PSCI 470 Quiz 1

Toxicology

Study of poisons on living organisms

Poison

any chemical or substance that is capable of producing detrimental effects on a living organism

• alteration of structure components

• alteration of functional processes

Most common age poisoned in ND, most common location, most common poisonings

0-5 years old

residence

medications

Poison centers primary purpose

provide poison treatment information to healthcare professionals and the public

poison centers secondary purposes (3)

• develop standard treatment protocols

• data collection

• provide poison prevention education

LD50

lethal dose in 50% of population

ED50

effective dose in 50% of population

Therapeutic index formula

LD50/ED50=TI

Toxicity factors (5)

• composition

• concentration

• route of exposure

• metabolism

• state of health

ABC in Poison treatment

Airway, breathing, circulation

treatment of comatose patient (5)

• check vitals (ABCs)

• administer oxygen

• IV

• test glucose

• IV naloxone

Ways to manage poisoning emergency (4)

• external decontamination

• gastric decontamination

• enhanced systemic elimination

• antidotal therapy

Key points for external decontamination (4)

• do not neutralize

• flush with water 15-20 minutes

• remove contaminated clothing/contacts for eyes

• no creams/ointments

Key points for gastric decontamination (5)

• dilution - milk or water (children 4-8oz, adults 8-16oz)

• emetics - syrup of ipecac (not recommended)

• lavage

• activated charcoal

• whole bowel irrigation

Enhanced elimination

• forced diuresis

• pH alteration

• peritoneal dialysis

• hemodialysis

• charcoal hemoperfusion

Chemical antidote

• react with poison to form less toxic compound

• ex: chelators

Dispositional Antagonism (antidote)

• alteration of absorption, metabolism, distribution, excretion

• ex: n-acetylcysteine

Receptor antidote

• compete with poison for the receptor site

• ex: naloxone

Functional antagonist (antidote)

• acts on one biochemical system to produce effects that are opposite from those produced on another system

• ex: epinephrine for anaphylactic reaction

NAPQI

toxic metabolite produced by CYP450 from metabolizing APAP

Glutathione

removes NAPQI by conjugating with it

Phase 1 APAP OD

• 0.5-24 hours

• nausea, vomiting, diaphoresis, malaise

Phase 2 APAP OD

• 24-48 hours

• symptoms resolve

Phase 3 APAP OD

• 72-96 hours

• hepatic necrosis, coagulation defects, jaundice, renal failure, death

Phase 4

• 4-14 days

• recovery, resolution of dysfunction

Acute toxic dose APAP

200mg/kg or >10g total

Treatment of APAP OD (3)

• Gastric Decontamination

  • activated charcoal

  • cathartic

• Antidote

  • n-acetylcysteine (NAC)

____ in glutathion ___ NAPQI

increase, decrease

N-acetylcysteine dosing

• loading dose

  • 140mg/kg

• maintenance

  • 70mg/kg Q4H x 17 doses

Dilutions of NAC

10% volume diluted 1:1 with soda/juice

• 28ml NAC + 28ml juice = 56ml

20% volume diluted 1:3 with soda/juice

• 14ml NAC + 42ml juice = 56ml

Discontinue NAC when _____ (4)

• pt clinically well

• [APAP] in blood <10ug/ml

• INR <2.0

• liver enzymes normal or decreased 25-50%

Salicylates (ex: aspirin)

• analegsic

• antipyretic

• anti-inflammatory

Salicylate MOA

• respiratory alkalosis

  • CNS stimulation

  • hyperventilation (less plasma CO2)

• metabolic acidosis

  • uncoupling oxidative-phosphorylation

  • renal compensation (secrete bicarbonate, retain more H)

Kinetics of Salicylates

shifts from first-order to zero-order (takes longer to get out of body)

Salicylate toxicity symptoms

• GI

• CNS stimulation

• respiratory stimulation

• CNS depression

• Resp. depression

• death

Treatment of salicylate toxicity

• gastric lavage (rare, for massive OD)

• activated charcoal

• cathartics (not used often)

Addiction (4)

• primary chronic neurobiologic disease

• impaired control over drug use

• compulsive use, despite harm

• drug craving

Tolerance

• resistance or decreased responsiveness to expected actions of a drug

• higher or more frequent dosing necessary

Dependence

• neuroadaptation with specific withdrawal symptoms

• emotional need

Withdrawal phases

• acute - within hours, gradually resolves

• protracted - symptoms that persists, evolve, or appear past expected acute withdrawal timeframe

Categories of opioids (3)

• natural - morphine, codeine

• semi-synthetic - hydromorphone, oxycodone

• synthetic - fentanyl, methadone

opioids bind to _____ receptors which prevents release of ________ and binding to receptor. Leads to ____

Mu; GABA; increased dopamine release

Opioid characteristic triad

• coma

• pinpoint pupils (Miosis)

• respiratory depression

Opioids - treatment

• supportive - ABCs

• Gastric decontamination - activated charcoal

• antidote - naloxone

Meperidine metabolized to _____. Accumulation leads to _____.

Normeperidine; tremors, twitching, seizures

Unique symptom of meperidine toxicity

mydriasis (dilated pupils)