Toxicology Written Report

8/4/2019 Toxicology Written Report

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PAMANTASAN NG LUNGSOD NG MAYNILA

(University of the City of Manila)

Intramuros, Manila

GRADUATE SCHOOL OF HEALTH SCIENCES

A WRITTEN REPORT:

TOXICOLOGY

Presented By:

Joanne Paula O. Pineda, RN

Lannz P. Batalla, RN

Presented To:

Prof. Benjamin Tan Tablizo, Jr., MAN

September 3, 2011


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Principles of Toxicology and Treatment of Poisoning

TOXICOLOGY

Toxicology is the study of the nature and mechanisms underlying toxic effects exerted by

substances on living organisms and other biologic systems. It is the science of the adverse

effects of chemicals, including drugs, on living organisms. Toxicology also deals with

quantitative assessment of the adverse effects in relation to the concentration or dosage,

duration, and frequency of exposure of the organisms.

Toxicology has a broad scope. It deals with toxicity studies of chemicals used (1) in medicine for

diagnostic, preventive, and therapeutic purposes; (2) in the food industry as direct and indirect

additives; (3) in agriculture as pesticides, growth regulators, artificial pollinators, and animal

feed additives; and (4) in the chemical industry as solvents, components, and intermediates of

plastics and many other types of chemicals. It is also concerned with the health effects ofmetals (as in mines and smelters), petroleum products, paper and pulp, toxic plants, and animal

toxins. The discipline often is divided into several major areas. The descriptive toxicologist

performs toxicity tests to obtain information that can be used to evaluate the risk that exposure

to a chemical poses to humans and to the environment. The mechanistic toxicologistattempts

to determine how chemicals exert deleterious effects on living organisms. Knowledge of the

mechanism of action provides enhancement to the toxicological evaluation and provides a basis

for other branches of toxicology. Such studies are essential for the development of tests for the

prediction of risks, for facilitating the search for safer chemicals, and for rational treatment of

the manifestations of toxicity. The regulatory toxicologist judges whether a drug or other

chemical has a low enough risk to justify making it available for its intended purpose. It

attempts to protect the public by setting laws, regulations, and standards to limit or suspend

the use of very toxic chemicals as well as defines use conditions for others. Two specialized

areas of toxicology are particularly important for medicine. Forensic toxicology, which combines

analytical chemistry and fundamental toxicology, is concerned with the medico legal aspects of

chemicals. Forensic toxicologists assist in postmortem investigations to establish the cause or

circumstances of death. 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. Those in clinical toxicology administer antidotes to counter the specific

toxicity, and take other measures to ameliorate the symptoms and signs and hasten the

elimination of the toxicant from the body.

The knowledge gained is then utilized to assess the risk of adverse effects to the environment

and humans and is termed as risk assessment. A health risk assessment constitutes a written

document that is based upon all pertinent scientific information regarding toxicology, human

experiences, environmental fate, and exposure. These data are subject to critique and

interpretation. The aim of this assessment is to estimate the potential of an adverse effect that

occurs in humans and wildlife ecological system posed by a specific amount of exposure to a


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chemical. Risk assessments include several elements such as (1) description of the potential

adverse health effects based on an evaluation of results of epidemiologic, clinical, toxicological,

and environmental research; (2) extrapolation from these results to predict the type and

estimate the extent of health effects in humans under given conditions of exposure; (3)

judgments as to the number and characteristics of individuals exposed at various intensities

and durations; (4) and summary judgments on the existence and overall magnitude of thepublic health problem. Risk characterization represents the final and the most critical step in

the risk assessment process whereby data on the doseresponse relationship of a chemical are

integrated with estimates of the degree of exposure in a population to characterize the

likelihood and severity of a health risk.

The clinician must evaluate the possibility that a patient's signs and symptoms may be caused

by toxic chemicals present in the environment or administered as therapeutic agents. Many of

the adverse effects of drugs mimic symptoms of disease. Appreciation of the principles of

toxicology is necessary for the recognition and management of such clinical problems.

Toxicokinetics and Toxicodynamics

Toxicokinetics denotes the absorption, distribution, excretion, and metabolism of toxins, toxic

doses of therapeutic agents, and their metabolites. Toxicodynamics on the other hand is used

to denote the injurious effects of these substances on vital functions.

Special Aspects of Toxicokinetics: Volume Distribution

The Volume Distribution (Vd) is defined as the apparent volume into which a substance is

distributed. A large Vd implies that the drug is not readily accessible to measures aimed at

purifying the blood, such as hemodyalisis. Examples of drugs with large volumes of distribution(> 5 L/kg) include antidepressants, antipsychotics, antimalarias, opioids, propranolol, and

verapamil. Drugs with a relatively small volumes of distribution (


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lidocaine 1-2

methotrexate 1-2

morphine 2-5

neostigmine 0.7-0.9

nortriptyline 2-5

NXY-059 0.1-0.2

paracetamol 1-2

phenytoin 0.7-0.9

propranolol 2-5

sulfamethoxazole 0.1-0.2

theophylline 0.4-0.7

tubocurarine 0.2-0.4

warfarin 0.1-0.2

Special Aspects of Toxicokinetics: Clearance

Clearance is a measure of the volume of plasma that is cleared of drug per unit time. The total

clearance for most drugs is the sum of clearances via excretion by the kidneys and metabolism

by the liver.

