Nick Jones Posted March 14, 2023 Share Posted March 14, 2023 https://amp.theguardian.com/society/2023/mar/14/pholcodine-cough-medicines-withdrawn-in-uk-over-allergy-fears @JohnD have you ever experienced the alleged effect? Link to comment Share on other sites More sharing options...
RogerH Posted March 15, 2023 Share Posted March 15, 2023 Would it be easier to Euthanaise all those folk that suffer from Anaphalaxia Joke (sick) Roger Link to comment Share on other sites More sharing options...
Nick Jones Posted March 15, 2023 Author Share Posted March 15, 2023 The odd thing is that this is apparently and extremely rare event that may happen when you are anaesthetised having taken a pholcodeine product within (up to) the last year. This would seem to rank it very low down the list of life’s many risks and certainly well below (say) peanut products…. Link to comment Share on other sites More sharing options...
JohnD Posted March 15, 2023 Share Posted March 15, 2023 The drug in question is pholcodeine (pholcodine in the US). The clue is in the second part of the name, as it is a derivative of codeine, a member of the family of opium-like pain killers. All such drugs will suppress the cough reflex, and pholcodeine has been modified by a side chain on the codeine molecule that allegedly makes it more potent on that than on pain receptors. Hence it's use in "cough medicines" that are available without prescription, and widely used. Neuromuscular blocking drugs (NMBDs) are used solely in anaesthesia. They act at the junction between the motor nerve ending and the receptor on muscle cells, to block transmission of nerve signals, resulting in complete paralysis, not only of limbs but of the muscles with which we breath. A terrifying experience, and shortly fatal, unless used during surgery and while a ventilator keeps the patient breathing, to allow less anaesthetic drug to be used which reduces the risk. "Balanced" anaesthesia, using highly specific, highly potent drugs to produce anaesthetic sleep, profound pain relief and surgical paralysis in the right proportions is the epitome of modern anaesthesia, and a completely different fish kettle from getting the patient deep enough on ether! Anaphylaxis is a severe form of allergy, where the whole of the immune system overreacts. The blood pressure drops catastrophically, the heart races, the lungs tighten as in an asthma attack, leading to death unless correctly and rapidly treated. Fortunately, anaesthetists have sometimes wondered if they should change the title of their specialty to "Resuscitology", because of their role outside the operating theatre! A classic line in medical drama, when the s4it hits the fan is "Call the anaesthetists!", and as shown by the results below, it's what we do best! If - and it's a big if! - the paralysing effects of NMBDs are compensated for as above, they are a very safe group of drugs. Anaphylaxis does occur with their use, but very rarely. The actual incidence is difficult to estimate, but this paper https://academic.oup.com/bja/article/110/6/981/245571 looked at those cases that happened in Western Australia. In that state of Oz, over nine years, 80 cases of anaphylaxis associated with an NMBD were reported. The paper could not estimate the number from that population who received an NMBD in this time, but the population of Western Australia is more than two and half million people, so this is a rare complication. All of the cases survived but many had their surgery postponed and half of them needed ICU admission. The discussion that concludes the paper examined many previous reports, that found an incidence of one case of anaphylaxis in between 6000 to 20,000 administrations of an NMBD, and they commented that "NMBD anaphylaxis is a feared complication but one that is difficult to study" because of its rarity. The paper did point out that some NMBDs are more likely to cause an anaphylaxis than others. Sorry about the tutorial, but you did ask! And you asked if banning pholcodeine was an overreaction. I think that there is an association - there has long been one between the incidence of NMBD anaphylaxis and the sales of cough medicine by country. See: Florvaag E, Johansson SG, Oman H, et al. Prevalence of IgE antibodies to morphine. Relation to the high and low incidences of NMBA anaphylaxis in Norway and Sweden, respectively. Acta Anaesthesiologica Scandinavia 2005; 49: 437– 44. Norway had six times more NMBD reactions than Sweden, where such cough medicines had long been banned. The incidence with Rocuronium is three times greater than with vecuronium, but those drugs have different properties which make them ideal in certain circumstances, and to ban one NMBD would not prevent anaphylaxis cases. Despite the lack of deaths in the Australian study, anaphylaxis is a most dangerous complication that kills, whereas a tickly cough is an irritation, usually temporary, and anyway, pholcodeine is rarely a cure. John 1 Link to comment Share on other sites More sharing options...
Nick Jones Posted March 15, 2023 Author Share Posted March 15, 2023 Thanks for that - which I’m going to need to read carefully a couple more times…. But I’m not quite getting the link between the pholcodine and the NMBDs…. Link to comment Share on other sites More sharing options...
