UPDATE: New Oral Covid Pills

Empower the listener to gain access to the best healthcare possible. Good day and welcome to Medicine Health with Dr. Paul Anderson. That's me, I'm Dr. Paul. And today, more, more questions and answers. If you saw the title, this is sort of Very topical if you're listening live anyway, which would be November 11th, 2021. So topical if you're listening live here, and if you're on the PodBurner or YouTube or any of our other routes of getting this out and it's anywhere near November 2021, this is, this is probably pretty topical. It'd be interesting if you're listening later, and so we'll speak to you folks in the future, uh, to see how some of, some of this turns out. Because, you know, one of the things we talk about a lot with respect to treatments and viruses and COVID and all of these things is we have to work a lot with very emerging data and emerging, you know, new information. And what I always say is, you know, that this is how it looks right now. And, you know, give it a year, give it 2 years, give it 5 years, and let's see how it really, you know, turns out over time. But one of the things that had come up that I thought would be good to kind of dive into, because the companies that make these drugs have just put out some information in press releases. And in case I get lost, I have not only press releases, but some of the data here, the publications, et cetera. And that is, there's 2 companies that each have a new drug that is a reported treatment if you get COVID. Okay, so we have preventive things that help us, you know, not get COVID. And then if we do get COVID, we have treatment things to deal with the virus. And so these particular drugs fit into that treatment category right there. So the— we want to talk about that today because I got a whole bunch of people asking me, uh, you know, how do these even work and how did they get these new drugs, you know, designed and all of this business. Um, and so I want to start out with this, and it's, um, 2 oral drugs for COVID if you have it. So these are not for prevention. Uh, these are you know, for once you get COVID, if you get COVID. One comes from Merck, pharmaceutical company called Merck, the other from Pfizer. You've probably heard of both of those pharmaceutical companies. They're some of the largest pharma companies in the world, so they make a lot of things. And they have 2 drugs that work similarly but not quite exactly the same. So I wanted to talk about that because the gravity of the questions that I was getting was around You know, okay, I heard maybe one or maybe there was 2 drugs. How do they work? How does an antiviral drug work anyway? Is it like an antibiotic or an antifungal drug? And specifically with COVID how do these 2 things, you know, help us if we already have COVID? And then got some questions about, okay, are these similar in the way that they act? to other things that we know about. Now, because there's a lot of antiviral pharmacology, and there's a lot of things that we never even knew were antiviral before, at least people outside of that end of the virology business didn't know, there's a lot of things that we've talked about in prior programs that have antiviral effect that have some crossover here. There's some mechanistic crossovers, and then there's some things that work kind of totally differently. So to start out with, one of the things that we want to think about is the Merck drug is— and these were, I don't recall exactly the timing. Again, it's November 11th, 2021, if you're listening in the future. The Merck drug is called Molnupiravir, and they did a study with close to 800 people where they gave it for— it was around the 5th day of symptoms, so people with significant risk for hospitalization or death. And in that particular study, so this was sort of their proof of concept study with humans, it decreased hospitalization and death by 50%. over the placebo group. So if you go into these trials and you say, yeah, I want to sign up for this new COVID drug trial, you need to remember that you— if it's a randomized trial, you've got a placebo-controlled trial, you got a 50% chance of getting nothing, like a dummy drug, or 50% chance of getting the actual test drug. Now, When it's a randomized trial, it means that you come in and then they put you in a randomized pool. And so who gets the drug is not based on— it's usually not based on the order you sign up or whatever. It's literally randomized. And placebo-controlled means that half get placebo, half get the drug, usually. And then there's the blinding. Okay, so when they say, you know, single-blind or double-blind, single-blind usually means the patient doesn't know whether they got placebo or drug. Double-blind means the healthcare provider and the research folks don't know either. So when you have a double-blind placebo-controlled trial, randomized controlled trial, you are supposed to be taking most of the margins of error out, such as, you know, the nocebo effect. Uh, And believing that you may have something that would work versus the provider knowing, and that's actually able to influence outcomes, other stuff like that. So this was a placebo-controlled randomized trial. And 800 humans randomized to one placebo or drug, and then a 50% reduction in hospitalization and death. Okay, so those are the 2 outcomes. So you have to pick something when you do a drug trial, and hospitalization and death is wonderful because what