Overdosage of a drug can alter the usual pharmacokinetic processes, and this must be

considered when applying kinetics to poisoned patients. For example, dissolution of tablets or

gastric emptying time may be slowed so that absorption and peak toxic effects are delayed.

Drugs may injure the epithelial barrier of the gastrointestinal tract and thereby increase

absorption. If the capacity of the liver to metabolize a drug is exceeded, more drugs will be

delivered to the circulation. With the dramatic increase in the circulation of the drug in the

blood, protein-binding capacity may be exceeded, resulting in an increased fraction of free drug

and greater toxic effect. At normal dosage, most drugs are eliminated at a rate proportional to

the plasma concentration. If the plasma concentration is very high and normal metabolism is

saturated, the rate of elimination may become fie. This change n kinetics may markedly prolong

the apparent serum half-life and increase toxicity.

Special Aspects of Toxicodynamics

The general dose-response principles are relevant when estimating the potential severity of

intoxication.When considering quantal dose-response data, both the therapeutic index and theoverlap of therapeutic and toxic response curves must be considered. For instance two drugs

may have the same therapeutic index but unequal safe dosing ranges if the slopes of their dose-

response curves are not the same.
http://en.wikipedia.org/wiki/Lidocainehttp://en.wikipedia.org/wiki/Methotrexatehttp://en.wikipedia.org/wiki/Methotrexatehttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Neostigminehttp://en.wikipedia.org/wiki/Nortriptylinehttp://en.wikipedia.org/wiki/Nortriptylinehttp://en.wikipedia.org/wiki/NXY-059http://en.wikipedia.org/wiki/Paracetamolhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Propranololhttp://en.wikipedia.org/wiki/Sulfamethoxazolehttp://en.wikipedia.org/wiki/Sulfamethoxazolehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Tubocurarinehttp://en.wikipedia.org/wiki/Tubocurarinehttp://en.wikipedia.org/wiki/Warfarinhttp://en.wikipedia.org/wiki/Warfarinhttp://en.wikipedia.org/wiki/Warfarinhttp://en.wikipedia.org/wiki/Tubocurarinehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Sulfamethoxazolehttp://en.wikipedia.org/wiki/Propranololhttp://en.wikipedia.org/wiki/Phenytoinhttp://en.wikipedia.org/wiki/Paracetamolhttp://en.wikipedia.org/wiki/NXY-059http://en.wikipedia.org/wiki/Nortriptylinehttp://en.wikipedia.org/wiki/Neostigminehttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Methotrexatehttp://en.wikipedia.org/wiki/Lidocaine


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Medical Treatment: Physical Assessment and History

The initial management of a patient with coma, seizures, or otherwise altered mental status

should follow the same approach regardless of the poison involved. Attempting to make a

specific toxicologic diagnosis only delays the application of supportive measures that form the

basis (ABCDs) of poisoning treatment.

Airway the airway should be cleared of vomitus or any other obstruction and an oralairway or endotracheal tube inserted if needed. For many patients, simple positioning in

the lateral decubitus position is sufficient to move the flaccid tongue out of the airway.

Breathing breathing should be assessed by observation and oximetry and, if in doubt,by measuring arterial blood gases. Patients with respiratory insufficiency should be

intubated and mechanically ventilated.

Circulation the circulation should be assessed by continuous monitoring of pulse rate,blood pressure, urinary output, and evaluation of peripheral perfusion. An intravenous

line should be placed and blood drawn for serum glucose and other routine

determinations. Dextrose patients with altered mental status should receive a challenge with

concentrated dextrose, unless a rapid bedside blood glucose test demonstrates that the

patient is not hypoglycemic. Adults are given 25 g (50mL of 50% dextrose solution)

intravenously, and children are given 0.5 g/kg (2mL/kg of 25% dextrose).

One can begin a more detailed evaluation to make a specific diagnosis once the essential ABCD

interventions have been initiated. Gathering available history and performing a toxicologically

oriented physical examination are imperative in assessing the patient who is believed to be

poisoned.

History

Obtaining an adequate history remains the most important aspect of the management of a

potentially poisoned patient. In many cases, a precise medical history can define the exact

nature of the exposure. In others it delineates the potential agents to which the patient may

have access at home or work. Although occasionally unreliable (for example, in patients with

dementia or suicidal ideation), the medical history permits a focused investigation into the

potential for patient harm and guides initial management. The process of taking the medical

history is guided by the clinical situation, but the history usually includes questions about the

timing, nature and circumstances of the exposure and the patient's initial symptoms, symptom

progression, and complicating medical conditions.

