Organophosphorous compounds work by inhibiting acetylcholinesterase, leading to overstimulation of muscarinic and nicotinic receptors. Signs and symptoms include muscarinic effects like excessive sweating, urination, and salivation ("DUMBELS") and nicotinic effects like muscle weakness. Treatment involves atropine to reverse muscarinic effects, pralidoxime to reactivate acetylcholinesterase within 48 hours, benzodiazepines for seizures, and supportive care like ventilation and fluid management. Measuring red blood cell acetylcholinesterase levels can help confirm exposure.

1. Organophosphorous compounds
poisoning

2. Introduction
 Organophosphate (OP) compounds are a
diverse group of chemicals used in both
domestic and industrial settings.
 Examples of organophosphates include
1-insecticides (malathion, parathion, diazinon,
fenthion)
2- nerve gases (sarin)
3- ophthalmic agents (echothiophate,
isoflurophate)
 Exposure to organophosphates is also possible
via intentional or unintentional contamination of
food sources.

3. Mechanism of toxicity
 The primary mechanism of action of
organophosphate is inhibition of
acetylcholinesterase (AChE).
 Phosphate radical of organophosphates
interacts with active enzyme site forming a
covalent bond leading to increase of Ach at
the synapses and neuro-muscular junction.
 Once AChE has been inactivated, ACh
accumulates throughout the nervous system,
resulting in overstimulation of muscarinic and
nicotinic receptors.

5.  Clinical effects are manifested via activation of
the autonomic and central nervous systems
and at nicotinic receptors on skeletal muscle.
 Once an organophosphate binds to AChE, the
enzyme can undergo one of the following:
1. Endogenous hydrolysis of the phosphorylated
enzyme by esterases
2. Reactivation by a strong nucleophile such as
pralidoxime (2-PAM)
3. Irreversible binding and permanent enzyme
inactivation (aging)

6. Types of cholinesterases
 two types of cholinesterase. Both are inhibited
by organophosphates, but RBCs
cholinesterase may serve as a reliable index of
organophosphate poisoning as it contains true
cholinesterase and reflects the status of the
CNS.
type True cholinesterase Pseudo cholinesterase
substrate acetylcholine
Ach and other
choline esters as
succinyl choline
Site of existence
CNS
RBCs
Plasma
liver

7. Routes of intoxification
 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, duration.

8. Mortality
 About 3-22%
 Mortality rates depend on:
the type of compound used, amount ingested,
general health of the patient, delay in discovery
and transport, insufficient respiratory
management, delay in intubation.
 Complications include severe bronchorrhea,
seizures, weakness, and neuropathy.
Respiratory failure is the most common cause
of death.

9. Signs and syymptoms
 Signs and symptoms of organophosphate
poisoning can be divided into 3 broad
categories, including (1) muscarinic effects,
(2) nicotinic effects, and (3) CNS effects.
1. CNS manifestations:
Ach is an excitatory neurotransmitter (NT). CNS
manifestations include:
Anxiety, restlessness, confusion, slurred speech,
ataxia and seizures.


10. 2. Muscarinic manifestations:
 Can be summarized as DUMBELS:
(diaphoresis and diarrhea; urination; miosis;
bradycardia, bronchospasm, bronchorrhea;
emesis; lacrimation; and salivation and sweating).
 Muscarinic effects by organ systems include the
following:
a) CVS: bradycardia, hypotention. [at last?]
b) Respiratory - Rhinorrhea, bronchorrhea,
bronchospasm, cough, severe respiratory
distress
c) Gastrointestinal - nausea and vomiting,
abdominal pain, diarrhea, fecal incontinence

11. d- Genitourinary- incontinance
e- Ocular - Blurred vision, miosis
f- Glands - Increased lacrimation, diaphoresis
3- Nicotinic manifestations:
a- NMJ (NM) : muscle twitching, cramping,
weakness, decrease in respiratory effort,
cyanosis and paralysis due to prolonged
stimulation of muscles.
b- Sympathetic ganglia [Nn]: tachycardia, HTN
[initially WHY??] due to stimulation of adrenal
medulla.

13.  Nicotinic manifestations are symbolized as
MATCH
(Muscle weakness / Adrenal hyper activity +
Ataxia/ Tachycardia/ Cramps/ HTN)


14. Managment
– For confirmed diagnosis measure RBCs level of
AChE.
1. Prevent any further exposure.
 Remove all clothing and gently cleanse patients
suspected of organophosphate exposure with
soap and water because organophosphates are
hydrolyzed readily in aqueous solutions with a
high pH. Consider clothing as hazardous waste
and discard accordingly.
 Health care providers must avoid contaminating
themselves while handling patients.

16.  Irrigate the eyes of patients who have had
ocular exposure using isotonic sodium chloride
solution or lactated Ringer's solution.
2. History and physical examination of the patient
3. Symptomatic and supportive treatment:
ensure patent airways and ventilatory support.
Copious secretions may necessitate their
suction from oropharynx and upper airways.

17. 4. gastric evacuation by ipecac or lavage.
5 -Continuous cardiac monitoring should be
established;
an ECG should be performed.
Torsades de Pointes should be treated in the
standard manner. The use of intravenous
magnesium sulfate has been reported as
beneficial for organophosphate toxicity. The
mechanism of action may involve
acetylcholine antagonism or ventricular
membrane stabilization.

18. 6. The mainstays of medical therapy
in organophosphate poisoning include atropine,
pralidoxime (2-PAM), and benzodiazepines (eg,
diazepam).
 A-Initial management must focus on adequate use
of atropine. Intravenous diphenhydramine may
provide an alternative centrally acting
anticholinergic agent used to treat muscarinic
toxicity if atropine is unavailable or in limited
supply.
It is capable of reversing CNS and Muscarinic
manifestations.


19. It may serve as a diagnostic tool for
organophosphate poisoning.
Dose: 1-4 mg I.V. dose repeated every 5-60 mins
until the patient demonstrates the S&S of mild
atropinism [mydriasis], then widen the interval
to 2-6 hrs for 48 hrs to keep the patient free of
cholinergic symptoms.

20. B- Pralidoxime
MOA: it reactivates acetylcholinesterase by
cleaving the covalent bond
Indications: the presence of nicotinic mediated
symptoms as muscle fasciculations, weakness
and paralysis.
Dose: initial dose 1 gm infused over 15-30 mins.
If weakness persists after one hr the dose may be
repeated.
Additional doses may be required at intervals for up
to 48 hrs to maintain relief of S & S.
.

21. It must be administered within 48 hrs of
intoxication, otherwise, the binding became
irreversible, the enzyme is destroyed and re-
synthesis must occur to replenish enzyme
stores [it takes about 4 weeks]
Because it does not significantly relieve
depression of respiratory center or decrease
muscarinic effects of AChE poisoning,
administer atropine concomitantly to block
these effects of OP poisoning