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Contents
Toxicology.................................................................................................................................. 2
Defination................................................................................................................................... 2
Toxicokinetics ............................................................................................................................ 2
Absorption into the body ......................................................................................................... 2
Distribution within the body ..................................................................................................... 2
Metabolism/ biotransformation of toxic substances ................................................................. 2
Toxicodynamics ......................................................................................................................... 2
Management of the Poisoned Patient ........................................................................................ 3
The initial management .......................................................................................................... 3
History and Physical Examination........................................................................................... 3
History ................................................................................................................................ 3
Physical Examination .......................................................................................................... 3
Laboratory and Imaging Procedures ....................................................................................... 4
Artial Blood Gas .................................................................................................................. 4
Electrolytes ......................................................................................................................... 4
Renal funtion test ................................................................................................................ 5
Serum osmolality ................................................................................................................ 5
Electrocardiagram ............................................................................................................... 5
Imaging finding ................................................................................................................... 5
Decontamination .................................................................................................................... 5
Skin..................................................................................................................................... 5
GIT...................................................................................................................................... 5
Method of enhancing elimination of toxiin ............................................................................... 5
Peritoneal dialysis ............................................................................................................... 5
Hemodialysis ...................................................................................................................... 5
TOXICOLOGY
Defination
The study of the symptoms, mechanism, diagnosis and treatment or management of
biological poison.
Toxicology is the study of how natural or man-made poisons cause undesirable effects in
living organisms
chemicals could be toxic but the degree of harm that a chemical can inflict on a human or
any other living being depends on the dose or the degree of exposure as well as on other
factors.
In other words the risk (i.e. that product of the likelihood and the severity of harm) from a
toxic hazard depends on the exposure.
Over 1 million cases of acute poisoning occur in the USA each year, although only small
number are fetal.
Most death are due to intentional suicidal overdose by an adolescent or adult.
Childhood deaths due to accidental ingestion of the drug or toxic household products.
Toxicokinetics
Absorption into the body
As a general rule, fat soluble liquids are readily absorbed through the skin and fat soluble
vapours are readily absorbed through the lungs.
Notably these routes apply to organic solvents such as hexane, toluene, trichlorethylene and
many others.
Distribution within the body
Many factors affect the distribution of a toxic substance but water or fat solubility is very
important.
Thus for example water soluble compounds of lead are found (amongst other places) in the
red blood cells, while fat soluble ones concentrate in the central nervous system (CNS).
The distribution of a toxic substance determines its concentration at a particular tissue and
therefore the number and type of cells exposed to high concentrations of it.
Metabolism/ biotransformation of toxic substances
Toxic substances may be converted into other substances (metabolites) by organs such as
the liver and kidneys
Thus non-polar and therefore not water soluble organic compounds tend to be oxidised
within the liver e.g.:
trichloroethane oxidised to trichloroethanol trichloroacetaldehyde and trichloroacetic
acid
dichloromethane (methylene chloride CH2Cl2) oxidised to carbon monoxide (CO)
Water soluble metabolites are then more easily excreted by the kidney
Metabolism or biotransformation does not necessarily result in less toxic compunds. For
example benzene may be oxidised to an expoxide which then inflicts damage on the DNA in
genes, i.e. it is genotoxic and hence carcinogenic
Toxicodynamics
Acute effects refer to the short term consequences of exposure.Chronic effects relate to a
much longer time scale, while sub-acute are in between acute and chronic). Some effects
may be dose related - the higher the exposure the worse it gets e.g. irritant effects on the
skin, asthma, asbestosis etc.
Other effects are 'all or none' and for a given exposure there is an element of chance
(stochastic) as to whether or not the disease develops.For example, the development of
cancer (carcinogenesis) or some forms of developmental damage to the foetus
(teratogenesis)
An understanding of common mechanisms of death due to poisoning can help prepare the
caregiver to treat patient effectively.
Many toxins depress the CNS, resulting in coma.
Comatose patients frequently lose their airway protective reflexes and their respiratory drive.
Thus, they may die as a result of airway obstruction by flaccid tongue, aspiration of gastric
contents in the tracheobronchial tree, or respiratory arrest. E.g Narcotics, sedative and
hypnotics.
