What Is a Drug Interaction?

Drug interaction (DI) refers to the compound effect produced by patients taking two or more drugs at the same time or within a certain period of time, which can strengthen the efficacy or reduce the side effects, and can also weaken the efficacy. Or there should be unwanted side effects. Enhanced effects include increased efficacy and increased toxicity, and reduced effects include reduced efficacy and reduced toxicity. Therefore, in the clinical use of combined drugs, care should be taken to take advantage of the characteristics of various drugs, give full play to the pharmacological effects of each drug in the combined drug, in order to achieve the best curative effect and the least adverse drug reactions, thereby improving drug safety. According to the principle of occurrence, it can be divided into pharmacokinetics and / or pharmacodynamic interactions. The results of pharmacodynamic interactions include four types: irrelevant, synergistic, additive, and antagonistic. Pharmacokinetic interactions are mainly due to the absorption and distribution of drugs. , Metabolism and excretion. Consequences of drug interactions include desirable, inconsequential, and adverse. Of these, the irrelevant ones account for the vast majority, and our concern is harmful DI.

Drug interaction (DI) refers to the compound effect produced by patients taking two or more drugs at the same time or within a certain period of time, which can strengthen the efficacy or reduce the side effects, and can also weaken the efficacy. Or there should be unwanted side effects. Enhanced effects include increased efficacy and increased toxicity, and reduced effects include reduced efficacy and reduced toxicity. Therefore, in the clinical use of combined drugs, care should be taken to take advantage of the characteristics of various drugs, give full play to the pharmacological effects of each drug in the combined drug, in order to achieve the best curative effect and the least adverse drug reactions, thereby improving drug safety. According to the principle of occurrence, it can be divided into pharmacokinetics and / or pharmacodynamic interactions. The results of pharmacodynamic interactions include four types: irrelevant, synergistic, additive, and antagonistic. , Metabolism and excretion. Consequences of drug interactions include desirable, inconsequential, and adverse. Of these, the irrelevant ones account for the vast majority, and our concern is harmful DI.

Chinese name

medicine interactions

Foreign name

drug interaction, DI

Clinical manifestation

Drug interactions are common

Function

Irrelevant, synergistic, additive and antagonistic

Drug Interaction Classification

1.1. Pharmacokinetic interactions

It can occur in the four stages of absorption, distribution, metabolism, and excretion, with the highest incidence of drug-drug interactions (DDIs) of metabolic drugs, accounting for about 40% of pharmacokinetic interactions. Metabolic drug interaction refers to the interference of two or more drugs in the metabolic process when they are used simultaneously or sequentially, resulting in enhanced efficacy or even adverse reactions, or weakened or even failed treatment. Enzymatic drugs generally accelerate the metabolism of another drug and shorten the half-life. For example, phenobarbital is an inducer of liver drugs, which increases the metabolism of other drugs and weakens its effect. In contrast, a drug with an enzyme inhibitory action slows down the metabolism of another drug, thereby extending the half-life of that drug. For example, digoxin can be metabolized into dihydrodigoxin through the normal flora in the intestine. If erythromycin is used in combination, the normal flora can be inhibited and the blood concentration of digoxin can be increased. Clopidogrel is a prodrug, which becomes an active metabolite through hepatic cytochrome P450 metabolism, which can significantly and irreversibly block platelet ADP P2Y12. Some drugs that inhibit CYP2C19 include some proton pump inhibitors (PPI), which reduce the production of clopidogrel active metabolites, thereby increasing adverse events and reducing the clinical effectiveness of the drug. In patients receiving clopidogrel, the combination of PPI and clopidogrel should be avoided as much as possible. Research by Ho et al. And Juurlink et al. Showed that the use of H2 receptor blockers does not increase the risk of recurrent cardiovascular events, so patients who need acid suppression therapy may consider using H2 receptor blockers such as Raney Titin et al. However, care must be taken in patients who must use PPI to minimize the use time. In addition, taking lipophilic statins such as atorvastatin and simvastatin at the same time can compete with clopidogrel for the CYP3A4 receptor to weaken the platelet inhibitory effect of clopidogrel. For this reason, it is clinically preferred to use clopidogrel concurrently with statins that do not affect CYP3A4 metabolism.