know is if we can keep you out of the hospital, you have more of a chance of living anyway. Also, it lowers your chances of other side effects and other encounters with drugs. And so the more you can keep people out of the hospital, the better. Now, if you go back, and I don't know why you would do this, but if you go back and you were to listen to— and we'll bring this up a little bit later— but some of our very early programs, podcasts on COVID, when we were first seemingly getting outbreaks here in the United States, one of the things that I was talking about was who had had COVID longer than us. It was China. And I had done some work publishing some things about what they were doing in China. And when we looked, you know, this is what they were saying was our goal is to keep people out of the hospitals because you can overburden the hospital, obviously. But also, once you get in the hospital, in the ICU, and especially if you get on a ventilator, your chance of leaving the hospital is pretty low. So we want to, you know, we want to keep people out of the hospital. So for the entire time that we've known we have COVID, everybody has said, yeah, let's keep everybody out of the hospital that we can. So to have a drug that keeps 50%, you know, you know, of the people out and lowers death and hospitalization, that's great, you know. Um, so, but when we're thinking about that, uh, you want to think, well, okay, so what's a potential, um, way that maybe those numbers might have been better? Well, one way would be instead of waiting, you know, 5 days and after symptoms. If you can get the drug into the person earlier, it's better. Okay, and this is kind of axiomatic with almost any infection. The longer you let the infection sit there and fulminate, the worse it's going to get. And so sure, that makes a lot of sense. So, so a 5-day wait, that may have affected their numbers. Now, this is surmising, but that's, you know, the way that the drugs work. So that leads us to, well, how does this Merck drug work? So this is literally a pill if it's approved. So these are not approved yet, but they're waiting for emergency use authorization like the vaccines and some other stuff that we have. And so your doctor might interact with you, you get a positive COVID test, you got symptoms, they This might be a drug that they actually gave you that you would take orally as a pill. So it's not a shot, it's not an IV. And so when we look at this and we think, well, what way do these work? Well, in the case of molnupiravir, it's a lot like the drug you've heard about, remdesivir, which is a repurposed antiviral drug that's been being used in hospitals for COVID. And you've heard some probably good and bad things about remdesivir, but it's in the category of nucleoside analog. Well, if you think about the way that a virus works— so a virus is very much machine-like, okay? And so you have viral activity, and the virus then has to go to a host cell and hijack the nuclear material, the, the stuff that makes your DNA if it's you, or, or let's say, you know, if it's a, if it's a mouse, the mouse's DNA or whatever. And it has to hijack it inside the cell and then make more of the virus. This is how viruses perpetuate themselves. So it's a very mechanical process. So The new drug from Merck actually gets into— so nucleosides are a piece of the genome. They get incorporated into the genome. So this is a nucleoside analog, meaning it's going to fake out the virus, gonna get incorporated into the viral genome. And so it's a little different than remdesivir in that remdesivir has a slightly different way of doing this little trick with the genomics, but it's close. So once the Merck drug gets incorporated into the DNA, the process, the replication process really of the nuclear material, It starts to cause replication that is defective. And so you have the new viruses that are being born that are defective viruses, and then if those try and replicate, they kind of reach an end of the line. Whereas most viruses, the, the more human cells they can get into, the more virus you can make. So usually the viral count goes up in an infection if you have an active, working viral replicating substance. So nucleoside analog is nice, and it can get in there, and it basically creates a dysfunctional virus that then replicates as more dysfunctional, that then either replicates or can't replicate. anymore, and they literally call this replication to death. Okay, so the more it replicates, the weaker it gets, and the more it just can't function anymore. So that's cool, that's a really nice way to do antiviral work. So how does this relate back, this mechanism relate back to, um, maybe if we gave it earlier, uh, we'd have more than 50% increase in survival. So already, like, you know, 50% better, you know, outcome is still 50% better. But could we improve on that? Well, think about it. If you just start to have symptoms and then you somehow get a treatment into you that can slow down or stop viral replication, then you are going to have a lower viral load, because the earlier you get in, the more you stop the virus from replicating. Your immune system is going to have an easier time dealing with a lower viral load, and then you are more likely to get out of all of that. Okay, so if we could move back from 5 days in to say 2 or 3 days in, you might actually have a chance. Now, is there a model for this? Well, a lot of antivirals, there's actually a model for