hours to get full effect
• could be used when poison is a volatile hydrocarbon
• avoid Mg in renal failure and Na in CHF

• not used very often if ever
• requires that you know exactly what was ingested and that you have the specific inactivator

• sodium formaldehyde sulfoxylate converts mercuric ions to less soluble metallic Hg
• NaHCO3 converts ferrous iron to ferrous carbonate which is poorly absorbed

vinegar, OJ, lemon juice

treatment of choice

• antacid, NaHCO3 + acid --> CO2
• excess gas --> GI perforation (w/o belching)

treatment of choice

• remove patient from source
• wash skin thoroughly
• remove contaminated clothing
• if it involves the eye, irrigate

• blood passed through charcoal column to adsorb drug
• useful when the drug is already absorbed and pts condition is life threatening
• very effective for some agents; not effective for those agents with high Vd

• many drugs metabolized by P450 system in the liver
• system can be induced by several drugs, but takes too long (a few weeks)

many drugs metabolized to more toxic chemicals and therefore, inhibit metabolism can decrease toxicity

• examples: ethanol can be used to inhibit conversion of methanol to formic acid via alcohol dehyrogenase
• APAP becomes toxic when its metabolism depletes liver of glutathione and then attacks liver cells; N-acetylcysteine prevents depletion of GSH

can only impair reabsorption by favoring ionized form

• acidification will promote excretion of basic drugs (administer ascorbic acid)
• alkalization of urine will promote excretion of acidic drugs (administer NaHCO3 or antacid)

naloxone

flumazenil

vitamin K

2-PAM & atropine

• heavy metals - chelators
• digoxin - digoxin immune Fab

give drug that produces opposite effect of original agent

• example: drug induced seizures - give anticonvulsant
• respiratory deppression - CNS stimulants to reverse may be more harmful than good
• control BP - give vasodilators or vasoconstrictors

• airway: cleared of any obstructions
• breathing: watch for rise and fall of chest
• circulation: check for pulse
• drugs: glucose, O2, naloxone, thiamine

amphetamine

alpha blockade, TCAs, phenothiazine

salicylates

any anticholinergic

drug + environment: EtOH, clonidine, beta-blockers, barbs, BZDs

opioids, cholinesterase inhibitors

amphetamine, atropine, LSD

PCP (pathognomonic)

caustic (acid/alkali)

alcohol, solvents (petroleum products, organic solvents)

atropine/anticholinergic

sympathomimetics - amphetamine

iron

opioids, anticholinergics

• anion gap = (Na + K) - (HCO3 + Cl)
• normal: 12-16

likely metabolic acidosis

• diabetic keto acidosis
• renal failure
• ASA/salicylates, methanol, iron

TCAs

phenothiazine

digoxin

abnormal EKGs

iron tabs and EC products in stomach

• only if results will alter management of patient
• tox screens can be inaccurate, misleading, and are expensive

• 24 hours
• GI upset (N/V) & sweating
• if huge dose (75 g) --> metabolic acidosis and arrhythmias

• 1-3 days
• hepatotoxicity begins - hepatic enzymes appear in blood, prothrombin time increases and bilirubin inreases
• huge doses - renal failure & hepatic encephalopathy

• 3-5 days
• irreversible liver damage - death could occur

recovery begins - start to see enzyme/protein levels return to normal

• 125 - 200 mg/kg
• adults ~10 g
• children ~ 5 g

• acetaminophen dose increases, glutathione becomes depleted
• quinoid intermediate now attaches via a covalent bond to proteins located within the cell leading to cell death
• considered basis for drug toxicity

its sulfhydryl groups act as a replacement for glutathione to bind quinoid intermediate

• chronic ethanol induces CYP2E1, which metabolizes APAP to its toxic form
• more of toxic metabolite synthesized
• chronic ethanol also decreases glutathione levels

• acute ethanol slows degradation of CYP2E1
• ability to form toxic metabolite is enhanced

• competes with APAP for metabolism by CYP2E1 & prevents formation of APAP's toxic metabolite
• but will not protect liver!

if given within 30 minutes

when patient has a plasma level above probable risk line (to the right)

• APAP OD
• within 8 hours
• up to 24 hours post ingestion

• 72 hours regimen
• LD of 140 mg/kg IV, then 70 mg/kg every 4 hours x 17 doses

• 24 hour regimen
• same dosing but stop at 24 hours

• same as IR APAP
• activated charcoal (AC) would be used if within 30 minutes but acetlcysteine still most effective
• when drawing plasma levels, need at least 2 levels to find peak

• mostly GI-related: N/V/D, GI bleeding
• tinnitus: first sign

confusion, disoriented, hyperventilation, or tachypnea

hallucinations, coma, seizures, metabolic acidosis

• 12 hours
• tachypnea (ending in respiratory alkalosis)
• urine becomes alkaline, impaired consciousness

• 12-24 hours
• moving toward metabolic acidosis, urine --> acid
• + bleeding problems

• > 24 hours
• metabolic acidosis

• 200 mg/kg
• adults ~ 15 g
• fatal at 300 mg/kg ~ 20 g

• metabolism becomes saturable at these doses
• half-life changes from 4 hours to 18-36 hours

• activated charcoal with sorbitol
• 1 g activated charcoal binds 550 mg salicylate

supportive: NaHCO3 IV to treat metabolic acidosis

• watch for bleeding gums or blood in stool
• avoid taking with warfarin
• notify physician if ringing in ear

• morphine
• codeine
• heroin
• oxycodone
• hydrocodone
• methadone
• meperidine
• propoxyphene

• analgesic
• anti-diarrheal
• anti-tussive
• anesthetics

• antifreeze
• blow
• cube juice
• flea powder
• good-n-plenty
• horse (heroin)
• smack
• solid gold
• tootsie roll
• belushi (coke & heroin)