Oral statements about the amount and even the type of drug ingested in toxic emergencies

may be unreliable. Even so, family members, police, and fire department or paramedical

personnel should be asked to describe the environment in which the toxic emergency occurred

and should bring to the emergency department any syringes, empty bottles, household

products, or over-the-counter medications in the immediate vicinity of the possibly poisoned

patient.


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Physical Examination

A brief examination should be performed, emphasizing those areas most likely to give clues to

the toxicologic diagnosis. These include vital signs, eyes and mouth, skin, abdomen, and

nervous system. Obtaining an adequate history remains the most important aspect of the

management of a potentially poisoned patient. A precise medical history can define the exactnature of the exposure. It delineates the potential agents to which the patient may have access

at home or work. Although occasionally unreliable (for example, in patients with dementia or

suicidal ideation), the medical history permits a focused investigation into the potential for

patient harm and guides initial management. The process of taking the medical history is

guided by the clinical situation, but the history usually includes questions about the timing,

nature and circumstances of the exposure and the patient's initial symptoms, symptom

progression, and complicating medical conditions.

A. Vital SignsCareful evaluation of vital signs (blood pressure, pulse, respirations, and temperature) is

essential in all toxicologic emergencies. Hypertension and tachycardia are typical withamphetamines, cocaine, and antimuscarinic (anticholinergic) drugs. Hypotension and

bradycardia are characteristic features of overdose with calcium channel blockers, -

blockers, clonidine, and sedative-hypnotics. Hypotension with tachycardia is common

with tricyclic antidepressants, phenothiazines, vasodilators, and theophylline. Rapid

respirations are typical of salicylates, carbon monoxide, and other toxins that produce

metabolic acidosis or cellular asphyxia. Hyperthermia may be associated with

sympathomimetics, anticholinergics, salicylates, and drugs producing seizures or

muscular rigidity. Hypothermia can be caused by any CNS-depressant drug, especially

when accompanied by exposure to a cold environment.

B. EyesThe eyes are a valuable source of toxicologic information. Constriction of the pupils

(miosis) is typical of opioids, clonidine, phenothiazines, and cholinesterase inhibitors

(eg, organophosphate insecticides), and deep coma due to sedative drugs. Dilation of

the pupils (mydriasis) is common with amphetamines, cocaine, LSD, and atropine and

other anticholinergic drugs. Horizontal nystagmus is characteristic of intoxication with

phenytoin, alcohol, barbiturates, and other sedative drugs. The presence of both vertical

and horizontal nystagmus is strongly suggestive of phencyclidine poisoning. Ptosis and

ophthalmoplegia are characteristic features of botulism.

C. MouthThe mouth may show signs of burns due to corrosive substances, or soot from smoke

inhalation. Typical odors of alcohol, hydrocarbon solvents, or ammonia may be noted.

Poisoning due to cyanide can be recognized by some examiners as an odor like bitter

almonds.


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D. SkinThe skin often appears flushed, hot, and dry in poisoning with atropine and other

antimuscarinics. Excessive sweating occurs with organophosphates, nicotine, and

sympathomimetic drugs. Cyanosis may be caused by hypoxemia or by

methemoglobinemia. Icterus may suggest hepatic necrosis due to acetaminophen orAmanita phalloides mushroom poisoning.

E. AbdomenAbdominal examination may reveal ileus, which is typical of poisoning with

antimuscarinic, opioid, and sedative drugs. Hyperactive bowel sounds, abdominal

cramping, and diarrhea are common in poisoning with organophosphates, iron, arsenic,

theophylline, andA phalloides.

F. Nervous SystemA careful neurologic examination is essential. Focal seizures or motor deficits suggest astructural lesion (such as intracranial hemorrhage due to trauma) rather than toxic or

metabolic encephalopathy. Nystagmus, dysarthria, and ataxia are typical of phenytoin,

carbamazepine, alcohol, and other sedative intoxication. Twitching and muscular

hyperactivity are common with atropine and other anticholinergic agents, and cocaine

and other sympathomimetic drugs. Muscular rigidity can be caused by haloperidol and

other antipsychotic agents and by strychnine. Seizures are often caused by overdose

with antidepressants (especially tricyclic antidepressants and bupropion), cocaine,

amphetamines, theophylline, isoniazid, and diphenhydramine. Flaccid coma with

absentreflexes and even an isoelectric EEG may be seen with deep coma due to opioid

or sedativehypnotic intoxication and may be mistaken for brain death.

G. Laboratory and Imaging Procedures Arterial Blood Gases

Since the adequacy of ventilation and oxygenation may be difficult to assess

clinically and with pulse oximetry, the determination of the arterial blood gases

is crucial. Although invasive, important information is gleaned from the

assessment of a symptomatic patient's acid-base (pH), ventilatory (PCO2) and

oxygenation (PO2) status. For example, a metabolic acidosis in an unconscious

patient may suggest that the patient ingested methanol or had a recent seizure.

