1. Emesis Indications
    • after oral ingestion only
    • not useful if drug given IV, SC, transdermal, or inhalation
  2. Emesis Contraindications
    • 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)
  3. Syrup of ipecac description
    • alkaloid - emetine - given PO
    • induces vomiting in 5-20 min in 85% pts
  4. Syrup of ipecac dosing
    • 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
  5. syrup of ipecac MOA
    local irritant to stomach and simulates CTZ
  6. gastric lavage description
    • 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    • solution containing poison is withdrawn via the tube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
  7. gastric lavage technique
    • 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)
  8. gastric lavage efficacy
    • no evidence to demonstrate a clear benefit to clinical outcomes
    • procedure not used routinely
  9. whole bowel irrigation description
    • 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
  10. whole bowel irrigation useful in...
    • sustained release products
    • drugs that don't bind activated charcoal
    • body packers
  11. Cathartics description
    • 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
  12. cathartic problem
    • 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
  13. chemical inactivation
    • not used very often if ever
    • requires that you know exactly what was ingested and that you have the specific inactivator
  14. chemical inactivation examples
    • sodium formaldehyde sulfoxylate converts mercuric ions to less soluble metallic Hg
    • NaHCO3 converts ferrous iron to ferrous carbonate which is poorly absorbed
  15. neutralization: alkali
    vinegar, OJ, lemon juice

    treatment of choice
  16. neutralization: acid ingestion
    H2SO4, HF, HCL (muratic acid)
    • antacid, NaHCO3 + acid --> CO2
    • excess gas --> GI perforation (w/o belching)

    treatment of choice
  17. inhalation or dermal exposure
    • remove patient from source
    • wash skin thoroughly
    • remove contaminated clothing
    • if it involves the eye, irrigate
  18. dialysis
    • 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
  19. biotransformation
    • many drugs metabolized by P450 system in the liver
    • system can be induced by several drugs, but takes too long (a few weeks)
  20. biotransformation (inhibiting metabolism)
    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
  21. urinary excretion
    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)
  22. drug-receptor antagonism
  23. drug-receptor antagonism
  24. drug-receptor antagonism
    vitamin K
  25. drug-receptor antagonism
    2-PAM & atropine
  26. physical interactions
    • heavy metals - chelators
    • digoxin - digoxin immune Fab
  27. functional antagonism
    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
  28. initial management of poisoned patient
    • airway: cleared of any obstructions
    • breathing: watch for rise and fall of chest
    • circulation: check for pulse
    • drugs: glucose, O2, naloxone, thiamine
  29. HTN, tachycardia
  30. hypotension and tachycardia
    alpha blockade, TCAs, phenothiazine
  31. rapid respiration
  32. hyperthermia
    any anticholinergic
  33. hypothermia
    drug + environment: EtOH, clonidine, beta-blockers, barbs, BZDs
  34. pupil constriction
    opioids, cholinesterase inhibitors
  35. pupil dilation
    amphetamine, atropine, LSD
  36. vertical and horizontal nystagmus
    PCP (pathognomonic)
  37. mouth burns
    caustic (acid/alkali)
  38. mouth odors
    alcohol, solvents (petroleum products, organic solvents)
  39. hot, flushed, and dry skin
  40. sweating skin
    sympathomimetics - amphetamine
  41. hyperactive bowel sounds, diarrhea, cramping
  42. ileus (bowel obstruction)
    opioids, anticholinergics
  43. measuring electrolytes
    anion gap formula
    normal value
    • anion gap = (Na + K) - (HCO3 + Cl)
    • normal: 12-16
  44. anion gap > 16
    likely metabolic acidosis
  45. causes of metabolic acidosis
    • diabetic keto acidosis
    • renal failure
    • ASA/salicylates, methanol, iron
  46. widening of QRS complex on electrocardiogram
  47. prolonged QT interval on electrocardiogram
  48. ventricular arrhythmias
  49. electrolytes abnormalities and ischemia
    abnormal EKGs
  50. which drugs can be seen with x-ray films?
    iron tabs and EC products in stomach
  51. when use drug screening (tox screening)?
    • only if results will alter management of patient
    • tox screens can be inaccurate, misleading, and are expensive
  52. Acetaminophen s/s of acute OD
    phase I
    • 24 hours
    • GI upset (N/V) & sweating
    • if huge dose (75 g) --> metabolic acidosis and arrhythmias
  53. Acetaminophen s/s of acute OD
    phase II
    • 1-3 days
    • hepatotoxicity begins - hepatic enzymes appear in blood, prothrombin time increases and bilirubin inreases
    • huge doses - renal failure & hepatic encephalopathy
  54. Acetaminophen s/s of acute OD
    phase III
    • 3-5 days
    • irreversible liver damage - death could occur
  55. Acetaminophen s/s of acute OD
    phase IV
    recovery begins - start to see enzyme/protein levels return to normal
  56. toxic APAP dose
    • 125 - 200 mg/kg
    • adults ~10 g
    • children ~ 5 g
  57. APAP mechanism of toxicity
    • 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
  58. acetylcysteine antidote mechanism of action
    its sulfhydryl groups act as a replacement for glutathione to bind quinoid intermediate
  59. role of chronic ethanol use in APAP toxicity
    • chronic ethanol induces CYP2E1, which metabolizes APAP to its toxic form
    • more of toxic metabolite synthesized
    • chronic ethanol also decreases glutathione levels
  60. role of acute ethanol use in APAP toxicity
    • acute ethanol slows degradation of CYP2E1
    • ability to form toxic metabolite is enhanced
  61. alcohol as liver protectant?
    • competes with APAP for metabolism by CYP2E1 & prevents formation of APAP's toxic metabolite
    • but will not protect liver!
  62. activated charcoal use in APAP OD
    if given within 30 minutes
  63. when to use acetylcysteine in APAP OD
    when patient has a plasma level above probable risk line (to the right)
  64. how soon to use acetylcysteine?
    • APAP OD
    • within 8 hours
    • up to 24 hours post ingestion
  65. acetylcysteine dosing?
    • 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
  66. treatment of sustained release APAP
    • 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
  67. Acute OD of aspirin/salicylates
    mild cases
    • mostly GI-related: N/V/D, GI bleeding
    • tinnitus: first sign
  68. Acute OD of aspirin/salicylates
    moderate cases
    confusion, disoriented, hyperventilation, or tachypnea
  69. Acute OD of aspirin/salicylates
    severe cases
    hallucinations, coma, seizures, metabolic acidosis
  70. Acute OD of aspirin/salicylates
    phase I
    • 12 hours
    • tachypnea (ending in respiratory alkalosis)
    • urine becomes alkaline, impaired consciousness
  71. Acute OD of aspirin/salicylates
    phase II
    • 12-24 hours
    • moving toward metabolic acidosis, urine --> acid
    • + bleeding problems
  72. Acute OD of aspirin/salicylates
    Phase III
    • > 24 hours
    • metabolic acidosis
  73. Acute OD of aspirin/salicylates
    toxic doses
    • 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
  74. treatment of OD of aspirin/salicylates
    • activated charcoal with sorbitol
    • 1 g activated charcoal binds 550 mg salicylate