this. We see this with the herpes drugs, for example. The sooner you get it in the patient, the lower their viral load is. You see it sometimes with other types of rapid onset virus, like some of the influenza drugs and things. So there's some— and we all know that like influenza, which of course no one's been thinking much about with COVID but influenza can be pretty bad. And there's a lot of shade thrown on some of the anti-influenza drugs, but having used them in people, what I really saw personally, and if you look at the data, this kind of matches what we saw clinically, is they really only worked if you got them into the patient like their first, you know, they say 48 hours of illness. Really the first 12 to 24 hours is when they really worked well. And why would that be? Probably because they're blocking viral replication. And with influenza, by the time you hit 48 hours, even though you're technically in the drug window, you know, you have this giant amount of increase in virus in the person. You know, 'cause if you ever had influenza, especially like influenza A, you get sick very rapidly and you get a high fever rapidly. Your immune system is fighting quickly. The virus is going crazy. So think about it that way. So if you look at the studies on some of the anti-influenza drugs, they don't turn out to work very well, but that's because they probably only work in a tiny window, which is really early on. So then you get to drugs like this and you're thinking, well, then you got something like COVID-19 disease, SARS-CoV-2, to infection. That's a whole thing that we'd like to cut off the viral replication as early as possible. So the Merck drug, molnupiravir, decreased in 775-some number of people, placebo-controlled trial, decreased hospitalization, death by 50%. And my theory is the percent might be higher if you got it in the patient earlier than on average of 5 days. And so if we look at the information here that was put out about these, you know, it's considering that at least for COVID-branded drugs, we're going to talk about things that might work that aren't COVID-branded. know, that's not bad. Okay. Um, so then what did Pfizer do? Well, now Pfizer, we hear a lot about because they have, you know, one of the mRNA vaccines. So Pfizer's, you know, going all out in the COVID market here. And they certainly have the resources to develop these things, plus the At least in the US. I don't know where you're listening from, but in the US, our government has given these companies a great deal of money and financial incentive to develop stuff. So remember, these are non-hospitalized people. With the Pfizer people, their drug is called Paxlovid, okay, with a P. And they had over 1,000 people in their early trials, and the trials were sort of split up. You know, into different layers and stuff, so I won't get too crazy quoting numbers, but it's again, so, you know, Merck had around close to 800, Pfizer over 1,000. And again, I've got— when we put this up onto YouTube, which is probably where you're watching it if it's anything other than live, I will have the links to some of these reports and news. outlet things and scientific papers and stuff. I'll have that in the description box below. But by the way, if you're watching on YouTube, please like, share, and subscribe. The channel's growing and we need more support. But one of the things that they did a little bit differently, which I don't know if they planned this or not, I really wasn't able to get a whole lot of background information. I don't know a lot of people at either of these companies, but they started their dosing within 3 days of onset. Now remember I said the earlier with an antiviral, get in, in that window of acute onset, the lower the viral load. And in this greater than 1,000 group of people, there were actually no deaths in the treatment group, but it decreased hospitalization and death by 89% compared to placebo. So that's pretty good. Now, would the 2 days— so between, you know, 3 days on the Pfizer, evaluation and then 5 days on the Merck evaluation, would those 2 days really make that much difference? Possibly yes, because both of these companies used groups of people that were at higher risk for hospitalization and death anyway. So, you know, without getting too specific, just to generalize, they used people that were a little older than the median, had at least, in one of the research studies, at least one pre-existing condition that is associated with higher risk of hospitalization and death, etc. And that makes sense. I mean, you want to, you want to try things on a group where you can see an effect easily. Now, this is a research phenomenon, okay? You know, once something's made and approved and it's out in the world of medicine, you don't really care usually whether it's, you know, low risk or high risk or whatever. If they get sick and the drug works, you can use it. Okay, why in research would you, you know, pick a tougher crowd to, uh, study? Well, it's a lot like, uh, when I was doing cancer research with humans. There was a particular part of the, uh, research that I was in charge of, and my patients, my cancer patients, were all advanced cancer. They were all stage 4 cancer patients, so metastatic disease, very advanced. And when you ask the question, well, why, you know, why with your therapeutic things you were researching would you want more research on people that have advanced cancer? There's a number of answers to