Alternatively, a combined metabolic acidosis and respiratory alkalosis suggests

salicylate poisoning. Renal Function Tests

Some toxins have direct nephrotoxic effects; in other cases, renal failure is due

to shock or myoglobinuria. Blood urea nitrogen and creatinine levels should be

measured and urinalysis performed. Elevated serum creatine kinase (CK) and

myoglobin in the urine suggest muscle necrosis due to seizures or muscular

rigidity. Oxalate crystals in the urine suggest ethylene glycol poisoning.

Electrocardiograph


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The electrocardiograph serves several important roles in the management of

poisoned patients and should be performed in virtually all circumstances. In

patients with cardiovascular abnormalities, the evaluation of an

electrocardiograph may suggest the toxin. For example, calcium channel

blockers typically produce bradycardia with atrioventricular nodal block,

whereas digoxin typically produces ST segment abnormalities and first-degreearteriovenous (AV) block. Alternatively, and just as important, the

electrocardiograph may have a prognostic value. Patients with tricyclic

antidepressant poisoning usually have intraventricular conduction delays, such

as QRS widening, the magnitude of which is related to the likelihood of both

seizure and ventricular dysrhythmia.

Imaging FindingsA plain film of the abdomen may be useful because some tablets, particularly

iron and potassium, may be radiopaque. Chest x-ray may reveal aspiration

pneumonia, hydrocarbon pneumonia, or pulmonary edema. When head trauma

is suspected, a CT scan is recommended. Toxicology Screen Tests

The clinical examination of the patient and selected routine laboratory tests are

usually sufficient to generate a tentative diagnosis and an appropriate treatment

plan. While screening tests may be helpful in confirming a suspected intoxication

or for ruling out intoxication as a cause of apparent brain death, they should not

delay needed treatment. When a specific antidote or other treatment is under

consideration, quantitative laboratory testing may be indicated. For example,

determination of the acetaminophen serum level is useful in assessing the need

for antidotal therapy with acetylcysteine. Serum levels of theophylline,

carbamazepine, lithium, salicylates, valproic acid, and other drugs may indicate

the need for hemodialysis.

POISONS

The definitions of drug, toxin, and poison are cumbersome and vary with the context of the

terms' uses. A drug is a substance normally taken for a specific purpose. This may be

therapeutic in nature or for non-therapeutic use. A toxin is a substance that is not ordinarily

consumed as a drug. Toxins are poisons produced via some biological function in nature, and

venoms are usually defined as biological toxins that are injected by a bite or sting to cause their

effect. Apoison is a substance that interferes adversely with a physiological process. These aresubstances that can cause disturbances to an organisms physiological processes, usually by

chemical reaction or other activity on the molecular scale, when a sufficient quantity is

absorbed by an organism. Other poisons are generally defined as substances which are

absorbed through epithelial linings such as the skin or gut. Therefore, all drugs and toxins may

be poisons.
http://en.wikipedia.org/wiki/Chemical_substancehttp://en.wikipedia.org/wiki/Chemical_reactionhttp://en.wikipedia.org/wiki/Activity_%28chemistry%29http://en.wikipedia.org/wiki/Molecularhttp://en.wikipedia.org/wiki/Molecularhttp://en.wikipedia.org/wiki/Activity_%28chemistry%29http://en.wikipedia.org/wiki/Chemical_reactionhttp://en.wikipedia.org/wiki/Chemical_substance


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Defining what constitutes a poison is not simple. Some substances have virtually no known

beneficial effects in humans and can only be considered poisonous like cyanide. Many

substances that are normally harmless, or even necessary for life (e.g., oxygen, water), become

poisons when present in excess. In fact, all drugs in clinical use have the potential to have

beneficial or deleterious effects, and can, at some dose, be a poison. These clinical drugs may

be poisonous or therapeutic depending on the dose administered.

Specific Drugs or Toxins and Their Toxic Syndromes

TOXIN VITAL SIGNS MENTAL

STATUS

SIGNS AND

SYMPTOMS

CLINICAL

FINDINGS

Acetaminophen Normal (early) Normal Anorexia,

nausea,

vomiting

Right upper

quadrant

tenderness,

jaundice (late)

Amphetamines Hypertension,

tachycardia,

tachypnea,

hyperthermia

Hyperactive,

agitated, toxic

psychosis

Hyperalertness,

panic, anxiety

diaphoresis

Mydriasis,

hyperactive

peristaltism,

diaphoresis

Antihistamines Hypotension,

hypertension,

tachycardia,

hyperthermia

Altered

(agitation,

lethargy to

coma),

hallucinations

Blurred vision,

dry mouth,

inability to

urinate

Dry mucous

membranes,

mydriasis, flush,

diminished

peristaltism,

urinary retention

Arsenic (acute) Hypotension,

tachycardia

Alert to coma Abdominal pain,

vomiting,

diarrhea,dysphagia

Dehydration

Barbiturates Hypotension,

bradypnea,

hypothermia

Altered

(lethargy to

coma)

