For Love of the game
A wise man once warned about the growth of the military industrial complex and the consequences that would follow. If you did not believe him just look at the money spent recently on the war in Ukraine with no oversight and no opposition.
A wise man once warned about the growth of the military industrial complex and the consequences that would follow. If you did not believe him just look at the money spent recently on the war in Ukraine with no oversight and no opposition. To the companies that make money off war it is simply a game to be monetized and they do it well with bipartisan support because both parties are full of warmongering fools. The collusion he warned of has now infiltrated the entire federal government and the game is being played on multiple fronts healthcare included.
The largest factor in a drug's ability to generate revenue is its exclusive time on market as a brand name; this is where lucrative prices can be charged with no competition. Patents are awarded early on in development and that kicks off a race to the market as fast as possible. Extending the patent life by any means necessary has become a common strategy that expresses itself in a variety of ways. Make a few changes to your drug and it can be turned into an extended-release product with a fresh patent. Ambien turns into Ambien CR and the whole marketing mechanism simply pivots to the latest and greatest for example. Sometimes the new product is an actual improvement and other times it is obvious what is going on.
Flexeril (cyclobenzaprine), a muscle relaxer that's older than I am, was first approved and marketed at 10mg three times a day, because of its long half-life ~32 hours it would become immensely popular for non-muscle relaxer reasons. Decades later this would make a good reason to reduce the dose and we have the strange situation where a bottle of 10mg tablets that cost nothing is sitting beside a 5mg bottle that cost hundreds. Lots of money spent for little actual benefit is the hallmark of the game. Eventually cyclobenzaprine would also perform the previously mentioned extended-release trick and get a new name Amrix (15mg cyclobenzaprine ER) and a new price in the thousands. You may ask why an extended-release product is necessary for a drug with such a long half-life, I certainly did.
Hydrocodone and Oxycodone in differing combinations with other products were the most popular painkillers of the past two decades and they have had a variety of brand names over the years while performing the ole patent shuffle. Ironically reducing the amount of acetaminophen in these products in the name of safety was the most common maneuver but based on the list below they exhausted all pathways
List of Brand name Oxycodone & combination products
List of Hydrocodone & combination products
Claritin (Loratadine) however is the true winner of gaming the system because they realized going over the counter was the ultimate way to protect their patent. If it had remained a prescription product no insurance would have paid for it and the generic would have been mandated. Going over the counter however allows their marketing machine to roll onward and here they are selling brand name Claritin decades after the patent has expired. Clever ideas do not go unnoticed and other prescription antihistamines would follow this lead Zyrtec, Xyzal, Allegra just to name a few. Of course, if the patient is going to decide what to buy there is a limit to what you can charge. If its prescription, however there is no ceiling because the end consumer is not paying the bill directly. All these forms of patent recycling add incredible costs to the overall system for little or no added benefit.
The guiding principle here is a corporate maxim that next week we expect you to be more productive with less resources of course. A few hundred cycles later things start to get a little silly as all the rules are exploited in any way possible. The next evolution of the game is expanding your customer base; therefore, we have commercials for restless leg syndrome and every other manner of problem because it is hard to sell drugs for conditions that people do not know exist. The consumer must be constantly bombarded with information about all the ways they could be sick and what their doctor can write for to fix it. The excessive pushing of the covid vaccines despite a lack of convincing evidence for certain populations is merely the latest example of the game upping its game.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health, and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Gila Spit to Diabetes treatment
In 1964 researchers discovered something interesting about glucose and its effects upon insulin. Giving glucose by mouth would cause a large and rapid increase in plasma insulin levels. Giving the exact same amount parentally would result in lower levels.
In 1964 researchers discovered something interesting about glucose and its effects upon insulin. Giving glucose by mouth would cause a large and rapid increase in plasma insulin levels. Giving the exact same amount parentally would result in lower levels. The difference was about 65% and it would become known as the “incretin effect”. The hormones behind this effect would eventually be discovered glucagon-like peptide (GLP1) and gastric inhibitory protein (GIP). These hormones are produced when you eat and stimulate your pancreas to produce more insulin, GLP1 also slows down gastric emptying and peristalsis which results in you feeling full and not eating that fourth/fifth cupcake. These hormones do not hang around long because they are quickly metabolized by a small glycoprotein called dipeptidyl peptidase 4 (DPP4). DPP4 is widely expressed and found on the surface of nearly every cell so it makes quick work shredding up GIP/GLP1 giving you that second wind for the sixth cupcake.
