老年人用药原则（Medication principles for the elderly）

老年人用药原则（Medication principles for the elderly） 老年人用药原则(Medication principles for the elderly) Third lessons Medication principles for the elderly Pharmacokinetics of drugs in the elderly Concept: referred to as geriatric pharmacokinetics, describes drugs used in older adults The action (absorption, distribution, metabolism, and excretion) of blood drugs Time, process and characteristics of concentration rise and fall. We all learn in pharmacokinetic process there are age-related changes, can be directly Influence on serum concentration in the elderly. Characteristics of pharmacokinetics of senile drugs - absorption Absorption (absorption) - refers to the penetration of a drug from the site of the drug into the blood vessel The process of entering the circulation of the blood. Conclusion: the gastrointestinal mucosa in elderly people is gradually shrinking, peristalsis is slowing and blood supply is decreasing Less and gastric acid deficiency, but the absorption of drugs (passive operation absorption of drugs) Less affected Glucose, vitamin B1, calcium, and iron: ?? Absorption of drugs for active transport, relax, absorption decreases with age ?? The main reason: with the absorption of the drug required carrier and enzyme activity related to: Characteristics of pharmacokinetics of senile drugs - absorption Weakly acidic drugs: Why?: ?? Here, gastric stomach acid weak acid dissociation increases, gastric absorption rate decreases, But the decrease in gastric emptying, drug retention time relative increase drug absorption time increase ?? - small intestine peristalsis down, relax, counteract the intestinal absorption of drug supply And the decrease of absorbed area caused by the decrease of absorbed area The majority of drugs (drug absorption in the passive operation) on the elderly and absorption There was no significant difference between adults Distribution characteristics of pharmacokinetics in elderly patients Distribution (distribution) - refers to the continuous passage of a drug through the bloodstream The process of transferring vascular walls to organs and tissues 1.. Changes in body composition affecting the distribution of drugs Water soluble drugs?: ?? The muscle and parenchymal organs atrophy, intracellular fluid, the decrease in total liquid down from 10 to 15 %, caused by water soluble drugs (such as digoxin, morphine) distribution of blood volume decreases. The concentration increases, the onset may be faster than expected, drug effects and adverse reactions increase Distribution characteristics of pharmacokinetics in elderly patients 1.. Changes in body composition affecting the distribution of drugs Fat soluble drugs: ??: hormonal and physical down, adipose tissue = 10 ~ 20%, induced by lipid soluble drugs (such as lidocaine, amiodarone) distribution volume increase after drug blood concentration temporarily When it is low, the time to reach steady concentration is later than expected, but it is easy to use for a long time Cumulative poisoning Distribution characteristics of pharmacokinetics in elderly patients 2. protein binding rate Acidic drugs are readily conjugated to albumin ?? The liver protein synthesis ability decreases, plasma albumin concentration: 10 ~ 20%, If a drug with a high albumin binding rate, such as Hua Falin, is used The medicine down, up drug free, efficacy and adverse reactions of arrows. Distribution characteristics of pharmacokinetics in elderly patients 2. protein binding rate Alkaline drugs are bound to a1- glycoproteins Plasma a1- glycoprotein increases or remains unchanged with age, and propranolol is used Other basic drugs, drugs with drug free up, down, effect Can down, this may be partly compensated by liver dysfunction of propranolol inactivated reduction Blood concentration increases by less. Metabolic characteristics of geriatric pharmacokinetics Metabolism (metabolism) - refers to the chemical process of drugs in the body. The main organ of drug metabolism: the liver The three major factors that affect liver drug metabolism (impact results): Hepatic blood flow - important effects Phase I reactions (oxidation, reduction, degradation) - important effects Phase II reactions (acetylation, glucuronic acid) - no obvious effect The hepatic artery and portal vein blood flow increased with age: 40 ~ 45%. Liver extraction Drugs with high bioavailability have low bioavailability - hepatic first pass effect Metabolic characteristics of geriatric pharmacokinetics For example, lidocaine (a drug with a large head effect): 1., the rate of