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Toxicology 1

Learning Objectives

Describe common toxic syndromes

Explain information related to heavy metal poisoning and chelation therapy

List commonly used antidotes

Demonstrate understanding of natural medicinals

COMMON TOXIC SYNDROMES

Table XI-1-1. Signs, Symptoms, and Interventions or Antidotes for Common Toxic Syndromes

Compound(s)

 

Signs and Symptoms

AChE inhibitors

 

Miosis, salivation, sweats, GI cramps, diarrhea,

 

 

muscle twitches → seizures, coma, respiration failure

Atropine and

 

↑ HR, ↑ BP, hyperthermia (hot, dry skin), delirium,

muscarinic

 

hallucinations, mydriasis

blockers

 

 

Carbon monoxide

 

Nausea and vomiting, dyspnea with hyperventilation,

(>10% carboxyHb)

 

mydriasis, vertigo; cardiovascular signs prominent,

 

 

↓ BP, syncope, ↑ HR, arrhythmias

CNS stimulants

Anxiety/agitation, hyperthermia (warm, sweaty skin),

 

mydriasis, ↑ HR, ↑ BP, psychosis, seizures

Interventions and Antidotes

Respiratory support; atropine + pralidoxime (for irreversible AChE inhibitors)

Control cardiovascular symptoms and hyperthermia + physostigmine (crosses blood–brain barrier)

Hyperbaric O2 and decontamination (humidified

100% O2 okay in mild overdose)

Control cardiovascular symptoms, hyperthermia, and seizures— +/– BZs or antipsychotics

Opioid

Lethargy, sedation, ↓ HR, ↓ BP, hypoventilation,

Ventilatory support; naloxone at frequent

analgesics

miosis, coma, respiration failure

intervals

Salicylates

Confusion, lethargy, hyperventilation, hyperthermia,

Correct acidosis and electrolytes—urinary

(ASA)*

dehydration, hypokalemia, acidosis, seizures, coma

alkalinization, possible hemodialysis

Sedative-

Disinhibition (initial), lethargy, ataxia, nystagmus,

Ventilatory support—flumazenil if BZs

hypnotics and

stupor, coma, hypothermia, respiratory failure

implicated

ethanol

 

 

SSRIs

Agitation, confusion, hallucination, muscle rigidity,

Control hyperthermia and seizures—possible

 

hyperthermia, ↑ HR, ↑ BP, seizures

use of cyproheptadine, antipsychotics, and BZs

Tricyclic

Mydriasis, hyperthermia (hot, dry skin), 3 Cs

Control seizures and hyperthermia, correct

antidepressants

(convulsions, coma, and cardiotoxicity) → arrhythmias

acidosis and possible arrhythmias

*More details in antiinflammatory section

315

Section XI λ Toxicology

HEAVY METAL POISONING

Signs and symptoms are distinctive but usually result from inhibition of –SH groups on enzymes and regulatory proteins.

Table XI-1-2. Signs, Symptoms, and Interventions or Antidotes for Heavy Metal Poisoning

Metals and Source

 

Signs and Symptoms

Arsenic

Acute: gastroenteritis, hypotension, metabolic

(wood

acidosis, garlic breath, “rice water” stools, torsades,

preservatives,

seizures

pesticides, ant

Chronic: pallor, skin pigmentation (raindrop

poisons)

 

pattern), alopecia, stocking glove neuropathy,

 

myelosuppression

Interventions and Antidotes

Activated charcoal, dimercaprol

Penicillamine or succimer

Iron (medicinal

Acute (mainly children): severe GI distress →

for anemias

necrotizing gastroenteritis with hematemesis and

and prenatal

bloody diarrhea, dyspnea, shock, coma

supplements)

 

Lead (tap water,

Acute: nausea and vomiting, GI distress and pain,

leaded paint chips,

malaise, tremor, tinnitus, paresthesias,

herbal remedies,

encephalopathy (red or black feces)

gas sniffing, glazed

Chronic: multisystem effects—anemia (↓ heme

kitchenware, etc.)