These hormones would become obvious therapeutic targets for reducing blood sugar. The race was on to find something that could replicate the marvelous effects and the first candidate would come from the most unlikely of places: the saliva of a Gila monster. The drug discovered is now known as Byetta (exenatide) and it has been used successfully in millions of patients. Exenatide does many of the same things that GLP1 does with one key difference: it could hang around for hours as opposed to minutes. The only downside was the drug was not well absorbed orally and must be given as an injection. Recent developments in nanoparticle technology may have solved the absorption issue so an oral form of the drug may be on the horizon. Similar products would soon follow, Victoza, Bydureon, Trulicity, and Ozempic are all GLP1 receptor agonists.
GLP1 receptor agonists are NOT insulin which is a common misconception since they are an injectable medication for diabetes. They are also not approved for weight loss although many patients lose weight taking them Ozempic in particular. The newest drug to enter this class is called Mounjaro (tirzepatide) from Eli Lilly and it is getting all the attention because it is the first drug to act on both GLP1 and GIP receptors. While it is approved for diabetes the average weight loss for patients receiving the drug was between 12 and 25 pounds! When you add DPP4 inhibitors like Januvia and traditional drugs like metformin into the mix we pretty much have diabetes surrounded from a biochemistry perspective.
The cure for obesity is no mystery but exercise and self-control are tough to accomplish and difficult to monetize. Drugs however are easy to take and incredibly commercially viable, the price tag for this new medicine is about a thousand dollars a month. They could probably charge more if it lives up to the hype especially if they were to pursue an actual approval for weight loss. This drug could be a golden goose for Eli Lilly. An effective weight loss product with minimal side effects is like stumbling onto the holy grail for a drug company. If it ever gets that far I am curious if it will be mandated, after all the costs to society from obesity are astronomical.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health, and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Further reading and references
https://pubmed.ncbi.nlm.nih.gov/35651477/
https://pubmed.ncbi.nlm.nih.gov/35513765/
https://pubmed.ncbi.nlm.nih.gov/35593668/
https://pubmed.ncbi.nlm.nih.gov/33325008/
https://pubmed.ncbi.nlm.nih.gov/32730231/
https://www.multivu.com/assets/53897/documents/53897-Exenatide-History-FINAL-original.pdf
https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-020-00619-0
HEALING HONEY
Honey may be one of the oldest forms of natural medicine. Its wound healing and antimicrobial properties can be found mentioned in some of our oldest medical literature. The bible mentions it in proverbs 16:24 "Gracious words are a honeycomb, sweet to the soul and healing to the bones."
Honey may be one of the oldest forms of natural medicine. Its wound healing and antimicrobial properties can be found mentioned in some of our oldest medical literature. The bible mentions it in proverbs 16:24 "Gracious words are a honeycomb, sweet to the soul and healing to the bones." Hippocrates, the father of modern medicine who is turning a few thousand RPMs in his grave, was convinced that honey had a variety of healing properties, and he would use it in many of his treatments. He would treat pain with a combination of honey and vinegar. He also encouraged his patients to drink Mead, one of the oldest alcoholic beverages made by fermenting honey with water grains and other spices, the Greeks would refer to it as the "nectar of the gods".
Perhaps the earliest pharmacy compound in history was theriaca andromachi. A mixture of multiple ingredients including opium, cinnamon, and viper flesh was pulverized with honey and arabic gum into a paste. It would go viral as something could back then and we find it mentioned often in historic text. Galen the famous Greek physician would author an entire book on the remedy, and it was taken regularly by his most famous patient Marcus Aurelius. Pliny the Elder would note in his encyclopedic book "historia naturales" that the Arabians were producing honey strictly for medicinal purposes including applying it to wool and wrapping wounds.
