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There were several kiddos at the theatre and they did fine. Your son will probably never want to be an astronaut after watching this movie. There is some mild violence as you might imagine, so you'll need to take that into consideration.

Totally not EMS related, but get your arse out to the theatre and watch this movie. Don't be a cheap arse either, this movie deserves to been see in 3D, preferably on imax if possible.

No worries mate, have a great night. Hope to see you frequent the forums.

True, but I think we have different definitions of what an adequately understood mechanism of action is. With what I am currently doing, it is not uncommon to use differential equations and compartment modelling to make very accurate predictions about how things work and what they do. (Mostly pharmacokinetic models at this point). If there is a lack of highly accurate and precise models that can be used to make predictions that match experimentation, I would say the mechanism is not totally understood, even though it may be understood when taking a very broad approach. However, in the case of lipid emulsions, there are multiple proposed mechanisms with experimentation perhaps favouring some hypotheses over other hypotheses. For example, using fairly simple algebra in the form of Henderson-Hasselbalch, I can make very good predictions about the amount of ion trapping that will occur with ASA depending on it's pH. With that said, some may say that I do not have a good understanding because if you dig deep enough, you can eventually find things that are not well understood. Perhaps it is more interpretation bias and semantics in some cases? Dave, Goldfrank's is the boss when it comes to toxicology IMHO. It is easily my first go to resource when working on various assignments and projects. If your O-chem and biochem is weak, some of the concepts can be confusing as it assumes you have a pretty good understanding of basic sciences. Occasionally, my lack of chemistry preparation shows through. For example, I had a difficult time understanding how Florine acts as a good leaving group when dealing with Sarin. I simply did not appreciate the fact that the Florine is attached to a Phosphorous atom which is in turn attached to Oxygen atoms. This results in a rather polarised Phosphorous atom (Oxygen is highly electronegative like the Florine) that allows for the abstraction of fluorine under substitution with a hydroxyl group (ACHE molecule). Anyway, long winded, but basically, it's a great book but I find myself reaching form my gen chem and O-chem textbooks fairly often.

I think you guys pretty much got this. INH leads (by complex mechanisms) to decreased GABA synthesis by decreasing levels of pyridoxine. Therefore, benzodiazepines may not be effective. Basically, GABA acts as a ligand for an ionotropic receptor that when activated, allows Chloride ions to enter the neuron. The changes the resting potential and makes it much harder for the cell to depolarise as much more stimulus is required to meet the threshold. This in essence, depresses the neuron. As stated earlier, pyridoxone can be administer but it is not something commonly carried outside of the hospital. Additionally, other agents such as Diprivan may be effective alternatives until pyridoxone therapy can be administered. A good rule of thumb is administering 1 gram of pyridoxine for every suspected gram of INH ingested.

Welcome back, hope you are feeling and doing better. I wish I had an answer to the question of suffering, only to say that I have no particular belief that it is due to any sort of supernatural being's supreme plan. However, I am not here to talk about such things, only to welcome you back.

I'd also add that special modalities are something to consider as well. For example, people diving a rebreather may experience issues that open circuit divers would not.

On the right track. Why would a GABA deficiency cause seizures and why would benzodiazepines possibly not work?

Let us say we do not have access to RSI. A specific treatment has been mentioned, but I want to spend some time discussing the seizure issue before moving on. Do you guys expect benzodiazepines to work with this patient? Why or why not? What is the pathophysiology of the suspected problem?

How would you know if the seizures were controlled once paralytic agents are administered?

Noted. The patient continues to experience tonic-clonic activity that is seemingly unresponsive to the diazepam.

You can't make heads or tails of his bottles and pill counts. Following diazepam administration, the seizures continue. What to do?

What do you want, how are you giving it and what dose are you going to administer?

The patient continues to have tonic-clonic activity.

Vital Signs: P-118, B/P- 150/102, SPO2-97% on a partial rebreather mask, T-38.2 Celsius, RR- 22 snoring resolves with that placement of a nasal airway and airway positioning (Patient does not accept an oral airway), BGL 7 mmol/L. Bystanders and not sure of the exact pulmonary history. The patient has several pill bottles in his bathroom. You see the following; rifampin, isoniazid, ethambutol and pyrazinamide. The patient begins to develop tonic/clonic activity...

Patient is breathing and has a pulse but is currently unresponsive with snoring respirations at a rate of 22/minute. Bystanders say the he collapsed and "twitched violently" for a few minutes. He's on medications for some "lung problem."

No apparent threats. Local residence. You see a male who appears to be in his 50's, in a supine position on the floor of the living room. He's surrounded by a few worried looking people. The patient does not appear to be moving or actively interacting with the environment.

You are called to the residence of a "man not acting right."

Iphone special, please forgive typographical errors.

