Organophosphates Poisoning (Opp)

Bronchodilatation REF: Textbook of Forensic Medicine and Toxicology: Principles and Practice, 5/e By Krishan Vij page 533

“Bronchoconstristition (bronchospasm) not bronchodilatation is seen in OPC poisoning”

Muscarinic signs of OPC poisoning can be remembered as SLUDGE- BBB: Salivation, Lacrimation, Urination, Defecation, Gastric upset, Emesis, Bronchospasm, Blurred vision (Miosis), Bradycardia.

Bronchodilatation

Organophosphorous poisoning causes bradycardia and not tachycardia.

Manifestations of organophosphorous poisoning includes muscarinic and nicotinic.

Muscarinic manifestations includes bradycardia, vomiting, diarrhea, abdominal cramps, miosis, bradycardia, sweating and excess salivation.

Nicotnic effects includes muscle fasciculations, tremors and weakness. 

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.

poor intensive care management. Treatment for acute poisoning is essentially supportive, with atropine, oximes, and diazepam.

Atropine is the mainstay of treatment but there are no clear guidelines on dose and duration.

Early resuscitation with atropine, oxygen, respiratory support, and fluids improves oxygen delivery to tissues.

A 2009 double blind randomised placebo controlled trial showed that pralidoxime, commonly given in acute poisoning, does not improve survival. New agents such as magnesium sulphate are in use, but clinical efficacy has not been shown.

Ref: 
1. Srinivas Rao CH, Venkateswarlu V, Surender T, Eddleston M, Buckley NA. Insecticide poisoning in south India—opportunities for prevention and improved medical management. Trop Med Int Health 2005;10:581-8.

2. Eddleston M, Buckley NA, Checketts H, Senarathna L, Mohamed F, Sheriff MH, et al. Speed of initial atropinisation in significant organophosphorus pesticide poisoning—a systematic comparison of recommended regimens. J Toxicol Clin Toxicol2004;42:865-75; 

3. M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F et al. Pralidoxime in acute organophosphorus insecticide poisoning— a randomised controlled trial. PLoS Med 2009;6:e1000104; Death by insecticide; BMJ 2013;346:f2029.

A i.e. Phosphorylate enzyme; B i.e. Irreversibly inhibit cholinsterase

B i.e. Plasma cholinesterase level

B i.e. Organophosphorous

B i.e. Edematous lung

A i.e. Dilated pupil

C i.e. Tachycardia

A i.e. Pupillary dilation

B i.e. Organophosphorus

– Most common way of suicide is by use of insectisidesQ.

– Malathion is alkyl phosphateQ, whereas parathion, paraoxon, diazinon (TIK-20) and folidol are aryl phosphatase. – Patient with organophosphorus poisoning presents with chromolacryorroea (sheding of pink tears d/t accumulation of porphyrin), increased bronchial secretion (edematous lung) & broncho-constriction simulating asthma, miosis/ pin point pupil (not mydriasis) , bradycardia (not tachycardia), hypertension, fasciculation, excessive lacrymation/ sweating/ salivation, confusion, unconsciousness, coma with depression of respiratory & circulatory centersQ.

Patients with organophosphorus poisoning have BradycardiaQ (not tachycardia). In Organophosphorus poisoning there is miosisQ due to cholinergic effect (not mydriasis).

Features of Organophosphorus ps. are ‘B³ with increased/ water loss’ i.e. Bronchospasm, Bradycardia, Blurring of vision & Sweating/ Lacrimation/ Salivation/ Micturation/ DiarrheaQ

– Organophosphorus irreversibly inhibit cholinesterases by phosphorylationQ. Plasma cholinesterase is more sensitive and falls more rapidly & prior to RBC cholinesterasesQ. Monitoring of levels are done as plasma ChE levels reach normal in 7-10 days in treated and 4 weeks in untreated cases. Oximes should be started as early as possible preferably within 24 hours before phosphorylated enzyme becomes resistant to hydrolysis.

The drug of choice for organophosphorous poisoning is AtropineQ. The cholinesterase reactivators, the oxime compounds (Pralidoxime, Obidoxime, Diacetyl monoxime) are used to supplement atropine. Atropine (antidote) is highly effective in counteracting peripheral muscarinic effects, and higher doses are required to antagonize central (CNS) effects. However it is not effective against nicotinic actionsQ. It is ineffective on respiratory centre in presence of severe asphyxia and also if BP fallsQ. When cyanosis is present maximum oxygenation should be achieved, before giving atropine to avoid increased risk of ventricular tacky cardiaQ associated with hypoxia.