The healing effects of honey are due to a combination of its antibacterial and antioxidant properties. The high viscosity provides a protective barrier to pathogens while maintaining a moisture rich environment that promotes healing. All honey is not created equal, and the chemical composition will depend on many factors. The polyphenol content of the honey will determine its antioxidant potential, the darker the honey appears the higher the content of polyphenols. A polish study examining several types of honey would show a significant variability depending upon what type of nectar the bees are using and the chemical composition of the resulting honey
Commercially there are now several medical grade honey products on the market around the world. Medihoney is the one you may be familiar with, but other trade names include Revamil, Mebo, Melladerm, and L-Mesitran. Studies have shown their effectiveness in breaking up biofilms of Pseudomonas Aeruginosa, one of our most notorious and commonly drug resistant infections. There have also been promising results in treating recurrent vaginal yeast infections and cold sores. Using honey or other bee products for therapeutic purposes or apitherapy has become an alternative therapy of sorts. It can be marketed in many ways from the benign consumption of honey all the way to the extreme of getting stung by bees on purpose. Of course, no alternative therapy would be complete without the possibility of covid prevention so here is an article on that topic https://pubmed.ncbi.nlm.nih.gov/32945590/
While the domestication of the honeybee certainly goes as far back as hungry humans do, modern beekeeping has not changed much over the past hundred and fifty years. The Reverend Lorenzo Langstroth's book "On the Hive and the Honeybee" first published in 1853 is still considered to be the foundation of modern beekeeping. The Langstroth beehive still bears his name and is what comes to mind when most people picture one. The book is also a great read albeit a bit preachy, but the man was a Reverend so finding God in his honeybees should not be a surprise.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health, and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Further reading and references
https://www.buzzaboutbees.net/Honey-And-Ancient-Medicine.html
https://pubmed.ncbi.nlm.nih.gov/23569748/
https://pubmed.ncbi.nlm.nih.gov/30126199/
https://pubmed.ncbi.nlm.nih.gov/21530807/
https://pubmed.ncbi.nlm.nih.gov/33291554/
https://pubmed.ncbi.nlm.nih.gov/34436203/
https://pubmed.ncbi.nlm.nih.gov/31505796/
https://pubmed.ncbi.nlm.nih.gov/34959664/
https://pubmed.ncbi.nlm.nih.gov/35047540/
Fentanyl
The wave of overdose deaths that swept across the nation in this past year claimed over a hundred thousand lives according to the CDC in a recent statement. Overdose deaths are one of the few things increasing faster than inflation. Drug use is part of the human condition and like everything else it is only getting worse. People have been seeking to expand their mind or numb their pain forever and drugs have always been a popular option for achieving that. Today though it is a much more dangerous game than it once was, the line between potion and poison is blurrier than ever.
The wave of overdose deaths that swept across the nation in this past year claimed over a hundred thousand lives according to the CDC in a recent statement. Overdose deaths are one of the few things increasing faster than inflation. Drug use is part of the human condition and like everything else it is only getting worse. People have been seeking to expand their mind or numb their pain forever and drugs have always been a popular option for achieving that. Today though it is a much more dangerous game than it once was, the line between potion and poison is blurrier than ever.
The illicit drugs of the previous generation while having the potential to kill you did so far less often. The big reason is there were only a few different things you could be getting and if it were adulterated or cut with something it was usually with something inert that would reduce the potency of the product while expanding the seller's margin. This has always been a problem with powdered substances like cocaine, heroin, methamphetamine mix a little of that with a little of this and one pound of drugs can turn into two or ten. Today potent opiates like fentanyl or one of its derivatives are produced in mass quantities and used to turn one pound of drugs into one hundred pounds or more.
As a prescription fentanyl is normally prescribed as a patch in varying strengths that deliver micrograms over the course of three days. As the potency of these chemicals increases the window of forgiveness decreases. Poorly made street products are not always homogeneous mixtures. The cook measured wrong, his boss did the math wrong, or maybe the product they were starting with was not what they thought it was. Any one of these mistakes can turn profitable street products into powdered Russian roulette. Mistakes happen, we are all human or it could have been intentional, tainting a competitor's product is not unheard of even if it is bad business. Good news though a study using the IMF and DEA database revealed that the price of powdered drugs was down significantly between 2016-2021. Street drugs may be the only thing that is becoming more affordable even if the quality can be suspect.
Legal settlements for the opioid crisis are now so common you can easily get lost in the articles reporting them. Purdue usually gets the bulk of the blame and the largest financial settlement but even Mckinsey the consulting firm paid out 600 million for its role in marketing Oxycontin. While there is plenty of legal liability to go around at the root of it all is a problem that pre-existed any of these corporations or heck even any of these drugs. Preventing opioid overdoses is now a cash cow that can be targeted. The Naloxone nasal spray market has what investors would call growth potential. There is even talk of an opioid vaccine but don’t worry it's still in the animal testing phase but perhaps a decade from now they will be required for college admission.
Historically our current Fentanyl crisis has some striking similarities to the Opium wars. British and American merchants working with Chinese smugglers were moving large amounts of opium into China, the increased availability took what was once a rarely used medicine and turned it into a popular recreational drug. Between 1787 and 1833 the opium trade would grow extensively from 4000 chests annually to over 30,000. The emperor would issue several edicts over this time outlawing opium but their war on drugs was an even greater failure then ours. They would finally get fed up and in 1839 the emperor would command his Viceroy Lin Tse-Hsu to end the opium trade once and for all.