liver uptake was 70%, and the amount of oral drug was less Drug 2. hepatic blood flow down the first pass effect of inactivated down, bioavailability increase 3. after portosystemic shunt or congestive heart failure, The decrease in hepatic blood flow down, blood The effect of lidocaine clearance: down, up, up ADR The drug may affect the liver blood flow to affect drug clearance 1. glucagon and phenobarbital increase hepatic blood flow 2. to 33%: propranolol hepatic blood flow 3. if at the same time, the removal rate of propranolol lidocaine: 50%, Prone to adverse reactions. Metabolic characteristics of geriatric drugs - excretion Excretion (excretion) - refers to the drug in vivo or in its form or metabolism The process of excretion of an organ or excretory organ from the body. Excretory vital organs: kidneys (most drugs) Kidneys: the most obvious organ of age change 1. renal units after the age of 30 with the increase of age: 2. renal blood flow from the age of 40 or 1.5 down to 1.9% 3. renal units and decreased renal blood flow and cause GFR down, down 1% year after 30 years old The 4. year old >20, renal tubular function started down, down 0.5% year Metabolic characteristics of geriatric drugs - excretion Clinical significance: 1. because of renal glomerular and tubular function down, the renal excretion of the drug (e.g. Digoxin, aminoglycoside) excretion down, easy poisoning. 2. elderly skeletal muscle atrophy, creatinine down, even if the decrease in renal function, Serum creatinine concentrations remained within normal limits, so that the blood of the elderly was maintained Normal creatinine concentration does not mean GFR is normal. 3. elderly people should be based on creatinine when they use renal excreted drugs Clearance rates (Ccr) were adjusted and females were multiplied by 0.85. Metabolic characteristics of geriatric drugs - excretion Therapeutic index - the ratio of treatment concentration to poison concentration What is the adjustment factor? 1. drug treatment index 2.. Renal output Meaning?: 1. treatment of a small index drug (such as digoxin) with the reduced excretion of the essence must be reduced Amount and / or extension interval 2., and the treatment of large index drugs (such as beta lactam antibiotics) elderly Generally, there is no need for reduction, but renal function should be monitored. Aging drug effect kinetic characteristics [increased susceptibility to most drugs] Older drug effects dynamics - referred to as geriatric pharmacodynamics, is described The effect of drugs on the aged organism (age is less known at present) [susceptibility to most drugs] The old man using the drugs and doses can cause excessive toxicity for adults Satisfactory results can be obtained by using small dosage and low blood concentration. Aging drug effect kinetic characteristics [increased susceptibility to most drugs] 1.. Central nervous system drugs ?? Brain atrophy, cerebral blood flow decrease and advanced neural function reduction: 1. pairs of central sedative / analgesic / antipsychotics / antidepressants / PA Higginson's disease drug sensitivity increase 2., especially in hypoxia and fever Aging drug effect kinetic characteristics [increased susceptibility to most drugs] 2. cardiovascular drugs 1. because of coronary artery and myocardial aging and cardiac reserve function down, on the negative Strength of drugs (such as Vera Pammy) = sensitivity. 2. because of the retrograde nature of the heart conduction system, drugs that act as negative agents Gao Xin) = sensitivity Aging drug effect kinetic characteristics [increased susceptibility to most drugs] 3. anticoagulants 1. on warfarin sensitivity increases with the increase of age, dosage and pharmacodynamics down, mainly due to In the case of albumin, may also be one of the reasons 2., the incidence of bleeding increases in elderly patients after heparin use, especially in elderly women The cause is unknown 3. elderly people should refrain from using anti platelet drugs when using anticoagulant drugs Aging drug effect kinetic characteristics [increased susceptibility to most drugs] 4. drugs affecting the internal environment The old people in the lower environmental stability Application of antihypertensive drugs can cause orthostatic hypotension Use chlorpromazine, benzene, two nitrogen leather to be able to cause low temperature disease Hypoglycemia can be given to hypoglycemic agents Application of anticholinergic drugs can lead to constipation and retention of urine The use of diuretics is prone to electrolyte disturbances, low blood volume and hematuria Elevated acid metabolism Aging drug effect kinetic characteristics [sensitivity to a small number of drugs] ?? Heart beta receptor number or affinity for lower down, beta receptor agonists and block The decrease in drug sensitivity, increase or decrease in heart rate down effect. 