D i.e. Organophosphorus poisoning

Pinpoint pupils (miosis) is seen in ‘Bar Car OR Mor – Chlor’ i.e. Barbiturates, Carbolic acid (Phenol), Organophosphorus, Morphine (Opioid), Choral hydrate.Q & Pontine haemorrhageQ

So we are left with two options – Pontine haemorrhage & Organophosphorus.

A i.e. Organophosphorus; B i.e. Opium

Ans. is ‘b’ i.e., Esteratic site of AchEs

1. Acetylcholinesterase has two sites:

i)         Catalytic or esteratic site –9 Active site

ii)       Anionic site

• It is quite obvious that to inhibit the action of acetylcholinesterase the active site has to be inhibited and it is esteratic site:

i)        Organophosphates phosphorylate esteratic site.

Carbamates carbomylate esteratic site.

Ans. is ‘a’ i.e., Atropine

Pharmacological treatment of organonhosphatepoisoning

Atropine

o Atropine is the mainstay of treatment (antidote of choice).

o Atropine antagonizes the muscarinic parasympathetic effects of organophosphate (excessive secretion and vasodilation), but does not antagonize nicotinic effects, i.e., neuramuscular blockers (Atropine blocks muscarinic receptors, i.e., it is an antimuscarinic)

o Atropine antagonizes both peripheral as well as central nervous system effects of organophosphates. Cholinesterase regenerator compounds (oximes)

o Pralidoxime is most commonly used oxime.

o Unlike atropine, they antagonize both muscarinic and nicotinic effects.

o They antagonize only peripheral effects, but not central effects except for diacetylmonoxime (DAM) which crosses BBB and antagonizes central effects also.

Ans. is ‘d’ i.e., Is a competitive antagonist of acetylcholine

o Atropine acts as competitive antagonist at muscarinic receptors. It has no activity on nicotinic receptors and has nothing to do with Ach release.

Ans. is ‘c’ i.e., Acts on central and peripheral cholinergic receptors

o In organophosphate poisoning, atropine counteracts the peripheral muscarinic symptoms and at higher doses central effects as well.

o Atropine does not reverse nicotinic action i.e., peripheral muscular paralysis.

Ans. is ‘c’ i.e., Propoxur 

Ans. is `a’ i.e., Dieldrin

Ans. D i.e. Physostigmine

Organophosphate poisoning

• It results from exposure to organophosphates (OPs), which cause the inhibition of acetylcholinesterase (AChE), leading to the accumulation of acetylcholine (ACh) in the body.
• The effects of organophosphate poisoning on muscarinic receptors are recalled using the mnemonic SLUDGEM: (Salivation, Lacrimation, Urination, Defecation, Gastrointestinal motility, Emesis, miosis)
• An additional mnemonic is MUDDLES: miosis, urination, diarrhea, diaphoresis, lacrimation, excitation, and salivation.

Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor.

Ans. B i.e. Dilated pupil

Ans. C i.e. PAM

• Current antidotes for OP poisoning consist of a pretreatment with carbamates to protect AChE from inhibition by OP compounds and post-exposure treatments with anti-cholinergic drugs.
• Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE.
• Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime)

Ans. A: Physostigmine

The mainstays of medical therapy in organophosphate (OP) poisoning include ‑

• Atropine-arrests muscarinic effects,
• Pralidoxime (2-PAM)-acts by competing for the phosphate moiety of the organophosphorus compound and release it from the cholinesterase enzyme
• Benzodiazepines (e.g., diazepam)-For convulsions

Intravenous glycopyrrolate or diphenhydramine may provide an alternative centrally acting anticholinergic agent used to treat muscarinic toxicity if atropine is unavailable or in limited supply

Ans: A i.e. Heart rate

In organophosphate poisoning, atropine should be administered in doses of 0.6-2 mg i.v., repeated every 10-25 minutes until secretions are controlled, the skin is dr./ and there is sinus tachycardia.

Ans. Diethyltoluamide (DEET)

Ans. Endrin

Ans. Mydriasis

Ans. Organophosphorus poisoning

Ans. Late onset proximal myopathy

Ans. b. Organophosphate poisoning

• Pinpoint pupil, excessive salivation, tremors and red tears in a patient with 30% cholinesterase activity of normal are almost diagnostic of organophosphate poisoning.