His first action was to seize all the opium in Canton, and this would start a standoff that would last several days until finally Charles Elliot, a representative of the British government would arrive and essentially pay a ransom for the drugs which were immediately then destroyed. By the end of the standoff, it is estimated that about 1300 tons of opium was destroyed. The British government would not take kindly to this action and by 1840 they would authorize troops to impose reparations for the financial losses to English traders. By summer the Royal Navy was shelling the port of Macao. The combination of superior English firepower and a weakened Qing dynasty would result in a lopsided victory resulting in the Treaty of Nanking which opened China up to trade and ceded control of Hong Kong to Britain.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health, and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Further reading and references
https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm
https://pubmed.ncbi.nlm.nih.gov/35528111/
Endothelial Insult
Cardiovascular disease is a leading cause of death in the western world despite our vast knowledge on the subject. The pump gets the bulk of the attention when you think of your cardiovascular system, but the hoses are where the degradation begins. Inside all our blood vessels is a thin single cell layer known as the endothelium.
Cardiovascular disease is a leading cause of death in the western world despite our vast knowledge on the subject. The pump gets the bulk of the attention when you think of your cardiovascular system, but the hoses are where the degradation begins. Inside all our blood vessels is a thin single cell layer known as the endothelium. Think of it as a smooth protective film that helps keep the lumen open and flowing properly. Imagine over time this film becomes damaged and must repair itself, like how a superficial wound will scab over. The technical term for this scab is atherosclerotic plaque and it clogs up our blood vessels in the same manner that a hair can clog a drainpipe. As our endothelium ages it simply becomes less efficient and inflammatory particles accumulate over time. In extreme dysfunction scabs upon scabs accumulate on top of one another creating what is called a fibrous cap. The larger this becomes the more it sticks out from the vessel wall exposing it to the sheer forces of your blood pumping, worst case scenario it can snap off and be whisked away by the blood stream resulting in a heart attack or stroke depending upon the end location.
There is an interesting test that can be done to help determine endothelial dysfunction, using an ultrasound of the brachial artery and a blood pressure cuff. Pumping the cuff up and releasing it causes a rush of blood that can be measured with the ultrasound. A recent study using this method showed that covid survivors almost a year post infection displayed increased endothelial dysfunction compared to matched controls. Labs in these same patients would also show an elevated high sensitivity CRP and tumor necrosis factor that far out as well. They were even able to pull and compare labs to when the patients were hospitalized (table 2). These further confirm the inflammatory aftermath of infection and all the negative consequences that may follow. The study also raises a particularly important question: how long do these effects last?
The past two years have of course been the single largest endothelial insult in human history with the widespread transmission of Covid-19. The cardiovascular complications of infection are well documented and in no small part due to the inflammatory state that infection can induce. Some parties have used this as an argument for more extensive covid-19 vaccination of the population, downplaying potential adverse events from the vaccine in exchange for the potential benefits. If the vaccines were truly preventing transmission, then their adverse events may be worth the cost, but if you are on booster number five and you still get covid, we must now ask what role did five rounds of immunization play in your current inflammatory status? Is the inflammation caused by the vaccine additive or synergistic with repeat doses? The recent guidance from the CDC to increase the time in between shots to prevent adverse events seem to suggest this idea has merit.
A few months ago, some brave soul had the stones to publish some comments looking at cardiovascular biomarkers post vaccination in his patients at a preventative cardiology practice. The original version can be found below; it is a short read.
Honestly not sure how it was allowed to be published due to the author’s conclusion that sets off every alarm at thought police headquarters.
““mRNA [vaccines] dramatically increase inflammation on the endothelium and T cell infiltration of cardiac muscle and may account for the observations of increased thrombosis, cardiomyopathy, and other vascular events following vaccination.”
I waited several months to see if the author would continue to exist, which is the case because several corrections were made in December (link below).
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001053
There were indeed multiple corrections including grammar, spelling, and rewording that appears to obfuscate the conclusion but no corrections to the underlying data. The idea that the vaccines would cause an increase in inflammatory biomarkers is not far-fetched; it is exactly how they are supposed to work. The hope is that these elevated levels are transient and issues due to it are mild and worth the benefit. The labs were drawn between 2 weeks and 2.5 months after vaccination and compared to the patient’s own baseline scores.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Thank you for Reading feel free to share!