JohnD Posted March 15, 2023 Share Posted March 15, 2023 (edited) Try this, Nick. https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.2008.05866.x It's written for anaesthetists, obviously. See second page "Mechanism". All NMBDs carry a "quaternary ammonium ion", highly charged nitrogen atom (N+4). Vecuronium (as an example). The N+4 ion is part of the carbon ring on the right. This mimics the natural transmitter Acetyl Choline (ACh) that also carries a N+4 ion. Acetyl Choline. In this diagram the N+4 is on the left, with three methyl groups attached, no carbon ring. ACh is released by the nerve and crosses the synapse to stimulate the receptors and initiate contraction. The rest of the NMBD molecule acts as a scaffold to present the ion to a muscular receptors, to which they bind, but not being ACh does not stimulate, so no muscular contraction (except with suxamethonium). Most (not all) NMBDs are "competitive" inhibitors that compete with ACh for the receptors . While their concentration is high, they win the contest, while ACh is rapidly removed by the normal clearing mechanism which doesn't work on the NMBD, so that it stays there, for a period that depends on the drug. All that time, ACh cannot access the receptors and the muscle is paralysed. Again most, not all, NMBDs will stick around for some time, and to promote the return of normal function at the end of surgery, another drug is given that inhibits the ACH breakdown mechanism. This allows the concentration of ACh and its duration at the receptor to rise, reversing the result of the contest. Thing is that morphine and all the opiates, including pholcodeine also carry a N+4 ion. In those who use such drugs, Immunoglobulin E levels that are sensitive to their N+4 ions may be high, and the N+4 ions on NMBDs can stimulate the receptors on IgE , and initiate an allergic, or anaphylactic response. While there is a wide and varied use of opiates, both legal and illegal, even addicts do not seem to suffer more from this complication, but pholcodeine is especially 'immunogenic' in this respect, and produces higher levels of IgE. Hence, more risk of anaphylaxis. Thank you, Nick, you have made me think a lot more than I have for years about my old skills! John Edited March 15, 2023 by JohnD Link to comment Share on other sites More sharing options...
Gt64fun Posted March 15, 2023 Share Posted March 15, 2023 56 minutes ago, JohnD said: It's written for anaesthetists, obviously. No wonder it put me to sleep! Ian 1 Link to comment Share on other sites More sharing options...
JohnD Posted March 15, 2023 Share Posted March 15, 2023 KerChing! The Old Ones are the best ones, sometimes. Link to comment Share on other sites More sharing options...
PeterC Posted March 15, 2023 Share Posted March 15, 2023 John, Do you know of a drug that paralyses voluntary musculature (apart from the eyes) that leaves the patient aware, able to stand balanced, and breathing OK ? Is there a central pathway whose blockade could do that? Peter Link to comment Share on other sites More sharing options...
JohnD Posted March 15, 2023 Share Posted March 15, 2023 Are you "asking for a friend", Peter? My answer would be, no. The nearest might be ketamine, but that induces a dissociative mental effect, and they probably couldn't stand up. Try hypnosis? John Link to comment Share on other sites More sharing options...
Nick Jones Posted March 15, 2023 Author Share Posted March 15, 2023 3 hours ago, PeterC said: John, Do you know of a drug that paralyses voluntary musculature (apart from the eyes) that leaves the patient aware, able to stand balanced, and breathing OK ? Is there a central pathway whose blockade could do that? Peter Oh man...... what are you plotting?! Link to comment Share on other sites More sharing options...
Escadrille Ecosse Posted March 16, 2023 Share Posted March 16, 2023 (edited) Good stuff John. Cough medicines always seem to me to be not that far removed from 'snake oil' so I don't see this as a great loss. Edited March 16, 2023 by Escadrille Ecosse Link to comment Share on other sites More sharing options...
Nick Jones Posted March 16, 2023 Author Share Posted March 16, 2023 Yeah… but in my experience the pholcodeine containing ones were the most likely to work and help you get off to sleep….. Link to comment Share on other sites More sharing options...
PeterC Posted March 16, 2023 Share Posted March 16, 2023 16 hours ago, Nick Jones said: Oh man...... what are you plotting?! It's more trying to fathom how 'they' can do it. There are plenty of reports of witnesses being paralysed like that in close encounters eg https://www.thinkaboutitdocs.com/valensole-france-landing-maurice-masse-case/ Some brain neurones involved in movement control exhibit oscillatory calcium signals and ufo phenomena seem to be able to modify 'time'. In some ways Masse's paralysis resembles a Parkinson's 'off' state. Hooweverthe calcium oscillations in that pathway can be blocked by a drug without causing paralysis. On TRR forum theres a long running thread 'when you have 90 minutes' where I have been posting this paranormal stuff. Link to comment Share on other sites More sharing options...