Slurred speech,

ataxia

Dysconjugate

gaze, bulae,

hyporeflexia

Beta-adrenergic

antagonists

Hypotension,

bradycardia

Altered

(lethargy to

coma)

Dizziness Cyanosis, seizures

Botulism Bradypnea Normal unless

hypoxia

Blurred vision,

diplopia,

dysphagia, soreor dry throat,

diarrhea

Opthalmoplegia,

mydriasis, ptosis,

cranial nerveabnormalities,

descending

paralysis

Carbamazepine Hypotension,

tachycardia,

bradypnea,

Altered

(lethargy to

coma)

Hallucinations,

extrapyramidal

movements,

Mydriasis,

nystagmus


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hypothermia seizures

Carbon monoxide Often normal Altered

(lethargy to

coma)

Headache,

dizziness,

nausea,

vomiting

Seizures

Clonidine Hypotension,hypertension,

bradycardia,

bradypnea

Altered(lethargy to

coma)

Dizziness,confusion

Miosis

Cocaine Hypertension,

tachycardia,

tachypnea,

hyperthermia

Altered

(anxiety,

agitation,

delirium)

Hallucinations,

paranoia, panic

anxiety,

restlessness

Mydriasis,

nystagmus

Cyclic

antidepressants

Hypotension,

tachycardia

Altered

(lethargy to

coma)

Confusion,

dizziness, dry

mouth, inabilityto urinate

Mydriasis, dry

mucous

membranes,distended

bladder, flush,

seizures

Digitalis Hypotension,

bradycardia

Normal to

altered, visual

distortion

Nausea,

vomiting,

anorexia, visual

disturbances

None

Disulfiram/ethanol Hypotension,

tachycardia

Normal Nausea,

vomiting,

headache,vertigo

Flush,

diaphoresis,

tender abdomen

Ethylene glycol Tachypnea Altered

(lethargy to

coma)

Abdominal pain Slurred speech,

ataxia

Iron Hypotension,

tachycardia

Normal or

lethargy

Nausea,

vomiting,

diarrhea,

abdominal pain,

hematemesis

Tender abdomen

Isoniazid Often normal Normal or

altered

(lethargy to

coma)

Nausea,

vomiting

Seizures

Isopropanol Hypotension,

tachycardia,

bradypnea

Altered

(lethargy to

coma)

Nausea,

vomiting

Hyporeflexia,

ataxia, acetone

odor on breath

Lead Hypertension Altered Irritability, Peripheral


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(lethargy to

coma)

abdominal pain

(colic), nausea,

vomiting,

constipation

neuropathy,

seizures, gingival

pigmentation

Lithium Hypotension

(late)

Altered

(lethargy tocoma)

Diarrhea,

tremor, nausea

Weakness,

tremor, ataxia,myoclonus,

seizures

Mercury Hypotension

(late)

Altered

(psychiatric

disturbances)

Salivation,

diarrhea,

abdominal pain

Stomatitis, ataxia,

tremor

Methanol Hypotension,

tachypnea

Altered

(lethargy to

coma)

Blurred vision,

blindness,

abdominal pain

Hyperemic disks,

mydriasis

Opioids hypotension,

bradycardia,bradypnea,

hypothermia

Altered

(lethargy tocoma)

Slurred speech,

ataxia

Miosis, decreased

peristaltism

Organophosphates/

carbamates

Hypotension/

hypertension,

bradycardia/

tachycardia,

bradypnea/

tachypnea

Altered

(lethargy to

coma)

Diarrhea,

abdominal pain,

blurred vision,

vomiting

Salivation,

diaphoresis,

lacrimation,

urination,

bronchorrhea

defecation,

miosis,

fasciculations,

seizures

Phencyclidine Hypertension,

tachycardia,

hyperthermia

Altered

(agitation,

lethargy to

coma)

Hallucinations Miosis,

diaphoresis,

myoclonus, blank

stare, nystagmus,

seizures

Phenothiazines Hypotension,

tachycardia,

hypothermia

Altered

(lethargy to

coma)

Dizziness, dry

mouth, inability

to urinate

Miosis or

mydriasis,

decreased bowel

sounds, dystonia

Salicylates Hypotension,

tachycardia,

tachypnea,

hyperthermia

Altered

(agitation,

lethargy to

coma)

Tinnitus,

nausea,

vomiting

Diaphoresis,

tender abdomen,

pulmonary

edema

Sedative-hypnotics Hypotension,

bradypnea,

hypothermia

Altered

(lethargy to

coma)

Slurred speech,

ataxia

Hyporeflexia,

bullae


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Theophylline Hypotension,

tachycardia,

tachypnea,

hyperthermia

Altered

(agitation)

Nausea,

vomiting,

diaphoresis,

anxiety

Diaphoresis,

tremor, seizures

dysrhythmias

SOURCE: From Goldfrank et al. 1998.

