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Poison basic etiology

1. POISONING

2. Introduction
Organophosphate (OP) compounds are a diverse group of
chemicals used in both domestic and industrial settings.
 Examples of organophosphates include:-
 insecticides (malathion, parathion, diazinon, fenthion,
dichlorvos, chlorpyrifos, ethion),
nerve gases (soman, sarin, tabun, VX),
ophthalmic agents (echothiophate, isoflurophate), and
antihelmintics (trichlorfon).
 Herbicides (tribufos [DEF], merphos) are tricresyl phosphate–
containing industrial chemicals.

3. Introduction contd.
Massive organophosphate intoxication from suicidal and
accidental events, such as the Jamaican ginger palsy
incident in 1930, led to the discovery of the mechanism
of action of organophosphates.
In 1995, a religious sect, Aum Shinrikyo, used sarin to
poison people on a Tokyo subway.
Mass poisonings still occur today; in 2005, 15 victims
were poisoned after accidentally ingesting ethion-
contaminated food in a social ceremony in Magrawa,
India.
Nerve agents have also been used in battle, notably in
Iraq in the 1980s. Additionally, chemical weapons still
pose a very real concern in this age of terrorist activity.

4. Intrd.contd
Exposure to organophosphates (OPs) is
also possible via intentional or
unintentional contamination of food
sources. Although no clinical effects of
chronic, low-level organophosphates
(OPs) exposure from a food source
have been shown, advancements in risk
assessment and preparedness are
ongoing.
1,2

5. Pathophysiology
The primary mechanism of action of organophosphate
pesticides is inhibition of carboxyl ester hydrolases,
particularly acetylcholinesterase (AChE). AChE is an
enzyme that degrades the neurotransmitter
acetylcholine (ACh) into choline and acetic acid. ACh is
found in the central and peripheral nervous system,
neuromuscular junctions, and red blood cells (RBCs).
Organophosphates inactivate AChE by phosphorylating
the serine hydroxyl group located at the active site of
AChE. The phosphorylation occurs by loss of an
organophosphate leaving group and establishment of a
covalent bond with AChE.

6. Once AChE has been inactivated, ACh
accumulates throughout the nervous
system, resulting in overstimulation of
muscarinic and nicotinic receptors.
Clinical effects are manifested via
activation of the autonomic and central
nervous systems and at nicotinic
receptors on skeletal muscle.

7. Pathophysiology
Once an organophosphate binds to AChE, the
enzyme can undergo one of the following:
1.Endogenous hydrolysis of the phosphorylated
enzyme by esterases or paraoxonases
2.Reactivation by a strong nucleophile such as
pralidoxime (2-PAM)
3.Irreversible binding and permanent enzyme
inactivation (aging)
Organophosphates can be absorbed cutaneously,
ingested, inhaled, or injected. Although most
patients rapidly become symptomatic, the onset and
severity of symptoms depend on the specific
compound, amount, route of exposure, and rate of
metabolic degradation.
3

8. Signs and Symptoms (Doctor Sarah
Myhill)
Different people have different symptoms of
OP poisoning.
 Symptoms depend partly on how much OP
they have been exposed to, whether they
have had single massive exposure, or
chronic sub-lethal exposure, whether it has
been combined with other chemicals and
OPs and how good their body is a coping
with toxic chemicals.
Symptoms divide into the following
categories:

9. No obvious symptoms at all
A Government sponsored study at the
Institute of Occupational Medicine of
farmers who regularly handled OPs but
who were complaining of no symptoms
showed that they suffered from mild
brain damage.
Their ability to think clearly and problem
solve was impaired.

10. Sheep dip 'flu (mild acute poisoning)
This is a 'flu-like illness which follows exposure
to OPs. Sometimes the farmer just has a bit of
a headache, feels unusually tired or finds he
can't think clearly.
This may just last a few hours to a few days
and the sufferer recovers completely.
Most sufferers do not realise that they have
been poisoned and put any symptoms down to
a hard day's work.
 It can occur after dipping, but some farmers
will get symptoms after the slightest exposure,
such as visiting markets and inhaling OP
fumes from fleeces.

11. Acute Organophosphate
poisoning
This is the syndrome recognised by
doctors and Poisons Units.
 Symptoms occur within 24 hours of
exposure and include collapse, breathing
problems, sweating, diarrhoea, vomiting,
excessive salivation, heart dysrrhythmias,
extreme anxiety etc.
Treatment is with atropine.
You have to have a large dose of OP to
have this effect (e.g. drink some of the dip!)
and so this syndrome is rarely seen.

12. Intermediate Syndrome
This occurs 1-3 weeks after exposure
and is characterised by weakness of
shoulder, neck and upper leg muscles.
It is usually undiagnosed because it
goes unrecognised.

13. Long term chronic effects
These symptoms develop in some
susceptible individuals.
They can either occur following a single
massive exposure, or after several years
of regular sub-lethal exposure to OPs.
The treatment follows the same
principles as for any chemical poisoning.