Cardiovascular toxicity is also frequently encountered in poisoning. Peripheral vascular
colapse due to the blockage of -adrenoreceptor mediated vascular tone or cardiac
arrhythmias.
Lethal arrhythmias such as ventricular tachcardia and fibrilation can occur with overdoses of
many cardioactive drugs such as ephedrine, amphetamine, cocaine, digitalis nad
theophylline.
Seizures, muscular hyperactivity, and rigidity may result in the death. Seizure may cause
pulmonary aspiration, hypoxia and brain damage. Drugs and poison that often cause
seizure include antidepressant, cocaine, INH, diphenhydramine.
Finally, some patient may die before hospitalization because the behavioral effects of
ingested drug may result in traumatic injury.
Intoxication of alcohol and other sedative and hypnotic drugs is a common contributing
factor to motor vehicle accidents.
Management of the Poisoned Patient
The initial management
The initial management of a patient with coma, seizures, or otherwise altered mental status
should follow the same approach regardless of the poison involved:
Supportive measures are the basic (ABCD)
A-Airway should be cleared of vomitus or any other obstruction and an oral airway or
endotracheal tube inserted if needed.
B- Breathing should be assessed by the observation and pulse oximetry. If doubt the
patient should be intubated and mechanically ventilated.
C-Circulation- should be assessed by the continous 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 determination.
D-Dextrose- Every patient with altered mental status should receive a challenge with
concentrated dextrose unless the a rapid bedside blood glucose test demonstrates that the
patient is not hypoglcemic.
Adult are given 50ml of 50% dextrose solution intravenously. Children 0.5mg/kg.
The opioid antagonist naloxone may be given in a dose of 0.4-2 mg intravenously.
Naloxone reverses respiratory and CNS depression due to all verities of opioid drugs.
History and Physical Examination
Once the essential initial ABCD intervention have been instituted, one can begin in more
detailed evaluation to make a specific diagnosis.
History
oral statement about the amount of drug 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 described the environment in which the toxic emergencies occured
Physical Examination
A brief examination should be performed, emphasizing those areas most likely to give clue
to the toxicological diagnosis. These include,
Vital Sign- Careful evaluation of vital sign (BP, pulse, respiration, and temperature) is
essential in all toxicologic emergencies.
Drugs that may cause hyperkalemia despite normal renal function include potassium itself,
blockers, digitalis glycoside, potassium sparing diuretic.
Renal funtion test
Some toxins have direct nepherotoxic effects, in other cases renal failure is due to shock or
myoglobinouria. Blood urea nitrigen and creatinine levels should measured and urinalysis
performed
Elevated serum creatinne kinase (CK) and myoglobin in the urine indicate the muscle
necrosis due to seizure or muscular rigidity.
Oxalate crstals in large numbers in the urine suggest ethylene glycol poisoning.
Serum osmolality
The calculated serum osmolality is dependent mainly on the serum sodium and glucose and
the blood urea nitrogen and can be estimated from the following.
2 Na+ (mEq/L)+Glucose (mg/dL) + BUN(mg/dL)
18
3
The calculated value is normally 280-290 mOsm/L. ethanol and other alcohol may contribute
significantly to the measured serum osmolality but, since they are not included in the
calulation, cause an osmal gap:
Osmolar gap= measured osmolality calculated osmolality
Electrocardiagram
Widening of the QRS complex duration(to more than 100 milisecond) is typical of tricyclic
antidepressant and qunindine overdose.
The QTc interval may be prolonged (to more than 440 milliseconds) in many poisonings,
including qunindine, antidepressant, antipsychotics, lithium and arsenic
Imaging finding
Plain film of abdomen particularly for iron and potassium may radiopaque.
Chest X-rays for aspiration pneumonia, hydrocarbon pneumonia or pulmonary edema.
CT scan for head trauma
Decontamination
Skin
GIT
Emesis
Gastric lavage
Activated charcoal
Cathartic
Method of enhancing elimination of toxiin
Dialysis procedure
Peritoneal dialysis
Hemodialysis
B. Forced diuresis and pH manipulation