 

synthesis), neuropathy (wrist drop), nephropathy

 

(proteinuria, failure), hepatitis, mental retardation

 

(from pica), ↓ fertility and ↑ stillbirths

Gastric aspiration + carbonate lavage, deferoxamine IV

Decontamination—gastric lavage + dimercaprol (severe) or EDTA or succimer (penicillamine if unable to use dimercaprol or succimer)

Children: succimer PO

Mercury (elemental in instruments); salts used in amalgams, batteries, dyes, electroplating, fireworks, photography

Acute: vapor inhalation—chest pain, dyspnea, pneumonitis

Acute: inorganic salt ingestion—hemorrhagic gastroenteritis, acute tubular necrosis, shock

Chronic: organic Hg—CNS effects, ataxia, paresthesias, auditory and visual loss, loosening of teeth

Succimer PO or dimercaprol (IM)

Activated charcoal for oral ingestion, then support with succimer PO or dimercaprol (not IV) → causes redistribution of Hg to the CNS →↑neurotoxicity

316

Chapter 1 λ Toxicology

ANTIDOTES

Table XI-1-3. Summary of Antidotes

Antidote

 

Type of Poisoning

Acetylcysteine

 

Acetaminophen

Atropine + pralidoxime

 

AChE inhibitors—physostigmine, neostigmine, and

(for irreversible AChE

 

pyridostigmine; organophosphates, including

inhibitors)

 

insecticides, such as malathion and parathion

Deferoxamine

 

Iron and iron salts

Digoxin immune F(ab)

 

Digoxin

Dimercaprol (BAL)

 

Arsenic, gold, mercury, lead; oral succimer for milder

 

 

lead and mercury toxicity

EDTA

 

Backup in lead poisoning, then for rarer toxicities

 

 

(Cd, Cr, Co, Mn, Zn)

Esmolol

 

Theophylline, beta agonists

Ethanol, fomepizole

 

Methanol or ethylene glycol

Flumazenil

 

Benzodiazepines, zolpidem, zaleplon

Naloxone

 

Opioid analgesics

Oxygen

 

Carbon monoxide

Penicillamine

 

Copper (e.g., Wilson’s disease), iron, lead, mercury

Physostigmine

 

Anticholinergics: atropine, antihistamine,

 

 

antiparkinsonian—not tricyclics

Protamine

 

Heparins

Vitamin K

 

Warfarin and coumarin anticoagulants

Activated charcoal

 

Nonspecific: all oral poisonings except Fe, CN, Li,

 

 

solvents, mineral acids, or corrosives

317

Section XI λ Toxicology

NATURAL MEDICINALS

“Natural” medicinals are available without prescription and are considered to be nutritional supplements rather than drugs. Herbal (botanic) products are marketed without FDA review of safety and efficacy, and there are no requirements governing the purity or the chemical identities of constituents. Evidence supporting the clinical effectiveness of herbal products is commonly incomplete.

Table XI-1-4. Characteristics of Selected Herbals

 

 

 

 

Possible

 

 

Name

 

Medicinal Use(s)

 

Mechanism(s)

 

Side Effects

Echinacea

 

↓ Cold symptoms

↑ ILs and TNF

GI distress,

 

 

 

 

 

 

dizziness,

 

 

 

 

 

headache

Garlic

Hyperlipidemias,

Inhibits HMG-CoA

Allergies,

 

cancer (evidence is

reductase and

hypotension,

 

weak)

ACE

antiplatelet actions;

 

 

 

 

 

use caution

 

 

 

 

 

when used with

 

 

 

 

 

anticoagulants

Gingko

Intermittent

Antioxidant, free

Anxiety, GI distress,

 

claudication;

radical scavenger,

insomnia,

 

Alzheimer disease

↑ NO

antiplatelet actions;

 

(evidence is weak)

 

 

use caution when

 

 

 

 

 

used with

 

 

 

 

 

anticoagulants

Ginseng

Possible ↑ in

Unknown

Insomnia,

 

mental and physical

 

 

nervousness,

 

performance

 

 

hypertension,

 

(evidence is weak)

 

 

mastalgia, vaginal

 

 

 

 

 

bleeding

Saw

Symptomatic

5α-reductase

GI pain, decreased

palmetto

treatment of BPH

inhibitor and

libido, headache,

 

 

 

androgen

hypertension

 

 

 

receptor

 

 

 

 

 

antagonist

 

 

St. John’s

Depressive disorder

May enhance

Major drug

wort

(variable evidence for

brain 5HT

interactions:

 

clinical efficacy)

functions

serotonin syndrome

 

 

 

 

 

with SSRIs; induces

 

 

 

 

 

P450, leading to ↓

 

 

 

 

 

effects of multiple

 

 

 

 

 

drugs

318

Источник: https://studfile.net/preview/16445239/

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