Real Life Pharmacology - Pharmacology Education for Health Care Professionals

Testosterone replacement is primarily utilized in patients with hypogonadism. I discuss testosterone pharmacology, adverse effects, and drug interactions on this podcast episode. Testosterone is a controlled substance because it is most often diverted for its potential to build muscle in athletes for competitive sports. There is cardiovascular risks associated with the use of testosterone. Testosterone can raise blood pressure and also raise cholesterol levels which may be a contributing factor to its potential to cause cardiovascular events.

Morphine has opioid agonist activity that can cause respiratory depression and death in overdose. Morphine-6-glucuronide is the metabolite that can accumulate and cause CNS toxicity in renal failure. Be aware of CNS depressants that may enhance the effect of morphine and other opioids. Some examples of CNS depressants include gabapentin, benzodiazepines, older antihistamine, skeletal muscle relaxants, and pregabalin. Opioid withdrawal is a significant concern when patients have their morphine or another opioid abruptly stopped. Some signs of withdrawal include agitation, mood swings, anxiety, sweating, GI upset, pain, and insomnia.

Prasugrel is a P2Y12 inhibitor that is used in the setting of ACS. Be aware of patients who may be taking over the counter medications that can increase their bleed risk while taking prasugrel. Prasugrel is on the Beers list and in general, should be avoided in most situations for patients who are 75 years of age or older. Morphine has the potential to impact antiplatelet agents like prasugrel and make them less effective. Be sure this is clinically considered prior to using morphine with prasugrel.

Mirabegron is a beta-3 agonist that can help relax bladder smooth muscle and manage symptoms of overactive bladder. Mirabegron inhibits CYP2D6 which can negatively impact the effectiveness of tamoxifen. I discuss this in greater detail in the podcast. Tramadol and codeine effectiveness can be impacted by mirabegron. Be aware of this when using this medication. By inhibiting CYP2D6, mirabegron can increase the concentrations of many psychotropic medications such as fluoxetine, aripiprazole, clozapine, and paroxetine. I discuss this further in this episode of the podcast.

Erythromycin uniquely has some potential benefit in the setting of gastroparesis. Azithromycin you will likely not see used for this indication. Erythromycin binds the 50s subunit and ultimately prevents protein synthesis which is necessary for bacteria to grow and replicate. QTc prolongation is a risk with all macrolide antibiotics (erythromycin included). By inhibiting CYP3A4, erythromycin can be responsible for numerous drug interactions.

Naloxone is a life saving drug that can help manage an opioid overdose situation. Naloxone blocks opioids receptors so opioid agonists cannot bind there. One of the biggest risks with opioid overdose includes respiratory depression. Naloxone can help reduce the risk of this if administered in a timely manner. IV naloxone will have the quickest physiological onset of action, but nasal naloxone may be the best opportunity in the community to get this drug on board quickly.

Prochlorperazine has several potential mechanisms of action. It can block dopamine and alpha receptors as well as have anticholinergic effects. Prochlorperazine is classified as an antipsychotic and antiemetic. It is very seldom used as an antipsychotic in clinical practice and more used for its antiemetic effects. Because of the anticholinergic activity of prochlorperazine, there is potential for dry mouth, dry eyes, urinary retention, constipation, and other anticholinergic effects. Prochlorperazine does have the potential to have some alpha blocking activity. Keep an eye out for hypotension in patients who may be at risk.

Buspirone is an anti-anxiety medication that has the potential of having some serotonin agonist activity. Buspirone has a very high first-pass metabolism. This means that the body breaks much of the medication down prior to it getting into the systemic circulation. Buspirone is broken down by CYP3A4, so concomitant use with inhibitors or inducers can alter its concentrations Buspirone should not be used as needed as this medication takes a while to start to show benefit.

Ondansetron (Zofran) is a medication used for nausea and vomiting. In this episode, I lay out the pharmacology, adverse effects, drug interactions and more! Ondansetron has been reported to increase the risk of serotonin syndrome. I discuss this further on the podcast. Ondansetron can exacerbate QTc prolongation. Keep an eye out for patients who may have risk factors or be on other medications that can contribute to this. I discuss this further on this podcast. Ondansetron is often used for chemotherapy induced nausea and vomiting. I discuss this and other indications on the podcast.

On this episode "Acyclovir Pharmacology" I discuss the mechanism of action, important monitoring parameters, and drug interactions with acyclovir. I discuss why acyclovir has to be dosed so many times per day. Acyclovir can inhibit CYP1A2 which can impact a few drugs. I discuss a couple of those examples on this podcast episode. GI effects are one of the more common side effects of acyclovir. Rarely, neuropathy and nephropathy can be part of the adverse effect profile of acyclovir. I discuss this further on this episode.

Benzodiazepines act by enhancing the effect of GABA, an inhibitory neurotransmitter. Benzodiazepines can cause confusion, sedation, and respiratory depression. There are many potential indications for benzodiazepines. They can be used in anxiety, status epilepticus, insomnia, and alcohol withdrawal amongst other things. There is a boxed warning for the use of opioids with benzodiazepines. The primary risk of the combination is respiratory depression.

Celecoxib is easy to remember as its mechanism of action is "COX"-2 Inhibition. This can result in result in reduced prostaglandin formation and help with pain and inflammation. Kidney function is important to monitor in our patient on celecoxib. It is especially important in patients taking ACE inhibitors, ARBs, and/or diuretics. While GI bleed may be less likely with celecoxib compared to traditional NSAIDs like indomethacin and ibuprofen, it still needs to be monitored for. Digoxin concentrations may be increased with the use of celecoxib. Celecoxib is generally dosed twice per day as the half-life of the drug is in the ballpark of 10-12 hours.

Oseltamivir is an antiviral agent that is indicated for the treatment and prophylaxis of influenza. It is important to remember that oseltamivir is cleared at least in part by the kidney and dose adjustments should be made based upon kidney function. There is a low potential that oseltamivir could contribute to psych issues like delirium. Probenecid has the potential to raise the concentrations of oseltamivir.

Dolutegravir is an integrase inhibitor that is used in the management of HIV infection/ Carbamazepine along with other enzyme inducers can substantially lower the concentrations of dolutegravir. Dolutegravir can potentially increase blood sugars, this should be closely monitored in our patients with diabetes. CNS adverse effects like insomnia and dizziness can happen with dolutegravir.

On this podcast episode, I cover medroxyprogesterone acetate injection pharmacology (DMPA or Depo-Provera) Medroxyprogesterone acetate injection is given every three months for the prevention of pregnancy. Medroxyprogesterone acetate has a boxed warning for its risk of causing low bone mineral density. Classic enzyme inducers can cause lower concentrations of medroxyprogesterone which can potentially lead to contraceptive failure. Examples of enzyme inducers that can lower concentrations of medroxyprogesterone include carbamazepine, phenytoin, rifampin, and some agents used in the management of HIV.