STUDY - Technical - New Dacian's Medicine
Principles
of Drug Therapy (6)
Translation Draft
In this post we will "treat" drug side effects.
The beneficial effects of medicines are accompanied by an inevitable risk of unwanted effects. Morbidity and mortality due to these undesirable effects frequently cause diagnostic problems, as they can affect any organ and system of the body, often misinterpreted as signs of the underlying disease. Major advances in the research, development and regulation of medicinal products ensure, in most cases, that they are uniform, effective and relatively safe and that recognised risks are published.
However, the increased number and variety of medicines available without a prescription or prescription make it impossible for the patient or doctor to obtain and memorize the knowledge necessary for the correct use of all medicines. it is understood, therefore, that many of the medicines dispensed without prescriptions are used indiscriminately by the public, and restricted medicines may be incorrectly prescribed by the doctor. In practice, most doctors do not use more than 50 medicines, gaining good knowledge of their safety and effectiveness. Most patients probably use a small number of over-the-counter medicines.
However, many patients are cared for and receive prescriptions from several doctors, and in one month, many patients use more than three different non-prescription medicines containing nine or more chemical agents. 25-50% of patients make mistakes in self-administration of prescription drugs and these mistakes may be responsible for the adverse effects of medicines. Elderly patients are the group most likely to commit such errors, probably because, among other things, they consume more medicines.
A third or more of patients may also not follow the prescribed treatment. Similarly, patients commit errors in taking over non-prescription medicines by not reading or not following exactly the instructions for use set out in the leaflets accompanying the medicinal products. Physicians should recognise that prescriptions accompanied by instructions for administration do not always guarantee compliance (compliance with treatment). Each drug can produce unintended consequences, even when used according to standard or recommended methods of administration. When used incorrectly, its effectiveness may be reduced and side effects may be more common.
Simultaneous administration of several medicines can also lead to adverse interactions. In the hospital, all medicines should be administered under the control of the doctor, and the patient's participation is generally ensured. Errors can occur and so, drugs or wrong doses may be administered, or the drug may be given to the wrong patient, although improved drug distribution and administration systems have reduced the importance of this problem. On the other hand, there are no ways to control how outpatients take prescription drugs or those that are dispensed without a prescription.
From an epidemiological point of view, epidemiological studies of adverse drug reactions have been of great help in assessing the size of the problem in its entirety, in calculating the frequency of adverse reactions to specific medicinal products and in characterizing some determinants of adverse effects in medicinal products. During each hospitalization, patients receive, on average, 10 different medicines. The sicker the patient, the more medications he receives, with an appropriate increase in the likelihood of adverse reactions occurring. When hospitalized patients receive less than 6 different medicines, the probability of an adverse reaction is about 5%, and when they receive more than 15 medicines, the probability is 40%.
Retrospective analysis of outpatients revealed adverse drug reactions in 20% of cases. The importance of drug-related diseases is high. 2-5% of cases of admission to paediatric and internal medicine services are due to diseases attributed to medicines. The case/fatality ratio in drug-induced diseases in hospitalized patients varies between 2-12%. Furthermore, some fetal or neonatal abnormalities are caused by medications taken by the mother during pregnancy or parturition. A small group of widely used medicines is responsible for most adverse effects. Aspirin and other analgesics, digoxin, anticoagulants, diuretics, antimicrobials, steroids, antineoplastics and hypoglycaemic agents are responsible for 90% of the adverse reactions, although the drugs involved differ in patients treated in an outpatient than those hospitalized. The cost of morbidity and drug-induced mortality in the outpatient is estimated at huge amounts (in the U.S. alone it is "discussed" of amounts between $30 billion and $130 billion).
The "turn" of drug side effects in the elderly has come. Elderly people, as a group, have a higher pathological load and receive a higher number of drugs compared to other people. Therefore, it is not surprising that adverse reactions to drugs occur more frequently in the elderly. It has not been clearwhether an elderly person is more likely to develop an adverse reaction to medication than a young person with the same number of diseases and therapy. However, in population studies of non-institutionalized elderly people, more than 10% of them reported having had at least one adverse reaction to drugs in the past year. It appears that the incidence is higher in elderly hospitalized patients.
Although it is generally believed that the elderly are more sensitive to drugs than young people, this is not true for all medicines. For example, a marked decrease in sensitivity to drugs acting on beta-adrenergic receptors has been shown in the elderly. The consequences of adverse reactions to drugs may differ in the elderly, due to the higher likelihood of the existence of another disease. For example, the use of benzodiazepines with a long half-life is linked to the occurrence of hip fractures in the elderly, which probably reflects both a risk of fall due to these drugs and an increased incidence of osteoporosis.
