I feel like the drug in my system has subsided already so I can now properly think what to post.
Tramadol
Yesterday (January 14, 2018), I went to ER due to severe acute pain. Here again my “gallstone attack”, so I must have eaten something rich in cholesterol. I took Tramadol 50 mg to address the pain, but a single dose seemed to have no effect, so I doubled the dose. After about 2 hours, the pain became more unbearable which lead me to take one another pill. I had three doses of Tramadol 50mg in a span of four hours. This is an overdose already but still, I wasn’t able to get its clinical effect. I know it’s my fault to do self-medication, but I had the guts to face its consequences whatever effect it could have on my body. I just wanted to relieve my pain.
I was already in the E.R. The nurse on duty did the usual triaging, recorded my VS, probed my chief complaint, and referred me to the doctor on duty. The primary concern was to address the excruciating pain, and the doctor wanted me to undergo an ultrasound examination (the last time I had was December 23, 2017). Meanwhile, she ordered an analgesic to be administered intravenously ASAP. I said “Ketorolac po yung ininject sa akin doc dati” [Ketorolac was administered to me before] and she replied, “No, bibigyan kita ng mas malakas na gamot.” [No, I will give you a more potent one] A nurse came, infused intravenous fluid (Lactated Ringer’s Solution) and gave Omeprazole and the analgesic separately. While administering the drug, I asked “Anong analgesic po yan?”[What is that analgesic?] “Ziphanol”, she replied. Then I googled “zephanol”, and there appeared a limited information about the drug. I was assuming it was a brand name so I followed up, “What’s its generic name?”, “Wait lang, nakalimutan ko. Balikan kita”, [Wait, I forgot. I’ll get back to you] she politely said after administration of the two parenteral drugs. Then she came back and handed me the generic name of the drug, “butorphanol”. I honestly do not know some brand names of drugs even though I am a pharmacist, which is why I am more concerned on the generics since they are much more familiar to me, including their therapeutic effects.
Butorphanol
Butorphanol belongs to class of Morphine (a potent opioid analgesic) analogues called Morphinans. I remember this classification when I had discussed Opioid analgesics in Organic Medicinal Chemistry class just recently. Basically, one ring from the structure of Morphine is purposefully removed to modify its effect either by increasing/decreasing its potency while minimizing the toxicity. It depends on the goal but this process of structural modification is termed Simplification. The molecular structure of morphine is assigned with different letters (A, B, C, D, and E). In the case of Morphinans, ring D is structurally removed and this shall result to increased potency and longer duration of action than the morphine counterparts, but they have higher toxicity and comparable dependence characteristics. In other words, Butorphanol is a real potent opioid analgesic.
As pharmacist who had at least experience in clinical practice (I had my minor and major hospital/clinical pharmacy internship in PGH, and taught Clinical Pharmacy subject for three semesters), I screened the drugs being administered to me by checking for any existing drug interactions. I was hoping there is none, but I was so SHOOKD to find out that a MAJOR DRUG INTERACTION exists between Tramadol and Butorphanol. The doctor and nurse did not know I was on Tramadol. I was never asked during triaging and during initial encounter with the doctor on duty. But I took accountability for not sharing this clinically relevant information because for the perspective of a clinical pharmacist, I should have told them. Although at this moment, I was a patient who just so happened to be a pharmacist.
Drug to Drug Interaction
According to drugs.com, “concomitant use of tramadol increases the seizure risk in patients taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. CNS- and respiratory-depressant effects may also be additive. In patients who have been previously dependent on or chronically using opioids, tramadol can also reinitiate physical dependence or precipitate withdrawal symptoms.”
Their combination is generally avoided. Based on what I know about drug incompatibilities, there are three classifications of drug interaction based on severity – Major, Moderate, and Minor. Major Interaction is considered highly clinically significant – which means they must be really avoided in clinical practice because the risks of the interaction outweigh the benefits. Other references stated that it is life-threatening and can cause a permanent (physical) damage to the patient. SCARY.
The Adverse Event Experience
At this time, I could gradually sense the onset of drug effect. I started to feel lethargy, shortness of breath, and palpitation. The moment I read about the nature of the interaction, I couldn’t help myself but freak out already. I was hoping I would not experience any of those undesirable effects but the situation seemed to become worse when I started to have tremors and experienced episodes of seizures. I could barely press my phone to text or call my family and/or friends. I alarmingly called the doctor immediately, “Doc, doc, nagsseizure po ako [Doctor, I think I’m having seizure]! Is this normal?” She was also surprised to see her observation. It was then that I told her I was on Tramadol and there is a major interaction between tramadol and butorphanol. I asked, “Is this normal based on your experience in Butorphanol?” Because if it is, I should calm myself down, but if this is the first time they observe such effects, it must be the result of the interaction. She told me, “Huwag kang mag-panic, normal na effect yan”. [Please do not panic, it’s a normal effect] I completely understood her way of reducing my anxiety, but I refused to believe it was normal. She left me, presumably because she would do her research privately.
Thankfully, I was still able to call my friends and some doctor-friends for help about my situation over the phone (Thank you from the bottom of my heart! Huhu), when another doctor came to monitor me closely. This time, while still having tremors, my mouth/lips started to desiccate, and I thought I was floating for real! I could barely move and breathe as well. I insisted to fight somnolence because of the concern of not waking up if ever I sleep. Haha! This is too exaggerating, but how can you not think of those things when the night before I went to E.R., I sang the perilous “My Way”? In my mind, there is a truth behind its curse. HAHA JK. I was praying that time that God is in control of the situation and it is this fact that I held on to remain still amidst the adverse medical event. And knowing the truth that I am well taken care of by the most loving Father, I have this inexplicable courage within me to face my current condition. I declared I am healed already, in Jesus Name.