that, but, but the statistical reason is, you know, how these cancers turn out when they hit stage 4. We have very good statistics about how long a person lives after they're diagnosed with a stage 4 cancer of XYZ type. So if you can do an intervention with them and it makes a difference in their life length or their quality of life or something, you actually show it— you show a good treatment effect. Okay, well, it's the same thing here. If you're going to research a COVID drug, you pick people who are more likely to have a bigger problem, as opposed to, say, you know, children who, you know, have, you know, what is it, a hundredth of a percent chance of dying from COVID or something. So they'd be very hard to do a study in, whereas, you know, over 50-year-old, you know, people with one comorbidity, it's a higher chance there's going to be problems there. Now, length of treatment, um, was a little bit different in each side, but, um, they were, you know, they, they were at around 1 to 2 weeks. And normally they were with these tests, these, uh, trials, they usually check them at about 28 days out for, are you still alive and did you have to go to the hospital? Now, Just before we get into any more details about these studies and how that worked, I told you that the mechanism on the Merck drug, molnupiravir, um, was a nucleoside analog. And so that created this sort of viral replication to extinction because you replicate, you know, dud viruses and then they, they can't do anything. On the side of the Pfizer drug, It's something you hear a lot about now. It's, you know, interesting is COVID has brought a lot of discussion around drug mechanisms out that no one ever talked about prior outside of like virology and a little bit of, you know, medicine. So the Paxlovid is a protease inhibitor. And so protease, most things in science that end with -ase are probably an enzyme or create some enzymatic activity. Protease is used in viral replication. Without protease, it's harder for the virus to replicate itself. You see we're targeting a lot of replication here. Now, when you block protease, you block viral replication. Again, whether the mechanism is exactly the same, it goes back to just like the Molnupiravir. The earlier we get that in you and the more we block the replication, the less disease you have. So then the less likely you are to go to the hospital or die. All very good and worthy things. Now, in, uh, in some parallel studies, uh, this drug, Paxlovid from Pfizer, Then separately has been combined with another antiviral called ritonavir. And ritonavir is technically another protease inhibitor but was made for HIV. It's an HIV protease inhibitor. It's not an uncommonly used antiviral drug right now in the antiretroviral space. And so when they put ritonavir and, uh, paclovid together, they get a synergistic effect. So would you, if you go to the doctor or the hospital today, would you likely be given the Pfizer or the Merck drug? No. And that is because they're still in the phase 2-3 approval system. But as we know from the vaccine discussion, things can get approved as an emergency use authorization out of order. Okay, so you wouldn't have to wait till phase 3 trials are done, and you can push the drug out into, into the world. Now, when do they do this? Well, so far, the emergency use authorizations have tended to be for vaccines. Which you have seen, that's sort of old news. So now they would be looking at, well, you know, these drugs, if they are judged to have significant benefit with good safety, then like in a country like the US or other countries, they could be authorized for use, emergency use, even before they're approved. So something you need to keep in mind is, if you're using an EUA or emergency use authorization drug of any kind, it's not actually approved. It's just the gravity of the disease is so bad that we're going to kind of let everybody experiment to a certain degree. Now, what is, you know, a Phase 2/3 or Phase 3 trial? So that means it's gotten to the human trial. stage. And, you know, in the case— now I want to really make this clear— in the case of like the Pfizer drug, um, they had really no difference in adverse events, side effects, etc., between the placebo group and the drug group. Okay, now it's over 1,000 people, but that's still a small number when you're looking at people. So if we got this out, and let's say— and this has happened before— you get emergency use authorization authorization, you push the drug out, and now it's a million people have taken the drug, you're going to find a lot more side effects than back when it got its emergency use authorization. Now, does that mean they're all going to be real bad? No, it just means that statistically, you're not going to really see how these drugs do on the side effect side till they're out into the population of more people. And that actually has been echoed in some of the discussion between CDC and FDA around emergency use authorization for, say, vaccination is, you know, we don't know fully how this is going to do in bigger numbers of people, and we won't know until it's in bigger numbers of people, but we're going to push the drug out anyway. Well, it's highly possible, again, I don't work for the FDA. I work, I work with them sometimes, but I don't work for them, and I have no idea what they're thinking about EUAs for these things, but I have a suspicion they're going to authorize these things, okay, for emergency use. So you've got a Pfizer drug, Paxlovid, with a, you know, 89% reduction in hospitalization and death, and like I said, there was actually no deaths in that group. It's great. And then Molnupiravir from Merck, 50% reduction in hospitalization and death. But my theory is if they would've come in earlier with the drug like they did with the Pfizer drug, you may have picked up above 50%. Next thing is there might be other drugs, maybe previously used drugs that are already approved, like ritonavir, the HIV drug that might be put with them. And you say, well, why would you put like 2 things that do a similar job together? Well, it's because almost none of the drugs that we're going to talk about, but especially in the antiviral world, almost none of them work exactly the same, either in the metabolism of the drug in the human or in the activity of the drug at the level of the virus and its genomics that we're trying to mess around with. One way or the other, the drug may, even if they're both, say, protease inhibitors, they may inhibit differently. Or if they're a nucleoside analog, it could be a couple of avenues in there. So hard to say. I would bet money, and, and I'm not really betting with anyone, so what I would say is the probability is very high these things are probably going to get emergency use authorization and they will be out and available, I would imagine, soon. One of the things in the— and again, all in the YouTube description box when we get this up on YouTube, I'll put the links into some of these, but in the in the news release from Pfizer, which of course Pfizer loves to have these news releases where they have a positive experience with the drug, partly because it, you know, drives the stock price up, which is great if you have Pfizer stock. But also, you know, it's a way around sort of the standard scientific system to get your message out there as a news release. Well, you know, in their news release they're talking about, well, you know, this could be available to mass, you know, quantities of people around the world, and, uh, we still have a lot of trouble with COVID So, you know, having a drug that can treat it is, you know, is great. So let's do it. Of course, they're the people who make and sell the drugs, so of course that's in their best interest. But, uh, that's the story you're probably going to hear. Okay, now you might be asking yourself, which would be reasonable, Um, okay, so we're not on the preventive side. This is, I've already got COVID, I want to keep myself out of the hospital and not dead. 2 great outcomes. We got a couple of drugs that fit the bill there. And so that's great. We've got some treatment options, right? So treatment options are what we're talking about. But then you might think, what about the other antiviral drug that everyone's been seemingly using, remdesivir? Are we still using that, or are these drugs going to replace remdesivir, etc.? Now, a lot like ritonavir, the HIV drug that might be used off-label, remdesivir is an antiviral drug certainly developed way before COVID-19, at least that we knew about it. And so remdesivir was one of those off-label drugs that was brought in to say, could this work, right? Well, remdesivir is another one of these, um, viral replication, uh, you know, inhibitor— kind of messes with viral replication, uh, in the neighborhood of the way that these other drugs do. But what's the problem been with remdesivir? Well, the biggest problem with remdesivir has been, uh, number one, generally it's given intravenously. Number two, uh, it's hospital administration. Number three, um, you got a lot of people having bigger grade adverse events. Well, so What are the adverse events of remdesivir? Well, if you look at, you know, if you just look up remdesivir adverse event, you're gonna get a whole list of the standard common adverse events to almost every drug in the world. And those tend to be things like headaches, skin changes, itching, hives, respiratory changes, you know, kind of allergy-type symptoms that can go on. And certainly we have a lot of allergy-type things that go along, and those things happen, but that's not going to generally stop somebody from using a drug that may shorten a deadly disease. So the problems with remdesivir that have come out now that we're using it a lot with people around, around the world, but especially in North America who are in hospitals especially, is we're starting to get and have had elevations in liver enzymes. So the liver is becoming stressed. And then also problems with kidney function, which is actually more of a problem than stressing the liver. So one of the things that, you know, doesn't matter what it is, but let's say you've got a high-value disease that you're trying to treat, okay, say cancer or say deadly, you know, viral infection or something, and you have a drug, but the drug, as a lot of cancer drugs are or a lot of anti-infective drugs are, maybe has a lot of side effects. You also have to do a risk-benefit analysis of how much side effect are we willing to put up with to get the benefit of slowing the cancer down or slowing the virus down. keeping the patient alive and all that. Because you don't want to, you know, have the trade-off of, well, we could give you enough drug that it would kill you, then you sort of defeat the purpose of using the drug. What happens with remdesivir and cancer drugs, etc., is there's a tolerable amount of elevation in liver function