Further reading and references
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882598/
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001053
https://pubmed.ncbi.nlm.nih.gov/35064792/
https://pubmed.ncbi.nlm.nih.gov/35013457/
Pfizer Advertisements
Pharmaceutical companies advertise with extreme prejudice, their ad budgets alone sponsor entire television channels and is second only to their lobbying division. Only two countries in the world allow direct consumer marketing of prescription products: the United States on free speech grounds and New Zealand because they have more sheep than people and sheep love commercials
Pharmaceutical companies advertise with extreme prejudice, their ad budgets alone sponsor entire television channels and is second only to their lobbying division. Only two countries in the world allow direct consumer marketing of prescription products: the United States on free speech grounds and New Zealand because they have more sheep than people and sheep love commercials. Advertising works, it is extremely effective at driving customer demand. As always though there is regulation and that is why your drug commercials must be so long and drawn out so they can inform you of both the good and the bad that the drug could cause. The side effects listed on these commercials can be quite disturbing and much like the surgeon general's warning on cigarettes they usually go ignored, but they are there at least to give the appearance of balance.
Recently though I have noticed in my limited television watching that Pfizer changed the advertising game with their new commercials. At first it seems like any other commercial, happy people, sunny skies, healthy children playing everything needed to link Pfizer with raw emotional bliss, but it ends right there. There is no horrible list of side effects because there is no product they are selling in this commercial. It is a brilliant proactive advertising campaign, even if a bit dystopian. Long past having to bother marketing products to you they can leave that to their best sales representative, the state. Meanwhile they launch this new ad campaign telling us how great they are while never having to mention anything negative much less the over two billion in settlements against the company for alleged violations of the FDCA and False Claims Act in the past. Their skirting of regulation is impressive and if you believe in preventative medicine why not a proactive public relations campaign to protect against future legal liability the magnitude of which may be correlated with public opinion.
Advertisings place in health care has always been a little dubious; the best doctors are rarely also the best salespeople. If a product works then advertising should not be necessary and it should stand on its own merit. Sales can still be supercharged by a good marketing campaign though and it occurs at many more levels than just magazine and tv ads. Teams of attractive sales representatives for drug companies heavily promote new products to prescribers. Free drug dinners to learn about the latest branded product were common, often getting continuing education credit for attending. All drug companies would play these games pushing their most profitable products at the time. As patents would expire so would the marketing campaign for the drugs, the lunches and free pens would continue but with a different pharmaceutical sponsor every so often a lot like NASCAR. Today drug advertising is heavily regulated but pervasive as ever seeming almost symbiotic with mass media. Looking to the past we can find the best examples of malfeasance due to this collusion.
At the turn of the previous century, we lived in an age with zero regulation, and this would lead to the rise of patent medicines. Drugs claiming to have radical benefits and sold under brand names like Hamlin's Wizard Oil and Lydia E. Pinkham’s Vegetable Compound would saturate the market. These products were big sellers at the time and big buyers of advertising in the newspaper accounting for half of the ad revenue. James Harvey Young would write a more detailed history in his 1961 book The Toadstool Millionaires: A Social History of Patent Medicines in America before Federal Regulation. Unfortunately, a few of these products would sometimes contain dangerously addictive substances like morphine or heroin.
This would lead to the 1906 Pure Food and Drug Act which required drug products to be labeled with what they were and require them to disclose dangerous substances like alcohol or cocaine and no detail of the label could be false or misleading. The wording of the act was unfortunately vague enough to invite different interpretations and it would be challenged in the 1911 supreme court case U.S. vs Johnson. The result of that decision was the clarification that the law only applied to false or misleading statements regarding its ingredients. False therapeutic claims however were not forbidden by the 1906 act.
Congress realizing its intentions had been subverted would respond with the 1912 Sherley Amendment prohibiting false therapeutic claims intended to defraud the purchaser. Once again however the language of the law “intended to defraud” would be a high prosecutorial hill to climb and so it would do little to curb the problem. It would be almost three decades later before another wave of public outrage over a hundred deaths linked to a liquid sulfanilamide product would once again cause congressional action. The 1938 Food Drug and Cosmetic act would require products to prove they were safe and require FDA approval prior to marketing. Pfizer ranks second behind only Glaxo-Smith-Kline for settlements due to alleged violations of this act, those settlements are in the billions, a liability their new advertising campaign elegantly avoids.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Further reading and references
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690298/
Donohue J. A history of drug advertising: the evolving roles of consumers and consumer protection. Milbank Q. 2006;84(4):659-699. doi:10.1111/j.1468-0009.2006.00464.x
https://americanhistory.si.edu/collections/search/object/nmah_1215373
https://www.fda.gov/files/about%20fda/published/The-Sulfanilamide-Disaster.pdf