Organophosphate

Less severe cases of OPIDN exhibit a

characteristic high-stepping gait, the initial muscle weakness gives rise to a clumsy, shuffling gait. T

Psuedocholinesterase.

• More easily performed •Not correlate well with the severity of poisoning •A depression of 25% or more is strong evidence of exccesive organophosphate absorption

ACHE

•Provides a measure of the degree of toxicity. •Determine the effectiveness of antidote therapy.

Atropine (IV/IM)

- Initiated in patients with OP toxicity who present with muscarinic symptoms. - Competitive inhibitor at autonomic postganglionic cholinergic receptors, including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eye.

OPIDN treatment

-No specific treatment has been identified. -The early administration of pralidoxime and atropine does not seem to prevent the condition

Pralidoxime (2-PAM, Protopam)

-Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP molecule. -Used as an antidote to reverse muscle paralysis resulting from OP AChE pesticide poisoning but is not effective once the OP compound has bound AChE irreversibly (aged).

Decontamination

-Remove all clothing from -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. -Use personal protective equipment, such as neoprene gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolar substances such as latex and vinyl. -Use *charcoal cartridge* masks for respiratory protection when decontaminating patients who are significantly contaminated. -Irrigate the eyes of patients who have had ocular exposure using isotonic sodium chloride solution or lactated Ringer's solution. Morgan lenses can be used for eye irrigation.

OPIDN progression

-The neuropathic findings begin peripherally and proceed proximately. -Lower extremity paraesthesia may appear with a "stocking-glove" distribution and progress to weakness, ataxia, depression of deep tendon reflexes, and paralysis with occasional progression to the arms and hands. -Pain and weakness spreads rapidly, and patients become unsteady and unable to keep their balance. -This is subsequently replaced by spasticity, hypertonicity, hyperreflexia, clonus, and abnormal reflexes.

Management and treatment of OP poison patient:

-decontamination -Medications

organophosphate induced delayed polyneuropathy (OPIDP)

-is a rare delayed neurotoxic effect, which occurs 1-5 weeks after severe toxicity from some cholinesterase inhibitors. -However, it is not thought to be due to the effects on acetylcholinesterase itself. The cause of this condition is unknown -The condition is associated with symmetrical sensory-motor axonal degeneration of the peripheral nerves and spinal cord.

Although most patients with OP poisioning rapidly become symptomatic, the onset and severity of symptoms depend on the

-specific compound, -amount, -route of exposure, -and rate of metabolic degradation.

There are two types of cholinesterase levels •Provides a measure of the degree of toxicity. Determine the effectiveness of antidote therapy

1- Acetylcholinesterase (ACHE), also known as AChE, RBC cholinesterase or erythrocyte cholinesterase, true cholinesterase, choline esterase I, or (most formally) acetylcholine acetylhydrolase, 2- Butyrylcholinesterase (BCHE), also known as cholinesterase, choline esterase II, BChE, BuChE, pseudocholinesterase (PCE), plasma cholinesterase (PChE), serum cholinesterase (SChE), butylcholinesterase, or (most formally) acylcholine acylhydrolase,

Examples of organophosphates include:

1- Insecticides (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, ethion), 2- Nerve gases (soman, sarin, tabun, VX), 3- ophthalmic agents (echothiophate, isoflurophate), 4- Antihelmintics (trichlorfon). Herbicides (tribufos [DEF], merphos) are tricresyl phosphate-containing industrial chemicals.

Nicotinic signs and symptoms (high doses)

1- Neuromuscular junctions of skeletal muscles: muscle fasciculations and myotonic jerk followed by weakness and paralysis 2- Sympathometicnicotinic effects include hypertension, tachycardia, mydriasis, and pallor (increase sympathetic). *Sweating*, urinary retention

Once an organophosphate binds to AChE, the enzyme can undergo one of the following:

1- Reactivation by a strong nucleophile such as pralidoxime (2-PAM) 2-Irreversible binding and permanent enzyme inactivation (aging) 3-Endogenous hydrolysis of the phosphorylated enzyme by esterases or paraoxonases

When available, test results must be interpreted with caution, because of:

A- Interindividual and intraindividual differences in normal cholinesterase levels. b- Other medical conditions and substances that can alter cholinesterase levels. C- Laboratory errors.