1. elderly such as intravenous infusion of isoproterenol, HR = 25 times / min the dosage required for years 5 times as light as a human. 2. elderly control effect of vagus nerve on the heart down, up HR with atropine Use (4~5 times / min) less than adults obviously (20~25 times / min). ?? The clinical application is not blindly increment, increment will only increase due to adverse reaction Should not increase efficacy Aging drug effect kinetic characteristics - [decrease in tolerance to drugs] The elderly are well tolerated by a single or a few drugs, However, the tolerance to multi drug combination was lower, and the adverse reaction was increased Plus. Therefore, the clinical medication should be used as much as possible to reduce medication. The elderly pair The sensitivity of these drugs increases and the tolerance should be reduced, And strengthen monitoring. Aging drug effect kinetic characteristics [medication compliance is poor] Compliance - the degree to which a patient performs a medical order. ?? The elderly due to the decrease in memory, reaction down to the drug, do not understand or know a half Solution, ignore the importance of taking medicine according to doctor's advice, about 60% old people can not press The medicine prescribed by doctor's advice is manifested as "missed clothes", "more clothes" or "wrong clothes", thus affecting the medicine Efficacy or cause ADR to occur. The simplified regimen, clearly marked clearly, is to improve the compliance, The key to successful treatment. Characteristics of adverse drug reactions in the elderly ADR - the presence of a drug in normal dosage or usage Harmful reactions unrelated to the treatment purpose, including adverse drug reactions and toxicity Effects, allergies, secondary reactions, etc. Elderly ADR is very common, but it is easy to ignore. One of the reasons is that the Lack of understanding. Characteristics of adverse drug reactions in the elderly - [etiology Characteristics] 1. elderly people have risk factors for ADR Multi drug combination was the most important risk factor for ADR, followed by women and low body weight Dysfunction of the liver, kidney or kidney was again accompanied by multiple diseases and decreased compliance And so on, these factors make the elderly prone to ADR 2. pharmacokinetics changes in the elderly The old man: liver and kidney function, drug metabolism, excretion down, t1/2 = ADR =. The old man down with albumin, drug free drug down, up, up ADR Characteristics of adverse drug reactions in the elderly - [etiology Characteristics] 3.. Changes in pharmacodynamics in the elderly ?? Because homoiostasis function decrease, increase sensitivity to most drugs, easy to ADR 4. drugs, a disease interaction Coexistence of diseases can cause disease progression or dysfunction. Senile dementia with anticholinergic / diuretic drugs can cause delirium / delirium Non steroidal anti-inflammatory drugs / aminoglycosides / radiography in chronic renal insufficiency Agent can induce acute renal failure Characteristics of adverse drug reactions in the elderly - [etiology Characteristics] 5. drugs, one drug interaction ?? Multi drug combination, the interaction between drugs increase. The rate of drug interaction between the two drugs was 6% The 5 is 50% 8 of them are 100% For example, aspirin can be used in combination with Hua Falin, which can make the latter white Protein replacement, increasing anticoagulant effect, leading to bleeding But not all drug interactions can lead to ADR, but the potential risk of increase Characteristics of adverse drug reactions in the elderly - [clinical characteristics] ? 1., a high incidence The incidence of A.ADR is often 3 times higher than that of adults B. elderly women are higher than men The greater the age of C., the higher the incidence of ADR The more D. used, the higher the incidence of ADR Characteristics of adverse drug reactions in the elderly - [clinical characteristics] 2. degree weight? 