One patient I saw in the clinic used up to 19 types of medications. This includes 3 antihypertensive drugs, 3 hypoglycemic drugs, 2 lipid-lowering drugs, 1 anti-platelet drug, 3 prostate hypertrophy drugs, 1 fibrin-lowering drug, 2 brain metabolism improvement drugs, 1 cerebrovascular expansion drug, 1 coronary expansion drug, and 2 blood-stasis activating drugs. I can’t tell you what happens when you metabolize so many drugs in your body. I see the treatment of prostate drugs have a hypotensive effect; anti-platelet, blood circulation drugs are overlapping effects; lipid-lowering drugs are not necessary to use 2 kinds; improve brain metabolism, memory enhancement drugs are not the main conflict, not necessary drugs; hypoglycemic drugs are not necessary to use 3 kinds; fibrin-lowering drugs are often the doctor told the patient “need to take long-term “This will inevitably lead to “overuse of drugs”. After streamlining, the number of drugs can be reduced to 6, which is more than enough. Patients have reduced the burden on their liver and kidneys, as well as the financial burden and side effects of the drugs.
The World Health Organization warns that irrational drug use has become the number four killer in the world today, and surveys show that one-third of deaths worldwide are caused not by the disease itself but by irrational drug use. Costs associated with adverse drug events are $136 billion/year, higher than those for cardiovascular disease and diabetes, causing damage and death in 1/5 of hospitalized patients. During hospitalization, mortality rates, etc., are significantly higher than those of controls.
We need to understand some of the issues related to taking medication.
I. Drug interactions and adverse reactions
The U.S. Drug Research Institute reports that approximately 3.7% of patients experience clinically relevant adverse reactions, 20% of which are drug-related. In the United States, there are approximately 140,000 patient deaths related to adverse drug reactions each year, and drug interactions account for 1/3 of all adverse drug events. hospital admissions due to adverse drug interactions. If 4 or more drugs are used, the number of adverse reactions will increase exponentially.
Second, the harm of drug interactions
Clinically relevant drug interactions are events in which the efficacy and safety of a drug is altered by other substances, including concomitant drugs and other possible substances, such as food, alcohol, herbs, and cigarettes.
Because drug interactions can cause very serious, even fatal, adverse drug reactions, the Japanese Health Control Agency recommends that drug interactions must be considered during the development of new drugs, new drug approval, and post-marketing surveillance.
Pay attention to the following aspects.
1. the effect on drug metabolizing enzymes.
2. the induction of enzymes.
3. drug absorption.
4. renal clearance.
5. hepatic transport.
6, protein binding (substitution) In order to avoid toxic reactions caused by drug interactions, it is necessary to consider the possible mechanisms of drug interactions, to carefully obtain the relationship between the therapeutic dose of drugs and severe lethal toxicity, to consider the physical condition and basal level of the patient when combining drugs, and to collect information on drug interactions in clinical studies.
Weakening of the therapeutic effect of a drug can lead to treatment failure. Transitional enhancement of therapeutic effects, such as exceeding the body’s ability to tolerate, causing adverse reactions or toxic reactions. Enhanced side effects or toxicity, which can cause adverse events. Masking the symptoms of adverse reactions, resulting in more serious consequences. Some drugs often have adverse interactions with antimicrobials when used together. Aspirin and erythromycin combined with increased toxicity leads to tinnitus and hearing loss; Warfarin and penicillin, quinolone, erythromycin, chloramphenicol combined to adjust the dose.
Three, drug metabolic process
Phase I: oxidation, reduction and hydrolysis.
Phase II: conjugate binding.
Multi-phase distribution: differential expression of different kinds of enzyme systems in the population; in the Chinese population, fast metabolizers account for 40% and slow metabolizers 6%; enzyme activity can be changed by other things, causing drug interactions.
IV. Susceptible groups of drug interactions.
Patients who use drugs in combination with other physical diseases, those who use psychotropic drugs in combination, patients who need to take drugs for a long time for chronic physical diseases, patients with impaired liver and kidney functions that affect the metabolism and elimination of drugs, elderly people (the metabolism ability of drugs in the elderly is changed, and due to poor health condition, there are often cases of taking drugs in combination with multiple diseases), and HIV carriers.
V. Avoidance of adverse drug interactions and improvement of long-term prognosis.
The important role of disease relapse and reignition when poor efficacy or adverse drug reactions lead to poor patient compliance; prevent adverse events and improve patient compliance; accelerate patient recovery and improve long-term prognosis.
Calcium antagonists (nifedipine, nimodipine, verapamil, etc.) are widely used in the treatment of angina pectoris, hypertension, coronary artery disease, arrhythmias and other cardiovascular diseases in the middle-aged and elderly, but their “other effects” are adverse reactions. Dr. Fryberg in the United Kingdom collected data on thousands of cases and found that the incidence of love in those who took calcium antagonists was 3.04%, which was 1.72% higher than those who did not take calcium antagonists. Different calcium antagonists induced cancer in the following order of strength: verapamil, nifedipine, and diltiazem. The mechanism of cancer induced by calcium antagonists: Calcium antagonists block the information transmission of calcium ions and also inhibit the apoptosis mechanism of human cells under normal conditions. And this mechanism is an important process for the normal organism to destroy cancer cells.
