Gift from the Gila Monster

 

Asterix and Ozempix. When this illustration landed in my SM feed a few months ago it took me a while to figure that the skinny guy next to Asterix was actually Obelix. 

Also just like Obelix, many of my own friends are now becoming unrecognisable, slimmer, trimmer versions of themselves.  One thing they all have in common is that they were all on the heavier side and had all tried various methods of losing weight - gymming, cardio, dieting (keto, med), intermittent fasting - all to no avail. Then came injection pens from brands like Ozempic and Mounjaro...

What is this this oddly named injection the magic cure they seek? From where does this drug originate? What are its long-term side effects? 

Ozempic, Mounjaro, Wegovy, Zepbound, Saxenda, and Retatrutideand, and a host of other brand-names referred to a single chemical compound. These are all called Triple Agonist injections, an advanced class of multi-hormonal medications that simultaneously target three distinct metabolic receptors—GLP-1, GIP, and glucagon (GCG)—originally used to treat conditions like obesity and type 2 diabetes.

Today I finally came across a YT video that seems to present balanced view. 

According to Dr. Amin Hedayat, this drug, branded as Ozempic / Mounjaro was approved by US-FDA way back in 2005, not for weight loss, but for Type-2 Diabetes. Over a period of time, the drug manufactures discovered that this particular drug not only reduced blood sugar levels, hearts and kidneys got healthier, solved sleep apnea and slept better, women suffering from irregular periods got cured..

- How does a single drug solve such a wide range of health problems? In the 1980s three scientists (Abener, Mojsov and Holst) studying a chemical messenger in the stomach - Glucagon-like Peptide-1 (GLP-1). This messenger told the body to release insulin, the hormone that regulates blood sugar level. The original GLP-1 formulation was actually based on a chemical (exendin-4) found in the venom of the Gila Monster (!) because this version lasted longer in the body (why?) compared to the one produced by human bodies.

20 years after being used as a sugar regulator, scientists found that GLP-1 was actually a much more potent messenger. It tells many organs to regulate their own functions, to provide the the body only what it needs needs, not less, not more. The liver was told to regulate sugar output; told the stomach to slow down digestion; sent signals to the hypothalamus to send out signals for satiety - 'don't eat more than this'.

The body's own GLP-1 signals get damped by excessive consumption of ultra-processed foods, chronic inflammation and insulin resistance. So, ultimately, the GLP-1 injection is just a signal booster, effective only as long as your body re-learns to listen to its own signals.

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REFERENCES & LINKS

• Dr. Amin Hedayat - https://youtu.be/RFOrOt-z-Nk
• Gila Monsger - https://www.nhm.ac.uk/discover/the-monster-whose-bite-saves-lives.html

Delhi Belly +

Last week, I had the most unusual of Delhi Bellies.

As far as I can remember, this is the first time I spent more than 24 hours with symptoms that went way beyond the usual stomach upset. Even after I thought my body had expelled the last traces of a mutton biryani, I continued to double up with a stabbing pain on my sides, moving restlessly from the bed to the floor, to violent bouts of vomiting, as though the body was trying to yank out a knife that had got stuck deep inside my empty intestines.

Finally when we go around to seeing a doctor, this seemed to be so mundane, so ordinary a case that I was out in a few minutes with this Rx in hand:

•  Esoga RD (Abott) - Enteric coated Rabeprazole Sodium & Domperidone SR Capsules (BB 1-0-0 before breakfast) - ₹103 for strip of 10
• Taxim-O 200 (Alkem House) - Cefixime tablets IP (1-0-1 after meals) - ₹130/strip
• Drotin (Martin & Harris) - Drotaverine Hydrochloride (SOS) -
• Floristore (Zyventus) - Probiotic culture concentrate not less than 2.5B CFU capsules (1-0-1 about 30 minutes after meals)

The relief was almost immediate. That little knife in my intestines seemed to melt away, the vomiting ceased and I was up and about with a few hours.

How did this little miracle come about? What did the pills actually do inside my body?

Domperidone, seems to have acted on the dopamine receptors and stopped me from vomiting while the Rabeprazole Sodium - a proton pump inhibitor (PPI) - reduce the levels of acid in my stomach so that the real hero, an antibiotic named cephalosporin (Taxim / Cefixime) busted the bacteria (most likely Helicobacter pylori) which was the root-cause of the stomach infection.

On the sidelines, Drotaverine Hydrocholoride (Drotin) acting as an anti-spasmodic, helping with the vomit-control mechanisms. It is interesting to know that the same drug is used to 'enhance cervical dilation during childbirth'!

Th last set of capsules (Floristore) contained probiotic cultures to restore the ecosystem of friendly bacteria in my stomach that would have got destroyed by the antibiotics.

Medical science seems to have got the entire game figured out. The experience leaves me wondering how people coped with food poisoning before the advent of antibiotics...and with rising levels of antimicrobial resistance (AMR), who will we cope with bacteria that have learnt how to deal with broad-spectrum antibiotics like cephalosporins?

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REFERENCES & LINKS

http://www.rxlist.com/aciphex-side-effects-drug-center.htm

https://www.nlm.nih.gov/medlineplus/druginfo/meds/a690007.html

Why is Albumin Expensive?

Almost every egg has two parts -- a yellow yolk, and a clear, viscous liquid that turns into Egg White when heated. Egg white also goes by the name Albumin.

The human version is called human serum albumin, and it normally constitutes about 50% of human plasma protein. It is made up of water-soluble globular proteins, and it is unusual in the sense that it is not attached to any sugar molecule (not glycosylated), because of which it degrades easily.