CNS effects (high doses)

Anxiety Emotional lability Restlessness Confusion Ataxia Tremors Seizures Coma

medications

Atropine Pralidoxime (2-PAM) Benzodiazepines (e.g., diazepam)

muscarinic effects (low doses)

Do not affect skeletal muscles but do influence the activity of smooth muscle, exocrine glands (exception sweat gland), and the cardiac conduction system. (Increase parasympathetic).

aging of the enzyme

Progressive inhibition of cholinesterases by organophosphates results from phosphorylation of the active-site serine. Phosphorylated cholinesterases may undergo a dealkylation reaction of the organophosphorus moiety leading to "aged" enzyme, i.e. conversion of the inhibited enzyme into a non-reactivable form.

mnemonics for muscarinic effects

SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis) and DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea; emesis; excess lacrimation; and salivation).

Anticholinergic medications

These agents act as competitive antagonists at the muscarinic cholinergic receptors in both the central and the peripheral nervous system. These agents do not affect nicotinic effects.

Antidotes for OP

These agents prevent aging of AChE and reverse muscle paralysis with OP poisoning.

Organophosphate (OP) compounds are

a diverse group of chemicals used in both domestic and industrial settings

RBC and serum (uninhibited) cholinesterase levels are used to ___ These tests are_____ Initial emergency management should therefore be based on ____.

approximate levels in neural tissue, since the latter are impractical to obtain.// rarely available in time to guide the emergency treatment decisions.// clinical assessment

Organophosphates can be absorbed

cutaneously, ingested, inhaled, or injected.

Although organophosphates degrade faster than the organochlorides, they have

greater acute toxicity, posing risks to people who may be exposed to large amounts

Organophosphate pesticides degrade rapidly by

hydrolysis on exposure to sunlight, air, and soil, although small amounts can be detected in food and drinking water.

Exposure to any one of the organophosphates occurs on a daily basis through

inhalation, absorption, and ingestion, most commonly of food that has been treated with an organophosphate herbicide or insecticide.

Exposure to organophosphates is also possible via

intentional or unintentional contamination of food sources.

Optimizing oxygenation prior to the use of atropine is recommended to

minimize the potential for dysrhythmias.

In farm workers, chronic occupational exposure to organophosphate insecticides has been linked to

neuropsychological effects in some studies. These have included difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual-spatial functioning, and coordination

Emergency assessment and treatment should be based on the ----- It should not be delayed to await the results of these laboratory tests, which are rarely available in time to guide emergency treatment!

patient's history, signs, and symptoms.

Their ability to degrade made them an attractive alternative to the

persistent organochloride pesticides, such as DDT, aldrin, and dieldrin.

the most disabling features of OPIDN is

the paralysis of the legs, in severe cases quadriplegia with foot and wrist drop are seen, as well as mild pyramidal signs.

ACHE is found primarily in the

-blood on red blood cell membranes, -in neuromuscular junctions, -and in other neural synapses.

The endpoint for atropinization is

dried pulmonary secretions and adequate oxygenation. (Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. )

Psuedocholinesterase

is produced in the liver and found primarily in blood plasma.

Clinical effects of OP poisioning are manifested via

activation of the -autonomic - and central nervous systems - and at nicotinic receptors on skeletal muscle.

Signs of atropinization might occur earlier with

addition of 2-PAM to treatment regimen.

Initial management must focus on

adequate use of atropine.

Although no clinical effects of chronic, low-level organophosphate exposure from a food source have been shown,

advancements in risk assessment and preparedness are ongoing

The main concern with OP toxicity is

respiratory failure from excessive airway secretions.

Diazepame (Valium, Diastat, Diazemuls)For treatment of

seizures, depresses all levels of CNS (eg, limbic and reticular formation) by increasing activity of GABA.

Early symptoms of OPIDN

sharp, cramp-like pains in the calves.

2-PAM administration is not indicated for carbamate exposure

since no aging occurs

Signs and symptoms of organophosphate poisoning can be divided into three broad categories:

(1)muscarinic effects (2)nicotinic effects, and (3)central nervous system (CNS) effects.

Aging occurs rapidly when the inhibitor is

*soman* (a powerful nerve agent)

Current recommendation is administration of anti-dote within 48 h of OP poisoning.

Because it does not significantly relieve depression of respiratory center or decrease muscarinic effects of AChE poisoning,

Mechanism of action of organophosphate pesticides

Organophosphate + ACHE → ↑↑↑ acetylcholine (ACH)