10 to 20% of the elderly were admitted to hospital by ADR, compared with 3% in adults Antihypertensive drugs can cause falls due to orthostatic hypotension and lead to fractures, Subdural hematoma - complicated with hypostatic pneumonia, pulmonary embolism, death Negative transmission agents can cause Aspen syndrome due to complete AVB The elderly ADR can make the condition even can not save a sudden turn for the worse. Characteristics of adverse drug reactions in the elderly - [clinical characteristics] 3. special performance Similar to adults The more common specific symptoms are confusion, falls, syncope, and size Incontinence, constipation, ataxia, etc (3) special manifestations are common in elderly and frail elderly people and common diseases in elderly patients A similar shape, fallibility (leakage) diagnosis Fall causing drugs: diuretics, vasodilators, antidepressants, and guidance A laxative, sedative, etc Characteristics of adverse drug reactions in the elderly - [clinical characteristics] 3. special performance Drugs for delirium in the elderly: anticholinergic, antidepressant, and antipsychotic Drugs, antiepileptic drug, digitalis, anti Parkinson's disease drugs, corticosteroids, Zhen Static medicine, theophylline, opium and so on The elderly caused by fecal incontinence: a laxative, antibiotics and iron The drug induced urinary incontinence: a sedative, diuretic, theophylline, anticholinergic drugs, ah Tablets, calcium antagonists, etc. 4.. High mortality The elderly accounted for only 10% of the total population, but accounted for 50% of ADR deaths, and the elderly ADR has a high mortality rate and is a major victim of ADR Characteristics of adverse drug reactions in the elderly [diagnosis points] 1. elderly people, ADR is generally common and easy to handle, but easy to ignore. 2., the diagnosis of ADR in the elderly is mainly a matter of cognition 3., if the elderly in the course of medication appear any new symptoms, first of all should be tested The possibility of ADR is followed by the deterioration of the disease itself Characteristics of adverse drug reactions in the elderly [diagnosis points] The diagnostic criteria for ADR include: Risk factors for ADR Adverse reactions occurred after the treatment Symptoms disappeared after reduction or withdrawal Due to the complex relationship between aging and ADR, further analysis should be confirmed after ADR Pharmacokinetic changes, pharmacodynamic differences, drugs, diseases, or disorders Using drugs to interact with each other, which is very helpful for ADR prevention and treatment. Characteristics of adverse drug reactions in the elderly - [treatment points] 1. withdrawal A. recovered within a few days to 3 weeks B. multi drug use, it is difficult to distinguish between, if the disease is stable, disable all drugs When the condition is not allowed, the medicine with the most likely possibility is stopped Gradually deactivate the remaining drugs and use the same and different kinds of action Drug replacement After the disappearance of C., ADR reset the treatment program Characteristics of adverse drug reactions in the elderly - [treatment points] 2. use antagonists A. heparin is available in excess of protamine zinc, B. opium, sedative poisoning, available naloxone, C. digoxin overdose is available with specific antibodies, beta amines, and potassium magnesium supplementation. 3. symptomatic support treatment for moderate and severe patients Fluid, diuresis, speed up the excretion of drugs Maintain vital signs A respiratory stimulant; a respiratory stimulant Severe bradycardia - temporary pacemaker Medication principles for the elderly The aging of the tissues and organs of the elderly leads to pharmacokinetics And the corresponding changes in pharmacodynamics make the incidence of ADR in elderly people high and dangerous Therefore, the principle of using drugs in old people is obviously different from that of adults. Medication principles for the elderly 1 [benefit principle] How can the principle of benefit be implemented in clinical practice? Be sure to have a definite indication 2. The benefit / risk ratio of the requested medication >1 For the elderly, there is arrhythmia, but there is no organic heart disease The likelihood of sudden cardiac death is very high in patients with hemodynamic disorders Small, therefore, patients should be as little or no use of antiarrhythmic drugs. Choose the medicine with definite curative effect and little adverse reaction ?? For the elderly G- infection, should be selected from the three generation cephalosporins or quinolones Antibiotics, avoid aminoglycoside antibiotics Medication principles for the elderly 2. [principles of the five drugs] Content - that is, simultaneous medication, not >5 Objective - to avoid excessive drug use, resulting in a high incidence of ADR The more the number is, the higher the incidence of ADR 1. at the same time using