Organophosphorus Poisoning

• The effect of acute intoxication by one anti-choninesterase agents are manifested by muscarinic and nicotinic signs and symptoms.
• Systemic effects appear within minutes after inhalation of vapors or aerosols.
• In contrast, the onset of symptoms is delayed after GI and percutaneous absorption.
• Typical smell of organophosphorus compounds, which is a pungent garlic-like odou^Q

Organophosphorus irreversibly inhibits acetyl cholinesterase decreasing its activity

Manifestation:

• Nicotinic action at NMJ of skeletal muscle consists of fatigability and generalized weakness, involuntary twitchings, scattered fasciculations and eventually severe weakness and paralysis^Q
• The most serious consequence is paralysis of the respiratory muscleQ
• Ocular Manifestations: Miosis, pain, conjunctival congestion, diminished vision, ciliary spasm
• Respiratory effects: Tightness in the chest, wheezing respiration
• GI effects: Anorexia, nausea, vomiting, cramps
• Others: Extreme salivation, involuntary defecation, lacrimation, bradycardia, hypotension, penile erection

Red Tears or Chromolacryorrhea

• Shedding of red tears due to accumulation of porphyrin pigments in lacrimal glands
• Very rare phenomenon, seen in organophosphorus poisoning°

Treatment:

• Termination of further exposure to the poison
• Maintain patent airway, positive pressure ventilation if it is failing
• Supportive measures: Maintain BP, hydration, control of convulsions with judicious use of diazepam
• Specific antidote:
• – Atropine: It is highly effective in counteracting the muscarinic symptoms but higher doses are required to antagonize the central effects. It doesn’t reverse peripheral muscular paralysis^Q.

Ans. is ‘b’ i.e., Organophosphorous

• For organophosphorous (pesticides/insecticides) poisoning fatty tissue from abdominal wall, perinephric fat and brain are preserved.
• The viscera should be preserved in cases of suspected poisoning and must be send for toxicological examination. The viscera are preserved according to suspected poison :

1. Brain (100 gm of cerebrum or cerebellun) : Carbon monoxide, cyanide, organophosphates, organic volatile poisons, opiates, barbiturates, alkaloids, strychnine (nux vomica).
2. Spinal cord (entire length) : Strychnine.
3. Heart : Strychnine, digitalis.
4. Lung (one) : Gaseous poison (e.g. CO), alcohol, chloroform, cyanide.
5. Bone (10 cm shaft femur) : Subacute and chronic poisoning by heavy metals, e.g. arsenic, antimony, radium, thallium.
6. Hair (20-30 in number or 5 gm) and nails (all finger and toe) : Subacute and chronic poisoing by heavy metals, e.g. arsenic, antimony, radium, thallium.
7. Uterus, its appendages and upper part of vagina : Criminal abortion.
8. Fat (10 gm from abdomen or perinephric region) : Pesticides and insectisides.
9. Vitreous humor : Alcohol, chloroform.
10. Bile : Glutathione, cocaine, barbiturates, methadone, narcotics.
11. Skin : Injection of insulin, morphin, heroin, cocain etc.
12. Urine : Alcohol, barbiturate and opium.

Ans. is ‘c’ i.e., Symptomatic treatment 

• Paralysis due to organophosphate (OP) poisoning can be three types ‑

1. Type I (cholinergic phase)

• It involves acute paralysis secondary to persistent depolarization at the neuromuscular junction caused by persistent stimulation by excessive Ach.
• Treatment of choice is atropine with or without oximes.

2. Type II

• It is also called as intermediate syndrome.
• It develops 1-4 days after resolution of acute cholinergic symptoms.
• It is manifested as paralysis and respiratory distress.
• It involves proximal muscles with relative sparing of distal muscle groups.
• The pathogenesis presumed to be dysfunction of neuromuscular junction caused by downregulation of presynaptic and postsynaptic nicotinic receptors due to release of excessive Ach and Ca’ respectively.
• Atropine is ineffective, symptomatic treatment is given.

3. Type III

• It involves OP-induced delayed polyneuropathy (OPIDN).
• It occurs 1-3 weeks after exposure and is associated with demyelination of axons.
• It is not caused by cholinesterase inhibition but rather by neuropathy target esterase (NTE) inhibition.
• It involves distal muscles with relative sparing of neck muscles, cranial nerves, and proximal muscles.