Role of Pharmacist

There is no guide, chart, or computer software program for clinicians to clearly identify or quickly predict which drugs interact with the CYP enzymes and create clinically significant drug interactions in patients. More research and clinical drug trials need to be conducted and reported on these enzymes and their interactions. With the knowledge of how cytochrome P450 enzymes enzymes work and of their physiologic role in DIs, pharmacists can better predict significant interactions that are likely to occur or identify potentially problematic drugs.

Understanding which P450 isozyme is responsible for the metabolism of a drug will be essential when trying to predict and understand the magnitude of drug interactions. Some drug metabolism inhibitors are highly selective for certain CYP isozymes. Some drugs that are highly selective enzyme inhibitors may also be substrates for that same enzyme system and may cause an interaction by being a competitive inhibitor. Obviously, if it is known that a new drug is metabolized by a specific CYP isozyme system, it is logical to assume that the drug will exhibit DIs with known inducers and inhibitors of specific CYP isozyme(s).

Drugs having the highest capability for producing life-threatening or serious clinical consequences include those with a narrow therapeutic index. These drugs include warfarin, carbamazepine, lithium, procainamide, phenytoin, quinidine, theophylline, tricyclic antidepressants, and valproic acid, and/or highly protein bound agents such as warfarin, phenytoin, oral hypoglycemic agents, sulfonamides, and NSAIDs that may be substrates, inhibitors and/or inducers of either CYP1A2, CYP2C9, CYP2C19, CYP2D6, and/or CYP3A4 isozymes. Management of patients in a clinical setting can be simplified if drugs that are known to produce harmful DIs with each other are avoided or limited and the patient is closely monitored by a clinical pharmacist and/or physician.

If a drug interaction is suspected, the following approach may be helpful in determining the offending agents. First, determine that the drug interaction is not related to poor patient compliance or improper dosing of a drug. Second, determine if genetic polymorphism could be involved. Third, determine what new drugs have been recently added to or discontinued from the patient’s regimen and if the adverse effect seen is commonly associated with the new drug or any drug the patient routinely receives. Fourth, determine how each drug the patient receives is metabolized or eliminated from the body. Fifth, determine if any drug the patient receives is a substrate, inhibitor or inducer of any CYP isozymes. Lastly, after reflecting on the adverse effects the patient is experiencing, determine if these are commonly associated with any of the drugs. Consulting Tables 1–4 in this article can help identify possible interacting drugs. After the problem is identified, the drug(s) should be quickly replaced with an alternative drug not likely to produce the adverse effects.

Related posts:

1. Drug interactions: cytochrome P450. Part 2 Genetic Polymorphism Genetic polymorphism plays a major role modulating drug interactions with the CYP metabolic enzyme system,and contributes to the classification of an individual as either a “poor metabolizer” or an “extensive metabolizer.” Poor metabolizers probably lack a gene for certain isozymes and...
2. Drug interactions: cytochrome P450. Part 1 This installment focuses on drug interactions as a consequence of metabolism by the cytochrome P450 (CYP) enzyme system. Due to the complexity of this enzyme system and the massive amount of literature available on enzymatic interactions, this article will focus on some of the...
3. Drug interactions: cytochrome P450. Part 7 CYP2C Isoenzyme Metabolism The CYP2C subfamily consists of 2C9, 2C10, and 2C19 isozymes as well as others. While these enzymes metabolize a smaller number of drugs, many of these drugs are involved in clinically significant DIs. Drugs that are substrates for CYP2C isoenzymes include...
4. Drug interactions: cytochrome P450. Part 3 Metabolism These CYP enzymes are present in every cell and are responsible for metabolizing or detoxifying consumed foreign (i.e., xeno) biological substances (e.g., toxins, carcinogens, mutagens and drugs). The enzymes primarily involved in drug metabolism are located in the liver. About 30 of these...
5. Drug interactions: cytochrome P450. Part 4 CYP3A4 Isoenzyme Metabolism The CYP3A enzyme family is composed of four isozymes involved with metabolism: CYP3A, CYP3A4, CYP3A5, and CYP3A7. Of these, the CYP3A4 isozyme is the most common; however, these enzymes are so closely related, they are often referred to collectively by their...