Who Is Addressing the Availability, Safety & Efficacy of our Medications?

I watched all three presidential debates this summer with health care being a time-consuming topic for all. Universal health care and Medicare-for-All, with or without an option for private insurance, were debated and discussed at length.

At the same time NBC Nightly News presented a story documenting that all our antibiotics come from production in China. With globalization policies, which promote moving production to lower cost overseas factories, there is no longer any production of antibiotics in the USA. A former member of the Joint Chief of Staffs, citing the current trade conflicts and China’s aggressive military stance in the Pacific, considers this a security issue. I have heard not one question or comment on this topic in the debates?

This week, once again, the blood pressure medicines losartan and valsartan were recalled because they contained potential carcinogens. These generics were produced in India, Asia and Israel. These same drugs have been recalled multiple times in the last few years for similar problems.

Due to reduction in funding for FDA inspections, many of these foreign plants have not been inspected for years. We can add recalls of generics to drug shortages. We suffered a shortage of intravenous fluids for hydration because the primary production site in Puerto Rico was destroyed in a hurricane. We had shortages of morphine and its derivatives for treatment of orthopedic trauma and post-surgical pain. They substituted foreign-produced short acting fentanyl. I saw pediatric ER physicians unable to administer the most effective treatments for sickle cell crisis in children because it required the use of a narcotic drip to offset the dramatic pain the treatments induce as they stop the crisis.

Then there are the psychiatric patients on antidepressant generics who are paying hundreds of dollars per month for products that wear off in 16 hours rather than 24 as the brand product did. Their symptoms creep back in allowing them to tell time based on the reduced efficacy of these products. By law, generics are required to provide 80% of the “bioavailability” of the brand product but what does that mean and who is testing?

This all began when the Reagan Administration closed the FDA research lab. Prior to that, all new products were sent to that lab for approval prior to being released in America. On their watch, a pharmaceutical product never had to be recalled. Big Pharma complained they took too long as did some consumer groups. This resulted in the defunding and closing of the lab. Products are now outsourced to private reference labs and their reports are sent to the FDA for review. The frequent drug recalls contrast to the success of promoting safety when the FDA did it themselves.

Isn’t it time for the health care debate, especially the presidential debates, to discuss the safety, efficacy, supply and cost of pharmaceutical products? I am all for bringing production home to the USA, restoring the FDA funding for the reopening of their lab as an impartial test site and putting the cost of repeatedly testing the generics for efficacy even after approval and release on the backs of Big Pharma. Let’s see these topics introduced to the health care debate too.

Antibiotic Use – Independent of Physician Prescribing

A recent article in the Annals of Internal Medicine looked at individuals who took antibiotics without them being prescribed by physicians at a visit.  The authors looked at 31 published studies between January 2000 and March 2019.  The medications came from family and friends, online distribution sites, drugs prescribed for their animals by their veterinary doctors and those stored after a previous indicated use.   When asked about it, and the reasons why these patients took these medications, the main factors cited were lack of health insurance or lack of healthcare access, cost of physician visits or medications, long waiting times in clinics, embarrassment for needing antibiotics, lack of transportation and/or easy availability of antibiotics  from other sources.

We are currently going through an antibiotic resistance crisis in the world.  Most of the fault lays with agricultural industry feeding livestock tons of antibiotics to fatten them up. Patterns of resistance develop on the farms and are passed species to species.

To remedy this, the US agriculture industry, especially in chicken production, has cut back drastically on this process.  At the same time, we are requesting physicians to work with infectious disease doctors in stewardship programs to reduce their use of ineffective antibiotics and to prescribe with precision when these medications are needed.  It works. Studies are beginning to show the benefits of these programs.

Despite this, the pressure from patients to be given something when they pay for, and invest in, a medical evaluation for an infection is overwhelming. In the setting of telemedicine, as well as walk-in and urgent care centers, reviews and patient satisfaction survey results are tied to whether the patient was given an antibiotic whether it was indicated or not.