Even when a drug affects a function similarly in patients of different age groups, the lower level of function in the elderly may put them at a higher risk of side effects. When prescribing a medicine to an elderly patient, consideration should be given to the possibility that hepatic or renal excretion mechanisms may be affected. Adverse reactions to medicines may be less noisy in the elderly than in the rest of the population. and the doctor should be careful that the patient's signs or symptoms reflect an adverse effect of the medication.
From an etiology point of view, most adverse drug reactions can be prevented, and recent studies, using an analytical approach to systems, have suggested that the most common system failure associated with an adverse drug reaction is the insufficient dissemination of knowledge about medicines, their prescribing and administration. Most side effects are grouped into two groups. The most common results from the exaggerated but anticipated pharmacological action of the drug.
Other adverse reactions arise from toxic effects unrelated to the desired pharmacological actions. The latter are often unpredictable, are frequently severe and are the result of recognized mechanisms, but also of undiscovered ones. Some mechanisms, not related to the primary pharmacological activity of the drug, include direct cytotoxicity, initiation of abnormal immune responses and disturbances of metabolic processes in people with genetic enzyme defects. Further understanding of inter-individualized differences in the expression of enzymes responsible for drug metabolism contributed to the understanding of drug adverse reactions that were previously considered idiosyncrasy.
For example, haemotoxicity of dapsone, which includes hemolysis in patients with glucoso-6-phosphate dehydrogenase (G6PD) deficiency, as well as agranulocytosis, is assumed to be due to metabolism, by means of specific enzymes of cytochrome P450, in its hydroxylaminate metabolite. The extent to which dapsone is converted to this toxic metabolite depends on the activity of these cytochrome p450 enzymes, specific to each individual, which thus determines individual susceptibility to adverse reaction. Conversely, knowledge of the enzyme responsible for the production of the toxic metabolite may make it possible to co-administer specific enzyme inhibitors, which will prevent the toxic effect.
By taking into account from the outset factors known as altering the action of medicines, these side effects can often be prevented. The usual cause of these reactions is abnormally high concentration of the drug in the receptor (place of action), due to pharmacokinetic variability. For example, the reduction in the volume of distribution, the rate of metabolism or the rate of excretion, all result in a higher than expected concentration of the drug in the receptor, with a consecutive increase in the pharmacological effect. Recently, specific P450 cytochromes involved in drug metabolism have been identified.
Recognition of the polymorphic distribution of some of these enzyme activities in a population explains the interindividual variability of the drug's clearance. Also, with the carrying out of simple tests to characterize the individual activity of specific cytochrome P 450, it will be possible to identify, in advance, people with a particular risk of adverse reactions, dependent on the concentration of the drug.. For enzymes whose activity is distributed polymorphicly, a proportion of the population has a low or absent enzyme activity. In these individuals, the concentration of the drug is higher than normal and can have toxic effects. On the contrary, when toxicity or efficacy is produced by a metabolite, slow metabolizers toxicity or efficacy will be limited. Polymorphic distribution of drug metabolism enzymes may explain some adverse effects, previously labelled as idiosyncrasy.
Some descriptive elements such as alteration of the response dose curve intervene. Due to an increased sensitivity of the receptor, this alteration causes an increased effect of the drug at the same concentration. An example is the response to warfarin at normal or low blood levels. The shape of the dose-response curve may also determine the likelihood of adverse reactions to medications. Thus, drugs with a steep dose-response curve or a small therapeutic index are more likely to be associated with dose-related toxicity, as a small dose increase produces a large change in pharmacological effect. An increase in the dose of drugs with a non-linear kinetics, such as phenytoin, may produce a greater increase in serum levels, causing toxic phenomena.
And finally, concomitant administration of many drugs can affect their pharmacokinetics or pharmacodynamics. Pharmacokinetics may be affected by altering bioavailability, plasma protein binding or metabolism or excretion rate. Pharmacodynamics may be modified by another medicinal product, which competes for the same sites on the receptor, preventing the medicinal product from reaching its place of action or which antagonizes or increases the pharmacological effect. Inhibition of the metabolism of one drug by another may occur when both drugs bind to the same cytochrome P450. Therefore, with the identification of specific cytochrome P450, responsible for the metabolism of a particular drug, the anticipation of drug interactions has a more scientific basis. An important recent example of such a mechanism is the inhibition of terfenadin metabolism by CYP3A inhibitors of the type of erythromycin and systemic antimycotics. Such inhibition produced torsade of peaks and fatal cardiac arrhythmias.
I'm done for today... Don't forget that tomorrow is the holiday that triggers the end-of-year holidays, Saint Nicholas!