tests, meaning liver stress, that you're willing to put up with for the benefit of getting the patient out of the hospital, okay, or keeping them alive. And there's a certain amount of tolerance for kidney stress, but it's very small because your kidneys are very sensitive organs. And if you shut your kidneys down, you die very, very quickly. Now, yes, if you shut your liver down, you'll die too, but your liver takes a lot more work to shut down than your kidneys do generally. So, uh, in the— in the oncology world, we will tolerate, you know, like a 5-time elevation in liver stress measurements before we really adjust medications. We'll tolerate a tiny amount, you know, 20-30% kidney stress, and then you kind of have to start, you know, changing what you're doing. Well, it turns out that remdesivir, the kind of the current go-to antiviral, which was again not made for COVID, but it's what people are liking to use, A lot of patients have to go off it. Okay. Um, so I had a couple of stories I was going to tell. Now, these are not research. These are not, you know, 1,000 people, whatever we call them— anecdotes, anecdotal stories that we relay. And you put enough of them together, sometimes you get something out of it. But I've heard this from a lot of other people. Um, get a patient, this particular patient who was in the hospital full-blown, you know, COVID, not only positive tests but all the symptoms you don't want. Didn't have to go on a ventilator, thankfully, but, uh, they were on remdesivir, and the hospital actually had them on some, you know, oral vitamin C and zinc and some other goodies like that. So the hospital's trying hard. Well, they got some liver and kidney stress to the point where the hospitalist, an infectious disease doctor, said, we're gonna have to shut the remdesivir off. We'll just keep you on the other stuff and monitor you. And so in that case, there was a backup off-label. So the remdesivir is off-label. There's another off-label drug that we were able to start. And the person started to turn around, and it also was not affecting their kidneys and liver function as much. And we were able to get the patient out of the hospital and then transferred to oral drug therapy to get them past the COVID experience. And that person— super high-risk person, by the way— so this person, you know, elderly, overweight, diabetic, full-blown medication-dependent diabetic, cancer survivor, etc., etc., you know, like had one of everything, did fine, and, you know, is now alive. And this has been repeated in a number of cases. So sometimes the drug might work great, but like you can't keep using it if it's harming the patient. Well, what remains to be seen with these new drugs from Pfizer, and Merck is if we— so we get them in 1,000 people or 2,000 people, looking good so far. We mass market them, get them out there, you know, and start using them for COVID treatment. If we keep to low side effects, that's golden. That's really what you want. If they can work with low side effects like some of the other antiviral drugs that we use for other virus, uh, great. You know, what I'm saying is, here on November 11th, 2021, where they don't even have an emergency use authorization yet, we don't know what they're going to do in large numbers of people. But I bet, and I would wager probability-wise, that we're going to find out, because I bet these things are going to get emergency use authorization, get approved, put out there. Now, another question that comes up because I talk about it so much is, will these new drugs from Merck and Pfizer, will they help with the co-infections? Because you're always telling us that whenever we look at— okay, so you got SARS-CoV-2 infection creating COVID-19 disease, then you look for other infections, you always find 1 or 2 or sometimes 3 or 4. And if you don't kill the co-infections, it's harder to get rid of your SARS-CoV-2. So COVID-19 is, you know, The whole thing. Well, these drugs are unlikely to kill very many of the other co-infections just because they're not aimed at those sort of bugs. Most of the co-infections give you trouble are bacterial atypical pneumonia organisms, fungal organisms, some parasite-type organisms, and some other odd bacteria as well. And that's in a lot of research around COVID and co-infections. So these drugs are not going to do a lot for those type of infections. So in the case of the person I was just telling you about, where we had to take them off the remdesivir and put them on another off-label drug, the off-label drug that was used to transfer over actually covered the viral and a couple of the other co-infection areas, and then we gave them some antibacterial and antifungal help as well. So, co-infections, no, these new drugs are not likely to do much with that. You still have to deal with the co-infection side of it. Other things to consider. A question came up and it'll be in one of the links here, I think, probably the second or third link, but you can find it in there. Do, you know, Merck and Pfizer, are they saying, well, We have these new antiviral drugs for COVID-19, we want to get emergency use authorization. Does that mean, you know, Pfizer and Merck now are down on vaccination? So Pfizer and Merck are very foursquare pro-vaccination that, you know, they haven't changed their stance on that. They're just saying this is another tool in the armamentarium. if you wind up getting sick, you can have something to treat it