14. Signs of organophosphate poisoning include:
salivation
lacrimation
urinary incontinence
defecation
GI upset/diarrhea
emesis
miosis

15. Mnemonic acronym
The mnemonic acronym "SLUDGE" is
frequently cited as an aid for healthcare
professionals in recognizing the first six signs
listed above.
S- salivation
L- lacrimation
U- urinary incontinence
D- defecation
G- g.i upset(diarrhoea)
E- emisis

16. Description
agLearn.net, network for sustainable
agriculture: (agLearn.net) describes the
signs and symptoms of onset of
organophosphorous poisoning:
At first:
Person feels sick
Complains of headache
General weakness or tiredness

17. Then:
Person begins to sweat and salivate,
may vomit and have diarrhoea
Complains of stomach cramps
Pupils (of the eyes) become very small
Person may mention blurred vision
Muscles twitch and hands shake
Breathing becomes bubbly
Person has a fit and becomes
unconscious

18. Signs and Symptoms contd.
Signs and symptoms of organophosphate
poisoning can be divided into 3 broad
categories, including
(1) muscarinic effects, (2) nicotinic effects, and
(3) CNS effects.
Mnemonic devices used to remember the
muscarinic effects of organophosphates are
SLUDGE (salivation, lacrimation, urination,
diarrhea, GI upset, emesis) and
DUMBELS (diaphoresis and diarrhea;
urination; miosis; bradycardia, bronchospasm,
bronchorrhea; emesis; excess lacrimation; and
salivation).

19. 1. Muscarinic effects by organ
systems include the following:
Cardiovascular - Bradycardia, hypotension
Respiratory - Rhinorrhea, bronchorrhea,
bronchospasm, cough, severe respiratory
distress
Gastrointestinal - Hypersalivation, nausea and
vomiting, abdominal pain, diarrhea, fecal
incontinence
Genitourinary - Incontinence
Ocular - Blurred vision, miosis
Glands - Increased lacrimation, diaphoresis

20. 2. Nicotinic signs and symptoms
include
muscle fasciculations, cramping,
weakness, and diaphragmatic failure.
Autonomic nicotinic effects include
hypertension, tachycardia, mydriasis,
and pallor.
3. CNS effects include: anxiety, emotional
lability, restlessness, confusion, ataxia,
tremors, seizures, and coma.

21. Physical
Note that clinical presentation may vary, depending on
the specific agent, exposure route, and amount.
Symptoms are due to both muscarinic and nicotinic
effects.
Interestingly, a review of 31 children with
organophosphate (OP) poisoning described that, in
contrast to adults, the most common presentations were
seizure and coma with relatively less muscarinic or
nicotinic findings.

The authors hypothesized the difference may be due to
difficulty in detecting muscarinic findings in infants (eg,
crying) and ingestion of contaminated produce instead
of organophosphate (OP) directly.

22. Vital signs:
Depressed respirations, bradycardia,
and hypotension are possible
symptoms.
Alternatively, tachypnea, hypertension,
and tachycardia are possible.
Hypoxia should be monitored for with
continuous pulse oximetry.

23. Paralysis 
Type I: This condition is described as acute paralysis
secondary to continued depolarization at the
neuromuscular junction.
Type II (intermediate syndrome): Intermediate
syndrome was described in 1974 and is reported to
develop 24-96 hours after resolution of acute
organophosphate poisoning symptoms and
manifests commonly as paralysis and respiratory
distress.
 This syndrome involves weakness of proximal
muscle groups, neck, and trunk, with relative sparing
of distal muscle groups.
Cranial nerve palsies can also be observed.
Intermediate syndrome persists for 4-18 days, may
require mechanical ventilation, and may be
complicated by infections or cardiac arrhythmias.

24. Paralysis contd.
Although neuromuscular transmission defect and
toxin-induced muscular instability were once thought
to play a role, this syndrome may be due to
suboptimal treatment.
Type III: Organophosphate-induced delayed
polyneuropathy (OPIDP) occurs 2-3 weeks after
exposure to large doses of certain organophosphates
(OPs) and is due to inhibition of neuropathy target
esterase.
 Distal muscle weakness with relative sparing of the
neck muscles, cranial nerves, and proximal muscle
groups characterizes OPIDP. Recovery can take up to
12 months.

25. Neuropsychiatric effects:
Impaired memory, confusion, irritability, lethargy, psychosis,
and chronic organophosphate-induced neuropsychiatric
disorders have been reported. The mechanism is not proven.
Extrapyramidal effects: These are characterized by dystonia,
cogwheel rigidity, and parkinsonian
 features (basal ganglia
impairment after recovery from acute toxicity).
Other neurological and/or psychological effects: Guillain-
Barré–like syndrome and isolated bilateral recurrent laryngeal
nerve palsy are possible.
Ophthalmic effects: Optic neuropathy, retinal degeneration,
defective vertical smooth pursuit, myopia, and miosis (due to
direct ocular exposure to organophosphates) are possible.

26. Neuropsychiatric effects co0ntd
Ears: Ototoxicity is possible.
Respiratory effects: Muscarinic, nicotinic, and
central effects contribute to respiratory distress
in acute and delayed organophosphate toxicity.
Muscarinic effects: Bronchorrhea,
bronchospasm, and laryngeal spasm, for
instance, can lead to airway compromise.
Respiratory failure is the most life-threatening
effect and requires immediate intervention.
Nicotinic effects: These effects lead to
weakness and paralysis of respiratory
oropharyngeal muscles.
Central effects: These effects can lead to
respiratory paralysis.

27. Neuropsychiatric effects contd
Rhythm abnormalities: Sinus tachycardia, sinus
bradycardia, extrasystoles, atrial fibrillation,
ventricular tachycardia, and ventricular fibrillation
(often a result of, or complicated by, severe hypoxia
from respiratory distress) are possible.
Other cardiovascular effects: Hypotension,
hypertension, and noncardiogenic pulmonary
edema are possible.
GI manifestations: Nausea, vomiting, diarrhea, and
abdominal pain may be some of the first symptoms
to occur after organophosphate exposure.
Genitourinary and/or endocrine effects: Urinary
incontinence, hypoglycemia, or hyperglycemia is
possible.