In this post we will "treat" drug side effects.
The beneficial effects of medicines are accompanied by an inevitable risk of unwanted effects. Morbidity and mortality due to these undesirable effects frequently cause diagnostic problems, as they can affect any organ and system of the body, often misinterpreted as signs of the underlying disease. Major advances in the research, development and regulation of medicinal products ensure, in most cases, that they are uniform, effective and relatively safe and that recognised risks are published.
However, the increased number and variety of medicines available without a prescription or prescription make it impossible for the patient or doctor to obtain and memorize the knowledge necessary for the correct use of all medicines. it is understood, therefore, that many of the medicines dispensed without prescriptions are used indiscriminately by the public, and restricted medicines may be incorrectly prescribed by the doctor. In practice, most doctors do not use more than 50 medicines, gaining good knowledge of their safety and effectiveness. Most patients probably use a small number of over-the-counter medicines.
However, many patients are cared for and receive prescriptions from several doctors, and in one month, many patients use more than three different non-prescription medicines containing nine or more chemical agents. 25-50% of patients make mistakes in self-administration of prescription drugs and these mistakes may be responsible for the adverse effects of medicines. Elderly patients are the group most likely to commit such errors, probably because, among other things, they consume more medicines.
A third or more of patients may also not follow the prescribed treatment. Similarly, patients commit errors in taking over non-prescription medicines by not reading or not following exactly the instructions for use set out in the leaflets accompanying the medicinal products. Physicians should recognise that prescriptions accompanied by instructions for administration do not always guarantee compliance (compliance with treatment). Each drug can produce unintended consequences, even when used according to standard or recommended methods of administration. When used incorrectly, its effectiveness may be reduced and side effects may be more common.
Simultaneous administration of several medicines can also lead to adverse interactions. In the hospital, all medicines should be administered under the control of the doctor, and the patient's participation is generally ensured. Errors can occur and so, drugs or wrong doses may be administered, or the drug may be given to the wrong patient, although improved drug distribution and administration systems have reduced the importance of this problem. On the other hand, there are no ways to control how outpatients take prescription drugs or those that are dispensed without a prescription.
From an epidemiological point of view, epidemiological studies of adverse drug reactions have been of great help in assessing the size of the problem in its entirety, in calculating the frequency of adverse reactions to specific medicinal products and in characterizing some determinants of adverse effects in medicinal products. During each hospitalization, patients receive, on average, 10 different medicines. The sicker the patient, the more medications he receives, with an appropriate increase in the likelihood of adverse reactions occurring. When hospitalized patients receive less than 6 different medicines, the probability of an adverse reaction is about 5%, and when they receive more than 15 medicines, the probability is 40%.
Retrospective analysis of outpatients revealed adverse drug reactions in 20% of cases. The importance of drug-related diseases is high. 2-5% of cases of admission to paediatric and internal medicine services are due to diseases attributed to medicines. The case/fatality ratio in drug-induced diseases in hospitalized patients varies between 2-12%. Furthermore, some fetal or neonatal abnormalities are caused by medications taken by the mother during pregnancy or parturition. A small group of widely used medicines is responsible for most adverse effects. Aspirin and other analgesics, digoxin, anticoagulants, diuretics, antimicrobials, steroids, antineoplastics and hypoglycaemic agents are responsible for 90% of the adverse reactions, although the drugs involved differ in patients treated in an outpatient than those hospitalized. The cost of morbidity and drug-induced mortality in the outpatient is estimated at huge amounts (in the U.S. alone it is "discussed" of amounts between $30 billion and $130 billion).
The "turn" of drug side effects in the elderly has come. Elderly people, as a group, have a higher pathological load and receive a higher number of drugs compared to other people. Therefore, it is not surprising that adverse reactions to drugs occur more frequently in the elderly. It has not been clearwhether an elderly person is more likely to develop an adverse reaction to medication than a young person with the same number of diseases and therapy. However, in population studies of non-institutionalized elderly people, more than 10% of them reported having had at least one adverse reaction to drugs in the past year. It appears that the incidence is higher in elderly hospitalized patients.
Although it is generally believed that the elderly are more sensitive to drugs than young people, this is not true for all medicines. For example, a marked decrease in sensitivity to drugs acting on beta-adrenergic receptors has been shown in the elderly. The consequences of adverse reactions to drugs may differ in the elderly, due to the higher likelihood of the existence of another disease. For example, the use of benzodiazepines with a long half-life is linked to the occurrence of hip fractures in the elderly, which probably reflects both a risk of fall due to these drugs and an increased incidence of osteoporosis.
