Clinical toxicology

Focuses on diseases that are caused by or are uniquely associated with toxic substances. Clinical toxicologists treat patients who are poisoned by drugs and other chemicals and develop new techniques for the diagnosis and treatment of such intoxications*

PREVENTION AND TREATMENT OF POISONING For clinical purposesall toxic agents two classes : 1. specific treatment or antidote 2. no specific treatment

supportive therapy is the mainstay of the treatment of drug poisoning "Treat the patient, not the poison," the most basic and important principle of clinical toxicology symptomatic medical care that supports vital functions is the only strategy*

.Treatment of acute poisoning :Goal of treatment

1.to maintain the vital functions if their impairment is imminent 2.to keep the concentration of poison in the crucial tissues as low as possible by : -preventing absorption -enhancing elimination 3.to combat the pharmacological and toxicological effects at the effector sites.

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Prevention of Further Absorption of Poison

Emesis

- To stimulate pharynx posterior-indicated for immediate intervention after poisoning by oral ingestion of chemicals -is contraindicated in certain situations:

(1) If the patient has ingested a corrosive poison, such as a strong acid or alkali (e.g., drain cleaners), emesis increases the likelihood of gastric perforation and further necrosis of the esophagus*

(2) if the patient is comatose or in a state of stupor or delirium, emesis may cause aspiration of the gastric contents

(3) if the patient has ingested a CNS stimulant, further stimulation associated with vomiting may precipitate convulsions

(4) if the patient has ingested a petroleum distillate (e.g., kerosene, gasoline, or petroleum-based liquid furniture polish), regurgitated hydrocarbons can be aspirated readily and cause chemical pneumonitis

In contrast, emesis should be considered if the ingested solution contains potentially dangerous compounds, such as pesticides. *

Ipecac. Ipecac acts as an emetic because of its local irritant effect on the enteric tract and its effect on the chemoreceptor trigger zone (CTZ) in the area postrema of the medulla. Syrup of ipecac, which may be purchased without prescription. The drug can be given orally 15 to 30 minutes to produce emesis The oral dose is 15 ml in children from 6 months to 12 years 30 ml in older children and adults. Because emesis may not occur when the stomach is empty, administration of ipecac should be followed after drinking water. Ipecac may be indicated when it can be administered to conscious, alert patients within 60 minutes of poisoning. *

Apomorphine.

Apomorphine stimulates the CTZ and causes emesis Apomorphine is not effective orally and must be given parenterally, usually by the subcutaneous route. However, this can be an advantage over ipecac in that it can be administered to an uncooperative patient and produces vomiting in 3 to 5 minutes

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GASTRIC LAVAGEGastric lavage is accomplished by inserting a tube into the stomach and washing the stomach with water or normal saline, to remove the unabsorbed poison.

should not be used routinely in the management of the poisoned patient should be reserved for patients who have ingested a potentially life-threatening amount of poison and the procedure can be undertaken within 60 minutes of ingestion.

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CHEMICAL ADSORPTION

Activated charcoal adsorbs drugs and chemicals on the surfaces of the charcoal particles, thereby preventing absorption and toxicity chemicals are adsorbed by charcoal :theophylline, phenobarbital carbamazepine, dapsone and quinine .

Chemical are not well adsorbed by activated charcoal : alcohols, hydrocarbons, metals, and corrosives

should not be used simultaneously with ipecac because charcoal can adsorb the emetic agent in ipecac and thus reduce the drug's emetic effect.

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Charcoal also may adsorb and decrease the effectiveness of specific antidotes

an adsorbent (charcoal) in the intestine may interrupt enterohepatic circulation of a toxicant, thus enhancing its excretion tricyclic antidepressants and glutethimide

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CHEMICAL INACTIVATION need more time than charcoal and gastric lavage

Antidotes can change the chemical nature of a poison by rendering it less toxic or preventing its absorption

Exp :Formaldehyde + ammonia hexamethylenetetramine Sodium formaldehyde sulfoxylate can convert mercuric ion to the less soluble metallic mercury

Sodium bicarbonate converts ferrous iron to ferrous carbonate, which is poorly absorbed