POISON MANAGEMENT

Preventing Absorption: Decontamination

Just like other medical emergencies, supportive therapy is the mainstay of the treatment of

drug poisoning. The adage, "Treat the patient, not the poison," remains the most basic and

important principle of clinical toxicology.

Treatment of acute poisoning must be prompt. The first goal is to maintain the vital functions if

their impairment is imminent. The second goal is to keep the concentration of poison in the

crucial tissues as low as possible by preventing absorption and enhancing elimination. The third

goal is to combat the pharmacological and toxicological effects at the effector sites.

Primary prevention of toxicity, such as parental education, drug storage in child-resistant

containers, or the use of computerized adverse drug effects programs by medical professionals,

are the optimal means of reducing the incidence of poisoning. Although typically helpful, such

measures cannot eliminate poisoning. Those patients who are exposed to a potentially toxic

substance subsequently require decontamination as a method of secondary prevention. As

most exposures occur through the gastrointestinal tract, the major focus must be on

gastrointestinal decontamination. This form of decontamination is often invasive and difficultto perform. Additionally, it includes small but genuine risks such as gastrointestinal perforation

or pulmonary aspiration. However, gastrointestinal decontamination is the cornerstone in the

early management of acutely poisoned patients.

Eyes, Skin, or through Inhalation

When a poison has been inhaled, the first priority is to remove the patient from the source of

exposure. Similarly, if the skin has had contact with a poison, contaminated clothing should be

completely removed and wash contaminated skin thoroughly with water. Contaminated

clothing should be double-bagged to prevent illness in health care providers and for possible

laboratory analysis. Initial treatment of all types of chemical injuries to the eye must be rapid;thorough irrigation of the eye with water for 15 minutes should be performed immediately.

Gastrointestinal Decontamination

Prevention of absorption of toxin remaining in the GI tract is important in managing the

poisoned patient. The method used to provide gastrointestinal decontamination following

ingestion of a potential toxin primarily depends on the clinical condition of the patient, the


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nature and quantity of the toxin, and the relative risk of toxin-associated or therapy-associated

morbidity and mortality.

1. EmesisEmesis still may be indicated for immediate intervention after poisoning by oral

ingestion of chemicals, it is contraindicated in certain situations: (1) If the patient hasingested 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; and (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.

Vomiting or emesis can be induced mechanically by fingertip stimulation of theposterior pharynx.

Ipecac Syrup The most common household emetic is syrup of ipecac (notipecac fluid extract, which is 14 times more potent and may cause fatalities).

Syrup of ipecac is available in 0.5- and 1-fluid ounce containers (approximately

15 and 30 ml), which may be purchased without prescription. The drug can be

given orally, but it takes 15 to 30 minutes to produce emesis; this compares

favorably with the time usually required for adequate gastric lavage. The oral

dose is 15 ml in children from 6 months to 12 years of age and 30 ml in older

children and adults. Because emesis may not occur when the stomach is empty,

administration of ipecac should be followed by a drink of water. Ipecac issometimes used to treat childhood ingestions at home under telephone

supervision of a physician or poison control center personnel. Ipecac should not

be used if the suspected intoxicant is a corrosive agent, a petroleum distillate, or

a rapidly acting convulsant.

2. Gastric LavageGastric lavage involves the insertion of a large-bore tube (36-French tube or larger for

adults and a 24-French tube or larger for children) via the esophagus into the stomach

and washing the stomach with water, normal saline, or one-half normal saline to

remove the unabsorbed poison. Lavage solutions (usually 0.9% saline) should be at bodytemperature to prevent hypothermia. The procedure should be performed as soon as

possible, but only if vital functions are adequate or supportive procedures have been

implemented. The contraindications to this procedure generally are the same as for

emesis, and there is the additional potential complication of mechanical injury to the

throat, esophagus, and stomach. According to the American and European clinical

toxicologists, they concluded that gastric lavage should not be used routinely in the

management of the poisoned patient but should be reserved for patients who have


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ingested a potentially life-threatening amount of poison and when the procedure can be

undertaken within 60 minutes of ingestion.

For patients who are comatose, have seizures, or has lost gag reflex, an endotracheal

tube with an inflatable cuff should be positioned before lavage is initiated to prevent.

During gastric lavage, the patient should be placed on his or her left side because of theanatomical asymmetry of the stomach, with the head hanging face down over the edge

of the examining table. If possible, the foot of the table should be elevated. This

technique minimizes chances of aspiration.

The contents of the stomach should be aspirated with an irrigating syringe and saved for

chemical analysis. The stomach then may be washed with saline solution. Only small

volumes (120 to 300 ml) of lavage solution should be instilled into the stomach at one

time so that the poison is not pushed into the intestine. Lavage is repeated until the

returns are clear, which usually requires 10 to 12 washings and a total of 1.5 to 4 L of

lavage fluid. When the lavage is complete, the stomach may be left empty, or an

antidote may be instilled through the tube. If no specific antidote for the poison is

known, an aqueous suspension of activated charcoal and a cathartic often is given.

