Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
“BIOLOGICAL AND EXOGENIC FACTORS” Lecture 3 Clinical practice showed that medicines having the same active substances in an identical dose, but produced by different manufactures, substantially differentiated both on therapeutic efficiency and on frequency and expressed of the side effects caused by them. Peculiarities of introduction medicines in a system blood stream, and also in those organs and fabrics where a specific action shows determine a biological action of medicinal substances. Biological availability of medicines and their types Biological availability (bioavailability) is a rate and extent to which a drug is absorbed or is otherwise available to the treatment site in the body. In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes (such as orally), its bioavailability decreases (due to incomplete absorption and first-pass metabolism) or may vary from patient to patient (due to interindividual variation). Bioavailability is one of the essential tools in Pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. For dietary supplements, herbs and other nutrients in which the route of administration is nearly always oral, bioavailability generally designates simply the quantity or fraction of the ingested dose that is absorbed. Bioavailability is defined slightly differently for drugs as opposed to dietary supplements primarily due to the method of administration and Food and Drug Administration regulations (FDA). Bioaccessibility is a concept related to bioavailability in the context of biodegradation and environmental pollution. A molecule (often a persistent organic pollutant) is said to be bioavailable when "it is available to cross an organism’s cellular membrane from the environment, if the organism has access to the chemical." • • • • • • • In pharmacology In pharmacology, bioavailability is a measurement of the extent to which a drug reaches the systemic circulation. It is denoted by the letter F. In nutritional sciences In nutritional sciences, which cover the intake of nutrients and non-drug dietary ingredients, the concept of bioavailability lacks the well-defined standards associated with the pharmaceutical industry. The pharmacological definition cannot apply to these substances because utilization and absorption is a function of the nutritional status and physiological state of the subject, resulting in even greater differences from individual to individual (interindividual variation). Therefore, bioavailability for dietary supplements can be defined as the proportion of the substance capable of being absorbed and available for use or storage. In both pharmacology and nutrition sciences, the bioavailability is measured by calculating the area under curve (AUC), of the drug concentration time profile. In environmental sciences Bioavailability is commonly a limiting factor in the production of crops (due to solubility limitation or adsorption of plant nutrients to soil colloids) and in the removal of toxic substances from the food chain by microorganisms (due to sorption to or partitioning of otherwise degradable substances into inaccessible phases in the environment). A noteworthy example for agriculture is plant phosphorus deficiency induced by precipitation with iron and aluminum phosphates at low soil pH and precipitation with calcium phosphates at high soil pH. Toxic materials in soil, such as lead from sloughed paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess. Organic pollutants such as solvents or pesticides may be rendered unavailable to microorganisms and thus persist in the environment when they are adsorbed to soil minerals or partition into hydrophobic organic matter. There are 3 kinds of bioavailability in medical practice: Bioavailability: General Absolute Relative A term “biological availability” was firstly applied in 1945 by Оsher and co authors. Levi defined biological availability as relation of amount of the unchanged medicinal substance absorbed and discovered in a blood after introduction as the explored medicinal form, to it amount after introduction as the standard medicinal form While parenteral introduction of the medicinal substance the bioavailibility is equal 100 % Amount of medicinal substance which gets in a system blood stream at the different ways of introduction, differs: At other ways of introduction (“per os”, “per rectum”, intramuscularly etc.) is less than 100 % While parenteral introduction of the medicinal substance the bioavailibility is equal 100 % The measuring of biological availability can be represented by the following formula: BA = А/В x 100 %, where: BA - biological availability of medicine, %; А - amount of the medicinal substance which absorbed after entering of the explored medicinal form; В - amount of the medicinal substance which absorbed after entering of standard medicinal form. Factors influencing on biological availability of medicines Pharmaceutical Biological Factors of external environment Physical state of medicinal substance Simple chemical updating Physical state (sex, age) Pathological processes and individual peculiarities of organism Auxiliary substances Medicinal form and ways of introduction Technological process Magnetic field and meteorological conditions Alcohol Smoking Biorhythms Body temperature Bioavailability of drugs versus dietary supplements In comparison to drugs, there are significant differences in dietary supplements that impact the evaluation of their bioavailability. These differences include the following: the fact that nutritional supplements provide benefits that are variable and often qualitative in nature; the measurement of nutrient absorption lacks the precision; nutritional supplements are consumed for prevention and well-being; nutritional supplements do not exhibit characteristic dose-response curves; dosing intervals of nutritional supplements are not critical in contrast to drug therapy. In addition, the lack of defined methodology and regulations surrounding the consumption of dietary supplements hinders the application of bioavailability measures in comparison to drugs. In clinical trials with dietary supplements, bioavailability