Management
Since the drug was directly administered intravenously, (meaning it’s already on my systemic circulation), the doctor increased the rate of IV drip to accelerate the excretion of drugs. Unfortunately, the metabolites of Tramadol are also active. I was ordered NPO (non per orem), so drinking water was not recommended. The other way of preventing the unwanted result of the interaction was to give an antidote. In Inorganic Medicinal Chemistry, there are three types of antidotal therapy – Physiological (counteracts the effects of a poison by producing other effects), Chemical (changes the chemical nature of the poison), and Mechanical (prevents the absorption of the poison). Based on their respective mechanism of action, Physiological antidote would be the most possible way to prevent any toxicity following the drug interaction. My (doctor) friend who I was able to talk to over the phone, told me the team can give me benzodiazepine to counteract the withdrawal effects of opioids, but the doctor who was monitoring me said they chose not to give any additional drugs, probably due to safety concerns. Since I had no choice but to suffer from the interaction effects, I still managed to research the pharmacokinetic properties of the drugs administered to me (i.e. Half-life, metabolism, toxicity, name it). Both drugs have relatively prolonged half-life (the time it takes for a drug to reduce its concentration to 50%), especially the Butorphanol. And since I had an overdose of Tramadol, it’s also expected to stay longer on my body. When I learned about this, I reflected on life already and repented for my sins haha, “Is God finished with me?”, “I’m going to see my mother in heaven yas!”, “Oh I just sang My Way!”, whatever, but I peacefully surrendered the situation to God. Perhaps those thinking were the other CNS effects of the drugs.
Need for Clinical Pharmacy
This time, I helplessly succumbed to excessive drowsiness, but was able to wake up after about three hours. The doctor came, “Kamusta ka na?” Mas ok na?” [How are you? Feeling better?] The pain has subsided by the way. “Okay na po Doc, nahihilo lang po ako at nasusuka.”[I’m fine. Feeling a little nauseated and about to vomit] Then the doctor said, there was no other potent analgesic available in the pharmacy so they gave butorphanol. Usually, according to her, what they give in situation like mine is Meperidine (Demerol®) because when she saw my response to pain, her decision was to give a potent opioid analgesic. She said they would give me Metoclopramide (Plasil®), which is commonly used to treat and prevent nausea and vomiting, so I’d feel better. When left alone, I checked again for any interaction which may exist between tramadol and meperidine. Since the latter is also a potent opioid analgesic, the nature of the interaction is the same with that of butorphanol. There I realized that regardless of my prior Tramadol intake, they would still not avoid giving me a drug that has a major interaction with Tramadol. According to treatment guidelines for pain management, a strong opioid with non-opioid and adjunct analgesic is given to patients with severe pain. This was my chief complaint in the first place, and therefore, the primary concern of the doctor plus of course the underlying cause behind it. The doctor did the right clinical judgment based on guidelines, but not if they have thorough knowledge on drug interaction. If there was only a professional in the team whose major duty is to check for drug compatibilities, take note of the non-medication and medication history of patients, monitor for adverse drug events, and prevent any medication error, the team could have managed my situation properly. In other words, the presence of a Clinical Pharmacist in the hospital, especially in the E.R. is highly recommended. Thank God I have had trainings on clinical pharmacy practice even for a short while, although I do not have actual hospital pharmacy practice. Could you imagine hospitals without clinical pharmacy practice? How do they address a preventable event such as this? Indeed, the clinical expertise of pharmacists is underutilized because they are often limited to performing dispensing activities in most hospitals. And thankfully, I am a pharmacist, considered as drug expert, who at this time, happened to be a patient.
Status Post
I feel better now. Because butorphanol would stay in my body for almost a day, I was able to have a prolonged, but much-deserved bed rest. Still feeling a little groggy even after long hours of sleep, but I’m fine. What’s important is I am still alive and I have a lot of purpose to fulfil yet in this life. Haha The doctor has recommended me to have cholecystectomy (surgical procedure to remove gall bladder) before any complication arises. I was diagnosed to have gallstone last December 23 and yes, during holiday season it is! How timely, right? And how did I develop this solidified stuff inside my body? Well, regardless of the cause, I have to just accept it and prevent it from getting bigger. The doctors have different opinions – whether to undergo surgery or not, but one recommendation was common among them, avoid fatty foods. I resisted foods that are rich in cholesterol as much as I can, but FOOD is just… irresistible…and life. HAHA Sorry, I am a non-compliant patient. The pain will attack if ever I’ll eat something fatty. I tried some “cleansing” routine as well based on the testimony of some patients who just pooped out gallstones following a certain natural regimen, although I knew that this is not sufficiently evidence-based and scientifically proven. Now, it’s up to me to decide when the operation will be performed. Based on literature, laparoscopic cholecystectomy remains the standard treatment for gallstones. I am aware of this technique since my mother who had her gallstones before, went through the same surgical procedure. I watched on YT about it and how it is performed. The fact that an internal organ is going to be taken out from my body again freaks me out, on top the direct medical and non-medical costs associated with the operation. But God remains the standard treatment for our life circumstances. Faith. That everything will fall perfectly according to His will. That He is a God of provisions – the doctors who will perform the operation, the healthcare team who will be part of managing my situation, any costs involved will be paid without me incurring any debt, the physical, mental, and emotional strength I need in preparation for this surgery. Oh what a beautiful life, isn’t it? I learned so much – clinically and spiritually. I assumed the doctors learned as well from my clinical case. I have another experience (or more of testimony) to share my students when I teach the subjects connected with this presentation. And one major take home lesson from this is to prioritize health. I don’t need to further elaborate this but health is really wealth. And finally, I can dare you sing “My Way”. Haha
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