Inside our blood, Albumin serves as molecular "taxis" ferrying hormones, salts, fatty acids, and a long list of drugs to their target sites. It also helps regulate the colloidal osmotic pressure of blood, controlling the amount of water in our bodies.

If the albumin molecules are so plentiful in nature (plants, animal tissue, eggs, milk), why is it so expensive in packaged form? Is it the manufacturing process that makes it so expensive? Or the Intellectual Property Rights?

There is no shortage of manufacturers, nor is there a shortage of demand. Albumin Serum is necessary to treat shocks, liver disorders, kidney disorders, and a host of diseases that result in an imbalance of body fluids.

Yet, a locally manufactured product like Alba-20% costs Rs.3900 / 100ml infusion. According to a recent report human albumin is currently scarcely available with prices ranging between Rs.3897 and Rs.4092 respectively.

A part of the problem is policy and regulations. Last year, the government brought out an order (DPCO-2013) which stipulated a price control formula for a list of "essential drugs", including Albumin. This brought the cost of 1ml (20% albumin infusion) to Rs. 36.6.

Considering the prevailing sales price, this does not seem like a huge cut (Rs.39- Rs.36), but many drug companies responded by just stopping the manufacture of Albumin for the domestic markets.

So, thanks partly to a well intended policy, we now have a huge artificial shortage of an essential drug.

The road to hell is indeed paved with good intentions... :(

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LINKS:

* http://www.britannica.com/EBchecked/topic/535912/serum-albumin
* MJ (2002) - The role of albumin in critical illnesses - http://bja.oxfordjournals.org/content/85/4/599.full

* The Drug Price Control Order 2013 - http://www.nppaindia.nic.in/DPCO2013.pdf
* Blood Banks supply plasma to sustain supply of Albumin - http://pharmabiz.com/NewsDetails.aspx?aid=85989&sid=1

- http://en.wikipedia.org/wiki/Human_serum_albumin
- http://en.wikipedia.org/wiki/Glycosylation

Gawande's Way: Changing Norms

An interesting article came my way yesterday:

* Gawande, Atul (2013): SLOW IDEAS, New Yorker, 29Jul13 --

"Slow Ideas" is about questions that trouble me to no end:  Why do some innovations spread fast? and how we could speed the ones that don't?

Atul Gawande tackles these in his chosen area of specialization: Medical Technology. He describes how Anesthesia was tested out for the first time in October 1846 by a dentist named William Morton, and how it spread "like a contagion, travelling through letters, meetings and periodicals". Within weeks the procedure had been passed on from Boston, across the Atlantic, to London and Paris. Within a year, it had become a standard procedure in hospitals across the world.

In sharp contrast, Joseph Lister's sterilization procedure spread at a snail's pace. Despite being the biggest cause of post-op deaths, the simple idea of excluding germs from the surgical field, using heat-sterilized instruments and surgical teams clad in sterile gowns and gloves, took more than 20 years to become popular.

Why?

Gawande lists possible reasons for this:

• Ideas that violate prior beliefs are harder to embrace  (germ theory seemed...so illogical!)
• Technical complexity -- taking a 'test drive' for gas-inhaled-anesthesia was easier than the painstaking attention to detail required for Lister's asepsis standards
• Visible immediate problem vs. invisible problem that pops up later (post-op infections)
• Makes life diffcult for the key player (Docs found scrubbing & cleaning a boring, time-consuming chore; gassing a patient was so simple!)

These days, a nation's health is indicated by two nifty acronyms - IMR and MMR - Infant Mortality Rate and Maternal Mortality Rate, respectively. Globally, 300,000 mothers and 6 million children die around the time of childbirth. In India, latest census reports (2011) indicate that MMR has come down to 212 per 100,000 births while IMR stands at 50 per 1000 live births. This is still far-far away from the Millenium Development Goals (MDGs) signed by India in 2000, under which we were to bring down these figures to 109 (MMR) and 29 (IMR) respectively, by 2015.

What went wrong? How is it that we are nowhere near achieving the targets?

Having seen some of our health sector projects in action, in Madhya Pradesh and Odisha, my own answer to this question had been that our medical administrative systems are riven by iron-clad hierarchies and biases. People at the cutting edge of service delivery - nurses, attendants, junior docs - get a raw deal from those sitting in far-away cities, in their cozy AC cabins. Few want to roll-up their sleeves and lead by example.

Gawande puts it nicely:

In the era of iPhone, FaceBook, and Twitter, we've become enamored of ideas that spread as effortlessly as ether. We want frictionless, "turnkey" solutions to the major difficulties of the world - hunger, disease, poverty. We prefer instructional videos to teachers, drones to troops, incentives to institutions. People and institutions can feel messy and anachronistic. They introduce, as the engineers put it, uncontrolled variability.

We yearn for frictionless, technological solutions. But people talking to people is still the way that norms and standards change.

Given our biases & hierarchies will merely talking be enough? -- most of the time, that seems to be the only thing we're doing!

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LINKS & REFERENCES

* Gawande, Atul (2013): SLOW IDEAS, New Yorker, 29Jul13 -- http://www.newyorker.com/reporting/2013/07/29/130729fa_fact_gawande?currentPage=all

India's IMR & MMR -- (ToI, 13May13) --http://articles.timesofindia.indiatimes.com/2013-05-13/india/39227265_1_india-imr-infant-mortality-rate
India Census Report - -Vital Stats 2011 -- http://censusindia.gov.in/vital_statistics/SRS_Bulletins/MMR_release_070711.pdf