As bacteria become resistant to common and inexpensive antibiotics, pharmaceutical manufacturers are not being incentivized to produce newer more efficacious medications.  At the same time, older useful antibiotics which do not generate much of a profit are not even being ordered and stored by chain pharmacies that lose money each time the older generics are prescribed.

To begin solving this problem, an improvement of our health literacy is required. Education in schools and in public health announcements, both in print and social media, need to realistically address the issue. This education will not replace the need for access to health care and health, but it is a beginning to make individuals understand how, when and why these “miraculous” medications can and should be used.

Scientific Reports, Media Reports and Ambiguity

Last week I read an article in a peer reviewed journal citing the benefits of a few eggs per week as part of a low carbohydrate dietary intervention for Type II Diabetes.  The information was so meaningful about a controversial food source of protein that I decided to write about it in my blog and pass it along to my patients.  Three days later the American Heart Association and American College of Cardiology discussed the increased risk of cardiovascular events and mortality in individuals consuming three or more eggs regularly. They talked about the detrimental cholesterol being concentrated in the yolk making egg white omelets look healthier than traditional omelets.

In the early 1970’s a VA study was published showing that veterans over 45 years of age who took an aspirin a day had fewer heart attacks and strokes and survived them better than those who don’t.  Fast forward almost 50 years and we have different recommendations for people who have never had an MI or CVA or evidence of cardiovascular disease compared to secondary prevention in individuals who have known coronary artery disease, cerebrovascular disease or diabetes. Throw in the controversial discussions of aspirin preventing colorectal adenomas from developing, aspirin preventing certain types of skin cancers and today’s report that suggests it may prevent liver cancer. Now three studies suggest that in older individuals (70 or greater) the risk of bleeding negates the benefits of cardio and cerebrovascular protection and aspirin may not actually prevent heart attacks and strokes in that age group.

We then turn to statins and prevention of heart attacks and numerous articles about not prescribing them to older Americans.  I saw articles on this topic covered by CNN, the Wall Street Journal, ARP Journal, AAA magazine and in several newsletters published by major national medical centers.  In each piece they caution you to talk to your doctor before stopping that medicine.

I am that seventy year old patient they all talk about.  I have never smoked. I exercise modestly on a regular basis, getting my 10,000 or more steps five or more days a week.  I battle to keep my weight down and find it difficult to give up sweets and bread when so many other of life’s pleasures are no longer available due to age and health related suggestions.

There are clearly no studies that look at patients who took a statin for 15 years and aspirins for over 20 years, stopped them and then were followed for the remainder of their lives.   How will they fare compared to patients who never took them?

I have this discussion every day with my patient’s pointing out the current guidelines and trying to individualize the suggestions to their unique lifestyle and issues. On a personal level, I still have no idea what the correct thing is to do even after discussing it with my doctors.  How can I expect my patients to feel any differently?

Cipro, Levaquin and Tendon Rupture

For many years, fluoroquinolone antibiotics such as Cipro and Levaquin have been integral components of treating bacterial urine infections, travelers’ diarrhea, skin infections and certain pulmonary infections.  Like any chemical or medication, they do not come with a “free lunch.”  There have always been potential side effects and adverse effects possible, in addition to drug to drug interactions with other medications, the prescribing physician needs to take into account before suggesting these products to patients.  In recent months, the use of these antibiotics has come under further critique from individuals developing unexpected tears of tendons and having an increased risk of rupturing a major blood vessel such as the aorta.

The subject of fluoroquinolone antibiotics and tendon rupture was addressed in a recent study of the United Kingdom Clinical Practice Research Datalink and discussed in the on line journal MPR.  They looked at 740,926 users of fluoroquinolone (FQ) antibiotics and tendon ruptures. Of that group, only 3,957 cases of tendon rupture were reported.  This correlated to a risk of 3.73 events per 10,000 person years with an even lower risk for Achilles tendon rupture of 2.91.

When they then looked at which patients with rupture were additionally taking corticosteroids such as prednisone they found the risk increased to 21.2 per 10,000 PY.  The study showed that females were more likely than males to develop a tendon rupture and those over 60 years old as well.