with. Now, another question which I think is a little more interesting and maybe a little bit spicy is, aren't there other off-label drugs that have real similar mechanisms to the Pfizer the Merck, or both? And the answer is yeah, there's a fair number. Okay, now I told you, uh, that with the, uh, Paxlovid from Pfizer, they will, in looking at it in, in early stages, combine it with an off-label antiviral, uh, ritonavir, and that seems to make the Paxlovid work better. Okay, so that's an example of, you know, taking another off-label and putting it together. Now, what's the difference semantically is these things are going to be on-label. These are COVID-19 drugs, right? So off-label just means it's probably been around for a long time, we used it for other stuff. So the ritonavir would be one example of that. There's also, um, the antiviral activity of some other drugs that we didn't used to know had antiviral activity. And it turns out that some of them have real similar effect, chemically speaking, against the virus to these new drugs that are being approved now. But they were never marketed or designed or studied for— in, in 2 cases, viruses at all, and certainly not COVID-19, because they existed long before COVID-19. So when you look, though, there's a couple of these, and a couple of these off-label drugs that are still used but aren't used very much. have a couple things going for them. One is they can bind up the ACE— hear about the ACE2 receptors, and that's sort of the entry point in for the virus, right? One mechanism. Well, a couple of these drugs bind up the, the receptor sites. Okay, if you can do that, then you actually stop the virus from getting into the cells. It's better even than blocking the replication. Now, usually you want to do both things, right? So then it turns out that both of these, uh, other off-label drugs that were not for viruses that turned out to have antiviral effect, not only can slow down the binding and uptake of the virus, but also if the virus gets in, they can slow down the replication. And there's a couple of different mechanisms by which these drugs do that. And so you're probably thinking, well, gee, you know, these sound pretty good. You haven't said any names. Well, um, at the risk of, you know, being deplatformed or something, um, I, I'm probably not going to say the names of either of the drugs. But one of them you've heard about starts with the same letter as ice cream, or ice, if you will. And it actually has that dual effect of blocking the ACE binding site and also acting as a replication blocker. So kind of two sides there. And I'll put links in for that. if you're interested. The other is actually doxycycline, which you probably have been given for something in your lifetime, which we think of as an antibiotic, which it is. It kills bacteria. So doxycycline is in the tetracycline family. It's got a cousin called minocycline, and it's, it's the whole family. They do similar things, but doxycycline is probably the most widely used one in, in the world right now. Well, it turns out that doxycycline is one of these where it's antibiotic. Why in the world would it have antiviral effect? We didn't know this. Doxy actually has an ACE2 blockade, so it blocks the uptake, and it has an RNA polymerase blockade as well. Why would doxycycline— and I'm not saying that people should just use doxycycline, certainly wouldn't hear this from any infectious disease doctor in a hospital, but often doxycycline is added on to protocols. Why would doxycycline be really nice if it has this antiviral effect with, say, a COVID-19 patient? It's because, remember, the co-infections— some of the more common co-infections that will make the COVID experience worse are the atypical bacterial pneumonias, and doxycycline is one of the primary drugs that we'll use for atypical bacterial pneumonias. So it's important to remember that it's not just about banging on the virus. The virus is a big part of the problem, but you got to remember that once the virus gets into you, and if you have these residual latent infections, or you get exposed to them while you got this big viral load, the other infections can drag you down further, even kill you. So, treating the co-infections is very important. Well, an agent like doxycycline that can go both ways is a really good multi-purpose agent. And there's other things too. Now, sometimes you hear about, you know, these zinc ionophore agents or drugs and natural things like Quercetin or some of the drugs that we've mentioned before. You know, they'll do that and they'll add like doxycycline or another antibiotic, azithromycin, on there? Well, part of it is to deal with the co-infections. In the case of doxy, it's actually to slow down the uptake and block the replication of the virus. Okay, now the other drug that you don't say the whole name of starts with I. That one has kind of the same thing. It's got an ACE binding site blockade. It's got an anti-replication activity on the inside. So it kind of goes both ways there, but it also kills a lot of other organisms. Both of these, doxycycline and then the one that starts with I, are fully approved in the US for human use. Contrary to a lot of news reports, these are human drugs. Interestingly, in the world of oncology, so cancer, These are also used off-label. Again, they weren't made as cancer drugs, but they're used off-label for manipulation of tumor biology in people who have cancer. So it's not uncommon