On this episode of the Real Life Pharmacology podcast, I take a dive into the most common mechanisms of drug interactions. Below I list some of the common drug interactions seen in practice and how they work!
Opposing Effects
Many drugs will work on various receptors throughout the body. To use as an educational point, there is no better example to point to than the beta receptor. Beta-blockers are frequently used in clinical practice for their ability to lower blood pressure and slow the heart rate. Both of these beneficial actions are primarily achieved by blocking the effects of beta-1 receptors.
Some beta-blockers have action on alternative beta receptors. Propranolol is one such beta-blocker that is classified as a non-selective beta-blockers. This means that in addition to the positive effects on beta-1 receptors, it can also have blocking effects on beta-2 receptors. The blockade of the beta-2 receptor by propranolol can also be life-changing. It can directly oppose beta-2 agonists like albuterol from having their beneficial effects of opening up the airway.
Enzyme Inhibition
Medication metabolism is arguably the largest and most clinically significant source for drug interactions. Medications that are primarily metabolized by enzymes in the liver can be greatly affected if we affect how those enzymes work. CYP3A4 is one of the most well studied and well-known enzymes that can impact hundreds to maybe even thousands of drugs.
Apixaban is an oral anticoagulant that is broken down at least in part by CYP3A4. By using a CYP3A4 inhibitor like erythromycin, there is the potential to raise concentrations of apixaban. This could lead to a higher risk of bleeding.
Enzyme Induction
Carbamazepine is a drug that you must know. This drug is a potent enzyme inducer. This differs significantly from an enzyme inhibitor and will have the exact opposite clinical effect. Drugs that are inactivated by liver enzymes will be inactivated more quickly in a patient taking an enzyme inducer. Going back to our prior apixaban example above, carbamazepine can induce CYP3A4 and facilitate a more efficient and swifter breakdown of the drug. Bleeding will be less likely. The risk for treatment failure, usually in the form of a blot clot, will be more likely. Here’s more information from the past on carbamazepine.
Alteration in Absorption
Binding interactions can be consequential and are one of the most common types of drug interactions. Many medications have the potential to bind one another in the gut. This can lead to lower concentrations of a specific medication. Calcium and iron are two of the most common examples of medications that can bind other drugs.
Alteration in Protein Binding
By remembering that unbound drug is an active drug, you should appreciate the risk for protein binding alterations. A significant number of medications can bind proteins in the bloodstream. As this occurs, that drug is not freely available to create physiologic effects. When another medication is added that can also bind these proteins, this can displace other medications and increase the quantity of free drug in the bloodstream. This essentially allows for enhanced physiologic effects.
Warfarin is a medication that is highly protein-bound. When another drug is added that can kick warfarin off of those protein binding sites, it can free up warfarin which will increase the likelihood of elevating the patient’s INR and increase their bleed risk.
Alteration in Renal Elimination
Some drugs can alter the way other medications are eliminated through the kidney. Chlorthalidone, like all thiazide diuretics, has the potential to block the excretion of lithium from the kidney. This can lead to lithium toxicity.
This type of interaction, while significant, is much less common than drug interactions involve the liver and CYP enzyme pathways.
Effects on Transporters
One of the last types of drug interactions is the effect on transporters. P-glycoprotein is a protein found in many cell membranes in the body and essentially acts as a pump. P-glycoprotein can pump drugs across cell membranes. This can alter drug concentrations and ultimately efficacy and safety.
On this podcast episode, I discuss insulin aspart pharmacology, adverse effects, drug interactions, and much more.
Insulin apart is a rapid acting insulin product meant to bring down blood sugars quickly (most often after meals).
It is important to remember a couple of medications that may counteract the effects of insulin and apart and raise blood sugar. I talk about corticosteroids and thiazide diuretics in the drug interaction section.
Fiasp is a slightly modified insulin aspart molecule that allows for quicker absorption. This quicker absorption will allow for blood sugars to come down sooner than the Novolog formulation.
On this podcast episode, I discuss fenofibrate pharmacology, adverse effects, kinetics, drug interactions, and much more!
Fenofibrate is typically only used for hypertriglyceridemia. The primary risk of hypertriglyceridemia is pancreatitis so we treat these levels because of this risk.
LFTs elevation has been associated with fenofibrate use as well as myopathy. In the presence of myopathy, checking CPK may be considered.
Fenofibrate is a weak CYP2C9 inhibitor. Warfarin and phenytoin are two important medications that may be affected by the use of fenofibrate.
On this podcast episode, I discuss levofloxacin pharmacology, adverse effects, boxed warnings, interactions, and much more.
Levofloxacin is well known to cause QTc prolongation and many drugs can increase this risk such as antiarrhythmics, citalopram, antipsychotics, and many more.
Binding interactions are important when discussing levofloxacin pharmacology. Calcium, iron, magnesium, and many other cations can block the absorption of this medication.
I discuss tendon rupture in relation to levofloxacin use and what factors may increase the risk of this rare adverse effect.
On this podcast episode, I discuss darifenacin pharmacology, adverse effects, drug interactions and much more.
CYP3A4 and CYP2D6 are important enzymes in relation to darifenacin. I breakdown the importance of these enzymes and how they can impact drug therapy.
Darifenacin has anticholinergic activity but affects the central nervous system less than other agents in its class such as oxybutynin and tolterodine.
Darifenacin’s pharmacology is selective for the Muscarinic-3 (M3) receptor in bladder tissue which helps reduce the risk for CNS adverse effects.
In this podcast episode, I discuss naltrexone pharmacology, adverse effects, drug interactions, and much more.
Naltrexone is an opioid antagonist and can blunt the effects of opioid agonists. Because of this, the medication can be used to manage opioid use disorder.
Hepatotoxicity is a concern of naltrexone and because of this, it is recommended to monitor LFTs.
There is an injectable, long-acting formulation of naltrexone that can be used for opioid and alcohol use disorder treatment.
On this podcast episode, I discuss alfuzosin pharmacology, adverse effects, drug interactions, and much more!
Alfuzosin is an alpha blocker used to help relieve the symptoms of BPH.
Low blood pressure is a possible adverse effect of alfuzosin and is more likely when combined with PDE-5 inhibitors like sildenafil.
CYP3A4 is an important enzyme in the metabolism of alfuzosin. Inhibitors of CYP3A4 can raise concentrations and increase the chance of alfuzosin toxicity.