3. Activated CharcoalActivated charcoal can adsorb many drugs and poisons because of its large surface area.

It is most effective if given in a ratio of at least 10:1 of charcoal to estimated dose of

toxin by weight. It is effective immediately after administration, and its utility is not so

compromised by pyloric outflow, since toxins may bind within the duodenum. It may be

administered as a drink to conscious patients and through a conventional nasogastric

tube in patients with altered consciousness, minimizing the complications associated

with large-bore orogastric tubes. Many, but not all, chemicals are adsorbed by charcoal.

Charcoal does not bind to iron, lithium, or potassium, and it binds to alcohols and

cyanide only poorly. It does not appear to be useful in poisoning due to corrosive

mineral acids and alkali. Recent studies suggest that oral activated charcoal given alone

may be just as effective as gut emptying followed by charcoal. Also, other studies have

shown that repeated doses of oral activated charcoal may enhance systemic elimination

of some drugs (including carbamazepine, dapsone, and theophylline) by a mechanism

referred to as "gut dialysis."

Activated charcoal usually is prepared as a mixture of at least 50 g (about 10 heaping

tablespoons) in a glass of water. The mixture is then administered either orally or via a

gastric tube. Because most poisons do not appear to desorb from the charcoal if

charcoal is present in excess, the adsorbed poison need not be removed from thegastrointestinal tract. Activated charcoal should not be used simultaneously with ipecac

because charcoal can adsorb the emetic agent in ipecac and thus reduce the drug's

emetic effect. Charcoal also may adsorb and decrease the effectiveness of specific

antidotes.


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4. CatharticsAdministration of a cathartic (laxative) agent may hasten removal of toxins from the

gastrointestinal tract and reduce absorption, although no controlled studies have been

done. Cathartics generally are considered harmless unless the poison has injured the

gastrointestinal tract. Cathartics are indicated after the ingestion of enteric-coated

tablets, when the time after ingestion is greater than 1 hour, and for poisoning byvolatile hydrocarbons. Sorbitol is the most effective, but sodium sulfate and magnesium

sulfate also are used; all act promptly and usually have minimal toxicity. However,

magnesium sulfate should be used cautiously in patients with renal failure or in those

likely to develop renal dysfunction, and Na+-containing cathartics should be avoided in

patients with congestive heart failure.

5. Whole Bowel IrrigationWhole-bowel irrigation has been used extensively to prepare the colon for surgery or

endoscopy. The administration of a non-absorbable, isotonic polyethylene glycol

solution (GoLYTELY, CoLyte) results in the evacuation of all intestinal contents after

ingestion of iron tablets, enteric-coated medicines, illicit drug-filled packets, and foreign

bodies. The solution is administered at 12 L/h (500 mL/h in children) for several hours

until the rectal effluent is clear over several hours.

The critical determinants for the success of whole-bowel irrigation are speed and

volume of administration. Delivery of 2 L/h to most adult patients results in

gastrointestinal clearance of drug within 3 hours.

Enhanced Elimination

1. Urine pH ManipulationIn manipulation of urine pH, the pH of the urine is most commonly raised to allow toxins

with low pKa values (e.g., weak acids or onions such as salicylate) to become ionized

within the renal tubule and collecting system. The ionized drug is trapped in the urine

since only nonionized substances can diffuse back across cellular membranes to be

reabsorbed. A pH change can only be of benefit if a drug or toxin is ionizable within the

pH range of urine, such as salicylic acid, phenobarbital, or formic acid.

Alkalinization of the urine is most commonly achieved by the administration of sodium

bicarbonate intravenously.

Acidification of the urine, which would conceivably enhance the elimination of weakbases with high pKa values, is considered dangerous, since many of the toxins that might

benefit from this maneuver (e.g., phencyclidine or amphetamine) are associated with

rhabdomyolysis. Acidification of the urine in this situation would allow myoglobin to

precipitate within and to obstruct the renal tubule.

For example, urinary alkalinization is useful in cases of salicylate overdose. Acidification

may increase the urine concentration of drugs such as phencyclidine and amphetamines


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but is not advised because it may worsen renal complications from rhabdomyolysis,

which often accompanies the intoxication.

2. DialysisThe utility of dialysis depends on the amount of poison in the blood relative to the total-

body burden Petironeal dialysis This is a relatively simple and available technique which

requires a minimum of personnel and can be started as soon as the patient is

admitted to the hospital. However, it is too inefficient to be of value for the

treatment of acute intoxications.