Cipro and Levaquin can certainly remain part of a treatment plan as long as we realize that patients taking steroids, especially women and patients over 60 years of age, are at higher risk than others. That risk, however is extremely small.

Statin Related Muscle Pain and Coenzyme Q 10

Statins are used to lower cholesterol levels in an effort to reduce the risk of developing cardiovascular disease. They are used after a patient has exhausted lifestyle changes such as changing their diet to a low cholesterol diet, exercising regularly and losing weight without their cholesterol dropping to levels that are considered acceptable to reduce your risk of vascular events.

Patients starting on statins often complain of muscles aches, pains and slow recovery of muscle pain after exercising. In a few individuals the muscle pain, inflammation and damage becomes severe. One of the known, but little understood, negative side effects of statin medications are the lowering of your Coenzyme Q 10 level. CoQ10 works at the subcellular level in energy producing factories called mitochondria. Statin drugs, which inhibit the enzyme HMG-CoA Reductase lower cholesterol while also lowering CoQ10 levels by 16-54 % based on the study reporting these changes.

The November 16, 2018 edition of the Journal of the American Medical Association published a review article by David Rakel, MD and associates that suggested that supplementing your diet with CoQ 10 would reduce muscle aches and pains while on statin therapy. Twelve studies were reviewed and the use of CoQ10 was associated with less muscle pain, weakness, tiredness and cramps compared to placebo. The studies used daily doses of 100 to 600 mg with 200 mg being the most effective dosage. Finding the correct dosage is important because the product is expensive with forty 200 mg tablets selling for about $25.

Since CoQ10 is fat soluble, you are best purchasing formulations that are combined with fat in a gel to promote absorption. As with all supplements, which are considered foods not drugs , it is best if they are UPS Labs certified to insure the dosage in the product is the same as listed on the label and that it contains no unexpected impurities.

Controlled Substances and Schedule Drugs

The right to prescribe narcotics and controlled substances is regulated by the Federal Government. Physicians, dentists and health care providers apply for licensing with the Drug Enforcement Agency and request the right to prescribe medication from the different “schedules.” State legislatures and state medical boards regulate this further. Most people are unaware which medications and drugs are in which schedules or categories.

Schedule I – For the most part, these are substances which have no current accepted medical usage and are easily abused.

Examples are: Heroin, LSD, Ecstasy (methylenedioxymethamphetamine), Quaaludes          (methaqualone) and peyote.

Schedule II – These are substances with high potential for abuse with a risk of physical and psychological dependence.

Examples are: Vicodin, cocaine, methamphetamine, methadone, hydromorphone (dilaudid), meperidine (Demerol), oxycodone (OxyContin), fentanyl, Dexedrine, Adderall, Ritalin

Schedule III – these are drugs with moderate to low potential for physical and psychological dependence.

Examples are: Products with < 90 milligrams of codeine per dosage unit such as Tylenol with codeine, ketamine, anabolic steroids and testosterone.

Schedule IV – These are drugs with a lesser risk for abuse and dependence.

Examples are: – Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, and AmbienTramadol.

Schedule V drugs have lower potential for abuse than Schedule IV drugs and contain limited amounts of narcotics. This would include antidiarrheal medications, antitussives, and mild analgesics. Cough medications with less than 200 milligrams of codeine per 100 milliliters such as Robitussin AC, Lomotil, Lyrica and Parapectolin.

All the medications on these schedules must be reported to E-Forcse, the Prescription Drug Monitoring Program, within 24 hours of dispensing by pharmacies. They all require the prescribing doctor to check E-FORSCE before prescribing.

A Clinician’s View of the Opioid Crisis

“Do Not Get Caught.” seems to be the real rule of the law in S. Florida, where I live.

I was trained to limit the use of controlled substances, narcotics, hypnotics and sedatives. Their use can affect consciousness, ability to drive a car and work.  More severe consequences include respiratory depression and overdose from too high of a dosage or mixing too many medications and over the counter items.