    supportive: NaHCO3 IV to treat metabolic acidosis
  75. patient counseling for ASA/salicylates
    • watch for bleeding gums or blood in stool
    • avoid taking with warfarin
    • notify physician if ringing in ear
  76. opioid analgesics
    • morphine
    • codeine
    • heroin
    • oxycodone
    • hydrocodone
    • methadone
    • meperidine
    • propoxyphene
  77. uses of opioids
    • analgesic
    • anti-diarrheal
    • anti-tussive
    • anesthetics
  78. opioid street names
    • antifreeze
    • blow
    • cube juice
    • flea powder
    • good-n-plenty
    • horse (heroin)
    • smack
    • solid gold
    • tootsie roll
    • belushi (coke & heroin)
  79. s/s of acute opioid OD
    • CNS depression
    • respiratory depression
    • miosis
    • decreased BP
    • decreased bowel sounds
  80. meperidine & propoxyphene unique s/s of OD
  81. treatment of opioid OD
    oral ingestion
    • AC can work
    • do not use ipecac if sedated
    • naloxone (opioid antagonist)
  82. treatment of opioid OD
    • maintain breathing
    • naloxone
  83. 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
  84. Methanol
    • 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
  85. methanol metabolism
    formaldehyde and formic acid (both toxic)
  86. toxic doses of methanol
    • 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
  87. methanol poisoning treatment
    • 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
  88. fomepizole (Antizol)
    • inhibitor of alcohol dehydrogenase
    • single 20 mg/kg dose is required
  89. isopropyl lethality
    • much less toxic than methanol
    • does not produce acidosis or blindness
    • lethal dose is 250 mL
  90. ethylene glycol info
    • antifreeze for cars
    • produces CNS depression, acidosis and renal failure
    • treatment: NaHCO3, EtOH or fomepizole
  91. propylene glycol
    • much less toxic
    • used as a solvent in drugs, cosmetics and ointments and found in food materials
  92. benzene
    • industrial solvent
    • long-term exposure --> leukemia and aplastic anemia
  93. toluene
    • this is the substance in glue that gives a high
    • not carcinogenic
  94. mechanism of heavy metal poisonings
    • 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
  95. treatment of heavy metal poisonings
    • 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
  96. penicillamine (CUPRIMINE)
    • 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
  97. Wilson's disease
    patient can't excrete or eliminate copper
  98. effectiveness of chelating agent depends on...
    • 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
  99. ideal chelator
    • 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
  100. sources of mercury
    elemental, salts, organic
    • 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)
  101. elemental mercury toxicities
    classic triad: excitability, tremors, and gingivitis
  102. mercury salt toxicities
    • early: ashen gray color mouth, abdominal pain, vomiting
    • late: metallic taste, foul breath, loss of teeth
    • most common and serious: renal failure
  103. organic mercury toxicities
    neurological: ataxia, mental deterioration, paralysis --> death
  104. lead sources
    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
  105. acute lead toxicity
    • 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
  106. chronic lead toxicity
    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
  107. edetate calcium disodium (VERSONATE) - EDTA
    • 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)
  108. calcium salt of EDTA...
    administered because it would otherwise chelate Ca in blood and cause cardiac problems
  109. succimer (CHEMET)
    • 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
  110. deferoxamine (DESFERAL)
    • 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
  111. dimercaprol (BAL in Oil)
    • 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
Card Set
PDA III New Material for Final