ORGANOPHOSPHATE POISONING --- MNEMONICS

ORGANOPHOSPHATE POISONING

ORGANOPHOSPHATES ARE ANTI CHOLINESTERASE IN NATURE.

EXAMPLES-- Dyflos (DFP), Echothiophate,Parathion, Malathion, Diazinon, (TIK-20), Tabun, Sarin, Soman.

What is acetyl choline esterase?
It is an enzyme which catalyzes the hydrolysis of acetyl choline to acetate and choline

The active region of acetylcholine esterase contains an aromatic anionic site [near tryptophan 86] and an esteratic site formed by serine 203, glutamate 334 and histidine 447

Mnemonic:
aromaTic has T, so does Tryptophan
eSteratic site has S, so does Serine.

How does acetyl choline react with acetyl choline esterase?
Hydrolysis of acetyl choline involves electrostatic attraction between the positive N+ of acetyl choline to the aromatic pocket and nucleophilic attack of serine-OH leading to acetylation of serine.

The acetylated enzyme reacts with water to produce acetic acid and choline :)


How do Organophoshates react with acetyl choline esterase?
Organophosphates attach to the esteratic site
The anionic site is free.

If the organophosphate molecule loses it's alkyl group, it becomes resistant to hydrolysis
This process is called aging

So if you have to rescue your acetyl choline enzyme from the evil force of Organophosphorous compounds, you'll have to do it before aging (6-8 hours) :P
How do you do it? Use cholinesterase reactivators!

What are choline esterase reactivators?
They are used to restore neuromuscular transmission in cases of Organophosphate poisoning
You basically give more reactive OH groups.. Since the phosphorylated enzyme reacts very slowly or not at all with water
In the presence of Oximes, [Generic formula R-CH=N-OH], reactivation occurs much faster

Example of an Oxime is Pralidoxime.

Pralidoxime has a quarternary nitrogen which attaches to the anionic site
It's oxime end reacts with the phosphorous atom attached to the esteratic site
The oximephosphonate so formed diffuses away leaving the reactivated cholinesetrase :)

CLINICAL PRESENTATION

Muscarinic 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). Muscarinic effects by organ system 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

Nicotinic effects

Nicotinic signs and symptoms include muscle fasciculations, cramping, weakness, and diaphragmatic failure. Autonomic nicotinic effects include hypertension, tachycardia, mydriasis, and pallor.

CNS effects

CNS effects include the following:

• Anxiety
• Emotional lability
• Restlessness
• Confusion
• Ataxia
• Tremors
• Seizures
• Coma

Treatment of organophosphorus poisoning mnemonic

1. Termination of further exposure to the poison:.--

poison-fresh air, wash the skin and mucous membranes with soap and water, gastric 1avage according to need.

 2. Maintain patent airway, positive pressure respiration if it is failing. 

3. Supportive measures-maintain BP, hydration­ , control of convulsions with judicious use of diazepam.

 4. Specific antidotes- ATROPINE AND CHOLINESTERASE REACTIVATORS.

I focus on how to remember the doses of the medications in this post.

Atropine. aTWOpine. 2 mg IV every 5-10 minutes till full atropinisation occurs.

Pralidoxime is also known as 2-PAM. Two. So 20 mg/kg in 20 minutes is the loading dose. Half that, 10 mg/kg/hr is the maintenance.

Remember to remove the patient from further exposure and wash the skin, give gastric lavage.
Also catheterize the patient before atropine is given (viva concept).

For symptoms of muscarinic poisoning, the common mnemonic is 

 "Cholinergics make you leaky"

That's all!