1.2. Pharmacodynamic Interactions

It means that when a drug is used in combination, one drug changes the pharmacological effect of another drug, but has no obvious effect on the blood drug concentration, but mainly various factors that affect the action of the drug and the receptor. Hydrochlorothiazide is a commonly used drug for elderly patients with hypertension and congestive heart failure. Long-term use can lead to decreased blood potassium, increased myocardial stress when hypokalemia occurs, increased myocardial sensitivity to cardiac glycosides, and prone to increase heart rate and arrhythmia . Therefore, cardiac glycosides should not be combined with potassium-releasing diuretics. The combination of roxithromycin, levofloxacin, clindamycin, etc. with theophylline drugs can reduce theophylline clearance and easily cause theophylline to accumulate poisoning in the body, and the blood concentration of theophylline should be monitored when combined.

Drug interactions

Most drugs are metabolized by the cytochrome P450 enzyme system in the intestine and 1 or the liver. The inhibition or induction of the P450 enzyme system is the main cause of metabolic DI. The clinical significance of enzyme inhibition is far greater than that of enzyme induction. Effect, accounting for about 70% of metabolic interactions, and DI induced by enzymes accounts for about 23%. Drug transporters are also an important factor in the production of DI.

2.1 Cytochrome P450

Drug metabolism in the body includes two-phase reactions: Phase I reactions are redox reactions, mainly involving the CYP enzyme family; Phase II reactions are binding reactions, involving glutathione, glucuronic acid, sulfate, and glycine. Generally, a drug is metabolized by multiple CYP enzymes, and only a few drugs are metabolized by a single drug enzyme. It is estimated that about 60% of prescription drugs are metabolized by CYP enzymes. The cytochrome P450 family has been identified to be 42 subfamilies of 18 families. The CYP enzymes involved in metabolism are mainly CYP3A4, CYP1A2, CYP2C9, CYP2C19, and CYP2D6, accounting for 95% of CYP enzymes. About 55% of the drugs are metabolized by CYP3A4, 20% are metabolized by CYP2D6, and 15% are metabolized by CYP2C9 and CYP2C19.

2.2 P protein

Effect on absorption The effect of P protein on drug absorption is due to its mediated drug interactions. P protein has a wide range of substrates, and its drug efflux is a major cause of differences in oral drug absorption and variation in bioavailability. The absorption of P protein substrates such as digoxin, cyclosporine, tacrolimus, etc. is easily affected by P protein inhibitors (such as verapamil, quinidine) or inducers (such as rifampin). Effect, resulting in an increase or decrease in bioavailability. For some drugs with a narrow therapeutic index, changes in bioavailability can cause corresponding changes in blood drug concentration, resulting in poisoning or ineffective treatment. P protein inhibitors mainly include verapamil, valsartan, quinidine, etc., but have low affinity and will produce great toxicity when the required inhibitory effect is achieved. Some ingredients in fruits and vegetables, herbs, and other foods, such as flavonols and coumarins, can regulate the activity of P protein, which in turn affects the treatment of drugs in vivo. Flavonoids mainly inhibit the P protein ATPase activity and increase substrate absorption; furanocoumarin in grapefruit juice simultaneously inhibits CYP3A4 enzyme and P protein, which significantly increases drug absorption.

Drug Interaction Prevention of Drug Interactions

3.1 Individualized administration

For children, the elderly, and the special population with impaired liver and kidney function, special attention should be paid to drug interactions in clinical use. Because the metabolism and excretion of the drug in the body are reduced, it will cause an increase in blood concentration and are prone to adverse reactions. Try to avoid the combination of drugs that make the treatment more difficult to control or drugs that are likely to cause serious adverse interactions, and it is best to choose a safer alternative.

3.2 Attention to drug instructions

When one drug is ineffective, it is necessary to change the drug or select other drugs for reasonable compatibility. But not all compatibility is reasonable, some compatibility will weaken the therapeutic effect of the drug, leading to treatment failure; some compatibility will increase adverse reactions or toxicity, causing serious adverse reactions; and some compatibility will make the therapeutic effect excessively enhanced beyond the body Tolerance can also cause adverse reactions. These are incompatible taboos. The instructions for drug selection and interactions are described in detail in the drug instructions. Physicians and pharmacists should read them carefully before use to ensure that they have the knowledge to avoid possible adverse interactions.

3.3 Pay attention to medication for high-risk groups prone to drug interactions

Domestic studies have reported that the incidence of bleeding events among patients aged 65 years and above is significantly higher than that of patients under 65 years of age. Therefore, for the elderly suffering from various chronic diseases, patients who need long-term application of drug maintenance treatment, patients with multiple organ dysfunction, and patients who have been treated by multiple hospitals or doctors should ask about their medication history in detail and take comprehensive consideration The condition, and strive to use less and refined medicine.