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PURGATIONto minimize absorption by hastening the passage of the toxicant through the gastrointestinal tract cathartic indicated after the ingestion of enteric-coated tablets when the time after ingestion is greater than 1 hour Exp. Sorbitol sodium sulfate avoided in patients with congestive heart failure. magnesium sulfate should be used cautiously in patients with renal failure *

Whole-bowel irrigation (WBI) polyethylene glycol

is a technique that not only promotes defecation but also eliminates the entire contents of the intestines

WBI may be considered in cases of acute poisoning by sustained-release or enteric-coated drugs and possibly toxic ingestions of iron, lead, zinc.*

INHALATION AND DERMAL EXPOSURE TO POISONS

When a poison has been inhaled remove the patient from the source of exposure Skin has had contact with a poison wash thoroughly with water Contaminated clothing should be removed chemical injuries to the eye thorough irrigation of the eye with water for 15 minutes should be performed immediately.

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Enhanced Elimination of the Poison

BIOTRANSFORMATION

Many chemicals are toxic because they are biotransformed into more toxic chemicals

Exp : methanol formic acid (highly toxic metabolite), by alcohol dehydrogenase ethanol is used to inhibit the conversion

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Acetaminophen is converted by the CYP system to an electrophilic metabolite that is detoxified by glutathione, a cellular nucleophile Acetaminophen does not cause hepatotoxicity until glutathione is depleted, whereupon the reactive metabolite binds to essential macromolecular constituents of the hepatocyte, resulting in cell death. The liver can be protected by maintenance of the concentration of glutathione, and this can be accomplished by the administration of N-acetylcysteine

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BILIARY EXCRETION the effect is slow in onset URINARY EXCRETIONDrugs and poisons excreted into the urine by glomerular filtration and active tubular secretion reabsorbed into the blood if they are in a lipid-soluble form that will penetrate the tubule or if there is an active mechanism for their transport. Passive reabsorption from the tubular lumen can be altered. Diuretics - inhibit reabsorption by decreasing the concentration gradient of the drug from the lumen to the tubular cell -increasing flow through the tubule. -Furosemide is used most often, others : osmotic diuretics - Forced diuresis should be used with caution, especially in patients with renal, cardiac, or pulmonary complications.*

anatomic segment of the nephron*

Acidic compounds such as phenobarbital and salicylates are cleared much more rapidly in alkaline than in acidic urine Urine alkalinization increases the urine elimination of chlorpropamide, diflunisal, fluoride, methotrexate, phenobarbital, and salicylateUrine alkalinization is contraindicated in the case of compromised renal function or failure *

Renal excretion of basic drugs such as amphetamine theoretically can be enhanced by acidification of the urine

Acidification can be accomplished by the administration of ammonium chloride or ascorbic acid. Urinary excretion of an acidic compound is particularly sensitive to changes in urinary pH if its pKa is within the range of 3.0 to 7.5; for bases, the corresponding range is 7.5 to 10.5.

DIALYSISHemodialysis and peritoneal dialysis Hemodialysis is much more effective than peritoneal dialysis and may be essential in a few life-threatening intoxications, such as with methanol, ethylene glycol, and salicylates

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ANTAGONISM OR CHEMICAL INACTIVATION OF AN ABSORBED POISONSpecific chemical antagonists of a toxicant, such as opioid antagonists Atropine as an antagonist of pesticide-induced acetylcholine excess fomepizole, an inhibitor of alcohol dehydrogenase, approved for treatment for poisoning by ethylene glycol and methanol Chelating agents with high selectivity for certain metal ions are used more commonly Antibodies offer the potential for the production of specific antidotes for a host of common poisons and for drugs that frequently are abused or misused Exp purified digoxin-specific Fab fragments of antibodies in the treatment of potentially fatal cases of poisoning with digoxin

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SPECIFIC ANTIDOTESPoisonAcetaminophenAcetylcholinesterases, OPs, physostigmineIron saltsMethanol, Ethylene glycolMercury, leadNarcotic drugsAnti/muscarinics-cholinergics

OP anticholinergics

AntidoteAcetylcysteineAtropine

DeferoximeEthanolMetal ChelatorsNaloxone

Physostigmine

Pralidoxime (2-PAM)*

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