chapter 17 - antidotes and treatment of poisoning

Fomepizole is an antidote for treatment of ethylene glycol poisoning because it :

a) facilitates excretion of ethylene glycol

b) blocks metabolism of ethylene glycol

c) increases detoxification of ethylene glycol

d) chelates ethylene glycol

e) none of the above

b

ethylene glycol toxicity require metabolism by the enzyme alcohol dehydrogenase,. fomepizol is also metabolized by this enzyme; when administered to a poisoned patient, fomepizol competes for the enzyme and blocks the metabolism of ethylene glycol, preventing its metabolism to a toxic metabolite

carbon monoxide is a toxic gas because it:

a) binds to cytochrome aa₃ in mitochondria

b) binds to hemoglobin

c) causes respiratory alkalosis

d) causes respiratory failure

e) forms methemoglobin

b, d

carbon monoxide binds to hemoglobin more strongly than oxygen to form carboxyhemoglobin. the lack of oxygen in the tissues results in damage, especially to the tissues that have a high demand for oxygen, such as brain and heart. death is usually due to respiratory failure. carbon monoxide also binds to other heme proteins such as cytochrome. the lack of oxygen leads to anaerobic respiration and lactic acidosis

ethylene glycol:

a) is an alcohol

b) causes metabolic acidosis

c) metabolizes to lactic acid

d) crystallizes in the brain

e) is metabolized by aldehyde dehydrogenase

a, b

ethylene glycol is a dihydric alcohol which is metabolized by alcohol dehydrogenase to an aldehyde and by aldehyde dehydrogenase to an acid. the final product is oxalic acid which crystallizes in the brain neurons. the increased production of NADH as a result of metabolism leads to excessive production of lactic acid and the presence of acidic metabolites causes acidosis

which of the following are true?

a) solvents cause death by sensitization of the myocardium

b) ethanol is toxic because it stimulates the central nervous system

c) ethanol is metabolized to formic acid

d) the major target organ for methanol toxicity is the liver

e) large doses of ethanol result in blindness

f) high doses of ethanol lower blood sugar levels

a, f

some solvents sensitize the myocardium leading to sudden death from heart attack in apparently healthy young people who have engaged in solvent abuse.

alcohol depresses the CNS, especially ate high doses. alcohol is metabolized to acetic acid. the major target for methanol is the eye - its toxic effects result in blindness. large doses of alcohol lower blood sugar (hypoglycemia)

match the antidote with its specific toxic agent

a) BAL

b) penicillamine

c) sodium thiosulfate

d) NAC

e) pralidoxime

BAL: arsenic poisoning

penicillamine: copper toxicity

sodium thiosulphate: cyanide poisoning - converts cyanomethemoglobin to thiosulphate and regenerates methemoglobin

NAC: acetaminophen overdose - helps to restore depleted glutathione levels

pralidoxime: organophosphate pesticide poisoning - binds the organophosphates in preference to acetylcholinesterase

discuss various types of general treatment for poisoning. explain the mechanism for the treatment approach.

general treatments for poisoning includ et ease of emetics to cause vomiting and so rid the stomach of the poison; gastric lavage to wash the poison out of the stomach; adsorbents which are given orally to the patient and absorb the poison in the stomach. enhancing excretion may be used which involves the administration of aqueous solutions by mouth or intravenously (forced diuresis) to increase urine flow. if bicarbonate or ammonium chloride is included in the aqueous fluid then the pH of the urine is made more basic or acidic, respectively. this will facilitate the excretion of acids or bases, respectively.

what is the role of the poison control center (PCC)?

the PCC provides the following roles and services for th therapeutic advancement of toxicological poisoning: product ingredient informational affords information on the treatment of poisoned patients; supplies direct information to patients; suggests diagnostic and treatment information to health care professionals; institutes education programs for health care professionals; and sponsors poison prevention activities

ABC treatment

Airway

Breathing

Circulation

what is the role of poison control centers

provide product ingredient info, add info on treatment of poisoned patients, supply direct info to patients, suggest diagnostic and treatment info to healthcare pros, institute education programs for health care pros, sponsor poison prevention activities

what are the staffing requirements for PCC?`

certified medical toxicologists, physicians with fellowship in toxicology

what are the general supportive measures?

induction of emesis, activated charcoal

ipecac syrup

started the gastric emptying process; not used much anymore

emetine

inhibits protein synthesis eukaryotic cells by irreversibly blocking ribosome movement along the mRNA strand, and inhibits PNA replication in the early S phase of the cell cycle; can go through 3 pathways: central, peripheral, and direct GI

absorbants

activated charcoal; to neutralize and diminish intestinal absorption of exogenous substances form the GI tract

ideal for high molecular weight organics by covalent forces - not effective for metals, hydrocarbons, acids, and alkalis

polyethylene glycol

flushes ingested toxins through the bowel

is useful for enhanced elimination of sustained-release preparation of capsules or tablets, cellophane packets of street heroin or cocaine, agents not effectively absorbed with charcoal

sodium bicarbonate

enhanced elimination: induces alkaline urine and ionized ingested acidic substances

aspirin

ammonium chloride

enhanced elimination: alkalizes the urine

methamphetamine overdose

hemodialysis

alcohol poisoning, aspirin, acetone, atenolol, acetaminophen, urates, chloral hydrate, ethylene glycol, theophylline, water soluble drugs

not useful in copper sulphate, benzodiazepines, organophosphates, kerosene, digitalis poisonings

hemoperfusion

passing blood through a bed of particles contained within. a device to which blood lines and a blood pump are attached. blood comes in direct contact with the membrane coated sorbent particle and not a continuous dialysis membrane, from plasma paresis in that no plasma is separated from blood

acetaminophen, barbiturate, carbamazepine, chloral hydrate, caffeine, CCl4, …

what is a requirement if you are to use a specific antidote?

you must have positive identification of the toxicant

e.g. cyanide poisoning

chelating agents

react with the command to form a water-soluble complex with enhanced elimination potential from the body

calcium-disodium-edetate: lead poisoning

penicillamine: copper and lead intoxication

British anti-lewisite (e): arsenic and mercury exposure

reactive species

NAC (n-acetylcysteine): increases detox of reactive metabolites, increases production of glutathione, which enhances deactivation of the reacting metabolate p-benzoquinoneimie, generated from acetaminophen overdose

amyl nitrite, sodium nitrite, sodium thiosulfate: stimulate detox of cyanide by increasing its metabolic conversion to thiocyanate, rendering it more soluble and ready for urinary excretion

receptor-based antidotes

block metabolic transformation of active poisons

fomepizole, ethanol: competitive inhibition of alcohol dehydrogenase to block ethylene glycol metabolism

naloxone: narcotic receptor antagonist, treats opioid overdose (morphine, fentanyl)

atropine plus pralidoxime: competitive inhibitor that reversed cholingeric crisis

flumazenil: benzodiazepine receptor blocker that antagonizes the effects of sedative/hypnotics (diazepam)

antibodies

used for rattlesnake bites, scorpion stings, spider bites

antivenom: specifically bind the proteins in venom

digibind

anti-digoxin antibody - indicated for the treatment of overdose with digoxin, a popular cardiac drug

anascorp

antibody that treat scorpion stings; is equine derived and has a low rate of serum sickness. has a long half life

clinical toxicology lab

responsible for detection (drug abuse, overdose, etc), does urine testing, includes drug rehabilitation clinics, hospitals, workplace, and schools

forensic toxicology labs

responsible for identifying drug ingredients predominantly of unknown origin. screen tests for several known classifications of compounds. results determine next series of tests to confirm specific compound. many analytical methods