Hemodialysis Hemodialysis (extracorporeal dialysis) is much more effectivethan peritoneal dialysis and may be essential in a few life-threatening

intoxications, such as with methanol, ethylene glycol, and salicylates.. It assists in

correction of fluid and electrolyte imbalance and may also enhance removal of

toxic metabolites (e.g., formate in methanol poisoning, oxalate and glycolate in

ethylene glycol poisoning).

Hemodialysis involves the passage of blood over a semipermeable membrane,

through which equilibration occurs with a balanced dialysate solution lacking the

toxin or substance that is to be removed. Toxins in the blood that are small

enough to pass through the membrane are cleared from the blood. However,

even small toxins may not pass through the membrane if they are bound to

plasma proteins. Moreover, toxins that are not predominantly in the blood

compartment cannot be substantially removed from the blood, even if they

easily cross the membrane. The volume of distribution (Vd) determines whether

a sufficient amount of toxin exists within the blood space to be cleared by

hemodialysis. Therefore, small, water-soluble molecules having masses less than

500 daltons and a Vd less than 1 L/kg and exhibiting low protein binding areremoved by hemodialysis.

Hemoperfusion Blood is pumped from the patient via a venous catheterthrough a column of adsorbent material and then recirculated to the patient.

Hemoperfusion does not improve fluid and electrolyte balance. However, it does

remove many high-molecular-weight toxins that have poor water solubility

because the perfusion cartridge has a large surface area for adsorption that is

directly perfused with the blood and is not impeded by a membrane. The rate-

limiting factors in removal of toxins by hemoperfusion are the affinity of the

charcoal or adsorbent resin for the drug, the rate of blood flow through the

cartridge, and the rate of equilibration of the drug from the peripheral tissues to

the blood. Hemoperfusion may enhance whole body clearance of salicylate,

phenytoin, ethchlorvynol, phenobarbital, theophylline, and carbamazepine.


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Antidotes

Selected Antidotes, Their Indications, and Other Comments


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Selected Antidotes, Their Indications, and Mechanisms of Action

ANTIDOTE INDICATION (TOXIN) MECHANISM OF ACTIONAntivenin Pit viper bite

Coral snake bite

Black Widow spider bite

Binding of toxin by antibody

Botulinal trivalent antitoxin Botulism Binding of toxin by antibody

Cyanide kit (amyl nitrite

inhalation, sodium nitrite

parenteral, sodium thiosulfate

parenteral

Cyanide poisoning Bind cyanide to

methemoglobin, then

enhance conversion to

thiocyanate for excretion

Deferoxamine mesylate

(Desferal)

Iron poisoning Chelate iron, enhance renal

excretionDigoxin-specific antibody

fragments (Digibind)

Digoxin poisoning (and

other cardiac

glycosides)

Binding of digoxin to

antibody

Dimercaptosuccinic acid (DMSA,

Succimer, Chemet)

Lead, mercury, arsenic

poisoning

Chelate heavy metal,

enhance renal excretion

Ethanol Methanol, ethylene Inhibit alcohol


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glycol poisoning dehydrogenase, slow

conversion to toxic

aldehydes and acids

Ethylenediaminetetraacetic acid

(calcium disodium EDTA)

Lead poisoning Chelate heavy metal,

enhance renal excretion

Methylene blue Methemoglobinemia Help reduce Fe+++ to Fe++,thereby improving oxygen

delivery to tissues

N-Acetylcysteine (Mucomyst) Acetaminophen

poisoning

Bind to toxic reactive

metabolite, protect liver cells

from damage

Octreotide Poisoning with oral

hypoglycemic agents

Block release of insulin from

pancreas

Oxygen Carbon monoxide

poisoning

Displace CO from

hemoglobin

Physostigmine salicylate(Antilirium)

Some cases ofpoisoning with

anticholinergic drugs

Enhance duration of actionof acetylcholine at

cholinergic receptors by

inhibiting

acetylcholinesterase

Pralidoxime chloride (Protopam) Organophosphate or

carbamate poisoning

Reactivate cholinesterase

inactivated by

organophosphate

Starch Iodine poisoning Convert iodine to iodide

(nontoxic)

Vitamin K1(AquamephytonKonakion)

Warfarin poisoning Enhance vitamin K1-dependent synthesis of

clotting factors II, VII, IX, and

I


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References

Brunton, L. L., Lazo, J. S., and Parker, K. L. (2006). Goodman & Gilmans the Pharmacological

Basis of Therapeutics, 11th

Ed. New York: McGraw-Hill.

Carruthers, S. G., Hoffman, B. B., Melmon, K. L., Nierenberg, D. W. (2000). Melmon and

Morrelli's Clinical Pharmacology, 4th Ed. New York: McGraw-Hill.

Klaasen, C. D. (2001). Casarett and Doull's Toxicology: The Basic Science of Poisons, 6th Ed. New

York: McGraw-Hill.

Williams, P.R.D., and Paustenbach, D. J. (2002). Risk Characterization. In: Human and Ecological

Risk Assessment: Theory and Practice. New York: John Wiley & Sons.

http:// www.wikipedia.com

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