The Joint Commission on Accreditation, medicine’s good housekeeping seal of approval authority, along with major medical organizations have accused clinicians of under treating pain. “Pain” is the fifth vital sign, they said.

This was accompanied by professional society leadership and academic researchers receiving grants from pharmaceutical companies touting the newer longer acting pain medications which “have very little addictive potential”. We were then informed we would be receiving evaluations and scores of our treatments of pain which would influence our reimbursement if we under treated pain.

In my current concierge medical practice I see 10 or fewer patients per day. In my previous general practice I saw 2- – 30 patients per day. I could go days without prescribing a narcotic pain medication. In most cases when I wrote out a script for a narcotic pain medication it was for a patient with a severe chronic pain problem, seeing a specialist for that problem, and requiring a pain pill because there were few effective alternatives. The patient visits to doctors and physical therapists and massage specialists and other alternative pain therapies were well documented in the medical record and mostly unsuccessful in attempts to relieve the pain.

This contrasts markedly with the opening of pain clinics in nearby counties with their own in-house prescribing pharmacies. One or two physicians wrote thousands of pain pill prescriptions per day. Patients lined up around the block to see these employed physicians of the pain clinic with many arriving in cars from other states. The cash flow generated was so vast that the clinics needed private security to protect the profits. Many of the security hired were off duty city and county police officers trying to supplement their income.

It’s hard to imagine that law enforcement and the DEA, were unable to recognize the difference between pill distributing centers and legitimate practices prescribing medications on a limited basis to individuals with documented needs. City, County and State governments gladly accepted the tax benefits, occupational license fees and pharmaceutical license fees from these sham clinics while drug dealers drove in and out of our state to obtain prescription pain medications for sale in their home towns. Of course the blame for this was placed on the doctors and dentists.

The State of Florida tightened up its laws and somehow law enforcement was given the tools to see and eradicate what was occurring right under their very noses. As prescription drugs dried up, the Mexican drug cartels got smart and flooded the market with cheap strong heroin. It was obviously the fault of the physicians and legitimate pharmacies that white working class people were buying plastic bags full of dope and inserting needles into their veins to avoid the pain of life.

As drug addiction soared, City and County Governments found it in their hearts to sit as zoning boards allowed drug rehabilitation centers to open up in the heart of their communities. There was little or no effective investigation of who was running these clinics and or their previous experience, methods and or success rates. If you want to read about where the soaring number of narcotic overdoses occur in our community – follow the zoning board’s placement of rehab centers and sobriety houses. What better way to increase your drug overdoses than to encourage unsuccessful addicts to come to your community and leave their money and their family’s money to improve the tax base and create new headaches for EMS and police officers?

Somewhere there should have been a higher level of thought by our elected and appointed officials about the consequences of bringing hundreds of drug dependent individuals into our area before they permitted these facilities to open.

Last week my advanced pancreatic cancer patient with severe back pain tried to purchase a controlled substance prescribed by his oncologist to relieve his suffering. Six pharmacies no longer stocked the product due to their fear of liability. It took hours to find a pharmacy that would order the medication for the patient. Physicians, pharmacists and law enforcement accessing our state narcotic registration website clearly can see that this patient only uses his medications as prescribed by one physician. This patient, and others like him, are victims of the government legitimizing of pain pill mills and drug rehabilitation centers in their communities.

As a physician we all have our failures in this area as well. I painfully recall the doctor’s wife I sent to a disciplined pain doctor to wean her off narcotics prescribed by a rheumatologist, urologist and gastroenterologist for legitimate reasons documented by tests and biopsies. I refilled the prescriptions for her convenience and ease never dreaming I was contributing to her problems.

I feel for my colleagues in the Emergency Department and in orthopedic offices having to daily differentiate acute pain requiring intervention with controlled substances as opposed to individuals with drug seeking personalities. This being said, the opioid crisis was caused by the most trusted members of the academic medical community in cooperation with the medical inspection and certifying agencies in concert with public officials and law enforcement looking the other way. They all made a great deal of money at the expense of the public. Now as they struggle to clean it up they give us medical and recreational marijuana.