less than 5 drugs, the incidence rate of ADR was 4% 2. >5 species is 27.3% How do you implement the five drug principles? Understand the limitations of the drug treatment of selected once Grasp the main contradiction, select the main drugs, and pay attention to non drug therapy Medication principles for the elderly 3 [small dosage principle] The individual difference is big, the effective dose may be several to ten times, only The principle of small dosage can be taken (II) 80% elderly patients with ADR are caused by pharmacokinetics, and they are dose dependent Sex, starting from small, slow increments, most ADR can be avoided This principle is to emphasize the need for older people to reduce dosage, not completely Use as recommended by pharmaceutical companies There is no dosage for the elderly, according to age, health status, weight, Liver and kidney function, treatment index and protein binding rate were considered The principle of small dose in the elderly is not a consistent small dose Start with a small dose, or a small dose of maintenance therapy, mainly with The type of drug involved Medication principles for the elderly 3 [small dosage principle] The need to use the first load of drugs (such as lidocaine, amiodarone, etc.) in order to ensure The drug works quickly, and the elderly first use the lower limit of the adult dose, and the small dose is the main Embodied in maintenance volume Most of the drugs do not need to use the load for the first time, small dose is mainly reflected in the beginning Stage, that is, "low starting point, slow increment", starts with medication from small doses (adult doses) 1/5 ~ 1/4) begins with close observation and slow increments It should be to maximize the efficacy and minimal adverse reactions as the criterion, to explore each of the elderly Optimum dose Medication principles for the elderly 4, [timing] The 1. timing principle is the circadian rhythm based on disease, pharmacokinetics, and pharmacodynamics, Choose the most appropriate medication time for treatment, in order to achieve improved efficacy and Reduce the purpose of adverse reactions. 2., such as the application of anti angina drugs, requiring effective time to cover angina pectoris The peak period of attack Variant angina occurs at 0:00 to 6:00, and is recommended for bedtime Long acting calcium antagonists can also be taken at bedtime or in the middle of the night by a short duration calcium antagonist Medication, but be careful with the morning medication time apart Medication principles for the elderly 4, [timing] 3. the renal Na+/K+ excretion rate of hydrochlorothiazide was highest in the morning and morning medication Not only increases the curative effect, but also can reduce the occurrence of hypokalemia The 4. largest iron absorption rate in 19:00, therefore, the drug is in after dinner As reasonable. After breakfast, the tl/2 with aspirin is long and the blood concentration is high Good effect. Medication principles for the elderly 5 [pause] 1. medication should always be alert to ADR may. As soon as it occurs, the medication is suspended The simplest and most effective treatment 2. elderly patients should be closely observed during medication, once any new symptoms occur Should be considered ADR or progress of the disease, the former drug withdrawal, the latter dosing 3. when suspected ADR, reduce or stop symptoms after improvement or disappearance, can be diagnosed ADR. After ADR disappears, reset the treatment plan. Medication principles for the elderly 6. [principles of timely discontinuation] The length of time taken depends on the type of disease and the condition of the patient Take off immediately: the infectious disease improves, the temperature is normal, and stops for 3~5 days Antibiotic drugs, some analgesics and other symptomatic treatment drugs, but also after symptoms disappeared Stop 2. Discontinued at the end of the course: depression, hyperthyroidism, epilepsy, etc The symptoms of the disease disappeared after the corresponding medication, and in order to avoid the recurrence of the disease, Continue to consolidate the treatment for a period of time, at the end of the course of withdrawal or gradual reduction, Stop Long term use of drugs: hypertension, chronic heart failure, diabetes, Parkinson's disease, and armour Diseases such as glandular hypofunction are long controlled after drug treatment Medication, or even lifelong medication, otherwise the condition will recur. But who has no actual effect, poor tolerance, not according to the prescribed drug use should be promptly discontinued