to see these drugs used in these, you know, non-standard settings. And one of the reasons that, you know, I started using these with COVID patients early on was for the co-infections. And then the more I looked into it and started to see, oh, there's a lot of the immune properties that these drugs have separate from their anti-infective properties that are beneficial to people with cancer. Well, it turns out a lot of things that make you real sick with COVID are immune dysregulation. It turns out these drugs help there too. Now, do they cure everything? No, it doesn't work that way. Probably these new drugs are not going to cure everything either, but they're all beneficial. I think the important thing to think of is that you want to have agents, and the more agents you have for one problem, the better, because there's going to be some people who tolerate some of the agents. There's going to be some people who need more than one agent, and a million other reasons. So what I try to promote, uh, with either patients I see or if doctor calls me to ask advice or whatever is, you know, let's do the best thing that we can for this person with COVID-19. So let's, let's track on the main, uh, problem. So the main problems being the virus. So we gotta do something with the viral thing. And that's a couple of things. One is uptake blocking, one is replication blocking, but then the other thing is kind of good old-fashioned hygienic things like, does the patient have enough basic biochemistry there to help them fight the virus? That's a very important thing as well. I've done other programs on that. You can go back and look at nutrients and other things. And then, you know, The co-infections are another big thing we've got to track on. So we want to make sure we have other therapies going in to deal with the atypical bacteria and fungus and all this other stuff that can go on. And then treating the fallout. So the longer you're sick, the more other things that will come up. So I look at it that, you know, there's usually no bad tool in medicine. Right. But there's, there's good and bad times to use tools. Okay, so just like, you know, you wouldn't go and build a house with just a hammer. Okay, it'd be great when you're pounding nails, but if you're trying to cut boards, you know, or do any other thing, the hammer has limited use. Whereas if you have a whole toolbox, you're more likely to be able to effectively build something and take care of something. It's kind of the same when it comes to treatments, and this— whether they're natural or synthetic or some combination thereof, you want to have the right tools at the right time. Sometimes you're building something and you don't need a whole lot. You need some measuring devices, something to cut with, something to fasten with, and you're good to go. Sometimes you have a more complex thing that you're going to build, and you may need a number of different ways to cut things, and you might need a number of different ways of measuring. You might need a number of different ways of fastening and all of that in order to make that thing work. The more complex it is, it's exactly the same with a, a complex infectious disease problem. If all you have is the virus, then you're going to focus on antivirals and you're probably going to be good to go. But if you got the virus and then you've got some co-infections and then you got some weakness everywhere else, You're gonna need more work. Okay, now, as I said, uh, when we put this over on YouTube, uh, in the description box, I'll put links to everything I talked about, including the DoxyInfo and the iDrugInfo and all of that business. Um, and I just want to end— I just have a couple of minutes left here, but I've got a really awesome story. And again, it's one patient, although I've had many other patients like this. One patient, so it's an anecdote. A person was in the hospital in a state not near here. I'm in Washington State in the US, and they were going way downhill way fast, and they got put on a ventilator. It's usually the end of the trail for your ICU experience with COVID And they were an employee of a physician who kind of put a call for help out to anybody who might know anything to do. in the hospital, and another physician was in this person's circle and sent them my publication on how to use IV vitamin C in the hospital with COVID patients, which I've talked a lot about on other programs. And then there's a review article I wrote for, you know, the research that's been done on vitamin C IV for COVID. And so they did that, and they actually got— because probably because they also knew a physician who could make this happen, they implemented our protocol for the IV vitamin C in the hospital. They got off the ventilator, and they were able to leave the hospital and go home and heal up, and they were on a trajectory to pass away. So, you know, there's hope. There's a lot of things that be done. This is why I keep my mind open. I'm happy to see new drugs coming. I'm also happy to see old drugs get repurposed and people to keep their minds open when it comes to helping people out, because that's what it's all about. All right. Well, I am now officially out of time. This is Dr. Paul Anderson for Medicine and Health with Dr. Paul Anderson. If you are on a podcast, please like the podcast. If you watch us on YouTube, please like, share, and subscribe, do all that stuff. And I will see you next week on the radio. Thank you.