Q1: A patient asked: long-term use of a drug found not as good as the initial treatment effect, the regular dose of the efficacy is not obvious, on the contrary, there will be some side effects, why is this, what should be done? Answer: This situation occurs because the long-term use of drugs produced drug resistance, metabolized residual drug accumulation in the body to produce side effects. Due to individual differences, even the efficacy of the same drug for different patients may be different, drug efficacy and side effects depend more on the blood concentration rather than the dose and time of taking the drug. Zhao Ningmin, Department of Pharmacy, Henan Provincial People’s Hospital, when the patient appears to have reached the regular dose of drugs can not control the disease, the first should monitor the blood concentration of therapeutic drugs to clarify whether the therapeutic drugs to achieve effective blood concentration. According to the scientific data, pharmacists and physicians design individualized drug administration programs for patients, so that the therapeutic drug reaches the optimal level, to ensure that the patient’s safety and rational use of drugs. Q2: What is blood concentration monitoring of therapeutic drugs? What is the function of this monitoring? A: Therapeutic drug monitoring (TDM for short) is a new branch that has emerged in the medical field in the past 20 years. By determining the concentration of drugs in the blood (body fluids) and using the principle of pharmacokinetics and computer means, TDM can individualize the clinical drug administration program, improve the efficacy of the drugs, avoid or reduce the toxic side effects, and at the same time, it provides valuable laboratory basis for the diagnosis and treatment of drug overdose poisoning. In order to make the therapeutic drugs reach the optimal level, the modern therapeutic drugs follow the principle of “individualization”, that is, the physician selects the optimal drug administration and treatment plan suitable for individuals according to different patients. The core of therapeutic drug blood concentration monitoring is to realize the clinical individualization of drug administration, which enables physicians to understand more intuitively the reasons for the poor efficacy of the patient’s specific dosage, and the reasons for the toxic side effects of the drug even when the standard therapeutic dosage of the drug is given, as well as judging the patient’s adherence to medication, and discovering whether the patient stops taking the drug, reduces the dosage, or overdoses in the course of the treatment in a timely manner, and then provide scientific bases for optimizing the patient’s individualization of the therapeutic program. Scientific basis for optimizing patients’ individualized treatment plan. Q3: Is it necessary to monitor blood drug concentration? A: The efficacy and adverse effects of drugs mainly depend on the blood concentration rather than the dosage of drugs. Here is an example: Phenytoin sodium blood concentration (ug/ml) and efficacy and toxicity of the relationship between blood concentration 10 ~ 2020 ~ 3030 ~ 40 > 40 clinical effects of effective nystagmus movement disorders mental anomalies Aspirin blood concentration (ug/ml) and efficacy and toxicity of the relationship between blood concentration 50 ~ 100 > 250350 ~ 400550 ~ 850800 ~ 1100 1250 ~ 1500 1600 11001250~15001600~1800Clinical effectAnalgesicAnti-rheumaticAnti-inflammatoryMild poisoningModerate poisoningSevere poisoningDeathIt can be seen that the blood concentration determines the therapeutic efficacy of the drug and the adverse reactions, the appropriate blood concentration will optimize the therapeutic effect and minimize the adverse reactions. Q4: What kind of patients need blood concentration monitoring? A: 1, patients taking drugs with low therapeutic index, narrow safety range and strong toxic effects, such as: digoxin; 2, patients taking drugs with non-linear metabolism and dose-dependent elimination rate, such as: phenytoin; 3, patients who have developed resistance to long-term use of the drug and those whose blood concentration may change abnormally, such as: valproic acid; 4, patients with significant changes caused by cardiac, hepatic, renal, and intestinal disorders, such as: patients with hepatic and renal impairment, organ transplant recipients, etc.; 5, patients who need to monitor blood concentration of the drug, such as: patients who are suffering from liver and renal impairment. Organ transplant recipients, etc.; 5, combined multiple drug therapy, due to drug-drug interactions caused by the body of the drug absorption, distribution, metabolism and excretion process changes, such as: combined hepatic enzyme inducer/inhibitor (Phenobarbital/Chloramphenicol); 6, the emergence of serious toxicity in the conventional dose, the diagnosis and treatment of overdose of drug poisoning, as well as for the drug-induced medical malpractice to provide the basis for. Q5: How should patients taking the above drugs have their therapeutic drug blood concentration monitored? What should be noted before monitoring? A: When designing a drug administration program for patients, if such drugs are involved, the physician will inform the patient that regular blood concentration monitoring is required to ensure that the patient’s medication is safe and effective; the patient can also make the monitoring request to the physician on his/her own, and ask the physician to issue a monitoring application form. Blood concentration monitoring of therapeutic drugs is carried out in the clinical pharmacy of hospitals, with professional pharmacists serving the patients. Sampling for blood concentration monitoring is generally done in the blood, and the time is early in the morning before taking the drug on an empty stomach, and there are also different requirements for individual drugs. The professional pharmacists in the clinical pharmacy will clearly inform the patients of these points of attention. Q6: Is it possible for Henan Provincial People’s Hospital to carry out this monitoring now? What are the specific drug monitoring programs? A: Clinical Pharmacy Department of Henan Provincial People’s Hospital has been carrying out blood concentration monitoring of therapeutic drugs for more than 20 years, with professional and technical talents and advanced monitoring equipment, adopting international newer monitoring methods, and currently carrying out blood concentration monitoring of more than 10 drugs, such as Vancomycin, Gentamycin, Cyclosporine, Tacrolimus, Valproic Acid, Carbamazepine, Phenobarbital, Digoxin, Theophylline and Phenytoin Sodium. Monitoring. Detailed address in Henan Provincial People’s Hospital outpatient clinic East District, negative one floor of the herbal pharmacy west of the gate inward 20 meters Contact Tel: 0371-65897521. this monitoring business to greatly enhance the hospital patients with medication to optimize the efficacy of drugs to reduce the adverse effects of drugs, but also for the patients to save the cost of treatment. For patients who need to undergo TDM in foreign countries, the department specially provides the intimate service of “free SMS notification of results”, so that patients can go home on the same day with peace of mind, and the results will arrive later! Q7: Is it still necessary to test blood drug concentration if several drugs are taken at the same time? A: In clinical practice, patients are often accompanied by other underlying diseases or multiple complications, and their treatment programs involve the combined application of multiple drugs, so attention should be paid to the impact of drug interactions. The following is an example of cyclosporine A to talk about the effects of drug interactions. Cyclosporin A is mainly used to prevent rejection of allografts, including kidney, liver, heart, heart-lung, and combined heart-pulmonary and pancreas-pulmonary transplants, and its most common serious toxic side effect is hepatic and renal impairment, and it is correlated with blood levels. Antiepileptic drugs such as barbiturates, carbamazepine, phenytoin sodium, and paromidone can accelerate the metabolism of cyclosporin A when combined with cyclosporin A and cause its blood concentration to decrease. Biphenyldiphenyl ester, neo-penicillin III, sulfadimethoxine IV, rifampicin, octreotide, probucol, sulfamethoxazole IV, arylimidazole, etc. can also reduce the blood concentration of cyclosporine when used in combination with cyclosporine. Gastric stimulants, such as cisapride, metoclopramide, domperidone and cyclosporine A can accelerate the gastric emptying of cyclosporine A, shorten the retention of cyclosporine A in the stomach, so that cyclosporine A quickly for the hepatic and intestinal circulation, cyclosporine A blood concentration increased. Cimetidine, ranitidine can inhibit gastric acid secretion, can inhibit cyclosporin A metabolism so that cyclosporin A blood concentration increased. Omeprazole, lansoprazole, chloroquine, macrolide antibiotics (erythromycin, cosamycin, punamycin), ketoconazole, fluconazole and itraconazole, deltamethasone, nicardipine, verapamil, oral contraceptives, danazol, methylprednisolone (high dose), allopurinol, amiodarone, bile acids and their derivatives, prednisolone, propafenone, etc., and cyclosporine, when combined with cyclosporine, can also increase cyclosporine blood concentrations . From the above, it can be seen that the combination of cyclosporin A with other drugs is blood concentration is variable, so there is more need to monitor the blood concentration of patients with and with other drugs. Q8: What is the relationship between in vivo processes of drugs and drugs in the blood? A: The relationship between the process in the body of the drug and the drug in the blood is shown in the following figure: Q9: What is the effect achieved by the blood drug concentration test? A: Over the years, the role of TDM in guiding and evaluating drug therapy has been fully recognized both at home and abroad: for example, the control rate of epileptic seizures has been increased from 47% to 74% through TDM and individual drug administration programs. Before TDM, when digoxin was used in elderly patients with heart failure, the toxicity rate reached 44%, but after TDM and adjustment of dosing regimen, the toxicity rate was controlled to less than 5%. Q10: Can you give a few clinical examples to illustrate the significance of blood drug concentration testing? A: Example 1: 47 years old, 62kg, male. Diagnosed with bronchopulmonary cancer, primary, central type, left lung, low differentiation, and has undergone 2 chemotherapy treatments. After admission, the patient had persistent high fever with a temperature of 39.5°C. Blood culture results were Staphylococcus aureus, and vancomycin, 0.5 g, q8h, was given intravenously. Vancomycin blood concentration was monitored after administration, and the blood concentration result showed a trough concentration of 4.1 μg/mL (effective concentration range 5~15 μg/mL) and a peak concentration of 16.2 μg/mL (effective concentration range 25~40 μg/mL). The pharmacist recommended increasing the dosage based on the blood concentration results, and changed the dosage to 0.5 g, q6h, IV for 60 min. blood concentration was monitored again, and the results showed a trough concentration of 10.7 μg/mL and a peak concentration of 31.2 μg/mL. the patient’s body temperature returned to normal after 4 days, and the infection was under control. Example 2: 66 years old, 61kg, male. Diagnosis of bronchial asthma, aminophylline 100 mg, q8h, the patient measured the trough concentration of 20.4 μg/mL. clinical manifestations of nausea, vomiting, measured the peak concentration of 30.1 μg/mL, far beyond the safe range, check the medical record, the patient due to gout attack at the same time oral allopurinol 0.1 g, tid, so adjusted the medication regimen of aminophylline to 50 mg, q8h. three days later, peak value of 16.2 g, q8h, the patient’s body temperature returned to normal, and the infection was controlled. Three days later, the peak value was 16.2 μg/mL and the trough value was 15.1 μg/mL, and the symptoms were well controlled. In this case, allopurinol inhibited the activity of xanthine oxidase (the enzyme that metabolizes xanthines such as aminophylline), resulting in a decrease in theophylline clearance and an increase in theophylline blood concentration. Example 3: 15 years old, 37kg, male. 4 months ago, the first epileptic grand mal seizure, taking phenytoin sodium 0.3g/d. In the past 1 week, the patient manifested the symptoms of mental instability, lazy speech, not answering questions, poor nutrition, dizziness, etc. The basic examination indexes are basically normal. As the basic examination indexes were basically normal, it was difficult to find the cause of the disease and confirm the diagnosis and medication. The patient was admitted to the hospital, and the blood concentration of phenytoin sodium was found to be 54.2 μg/mL (the effective concentration range was 10~20 μg/mL), and the preliminary diagnosis was: phenytoin sodium poisoning. After stopping the drug for 5 days, the blood concentration decreased to 38.1 μg/mL, at which time the patient’s spirit was obviously better than before, and he was able to have a conversation. After discharge from the hospital, the patient switched to phenytoin sodium dose of 0.2g/d. After 1 month, the patient was rechecked, the patient’s spirit was good, there was no seizure, and the blood concentration was checked to be 14.5μg/mL.