Thanks for the comments everybody. A discussion regarding additional therapies is definetly in order: Regarding lipid emulsions: This therapy shows promise and at least has efficacy in experimental models using animals. However, the mechanism of action is not well known. It may possible be one of four concepts; a sponge or 'fat sink" action, alteration of intracellular processes, interaction with stong ion channels and perhaps it may be as simple as reativating enzymes through the law of mass action. Most of the research has been bupivacaine induced toxicity in animals. I am not aware of significant human studies. However, large studies do not exist for glucagon significant observation evidence exists and few people would be willing to turn a cardiotoxic patient into a control when glucagon is generally accepted to work in spite of the lack of robust studies. Bottom line, there is promise but the data is lacking and it is unclear if lipids would be any more effective than glucagon.

Good discussion. Beta receptors are interesting and if you generalise the types of receptors within the body, you can take a big picture approach and say they fall into two categories: Ionotropic and Metabotropic. Ionotropic channels are ion channels that when activated or inhibited have direct consequences. For example, inhibiting a certain type of Sodium channel can prevent neurons from depolarizing and cause local anaesthesia among other things. Contrast this with a metabotropic receptor where it causes things to occur in a "less direct manner" if you will. Metabotropic receptors like Beta receptors typically work by causing the production or enhancing the production of a "secondary" messanger molecule within the cell, The process is complicated, but basically, an activated Beta receptor will in turn activate a g-protein with the cytoplasmic membrane. The g-protein then can act upon another protein/enzyme known as andeyl cyclase. Adenyl cyclase enhances a pathway that causes ATP to be turned into cAMP. The cAMP is what we call the secondary messenger because the cAMP can then go onto cause other things to happen within the cell. One thing is the activation of a molecule called protein kinase A (involved in the actual contraction of the heart). Additionally, cAMP is involved in gluconeogenesis and multiple other processes. So, blocking a Beta receptor will decrease intracellular production of cAMP. Glucagon has it's own receptors seperate from Beta receptos, but those receptos are also what we can call "g-protein coupled." This means that glucagon also results in increased levels of intracellular cAMP. This creates an almost "ah ha" moment when thinking about why we would use it in the setting of cardiotoxicity with Beta blocker overdose. Interestingly, glucagon also inhibits the phosphodiesterase molecule. This molecule is in part responsible for the inhibition of cAMP. Wile I have not looked deeply into the possible physiology, the evidence paints a very interesting picture of Beta blocker overdose. Certainly one that I did not expect and one with important clinical implications: I will be pulling much of my information from a book called Goldfranks Toxicologic Emergencies 9th edition. The book sites several pieces of literature that can be referenced. Therefore, I hope you all can trust what I am about to say: In reality, *isolated Beta blocker overdose in health patients is benign. When looking at the literature, 33% or more of overdose patients actually remained completely asymptomatic. In fact, Beta blockade is typically well tolerated in healthy patients and patients who do not need much sympathetic output to maintain cardiac output are particularly resistant to the effects of Beta blocker overdose. People like children for example. *I want to place emphasis on the word "isolated." If a patient with suspected Beta blocker overdose has significant cardiotoxic symptoms, I think a key take home point here is that you need to suspect polysubstance involvement and attempt to investigate for the presence of other substances if possible and practical. Recent systemic reviews of literature also reveal that in published cases, mortality is not appreciated in paediatric patients under the age of six who overdose on Beta blockers. Hypoglycaeima was noted however. Regarding observation time, this can be tricky. Most patients will develop signs and symptoms in a 6-8 hour window. However, sustained release formulations may fall outside of the bell curve, so to speak. Therefore, a 24 hour watch and wait period is not unreasonable in the absence of definitive toxicological advice. What is the bottom line so to speak: 1) Many patients who overdose on Beta blockers may not have any problems. Clearly, we still need to monitor and anticipate problems however. Additionally, activated charcoal administration early on in the management of overdose, prior to symptom onset, is a reasonable consideration. 2) If patients develop significant cardiotoxicity, gulcagon will be a primary therapeutic option as it can increase intracellular levels of cAMP. Additionally, if toxicity develops, we need to aggressively investigate and consider the possibility of other substances. This may be of benefit, because effective treatments may exist for the other substances or we may be able to better predict the consequences if we have an idea of what substances may be involved. Additionally, people with conditions that require good sympathetic output may be much more sensitive to Beta blocker overdose. 3) Be on the look out for hypoglycaemia and other problems associated with Beta blocker overdose such as respiratory problems in people with reactive airway disease. I hope you all found this scenario interesting and informative. I literally had my mind blown when looking at the evidence regarding the number of people who remain asymptomatic following overdose. Clearly, there is much variability in the evidence, but it is important and perhaps places emphasis on the importance of a good toxicological investigation if possible.

Something to think about indeed. How big a problem is isolated Beta blocker overdose in a "healthy" person?

It's certainly possible. How does Beta blocker toxicity occur. We are often taught that a Beta receptor is blocked and magic, mystical stuff occurs, leading to a decreased heart rate and so on. Asking how also leads to answers about how glucagon is an effective therapeutic agent in the setting of Beta blocker toxicity.

Let's say you check it and find it's 38 mg/dl. Is this consistent with Beta blocker overdose?

For the scenario, assume the vital signs are of no use at this time. Focus solely on the altered mental status. Is there something other than cardiac toxicity that Beta blockers can cause, particularly in children?