S2 Week 9: Neuropharmacology, Albuterol Toxicity, and Integrative Medicine Pain Management
This week started off with our first neurology exam which was a fun way to see just how much we had learned in such a short amount of time! After the exam was over, we immediately dove into some lectures on the hypothalamus, autonomic nervous system, and basic principles of autonomic pharmacology. These lectures helped set the stage for the upcoming week’s material.
Tuesday began with a fun run with Churro followed by an additional lecture on autonomic pharmacology. That afternoon we got to put our newly acquired knowledge to the test and were given a few clinical case studies. These were all focused on anatomic correlates of autonomic nervous system dysfunction. It is always nice to tie in case studies because it helps solidify the lecture material as well as remind everyone why it is so important to actually understand how things function on a mechanistic level.
Wednesday began with yet another lecture on autonomic pharmacology followed by another clinical case study. This case was centered around a dog with a corneal ulcer and tied in information from our lectures on the autonomic nervous system as well as autonomic pharmacology. It was also a great preview into this upcoming week’s material which will all be focused on the eye!
During lunch we had an amazing lunch talk from Dr. McCaughan! Dr. McCaughan is a graduate from Cornell University, School of Veterinary Medicine and enjoys working with all types of animals – dogs, cats, pocket pets, rabbits, and horses. She established the first Integrative Veterinary Hospital in Alameda, CA in 2018, and continues to oversee pain management cases at that location. She practices veterinary acupuncture (trained at the Chi Institute), is certified in Veterinary Chiropractic (Options for Animals) and has advanced training in musculoskeletal diagnostic ultrasound and regenerative medicine therapies. She is passionate about multimodal therapy for pain management, using stem cell therapy, PRP, cold laser therapy, acupuncture, Chinese herbs, and chiropractic treatments, in addition to conventional medicines.
This lunch talk focused on how to utilize integrative medicine in general practice to help manage pain and improve the lives of all of our patients. During her presentation Dr. McCaughan spoke about her path into integrative medicine and then discussed a few case studies. It was super interesting to hear how she has balanced western medicine with a holistic approach in order to create a better outcome for her patients. Her talk was also interactive, and she helped teach us how to better diagnose lameness in dogs and cats, as well as what types of questions to ask owners while collecting the patient’s history. I enjoyed her enthusiasm for integrative medicine, and it was apparent that she gains great personal satisfaction from helping our companions live longer, happier, and pain-free lives!
I recently had the privilege of being interviewed on the The Integrative Veterinarian Podcast and that episode is now live. Here is a link in case you were interested: Podcast! Integrative medicine is such an exciting branch of veterinary medicine and I love learning about different ways to address common issues that our furry friends face.
The afternoon concluded with a quick anatomy lab that went over the major arteries and nerves of the head!
Thursday kicked off with a lecture on the basic principles of autonomic toxicology. This lecture tied in information from the earlier pharmacology lectures and went over some key signs of drug toxicosis in companion animals as well as equine and livestock. We then transitioned into another case discussion that was focused on the physiology and pharmacology of the autonomic nervous system. This was a nice way to solidify the lecture concepts and correct any misunderstandings!
After the morning lecture and discussion, I was able to get a quick swim in before our afternoon lab. This lab was another sheep brain dissection but this time we were looking at some cross-sectional anatomy as well as doing a “deep dissection” of the brain. The prior dissections were primarily focused on identifying the large structures while this time we were diving deeper and examining structures that were packed tightly inside the brain such as the hippocampus.
Friday started off with a hot yoga session followed by two lectures on the pharmacology of sedatives and analgesics. It was super interesting to learn about the different ways that the central and peripheral nervous system can be affected through the use of chemical substances. Our awesome professor, and anesthesiologists, Dr. Brosnan, made these lectures extra enjoyable by bringing the whole class snacks! After these lectures were over, we transitioned into our last case discussion for the week. This case was focused on applying our knowledge from the toxicology lecture and tying it into the clinical effects that would be seen in the autonomic nervous system.
Our case was focused on a dog that had gotten into the owner’s inhaler and was now tachycardic, agitated, had scleral injection, and hyperemic conjunctiva. Based on the history provided, and the clinical signs, we were then instructed to find out why the patient was exhibiting these clinical signs.
We are about to dive into some pharmacology so if this is not something you are interested in learning about, feel free to skip to the end! I would also like to give a huge shoutout to Dr. Sprayberry, Dr. Burd, and Dr. Lyons from Cal Poly for providing such a strong pharmacology foundation prior to vet school!