Escadrille Ecosse Posted March 16, 2023 Share Posted March 16, 2023 Sorry Peter but please not on Sideways https://en.wikipedia.org/wiki/Falsifiability Link to comment Share on other sites More sharing options...
PeterC Posted March 16, 2023 Share Posted March 16, 2023 16 minutes ago, Escadrille Ecosse said: Sorry Peter but please not on Sideways https://en.wikipedia.org/wiki/Falsifiability Colin, What I am working on, and have been for 5years, IS falsifiable. The first step is to identify the 'that's odd ' observations, then to formulate a working hypothesis, then to test it with measurements. I have around 15 possible tests to date. The paralysis phenomenon is widely reported and is at the 'that's odd' stage. Peter Link to comment Share on other sites More sharing options...
Escadrille Ecosse Posted March 16, 2023 Share Posted March 16, 2023 Peter 'Widely reported' is a subjective statement, the where being as important as the what. My Dad was in the RAF and I was in the UAS. There was a rule in the Officers Mess that controversial topics were not discussed as they were likely to lead to dissent. I would politely suggest that these sort of 'alternative' views of reality fall into the category of parked. If TRR has pages of this stuff then that would be a good place too keep this discussion and keep Sideways clear of it. Link to comment Share on other sites More sharing options...
RedRooster Posted March 16, 2023 Share Posted March 16, 2023 22 hours ago, PeterC said: John, Do you know of a drug that paralyses voluntary musculature (apart from the eyes) that leaves the patient aware, able to stand balanced, and breathing OK ? Is there a central pathway whose blockade could do that? Peter Think your talking about GHB (aka date rape drug), were you a bit saire the day after going clubbing? Link to comment Share on other sites More sharing options...
Escadrille Ecosse Posted March 16, 2023 Share Posted March 16, 2023 4 minutes ago, RedRooster said: Think your talking about GHB (aka date rape drug), were you a bit saire the day after going clubbing? Link to comment Share on other sites More sharing options...
PeterC Posted March 16, 2023 Share Posted March 16, 2023 23 minutes ago, Escadrille Ecosse said: Peter 'Widely reported' is a subjective statement, the where being as important as the what. My Dad was in the RAF and I was in the UAS. There was a rule in the Officers Mess that controversial topics were not discussed as they were likely to lead to dissent. I would politely suggest that these sort of 'alternative' views of reality fall into the category of parked. If TRR has pages of this stuff then that would be a good place too keep this discussion and keep Sideways clear of it. You are obviously not aware of the UAPs that are being reported almsot daily by US Navy fighter pilots. Their UAP reports are now taken seriusoly by Congress and the Pentagon has been instructed to deliver annual reports. Google 'go-fast', 'tic-tac' and 'gimbal' for videos from US Navy fighters released by the Pentagon. Tis-tac was reported to the press by Cmdr Favor, in the top 20 most senior officers on USS Nimitz, the nuclear powered caarier. Link to comment Share on other sites More sharing options...
Nick Jones Posted March 16, 2023 Author Share Posted March 16, 2023 14 minutes ago, RedRooster said: Think your talking about GHB (aka date rape drug), were you a bit saire the day after going clubbing? Rohypnol..... 2 hours ago, PeterC said: On TRR forum there's a long running thread 'when you have 90 minutes' where I have been posting this paranormal stuff. Can we leave it on there please.... Link to comment Share on other sites More sharing options...
PeterC Posted March 16, 2023 Share Posted March 16, 2023 Ask yourselves: "How fast does time flow?" And then ask if the Nimitz tic-tac was manipulating 'time' in ways that science does not understand. But I'll not trouble you with any ideas, I'm away from here, too many closed minds. Link to comment Share on other sites More sharing options...
Escadrille Ecosse Posted March 16, 2023 Share Posted March 16, 2023 16 minutes ago, Nick Jones said: Can we leave it on there please.... My point exactly 4 minutes ago, PeterC said: But I'll not trouble you with any ideas I appreciate that Peter 1 Link to comment Share on other sites More sharing options...
JohnD Posted March 16, 2023 Share Posted March 16, 2023 2 hours ago, RedRooster said: Think your talking about GHB (aka date rape drug), were you a bit saire the day after going clubbing? No, and No. John Link to comment Share on other sites More sharing options...
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