Decades ago, I would get that occasional call from a friend: “do you know anything about… such and such drug?”. That drug was often acetaminophen, a.k.a. paracetamol. Other times it was acetylsalicylic acid, a.k.a. aspirin. People were terrified of giving acetaminophen to children and would rather think twice before taking it themselves. Today we are much less refractory to giving it not only to children, but also to babies. Back then, the common perception was that aspirin was a drug for cold or flu. According to the misfortuned-perception, aspirin was prescribed when apparently the physician was unable to find anything going wrong with you and had to give you something to show that care was provided. Can you imagine how wrong this perception was?? I heard it, I saw it. I know it was out there and I am afraid to estimate how many people died because of it.
It was a common stand-up comedy joke: “Let me guess. They put you on aspirin, right?”. Being prescribed aspirin to prevent a heart attack or during a heart attack (a common practice today) was looked at as blasphemy. Such a thing required a double check with your neighbor. Of course, only to get a “Nah, can’t you tell they’re only trying to sell you something?!?”. What about checking with another physician or a pharmacist instead? God forbid!
I was a neighbor too, so they called me
I got the call because, at the time, I was neither a physician, nor a pharmacist. People trusted my opinion because they had known me long enough to have validated on their own that I was better in sciences and math than others they knew. I was good at searching and finding. For them that was a BIG DEAL. I was vocal at social gatherings and my opinion seemed to make sense. That gained me their trust (it also got me in trouble later in life, but that’s another story for another day). I liked helping people and I had an itch to validate whether something I heard was right or wrong, true or false, applied correctly or not. I also wanted to gain enough knowledge to understand and apply it correctly or at least to find the right people to ask more. I kept questioning and this led me first to biochemistry. It wasn’t until years later that I became a clinical pharmacist.
Take it once-a-day vs. take it twice-a-day
I still remember a conversation I had with a quite well known scientist when I was an undergrad student in biochemistry. We were seeding antibiotic-resistant bacteria on agar plates and the discussion stirred around why antibiotics are prescribed to be taken once, twice or three times daily. The decision was thought to be a matter of bacteria growth rate – the faster the rate, the more often the drug had to be taken. Well, I did not have a pharmacy degree yet, no clinical experience, and had absolutely not attended one single pharmacokinetics or pharmacodynamics class. For the uninitiated, these two fields of applied mathematics define our understanding on what a human body does to a drug and what a drug does to a human body.
The belief that antibiotic dosing was a matter of bacterial growth-rate was painfully wrong… and it took me quite a while to figure this out the proper way. In fact, the answer required getting a whole new degree. No, this wasn’t my “reason” for going to pharmacy school, but it surely fed the desire to understand. In any case, I was accepted and going to pharmacy school. Hell, yes! I was soon able to be an even more reliable source of information for my friends and neighbors. Antibiotics were to be given once, twice or three time daily solely based on how long it took to the body to get rid of the drug, either by eliminating it or by modifying it through metabolism. It was actually the dose, the amount of drug in the pill, that determined how much drug a patient ended up having in the blood and whether that was sufficient to penetrate the place of infection and have a kill-effect or at least stop bacteria from growing.
Our body is very diligent at getting rid of the antibiotic, but not equally efficient at getting rid of the bacteria and that is why certain antibiotics in certain patients need to be given more than a pill a day. I will get back to this as I want you to understand what happens if you forget to take one of the two antibiotic pills you are supposed to take in a day or you took it 5 hours later than you should have. The consequence may be darn significant depending on whether that is your first, second or last day of taking the antibiotic! I know you care to understand how that works and I know you want to figure at once what is the matter with antibiotics use and having or not a beer. I will get into that too! You bet, I got this question way more than once thus far! It will be posted in my drug files.
Cancer drives the questions I hear today
Interestingly, lately I notice a dramatic difference in the questions I get from people. The difference is the impact of the answer they expect from me. The more the time has passed, the more the questions from those around me come closer to a life-and-death type of answer. The extent of co-morbidity increased in the recent decade, the complexity of the treatments increased as well and this led to more and more adverse effects. The chance of giving either much less or much more of a drug than needed has grown due to the variety of individuals requiring that particular drug and because of the wide difference of individual responses to the same drug treatment. The problem was even more complicated as we discovered the drug-drug, drug-food and drug-disease interactions. Then came the impact of one’s genetics on drug treatment response and last, not least, the drug-induced disease.
For each of the details enumerated here I could write hundreds of pages. If undetected or identified too late, all will converge to one unavoidable and inexorable event: DEATH. The path to that moment isn’t uneventful itself. It comes along with suffering, frustration, and debt, lots of debt. Drugs are expensive. The worse the treatment course goes, the more expensive it gets. Improper use of drugs is one of the most expensive societal mistakes we were capable of and – for God’s sake – we have made that mistake many times over.
