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 purposes

all 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
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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.

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
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(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

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

GASTRIC LAVAGE

Gastric 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
than charcoal and gastric lavage

need more time

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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PURGATION
to 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
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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.

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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 Nacetylcysteine
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BILIARY EXCRETION the effect is slow in onset

URINARY EXCRETION
Drugs 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.

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anatomic segment of the nephron

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 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 salicylate
Urine alkalinization is contraindicated in the case of
compromised renal function or failure

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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.

DIALYSIS
Hemodialysis 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

POISON
Specific 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 ANTIDOTES
Poison

Antidote

Acetaminophen
Acetylcholinesterases,
OPs, physostigmine
Iron salts
Methanol, Ethylene glycol
Mercury, lead
Narcotic drugs
Anti/muscarinicscholinergics

Acetylcysteine
Atropine

OP anticholinergics

Deferoxime
Ethanol
Metal Chelators
Naloxone
Physostigmine
Pralidoxime (2-PAM)
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