3.4 Keep in mind high-risk drugs that are prone to drug interactions

Such as anti-epileptic drugs (phenytoin sodium), cardiovascular drugs (quinidine, propranolol, digoxin), oral anticoagulants (warfarin, dicoumarin), oral hypoglycemic agents (glitazone) This urea), antibiotics and antifungals (erythromycin, rifampicin, ketoconazole) and digestive tract drugs (cimetidine, cisapride). Warfarin is a commonly used anticoagulant in clinical practice. It has high anticoagulant effect and is cheap, but it has the disadvantage of interacting with many drugs. For example, combined with cephalosporin antibiotics (cefoperazone, cefotaxime, etc.), macrolide antibiotics, amiodarone, etc. can enhance the anticoagulant effect of warfarin, and are related to vitamin K, oral contraceptives and estrogen. Enzyme protein can promote the production of coagulation factors , , , X, antagonize the effect of warfarin, and weaken the anticoagulant effect.

3.5 Should not change drugs frequently

In the process of treating or managing diseases, if a drug change is necessary and there is a drug interaction, since the time, process and degree of drug interaction vary depending on the drug and the patient, the therapeutic effect and Adverse reactions.

3.6 Timely monitoring of therapeutic drugs

Such as patients with important organ failure, when the disease itself affects the metabolism and excretion of the drug, monitoring of the therapeutic drug should be carried out in order to timely adjust the dosage and drug treatment plan to avoid serious adverse reactions and iatrogenic diseases.

3.7 The interaction between Chinese and Western medicine cannot be ignored

Licorice is a commonly used Chinese medicine. Most Chinese medicines have licorice in their prescriptions. However, for patients taking digoxin, taking licorice may increase the toxicity of digoxin. In addition, ginseng can increase the bleeding effect of heparin, aspirin, and non-steroidal anti-inflammatory drugs such as ibuprofen, naproxen, and ibuprofen. Zhang Yu reported a case of atrial fibrillation in patients with coronary heart disease, and safflower decoction overdose caused urinary bleeding during taking warfarin. Ginkgo biloba and simvastatin are cardiovascular drugs commonly used in combination. The test showed that when 20 mg / kg ginkgo biloba preparation was combined with simvastatin, no significant interaction occurred. When the dose was 200 mg / kg, it could induce the activity of CYP 3A and promote the metabolism of simvastatin in vitro. Take them separately when combined.

3.8 Taking into account the effects of food on drugs

Drug interaction mainly refers to the interaction between drugs and drugs, and also includes the interaction between drugs and tobacco, alcohol and food. There are many examples of food affecting the efficacy of drugs. For example, drinking alcohol while taking phenobarbitals may increase drug absorption and enhance the inhibitory effect of the nervous system. Grape juice should not be used with certain antihypertensive drugs and cyclosporine to prevent organ transplant rejection, because grape juice can cause the concentration of these drugs to increase in the body, thereby increasing the adverse reactions of these drugs. Grape juice also interacts with the anti-anxiety drug buspirone, the anti-malarial drug cyclohexanediol and the hypnotic drug Lelexin, causing blood pressure to rise. Caffeine in chocolate can also interact with irritating drugs such as Ritalin, increase the effects of drugs or reduce the effects of sedative hypnotic drugs such as Zolpidem.

3.9 Utilizing rational drug monitoring system

Use the rational drug monitoring system to improve the level of safe drug use in hospitals. This system is a standardized and automated management system. It is based on the basic characteristics and requirements of the professional work of clinical rational drug use. It uses computer database organization principles and technologies to carry out scientific, authoritative and updated medical, pharmacological and related subject knowledge. After standardized processing, it is applied to the review of medical orders and medical information query to prevent adverse drug events and achieve rational drug use. This system can provide real-time warning information such as in vitro compatibility contraindications between drugs, in vivo interactions, and adverse drug reactions during clinical drug treatment. It is completely incorrectly represented by a black symbol and unreasonably represented by a red symbol, which is helpful. Formulate and implement reasonable drug treatment plans for clinical medical staff.

Attaching importance to drug interactions is extremely important to improve the quality of medical treatment, safe and effective combination use. A thorough understanding of the absorption, distribution, metabolism and excretion of drugs in the body, and the interactions of various drugs in the body, can be beneficial to avoid harm, reduce adverse drug reactions, and ensure drug safety. ^[1]