People asking me questions today are not any longer concerned about acetaminophen, aspirin, or antibiotics. They ask if a certain chemotherapy is better than carrot juice, or if it is a good sign that they did not lose their hair, or that they got an awful rash throughout their body, or what means “metastatic”. Most of the questions I get today trace back and have a connection to cancer disease. Should we be always as aggressive as we can in treating cancer? How late is too late? Until what point in time can we prevent the cause of cancer and what does it take?
Some of my answers are far from pleasing. By this I mean: they raise serious individual concerns about lifestyle changes or overcoming strong beliefs about taking or not a certain treatment. Should I tell all I know? That depends on how much the one asking the question is ready to hear…
The real life story of a drug-related question
A couple of months ago I was sharing the thought of launching this blog with my cousin. The discussion was overheard by his roommates and one of them popped the question. Her father had been diagnosed with melanoma, but thankfully he was diagnosed with what she assumed to be stage 2 the month before, when she saw him last, and things were now good and under control. The question was about a medication he was prescribed and he was not very keen about taking. Well, being a pharmacist and registering these few details you can’t go easy. If a patient diagnosed with melanoma requires a drug, things are not “good and under control”, it is that simple. Early stages of melanoma that have good prognosis and “stay under control” tend to be approached and solved by surgery alone. If no drug is needed after the surgery, that is what I call “good and under control”. But, if the patient needs a drug and the patient is not keen about taking it, well that by no means sounds “good and under control” to me! The assumption about stage 2 was pure confusion. Either me or her was gaining a very wrong understanding about what was going on. As I asked more questions and learned more details, it turned out that there was a big, weird looking lesion on the leg that bled more than once before her father sought medical attention. I also learned that the respective leg was very swollen and he had difficulty walking. She told me that recently he rather sought “bioenergy healers” instead of taking his medication.
Well, at this point in the conversation I had to choose between giving her the wake-up answer or simply reinforce the need to take the medication as prescribed and let the things sort out on their own. That man could die at any moment without him having the chance to see his daughter again and he did not deserve this despite his poor decision to not take his medication! She deserved to see her father again before it was too late. That wasn’t a “stage 2”. That was likely metastasis. I decided to tell her the truth hoping she wouldn’t hate me for being the messenger. I explained to her what good news would have meant to me and what clinical action would have been taken thus far if the situation would have been under control. I explained to her the treatment strategy and what drugs do in melanoma (and I will explain it for you as well – check out my drug files). It was a walk through the dark, in complete blindness, waiting for her to realize that what she knew meant something way more alarming than what she had thought it meant. And she eventually did realize. I could feel it in her voice and in her decision. “I’m going back” she said. “That’s the wisest thing you can do”, I told her, “He needs you now more than ever”.
I continued explaining to her a handful of watch for this and watch for that type of information. Made her aware of what she might expect to occur and what each would mean clinically. Most importantly, I told her to watch for signs and labs that could give her hints as to whether his state was getting better or worse. It is established that patients diagnosed with melanoma who have elevated blood levels of lactate dehydrogenase tend to have poorer outcomes. A value of 2-3-digits would be decent for the given diagnosis, but a 4-digit value especially if suddenly increased could mean the worst. She absorbed everything like a sponge. She began messaging her family and an hour later I got a message from her with a picture of his labs, including lactate dehydrogenase. It was 474. His clinical bulletin also stated the presence of lung metastases. Damn! This wasn’t about to be an easy trip…
The following days, after she made it to her father’s bedside, we exchanged countless messages. Her father stopped eating, couldn’t walk, was in pain, dizzy and nauseated. He was rushed to the hospital and admitted. His lactate dehydrogenase spiked into the thousands. The clinical team refused to attempt any tumor-kill therapy. Hope slowly made room for panic. The more questions she had about cancer drugs and therapy options, the more I had to clarify that addressing comfort and providing supportive therapy had priority over attempting tumor-kill. Controlling nausea and being pain-free was far more important than optimizing or intensifying cancer drug treatment. It was quite obvious to me that his swollen leg could be the consequence of a blood clot, a fact soon confirmed while in the hospital. Increased clotting is itself a consequence of suboptimal cancer control (e.g. cancer progression). In a way, cancer can be looked at as a clotting disease. I hated being right and, as countless times before, I wished I wasn’t!
Luckily the communication with the clinical team went very well and her father could achieve symptomatic relief soon. He felt better and could get to sleep. In the care of such a case, we call this outcome an absolute success. One can’t hope for more success than the patient being able to rest peacefully in such a situation.
The next question came truncated in many messages: “are… his days… counted? Please be honest with me…!”. I hated myself once again. “Yes. It hurts me too to tell you this. I am so-so sorry!”. She was herself in pain, in tears, unprepared and afraid.
But she was there with him, and that has been my mission: to answer these questions with the best of my knowledge.
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