Poisoning and Overdose

by Carlo Raj, MD

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    00:00 What we’ll do here? We’ll take a look at poisoning and then the signs and then quickly the antidotes. All part of your critical care and some of this is going to then also affect your lungs as well. Acetaminophen is what we’re looking at here and, well, if you remember, in Pharmacology, Acetaminophen has an interesting metabolite called NAPQI, an N-acetyl-p-benzoquinone imine and that NAPQI is extremely toxic, especially when you talk about the zone 3 of your liver and the reason for that is because it has excess levels of your CYP 450 that wishes to break down Acetaminophen. At some point in time, because of this excess type of metabolite that’s being produced, your liver is going to go into failure. How important is that in our society? It is one of the most common causes of liver transplants in adolescents and young adults. That is how bad this is.

    00:52 Welcome to Tylenol, Acetaminophen poisoning. What is it that you’re trying to do with Acetaminophen poisoning? Walk over to the last column and you’re trying to replenish the Glutathione so that you can properly metabolise Acetaminophen further. Welcome to N-acetylcysteine. Take a look at salicylates. First thing it does is it, for really peculiar reasons, is going to stimulate the respiratory centre, stimulate it. Hear me. That’s the first thing that it’ll do. Early salicylate poisoning. What is this? Aspirin poisoning.

    01:26 Okay, so, if you stimulate the respiratory centre, okay, rapid deep breathing, you’re blowing off carbon dioxide. Take a look. Respiratory alkalosis, your pH is elevated early. Late, what is a salicylate? What is its property? It’s an acid. If you ingest an acid, then you have metabolic acidosis, right? Now, one of the things that we learnt when we did our acid-base pathology is how to then distinguish the two types of metabolic acidosis. Was it endogenous like diabetic ketacidosis, lactic acidosis or was it exogenous salicylate? And in your mind you should be thinking about something like your urinary osmolar gap. And then antidote here, alkalised blood, urine and maybe perhaps dialysis to properly get rid of the salicylate. Alkalinise, especially chronically.

    02:21 Tricyclics, wide, complex tachycardias more of the heart. Here, once again, you alkalise the blood. Benzodiazepine is something that you’d use perhaps in a patient that has anxiety or may be even different types of seizures. This is then going to do what? Opens up your chloride channels and increase frequency and do not forget though that with benzos, it is then going to cause some what sedation as a side effect, could potentially knock out your respiratory centre. If you knock out your respiratory centre, you tell me as to what your breathing rate is? Good. Hypoventilation may result in respiratory acidosis. And tell me about your A-a gradient. No widening. What is the antidote here? This is Flumazenil for Benzodiazepine. "zee" and "zee".

    03:10 Opiods, once again, big time. Now, you are worried. You’ve heard of Kurt Cobain from Nirvana and I want to point out that if you haven’t, that’s fine. I’m a little bit older. So, opiod overdose, knock out your respiratory centre. You end up have respiratory depression. Here, the antidote and treatment will be Naloxone. As you can see here, there are many drugs and I’m just going to group the big time important drugs that we see in clinical practice all the time and its associated diseases. Either the liver or respiratory centre is often times associated. Next, well if it’s methanol or ethylene glycol or isopropanol, you’re thinking about this osmolar gap we were referring to and plus or minus the anion gap as well because that becomes important. And with these, remember the mnemonic MUDPILES that we walked through. In MUDPILES, the issue was the fact that this was a metabolic acidosis and so therefore, how is your patient breathing to compensate? Breathing quickly. Good. The antidote here will be Fomepizole or perhaps your dialysis.

    04:14 Fomepizole is an important antidote. Beta blockers, here, you’re thinking about bradycardia, hypotension. Tell me about your bronchi. If it’s a non-selective Beta blocker, if you block the Beta 2, oh my goodness. Right, bronchospasms.

    04:31 Be careful when you use such Beta blockers in patients that are asthmatic. Could I be any more dramatic? Antidote here, give glucagon, pacing, inotropes. If your heart starts failing, and glucagon because every possibility that the patient may end up with hypoglycaemia. Give glucagon so that you can increase gluconeogenesis, an important point there. Calcium channel blockers. Here, bradycardia, hypotension, calcium, pacing, inotropes and DIG (Digitalis). With DIG arrhythmias, there is this slight, very rarely found side effect known light with halos, a green light sometimes what it's referred to, Digibind is what you’re looking at. That is a monoclonal antibody that is going to specifically go in there and remove the DIG. And close cardiac monitoring.

    05:20 Which electrolyte are you always monitoring? Potassium. And what type of potassium level would then exacerbate your DIG toxicity, Hypo or Hyperkalemia? Good. Hypokalemia. Remember, it takes the place of the potassium on the sodium-potassium pump. If your patient is hypokalemic, then DIG is going to then bind to the sodium-potassium pump excessively. Think about the mechanism of action of DIG please and then you’ll be good to go.

    About the Lecture

    The lecture Poisoning and Overdose by Carlo Raj, MD is from the course Pulmonary Critical Care.

    Included Quiz Questions

    1. NAPQI
    2. N-acetylcysteine
    3. Mercapturic acid conjugates
    4. NAC
    5. Glutathione
    1. Digitalis
    2. Calcium channel blockers
    3. Benzodiazepines
    4. Opiates
    5. Beta-blockers
    1. Flumazenil
    2. Naloxone
    3. Naltrexone
    4. Fomepizole
    5. N-acetylcysteine
    1. Benzodiazepines
    2. Salicylates
    3. Digitalis
    4. Methanol
    5. Acetaminophen
    1. Osmol gap = 7 mOsm/kg
    2. Anion gap = 10 mEq/L
    3. Anion gap = 20 mEq/L
    4. Osmol gap = 11 mOsm/kg
    5. Anion gap = 14 mEq/L

    Author of lecture Poisoning and Overdose

     Carlo Raj, MD

    Carlo Raj, MD

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