Cholecystitis and cholelithiasis are twin brothers. In the last 20 years or so, they have been called the “diseases of modern life”. Its formation is related to dietary habits, geographical and living environment and metabolic activity of the body. Pills can also cause gallstones: for example, high-dose birth control pills. Its main component estrogen can directly affect the liver and biliary function, so that bile synthesis is reduced, cholesterol secretion is increased, affecting the contraction and excretion function of the gallbladder, and numerous factors form gallstones. Long-acting growth inhibitor stimulant has a strong inhibitory effect on pancreatic enzyme secretion, because it has the function of inhibiting gallbladder contraction, leading to bile stasis and promoting the formation of gallstones. Total parenteral hypernutrition (TPN) consists of highly concentrated, highly nutritious substances such as amino acids, fatty acids and concentrated glucose, which can lead to cholestasis and cholelithiasis with long-term application. Calcium salts of ceftriaxone metabolites tend to precipitate in the gallbladder and become “stone nuclei”, which can induce gallstones with long-term use and other suitable conditions. Nonsteroidal anti-inflammatory drug sulindac is the same kind of substituted indomethacin (anti-inflammatory pain), and its metabolites are excreted through the gallbladder, which can form crystals (stone precursors) in the bile duct. Pansentine is a monoglucosidic acid conjugate, the vast majority of which is excreted from the bile. Long-term use leads to a lack of monoglucosidic acid conjugates and a decrease in the conjugation of pansentine, which can form insoluble substances when excreted in the bile due to the action of certain bacteria and precipitate in the bile of the gallbladder, contributing to stone formation. Long-term use of the above drugs should be done every six months for ultrasound examination of the gallbladder to detect gallstones in a timely manner and adjust the treatment medication.
Sixth, drug resistance (drug resistance)
It refers to the nature that the germs avoid being inhibited or killed by the drug through their own mutation after contacting the drug, thus the sensitivity to the drug decreases or even disappears. Bacteria may develop resistance to any antimicrobial drug, commonly arising from abuse or long-term application of insufficient doses. The number of infectious diseases and the probability of antimicrobial use in the elderly is greater than in adults, and thus the probability of developing resistance is significantly higher. The key to avoiding or delaying the onset of resistance is to use antimicrobials appropriately.
A patient recently came to the ward and said that he had been on antimicrobials for 9 months since his surgery last year because of a urinary tract infection and prostatitis that never got better. This shows that the misuse of antibiotics is a problem for both doctors and patients. Many people use “antibiotics and cold medicine” for themselves when they have a cold. In fact, 90% of colds are viral colds and antibiotics only kill bacteria but not viruses. Many homes always have antibiotics, excessive application, non-standard application, group antibiotic abuse, for the emergence of drug-resistant bacteria prepared for the excellent soil. Medical abuse of antibiotics is even more to blame. Both doctors do not know enough: for prophylactic use; for quick effect use; for convenience use, etc. The first thing you need to do is not to do a drug sensitivity test, not to follow the first oral, then intramuscular injection, and then injections, up to prescribe intravenous infusion.
Seven, the treatment is divided into primary and secondary
There is a primary and secondary contradiction in the use of drugs. A patient is a type A personality, the pursuit of perfection, while suffering from hypertension, hyperlipidemia, anxiety disorders. The cardiology department required that she must take antihypertensive drugs and lipid-lowering drugs, and the patient thought that this was necessary. However, we saw that she was terrified all day long and could not study and work because her anxiety seriously affected her quality of life, so she should be treated with anti-anxiety first; a patient suffering from cardiovascular disease, diabetes and renal failure, we should first consider using drugs that do not harm the kidney function.
Inappropriate medication is mainly manifested in: excessive dose of single medication, too many varieties of medication, resulting in repeated medication; long-term medication for chronic diseases; unauthorized use or discontinuation of medication. The rational use of drugs is related to both doctors and patients. Doctors should be familiar with drug properties and toxic side effects, and guide patients to take medication in accordance with the dosage of medication instructions. Patients should take and reduce the medication under the guidance of doctors, not to blindly extend the medication time, and strictly control the course of treatment. Long-term medication users should have their blood and liver and kidney functions tested regularly to prevent problems.
In addition, the efficacy of drugs is closely related to the time of administration. For example, anemia drugs taken at 7:00 p.m. are four times more concentrated in the blood than those taken at 7:00 a.m.; rheumatism and rheumatoid drugs are effective in the morning; ankyrin is effective at 7:00 a.m.; aspirin is highly effective and long-lasting at 7:00 a.m., but less effective in the afternoon and evening; cholesterol-lowering drugs are good at dinner because the production of blood lipids in the body increases at night; hypnotics, dewormers and contraceptives are suitable for taking at night. Glucose-lowering drugs are taken in the morning, and the glucagon should be chewed and taken during meals.
Traditional dosing standards are usually a disease a drug, different individuals eat the same dose of drugs, some people do not have a significant effect with drugs. Genetic factors play a significant role in influencing the efficacy of drugs. Individualized medication can reduce the incidence of adverse drug reactions, and reduce the number and time of medication adjustment for patients to reduce the pain and burden of patients. The Institute of Pharmacology of Central South University has successfully developed China’s first individualized drug therapy gene diagnosis kit and gene diagnosis chip for hypertension with independent intellectual property rights. It can detect genetic variants of multiple drug metabolizing enzymes and receptors. The detection of one locus corresponds to multiple diseases and drugs associated with it. Since the patient’s genetic information is not affected by factors such as age, the results of a single test can be beneficial for a lifetime. We look forward to the popularization of this method.