Toxicology

Poisoning

Incidence – Nationwide: 5 million injuries/year; 10% ER visits; 5% hospital visits; 20-30,000 deaths/yr

Definition –What is a poison?

"Anything" can be poisonous at a certain dose (even water)
Generally: Drugs, household products, chemicals, pollutants, plants, animals, insects
Poisoning isn’t just ingestion: inhalation, skin, eyes

Poison Control Center – Need patience! Poison Control Center takes time to evaluate a problem. "Lethal" doses in humans are generally unavailable! Can’t ethically test lethality in humans. Almost all info in toxicology is from Case-Reports, and can therefore be unreliable.

Determine magnitude of the problem – Will this amount kill the pt?

If accidental probably a small amount of drug intake, if suicide attempt probably a large amount.
Single or multiple exposure? – if chronic poisoning usually have (+) body stores of the drug
Environmental/Occupational exposure
Accurate Prognosis – Level of Intervention: Supportive Care, Antidotes, Active Removal
Accurate prognosis is a dynamic process which changes all the time and therefore, constantly influences intervention.

Antidotes

(1) Naloxone – anti-opiate, high affinity for opiate receptors – displaces other ligands, has zero intrinsic activity

(2) Pralidoxime Chloride (2-PAM), Atropine – Anticholinesterases, organophosphates
(3) Chelators – generally used for metal poisoning, makes it more water soluble
(4) Flumazenil – benzodiazepine antagonist, but only antagonizes sedative effects (as such differs from naloxone)
(5) Physostigmine salicylate – antimuscarinic, anticholinergic agents
(6) Cyanide Kit (nitrite, hydroxocobalamin)
(7) NAC (N-acetylcysteine) - acetaminophen
(8) Antivenins – protein derivates which prohibit immune reaction (can get anaphylactic reaction because B-cells react with the protein)
(9) Ethanol – used for methanol poisoning, competitive inhibition
(10) Dig-Fab – digitalis
(11) Vitamins

(12) Dimercaprol, EDTA - lead
With so few antidotes must do other things to fight poisons

Reducing Absorption – may work

Home remedies are ineffective and dangerous; salt water, finger gag – rarely work; safe alternative – soap water
Apomorphine – primarily of historical interest; emesis via CNS stimulation; rapid acting (20-40 min)

Ipecac – Universally available; central and local emetic effect; quick effect (20-40min); safe even with 2 doses; certain contraindications – compromised gag reflex (concerned about aspiration)

Gastric Lavage – equally effective as Ipecac; cleans out stuff in stomach (use large bore tube "hose" and suck it out), multiple small lavages is better than few large lavages

Cathartics– doesn’t work unless specifically indicated; limited data; only give when pt absolutely needs it

Activated Charcoal – adsorbs compounds reducing/preventing absorption, effective and safe!; only concern is aspiration; increased elimination (T½) from the body of drugs already absorbed (i.e., theophyline, valproic acid)

Enhanced Elimination – mostly useless

Metabolism – inducing or inhibiting CYP450 is unrealistic due to delay and variable effects! Can make toxic byproducts. Also can’t be used because can’t know how much has to be given in order to inhibit these enzymes!

Urinary Excretion – Forced diuresis (difficult/danger of overload); ion trapping (barbituates, amphetamines)

Artificial elimination – Ex: Dialysis/perfusion – invasive and depends on V_D and protein binding. Large V_D – means poison is not in blood and thus can’t be cleaned out. increased protein binding – free fraction in plasma is tiny compared to total amount in body.
Charcoal hemoperfusion
Often difficult to initiate