Safe Sedation Series: Navigating Drug-To-Drug Interactions

Dr. Leslie Fang, MD, PhD, enhances your knowledge of the interaction between sedation drugs and patient medications.

By Genni Burkhart, DOCS Incisor Editor

This topic is included in DOCS Education's Top 25 Safety Statements, compiled by our esteemed faculty. The first ten, by Dr. Leslie Fang, can be found here.

The CDC reports that over 48% of Americans take at least one prescription drug. Understanding how these drugs interact with sedation medications is critical to patient safety.

In this course, DOCS Education Medical Director Leslie Fang, MD, PhD, discusses drug metabolism mechanisms in the liver and intestines. Dr. Fang breaks down the critical nature of the P450 (CYP) enzyme system responsible for the metabolism of many drugs to help you recognize how medications, including those used for sedation, work together and against each other.

Primary objectives of this course include:

  • Understanding the role of the P450 (CYP) in drug metabolism.
  • Recognizing the critical actions of the metabolism of drugs.
  • Learning how certain supplements and juices can affect the CYP3A4 enzymes.
  • Identifying which drug and delivery system of a drug with C interactions isn’t the best choice.
  • Determining which types of interactions are concerning and which are not.

Drug Metabolism

While the liver is primarily responsible for drug metabolism, it’s now understood that the intestines also play an essential role.

Regarding sedation drugs, the enzyme system responsible for the metabolism of most of those drugs used for conscious sedation belongs to the Cytochrome P450 system, particularly CYP3A4. P450 is going to be (90%) found in the liver, but there appears to be CYP3A4 in the mucosa of the small intestine.

Drug-Drug Interactions

Whenever we talk about enzymatic metabolism by CPY3A4, triazolam will fit into the active site like a key into a lock and undergo a simple metabolic breakdown. Therefore, anything that interferes with that reaction is going to constitute drug-drug interaction. Two interactions to be aware of are:

  • C interaction: Minor may choose to sedate over it.
  • D Interaction: Major-requires modification.

For example, Dilantin (phenytoin) and barbiturates are D interactions. These drugs are potent inducers of CYP3A4 and are primarily used for seizure disorders. Sedation dentists must be aware that these drugs can have multiple drug-drug interactions. Therefore, clinical use of these particular medications is decreasing due to concerns about drug-drug interactions.

Because of the D interaction of these drugs, patients on these medications will require modification to their sedation protocol. Furthermore, it's critical that patients on these drugs do not stop them, or they can seize. When sedating these patients, use medications not mediated through CYP3A4, such as Lorazepam.

This is further evidence of why patients MUST report ALL prescription and non-prescription, including all nutraceuticals and supplements taken, including the likes of St. John’s wart (C interaction), which can interfere with sedation.


Agents known to inhibit CYP3A4 include (D interactions) such as:

  • Grapefruit juice, also called a “suicide inhibitor,” inhibits the CYP3A4 in the intestines but not the hepatic enzymes. Therefore, be sure to ask patients about consuming grapefruit juice.
  • Diltiazem (Cardizem)
  • Verapamil (Calan, Isoptin SR)
  • Clarithromycin (Biaxin)
  • Fluconazole (Diflucan)
  • Itraconazole (Sporanox)
  • Nefazodone (Serzone)

Possible Alternatives

While C interactions don’t cause the same inhibitions as D interactions, there are better ways around these drugs. Some of these medications include:

  • Omeprazole (Prilosec)
  • Esomeprazole (Nexium)
  • Fluoxetine (Prozac)

For all the drugs with C interactions, you can sedate over them or find a way around the interactions. When that’s not possible, consider the Lorazepam protocol.

Metabolism of Drugs

Drug metabolism is a complicated process involving P450 (CYP) and significant individual variability.

To ensure the most effective and safest sedation pharmacology, you should include the following questions in your health history screenings of patients:

  • Prescription drugs
  • Over-the-counter drugs
  • Nutraceuticals
  • Dietary history
  • Smoking history
  • Sugar consumption
  • Specific questions about grapefruit juice and St. John’s Wort

In Conclusion

Drug metabolism is a complex process that involves various enzymes and pathways in the human body.

One of the critical enzymes involved in drug metabolism is P450 (CYP), which plays a crucial role in breaking down drugs and toxins in the liver and other organs. However, drug metabolism can vary significantly from person to person, depending on factors such as genetic makeup, age, gender, diet, and other environmental factors.

This individual variability can affect not only the efficacy of sedation drugs but also their safety and potential side effects. Therefore, it is crucial for dental providers to carefully consider each patient's unique metabolic profile when considering conscious sedation and monitor their response to treatment.


For a more in-depth review, join DOCS Education Medical Director Leslie Fang, MD, PhD, here. This online course is worth 1 CE. Watch the video and complete the quiz to earn one CE credit. Scientific support and additional resources are available here.

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Author: With over 14 years as a published journalist, editor, and writer, Genni Burkhart's career has spanned politics, healthcare, law, business finance, technology, and news. She resides in Northern Colorado, where she works as the editor-in-chief of the Incisor at DOCS Education.

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