Rescue inhalers are typically filled with albuterol which is a beta2-agonist. This means that it activates adenyl cyclase and thus stimulates the production of the secondary messenger cyclic AMP. Cyclic AMP is involved in many signal transduction cascades and at a normal therapeutic dose it causes relaxation of bronchial, uterine, and vascular smooth muscles. At therapeutic doses it also produces minimal beta1-agonist activity. However, biting into an inhaler can cause an overdose and the beta1-agonist activity becomes more prominent. This leads to tachycardia, central nervous system stimulation, and fever which were all seen in our patient. It was also noted that overdosing on this beta2-agonist can cause hypokalemia and hypophosphatemia along with hypotension. (Plumbs)
We were then given additional information about our patient’s venous blood gas and electrolyte status. It was observed that our patient was hypokalemic, hyperlactatemic and hyperglycemic. Here is an explanation of how albuterol can contribute to each one of these clinical symptoms.
Hyperkalemia: Beta-adrenergics promote a shift of potassium from the plasma into the cell which is thought to be due to stimulation of Na+-K+-ATPase. This shift temporarily decreases the plasma potassium levels, since it is now in the cells.
Hyperlactatemia: Hyperlactatemia can be explained secondarily to Na+-K+-ATPase stimulated aerobic glycolysis (type B hyperlactatemia) associated with catecholamine stimulation through B2-adrenergic receptors. Glycolysis is increased which can lead to a relative deficiency in the amount of oxygen leading to excessive lactate production. Another mechanism is driven by inadequate oxygen availability or “type A hyperlactatemia”. Lactate is produced along with a hydrogen ion, and this creates lactic acid leading to hyperlactatemia. Both of these mechanisms are able to produce hyperlactatemia but the first one is more commonly seen with albuterol toxicity.
Hyperglycemia: The hyperglycemia may be explained secondarily to the hypokalemia which is associated with impaired insulin secretion and decreased peripheral glucose utilization. This results in carbohydrate intolerance which would result in hyperglycemia. (J Vet Emerg Crit Care). Another mechanism is that glycogenolysis is stimulated which makes more glucose molecules available to the bloodstream.
We were then given information on our patient’s blood pressure, and they were in fact hypotensive and still tachycardic. This was likely because albuterol induced peripheral and coronary vasodilation. This vasodilation resulted in hypotension and in attempt to compensate, the heart reflexively increases the rate at which it contracts thus leading to tachycardia.
We then had to decide how we would treat and what symptoms we would directly address…
After doing some research and diving into some articles from the Journal of Veterinary Emergency and Critical Care, specifically Volumes 32 and 33 Issue 4 and 6, here was my proposal... I would carefully treat the hypokalemia since rebound hyperkalemia has been seen in certain cases. The potassium was never truly lost from the body, it just moved intracellularly and with the use of a beta-blocker, it will move extracellularly. Rebound hyperkalemia was specifically seen in a case-study similar to ours where the pet was treated with IV Lactated Ringer’s solution at 90 mL/kg/day with 0.35 mEq/kg/h of potassium chloride. The following day the blood potassium levels of that patient were extremely elevated (which can be dangerous). It was also mentioned that the use of a beta-blocker is a more specific treatment for albuterol-induced hypokalemia since beta-blockade interferes with the cellular uptake of potassium and these drugs mediate potassium uptake into skeletal muscle, liver cells and adipose tissue. Administering a small concentration of diluted potassium chloride was seen to be beneficial in some cases and reflex hyperkalemia is not extremely common so depending on the severity of the hypokalemia, this may also be a good option. *Never give potassium chloride quickly as it can lead to cardiac arrest and death!
The other symptoms seem to be secondary effects and over time become regulated once the hypokalemia is resolved. I would not choose to directly treat the blood pressure alteration. I would however keep a close eye on it as well as monitor my patient’s ECG. During this time of monitoring, I will be assessing the efficacy of the beta-blocker (propranolol) that I had previously administered to make sure that it was working. If it was not creating the intended effects and my patient began to decline, I would address the blood pressure. I would also continue to monitor this patient’s electrolyte levels and address any changes accordingly.
Unbalanced electrolyte levels, especially potassium can be extremely detrimental to the heart so making sure that we have a normal rhythm is crucial. As mentioned earlier, I would also continue to monitor my patient’s blood pressure, temperature, as well as overall demeanor and make sure that they were comfortable and seemed to be improving.
On a positive note, the prognosis for albuterol toxicity is fairly good when the patient is given medical intervention fairly quickly. Full recovery is possible and with appropriate treatment, most dogs return to their normal physiologic state fairly quickly!
After the discussion was over, we were done for the afternoon, and I was able to get in a long 43-mile bike ride! I then spent the rest of the evening studying and hosting a virtual study session for some awesome undergrads at Cal Poly who are currently in a systemic anatomy and physiology course!
Saturday started off with a run with Churro followed by a hot yoga session. The rest of the weekend was spent studying in preparation of the next neurology exam on Monday!
Quote of the week: “It’s misleading but not inaccurate”
-Dr. Lein after answering a question about neuropharmacology
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