"Likely poisoned"
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https://edition.cnn.com/2020/08/24/europe/alexey-navalny-germany-poison-grm-intl/index.html
I read elsewhere that they suspect a "cholinesterase inhibitor" - @George-K - you know anything about that stuff?
@Klaus said in "Likely poisoned":
https://edition.cnn.com/2020/08/24/europe/alexey-navalny-germany-poison-grm-intl/index.html
I read elsewhere that they suspect a "cholinesterase inhibitor" - @George-K - you know anything about that stuff?
Used a cholinesterase inhibitor every day for 40 years.
The physiology is this:
Acetylcholine is the neurotransmitter that causes (among other things) muscles to contract. The pre-synaptic nerve releases acetylcholine and it interacts with post-synaptic receptors causing the muscle to depolarize (move ions in and out) and contract.
There's an enzyme found in the synapse, cholinesterase, that breaks down ACh, so it doesn't bind permanently. If it bound permanently, the muscle would contract, relax and stay relaxed. So you want ACh to work, and then go away.
Drugs like curare, pancuronium, and others work by blocking the post-synaptic receptor preventing acetylcholine from attaching. Most of these drugs have a portion of the molecule that "looks like" acetylcholine, and so it can bind to the receptor.
(nit pick distinction - some of these drugs also work by preventing release of ACh presynaptically, but that's not important for this)
This is how I paralyzed people.
Now, to reverse the action of the relaxant, two things have to happen:
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Some of the relaxant has to "wear off" naturally - it basically "washes out" of the synapse. However, a significant amount of receptors can still be blocked.
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ACh has to be present to "displace" the paralytic - simple mass action. When there's more ACh than curare, eventually, ACh will take over.
So, the point is to get more ACh into the synapse. This is done by inhibiting the breakdown of ACh by the naturally occurring enzyme, cholinesterase. There are two kinds of cholinesterase, but that's not really important.
By blocking the enzyme that degrades cholinesterase, more ACh is available to interact with the post-synaptic receptors, allowing the muscle to return to normal function.
Now, if you have too much ACh, that's a bad thing as well, because ACh, as I said, works in other places - it'll make you tear, it'll make you sweat, it'll make your bronchi secrete like crazy, it'll make you move your bowels. If you give an cholinesterase inhibitor without counteracting those effects, it's a pretty miserable experience.
Cholinesterase inhibitors are the basis of many nerve gasses (Sarin, for example) and the binding is irreversible.
It's an ugly way to die:
Nerve agents attack the nervous system. All such agents function the same way resulting in cholinergic crisis: they inhibit the enzyme acetylcholinesterase, which is responsible for the breakdown of acetylcholine (ACh) in the synapses between nerves that control muscle contraction. If the agent cannot be broken down, muscles are prevented from relaxing and they are effectively paralyzed.[2]:131–139 This includes the heart and the muscles used for breathing. Because of this, the first symptoms usually appear within seconds of exposure and death can occur via asphyxiation or cardiac arrest in a few minutes.
Initial symptoms following exposure to nerve agents (like sarin) are a runny nose, tightness in the chest, and constriction of the pupils. Soon after, the victim will have difficulty breathing and will experience nausea and salivation. As the victim continues to lose control of bodily functions, involuntary salivation, lacrimation, urination, defecation, gastrointestinal pain and vomiting will be experienced. Blisters and burning of the eyes and/or lungs may also occur. This phase is followed by initially myoclonic jerks (muscle jerks) followed by status epilepticus -type epileptic seizure. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the neuromuscular junction of the diaphragm.
More than you wanted to know, but I'm retired and I have time....
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Russian opposition leader Alexey Navalny was poisoned with a chemical nerve agent from the Novichok group, the German government said Wednesday.
Navalny, who fell ill on a flight from the Siberian city of Tomsk to Moscow last month, is being treated at a Berlin hospital.
In a statement, German government spokesman Steffen Siebert said it was "startling" that "Alexei Navalny was the victim of an attack with a chemical nerve agent in Russia.""The federal government condemns this attack in the strongest possible terms."
"We hope for a full recovery of Alexei Navalny," the statement added.
In 2018, former Russian spy Sergei Skripal was the target of a Novichok nerve agent attack in the English cathedral city of Salisbury.
https://en.wikipedia.org/wiki/Novichok_agent
As nerve agents, the Novichok agents belong to the class of organophosphate acetylcholinesterase inhibitors. These chemical compounds inhibit the enzyme acetylcholinesterase, preventing the normal breakdown of the neurotransmitter acetylcholine. Acetylcholine concentrations then increase at neuromuscular junctions to cause involuntary contraction of all skeletal muscles (cholinergic crisis). This then leads to respiratory and cardiac arrest (as the victim's heart and diaphragm muscles no longer function normally) and finally death from heart failure or suffocation as copious fluid secretions fill the victim's lungs.[70]
As can be seen with other organophosphate poisonings, Novichok agents may cause lasting nerve damage, resulting in permanent disablement of victims, according to Russian scientists.[71] Their effect on humans was demonstrated by the accidental exposure of Andrei Zheleznyakov, one of the scientists involved in their development, to the residue of an unspecified Novichok agent while working in a Moscow laboratory in May 1987. He was critically injured and took ten days to recover consciousness after the incident. He lost the ability to walk and was treated at a secret clinic in Leningrad for three months afterwards. The agent caused permanent harm, with effects that included "chronic weakness in his arms, a toxic hepatitis that gave rise to cirrhosis of the liver, epilepsy, spells of severe depression, and an inability to read or concentrate that left him totally disabled and unable to work." He never recovered and, after five years of deteriorating health, died in July 1992.
The use of a fast-acting peripheral anticholinergic drug such as atropine can block the receptors where acetylcholine acts to prevent poisoning (as in the treatment for poisoning by other acetylcholinesterase inhibitors). Atropine, however, is difficult to administer safely, because its effective dose for nerve agent poisoning is close to the dose at which patients suffer severe side effects, such as changes in heart rate and thickening of the bronchial secretions, which fill the lungs of someone suffering nerve agent poisoning so that suctioning of these secretions, and other advanced life support techniques, may be necessary in addition to administration of atropine to treat nerve agent poisoning.
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Russian opposition leader Alexei Navalny has been released from a Berlin hospital after more than a month’s treatment for poisoning, with doctors now believing that it’s possible he could see a “complete recovery” from the Soviet-era nerve agent, the hospital said Wednesday.
Navalny spent 32 days at Berlin’s Charite hospital, 24 of them in intensive care, before doctors deemed his “condition had improved sufficiently for him to be discharged from acute inpatient care.” He will remain in Germany for the time being to continue his rehabilitation, his team said.
As he was released Tuesday, the 44-year-old displayed his characteristic sarcastic sense of humor. In an Instagram post, he took swipe at Russian President Vladimir Putin, scoffing at reported comments by the Russian leader suggesting that Navalny might have intentionally poisoned himself.
Navalny, a politician and corruption investigator who is Putin’s most visible opponent, was flown to Germany two days after falling ill on Aug. 20 on a domestic flight in Russia. He spent those two days in a coma in a hospital in the Siberian city of Omsk, where Russian doctors said they found no trace of any poisoning.