• CNS depression
• respiratory depression
• miosis
• decreased BP
• decreased bowel sounds

seizures

• AC can work
• do not use ipecac if sedated
• naloxone (opioid antagonist)

• maintain breathing
• naloxone

• short acting - may need to give multiple injections
• given IV
• reverseseverything associated with opioid (even analgesia)
• restores breathing
• may cause w/d in dependent patients

• problem: may unmask another drug OD; ex: pt took opioid + stimulant; block opioid = CNS excitation
• dependence/withdrawals: N/V, diarrhea; pain

• aliphatic alcohol
• common industrial solvent, found in some antifreeze liquids, paints, varnishes, and paint thinners; added to ethanol to make it tax free for use as a solvent

formaldehyde and formic acid (both toxic)

• 15 mL - blindness: may be permanent at this low dose, if acute
• 70-100 mL - death: will experience blindness first then death within 24 hours

• supportive: NaHCO3 IV to treat met. acidosis followed by dialysis
• ethanol competes with methanol for alcohol dehydrogenase: give enough EtOH to saturate enzyme until drunk

• inhibitor of alcohol dehydrogenase
• single 20 mg/kg dose is required

• much less toxic than methanol
• does not produce acidosis or blindness
• lethal dose is 250 mL

• antifreeze for cars
• produces CNS depression, acidosis and renal failure
• treatment: NaHCO3, EtOH or fomepizole

• much less toxic
• used as a solvent in drugs, cosmetics and ointments and found in food materials

• industrial solvent
• long-term exposure --> leukemia and aplastic anemia

• this is the substance in glue that gives a high
• not carcinogenic

• heavy metals (lead, mercury, arsenic, cadmium) produce toxic effects by combining with proteins containing oxygen (-OH, -COO-, C=O, -OPO3H) sulfur (-SH, -S-S-) and nitrogen (-NH2)
• interfere with protein function and protein synthesis

• chelation: reaction of an electron donor (usually O, N, or S) with a metal to form a ringed system
• electron donor forms a 5 or 6 member H-bonded ring system

• treats copper poisonings (also chelates mercury, lead, and zinc)
• Cu poisoning rare and genetically determined
• normally, Cu from diet is excreted with ease from urine
• Wilson's disease: pt can't excrete or eliminate Cu
• Cu levels increase in liver, kidney, brain, and eyes
• also treats rheumatoid arthritis
• possible cross reactivity with PCN

patient can't excrete or eliminate copper

• selectivity for heavy metal vs essential body metals (Fe, Ca)
• distribution of chelator compared to metal
• ability of the chelator to be removed from body once it has chelated metal

• high solubility in water
• resistance to biotransformation
• ability to reach sites of metal storage
• forms non-toxic complexes with toxic metal
• retains chelating activity at pH of body fluids
• readily excreted
• must have greater affinity for heavy metals over endogenous metals

• elemental mercury: fillings in teeth (doesn't lead to neurological problems)
• mercury salts: occupational hazards - electronics and plastics industries
• organic mercury: very toxic - methyl mercury used to calibrate NMRs (lipophlic --> CNS)

classic triad: excitability, tremors, and gingivitis

• early: ashen gray color mouth, abdominal pain, vomiting
• late: metallic taste, foul breath, loss of teeth
• most common and serious: renal failure

neurological: ataxia, mental deterioration, paralysis --> death

environmental sources include leaded paint and drinking water stored in lead lined containers or plumbing with lead soldered fittings (include making moonshine in radiators in this category)

occupational exposure occurs with people working in lead smelters or battery factories

• relatively uncommon; may result from ingesting acid soluble lead cpmds or inhaling lead vapors
• s/s include N/V, abdominal pain, black stools, anemia, and renal failure
• death in 1-2 days: if patient survives, will likely experience s/s of chronic lead exposure

GI: metallic taste, intestinal spasm

neuromuscular: lead palsy, muscle weakness, paralysis

CNS: lead encephalopathy - ataxia & headache progressing to delirium, convulsions & coma

in children --> mental deficits

hematological: anemia b/c lead interferes with heme production

renal: renal failure

other: ashen-colored face, premature aging, and black gums

• chelator
• chelates di- and trivalent cations: useful in lead, manganese, zinc, iron and possible cadmium poisonings NOT MERCURY
• its affinity for lead is greater than that for Ca; Ca is displaced with Pb and the complex renally excreted
• Vd limited to ECF: does not go into tissue but heavy metal will redistribute to plasma as it is removed from plasma
• no reabsorption from kidney: excretion can't be hastened by altering urine pH
• given IV (5% PO administration)

administered because it would otherwise chelate Ca in blood and cause cardiac problems

• chelates Pb (approved use) and may be useful in Hg, As, and Cd
• does not significantly affect essential body metals (Cu, Zn, Fe)
• PO active, produces N/V/D and rash

• very specific for Fe and very little afinity for Ca
• does not remove Fe from hemoglobin or cytochrome enzymes
• very poor PO absorption; usually given IV or IM
• most common SE is allergic-like reactions

• arsenic antidote
• British anti-lewisite (BAL)
• arsenic causes toxicity by reacting readily with sulfhydryl groups; idea is to provide alternate sulfhydryl groups for metal to bind
• BAL more effective when given early; better at preventing attachment than reactivating proteins
• 2 molecules of BAL complexed with one molecule of the metal is a very stable complex; 1:1 complex is unstable and wen delivered to the kidney, may dissociate allowing the metal to cause renal toxicity
• alkalization of urine will help prevent dissociation in the kidney
• most common side effect: increased BP
• bad odor
• dissolved in peanut oil and administered IM
• treats Pb, Hg, and As poisoning