What is Vd?
Volume of Distribution is a proportionality term for the apparent volume into which a drug distributes (=L/kg)
= Dose (mg)/ Concentration
Ex. Low Vd = drug resides mainly in plasma and does not readily cross membranes (1 l/kg)
What are the Toxicokinetic Principles of Elimination and how are they different in overdose?
Zero Order Elimination vs First Order Elimination Kinetics (Half-Lives)
In an Overdose - people ingest way too much of something and see SATURABLE ELIMINATION KINETICS (Michaelis Menton Kinetics) where elimination of drug switches from First Order to Zero Order and can no longer think of Half-lives
Half-Life vs Duration of Action?
Half-life is how concentration of drug decreases over time
Duration of Action is how long drug activates receptor and effector proteins and measurable effects
Ex. Warfarin has half life 35 hours but duration of action is 5 days!
What are the generalizations about Pediatric Poisonings?
usually only ingest 1 substance
Usually a single and Acute ingestion with a short discovery time
What are the 1 Pill Killers in Pediatric Populations?
Clonidine - anti-hypertensive med
Sulfonylureas Bupropion, Calcium channel blockers, opioids, chloroquine
Other killers - Heparin, Hydrocarbons
What are the generalizations about poisonings in Adults?
more likely to be intentional suicide or abuse
more likely to be mixed substances with multiple causes and from drugs used for non-medically indicated uses
Can be acute or chronic Delay between ingestion and medical care
HIGHER morbidity and Mortality
Inaccuracy in History reporting
Most common analgesics, sedatives, antipsychotics, cleaning products, anti-depressants
What is the Sympathomimetic Toxidrome?
Increased HR, BP, RR, Temperature
Sweaty - diaphoretic
Causes: Cocaine and Amphetamines
What is the Anticholinergic Toxidrome?
Increased HR, BP, RR (or normal), Temperature
Agitated, Confused, Sedated, Hallucinating
DIFFERENCE FROM SYMPATHOMIMETIC IS DRY!!!! NOT SWEATY!!!
Flushed skin and pinkish but not sweating
No bowel sounds, urinary retention, clear chest sounds
Causes: Atropine, Scopolamine, Anti-histamines
What is the Opioid toxidrome?
Decreased HR, BP
RR WAY DOWN
Constricted Pupils and Disconjugate gaze
No change in skin
Lethargic and sleepy almost comatose
Decreased bowel sounds, Urinary retention
Causes: Morphine, Codeine, Oxy, Hydro, Fentanyl
What is the Cholinergic Toxidrome?
Decreased HR, BP INCREASED RR!!!!!
Lethargy and Sedation
SWEATTY!!! SLUDGE!!!!! Increased bowel sounds and Dumbels!
Causes: OP, Carbamate, Pesticides, Nerve agents and drugs that stop AchE
What happens in Acetaminophen Toxicity?
Tylenol can get metabolized by Sulfonation or Glucuronidation but also can be changed by Cytochrome P450 2E1 to NAPQI which mixes with macromolecules and causes Hepatocellular apoptosis!!!!!
Antidote = Acetylcysteine to replenish glutathione levels to get NAPQI away from hepatocytes
What is Anion Gap?
Differences between Cations and Anions in the blood
AG = [Na + K] - [Cl + HCO3] AG >15 is bad and caused by MUDPILES
What causes Anion Gaps?
AG >15 = MUDPILES:
Methanol (windshield washer fluid)
Ethylene Glycol (Antifreeze)
Ways to Prevent Absorption in the Poisoned Patient?
2) Gastric Lavage - only if administered within 1 hour of ingestions!!!
3) Activated Charcoal - most effective and causes ADsorption
4) Whole Bowel Irrgation
What can you NOT use Activated Charcoal for?
Hydrocarbons like Lamp oil, Kerosene, furniture polish
Alcohols like Ethanol, Methanol, Ethylene Glycol
Metals like Iron, Lead, Arsenic, Mercury
What do you use WBI for?
indicated for sustained release preparations, metals or foreign bodies mostly used for metal ingestions
What are ways to enhance elimination in the poisoned patient?
1) Multiple Dose Activated Charcoal - used for Enterohepatic recycling (drugs like Theophylline)
2) Urine Alkanization - ion trapping used for Salicylates and Phenobarbital
3) Extracorporeal Drug Removal like hemodyalysis or hemofiltration used for small mlcls with low protein binding and small Vd that are water soluble - Salicylates, Lithium, Toxic Alcohols
Antidote for Opioid OD?
Antidote for Acetaminophen OD?
Antidote for Digoxin OD?
Antidote for Snake bite?
Antidote for Sulfonylurea
Antidote for Ethylene Glycol or Methanol?
Antidote for Anticholinergics?
Antidote for OP or Carbamate?
Antidote for Lead, Arsenic, Mercury?
DMSA, BAL, CaNaEDTA, Penillamine