Even when a drug affects a function similarly in patients of different age groups, the lower level of function in the elderly may put them at a higher risk of side effects. When prescribing a medicine to an elderly patient, consideration should be given to the possibility that hepatic or renal excretion mechanisms may be affected. Adverse reactions to medicines may be less noisy in the elderly than in the rest of the population. and the doctor should be careful that the patient's signs or symptoms reflect an adverse effect of the medication.
From an etiology point of view, most adverse drug reactions can be prevented, and recent studies, using an analytical approach to systems, have suggested that the most common system failure associated with an adverse drug reaction is the insufficient dissemination of knowledge about medicines, their prescribing and administration. Most side effects are grouped into two groups. The most common results from the exaggerated but anticipated pharmacological action of the drug.
Other adverse reactions arise from toxic effects unrelated to the desired pharmacological actions. The latter are often unpredictable, are frequently severe and are the result of recognized mechanisms, but also of undiscovered ones. Some mechanisms, not related to the primary pharmacological activity of the drug, include direct cytotoxicity, initiation of abnormal immune responses and disturbances of metabolic processes in people with genetic enzyme defects. Further understanding of inter-individualized differences in the expression of enzymes responsible for drug metabolism contributed to the understanding of drug adverse reactions that were previously considered idiosyncrasy.
For example, haemotoxicity of dapsone, which includes hemolysis in patients with glucoso-6-phosphate dehydrogenase (G6PD) deficiency, as well as agranulocytosis, is assumed to be due to metabolism, by means of specific enzymes of cytochrome P450, in its hydroxylaminate metabolite. The extent to which dapsone is converted to this toxic metabolite depends on the activity of these cytochrome p450 enzymes, specific to each individual, which thus determines individual susceptibility to adverse reaction. Conversely, knowledge of the enzyme responsible for the production of the toxic metabolite may make it possible to co-administer specific enzyme inhibitors, which will prevent the toxic effect.
By taking into account from the outset factors known as altering the action of medicines, these side effects can often be prevented. The usual cause of these reactions is abnormally high concentration of the drug in the receptor (place of action), due to pharmacokinetic variability. For example, the reduction in the volume of distribution, the rate of metabolism or the rate of excretion, all result in a higher than expected concentration of the drug in the receptor, with a consecutive increase in the pharmacological effect. Recently, specific P450 cytochromes involved in drug metabolism have been identified.
Recognition of the polymorphic distribution of some of these enzyme activities in a population explains the interindividual variability of the drug's clearance. Also, with the carrying out of simple tests to characterize the individual activity of specific cytochrome P 450, it will be possible to identify, in advance, people with a particular risk of adverse reactions, dependent on the concentration of the drug.. For enzymes whose activity is distributed polymorphicly, a proportion of the population has a low or absent enzyme activity. In these individuals, the concentration of the drug is higher than normal and can have toxic effects. On the contrary, when toxicity or efficacy is produced by a metabolite, slow metabolizers toxicity or efficacy will be limited. Polymorphic distribution of drug metabolism enzymes may explain some adverse effects, previously labelled as idiosyncrasy.
Some descriptive elements such as alteration of the response dose curve intervene. Due to an increased sensitivity of the receptor, this alteration causes an increased effect of the drug at the same concentration. An example is the response to warfarin at normal or low blood levels. The shape of the dose-response curve may also determine the likelihood of adverse reactions to medications. Thus, drugs with a steep dose-response curve or a small therapeutic index are more likely to be associated with dose-related toxicity, as a small dose increase produces a large change in pharmacological effect. An increase in the dose of drugs with a non-linear kinetics, such as phenytoin, may produce a greater increase in serum levels, causing toxic phenomena.
And finally, concomitant administration of many drugs can affect their pharmacokinetics or pharmacodynamics. Pharmacokinetics may be affected by altering bioavailability, plasma protein binding or metabolism or excretion rate. Pharmacodynamics may be modified by another medicinal product, which competes for the same sites on the receptor, preventing the medicinal product from reaching its place of action or which antagonizes or increases the pharmacological effect. Inhibition of the metabolism of one drug by another may occur when both drugs bind to the same cytochrome P450. Therefore, with the identification of specific cytochrome P450, responsible for the metabolism of a particular drug, the anticipation of drug interactions has a more scientific basis. An important recent example of such a mechanism is the inhibition of terfenadin metabolism by CYP3A inhibitors of the type of erythromycin and systemic antimycotics. Such inhibition produced torsade of peaks and fatal cardiac arrhythmias.
I'm done for today... Don't forget that tomorrow is the holiday that triggers the end-of-year holidays, Saint Nicholas!
Love, Understanding and
Gratitude!!!
Dorin, Merticaru