primarily focuses on statistical descriptions of mean or average AUC differences between treatment groups, while often failing to compare or discuss their standard deviations or interindividual variation. This failure leaves open the question of whether or not an individual in a group is likely to experience the benefits described by the meandifference comparisons. Nutritional science: reliable and universal bioavailability. One way to resolve this problem is to define “reliable bioavailability” as positive bioavailability results (an absorption meeting a predefined criteria) that include 84% of the trial subjects and “universal bioavailability” as those that include 98% of the trial subjects. Influence of the way of application Introduction “per os”; Introduction parenteral; Introduction “per rectum”; Introduction by inhalation . Influencing of enzymes; Influencing of composition and temperature of food; Influencing of the kind of liquid which used for the application of medicines; Influencing of food products While application “per os” some enzymes influence on the medicine activity as following: gastric juice, mucyn, enzymes, bile. For example: erythromycin, benzylpenicylline, pancreatine, insulin are inactivated by gastric juice; medicines of cardiac glycosides are destructed complete by gastric juice; tetracycline and sulphanilamide medicines are sucked quickly by proteins. Advantages of rectal way of introduction: - Fast introduction of medicinal substances in the systemic blood circulation and remaining relatively unchanged in the place of their effect without any traumatism of the gastrointestinal tract and liver, as well as the inactivation of substances by the digestive juices. (While taking “per os” the passing through the liver is 100 %; 20 % of the absorbed substance comes to the liver with the rectal absorption at the 1st stage); - The opportunity of replacing the injection way of introduction since the absorption rate of many substances may be equal to the introduction rate of the medicine in the systemic blood circulation by the intramuscular injections. - A significant decrease of allergic responses when the medicine is introduced rectally. - The absence of the taste problem, smell of medicines, possibility to prescribe medicinal substances of various pharmacological groups with various physical and chemical properties. - A simple and painless introduction. - Convenience for elderly people treatment and use in children and psychiatric practice. However while rectal introduction some factors influence on the bioavailability of medicines, such as: - Individual peculiarities in blood system and rectum; - The state of mucous in rectum. - Gland in colon produce a ferruginous alkaline secret (pH is higher than 9 sometimes). - The changing of pH influence on the suction process of medicinal substances. Introduction of medicines by inhalation way. Medicines are quickly absorbed through the mucous membranes of bronchial tubes in a system blood stream. It is not exposed to primary metabolism in a liver. To a certain extent some factors while the inhalation way of introduction of medicines influence on their bioavailability: - concomitant diseases of the bronchial-pulmonary system, - smoking (factor cooperant to development of chronic bronchitis with the proper alteration of - structure of bronchial wall), - state of blood circulation in the bronchial-pulmonary system. The temperature of body and environment has substantial influence on the flow of physiological and biochemical processes in an organism. For example, increasing of temperature and air humidity promotes the return of the heat from an organism in an environment has difficulty and can be carried out only at tension of mechanisms of physical thermoregulation (expansion of peripheral vessels, strengthening of the elimination of perspiration). Overheating of organism lead to the increasing of body temperature, sharp excitation of СNS, breathings and circulations of blood, strengthening of exchange of substances and perspiration. Dehydration of organism, thickening a blood, decreasing of the volume of circulatory liquid, dysfunction of electrolyte balance. It cause to the changing of absorption processes, distributing and metabolism of medicines, their bioavailability. Influence of temperature factor on pharmakocynetiks of medicinees is necessary to take into account in clinical practice when medicinees are appointed by a patient with broken thermoregulation. Metabolism and transportation of medicinal substances Lowering of temperature are reduce Increasing of temperature are quicken While fever changes of function of organs and systems are developed: - excitability of respiratory center, - alveolar ventilation and partial tension of oxygen goes down in a blood, - frequency of cardiac reductions rises, - spasm of vessels of skin at the beginning of development of feverish reaction, - increase of common peripheral vascular resistance to the current of blood, - getting up of arterial pressure, - in the second stage of fever in connection with expansion of vessels, strengthening of hidropoiesis and loss of liquid by an organism arterial pressure falls. The fever is accompanied also by the considerable changes of metabolism: - disintegration of muscular albumen is rises, - gluconeogenesis is multiplied, - the synthesis of albumens in a liver, speed of biochemical processes in hepatocytes, cells of other organs are changes. Influensing of alcohol and other factors on the absorption of medicinal and rish substances. Alcohol or alcohol-contents drinks reduce the absorption of rish substances from foods. It change a pharmacological effect of medicinal substances, increase thei toxicity. An alcohol violates a many links of substances exchange: albumens, fats, carbohydrates, mineral salts. All these changes conduce to accumulation of acidic products in organs and fabrics, displacing a acidic-alkaline equilibrium, that results in seriously violations of exchange of substances at times incompatible with life. For example, alcohol potentisate the anticoagulats, such as: acetylsalicylic acid, dicumarin, phenilin, sincumarin). It cause to blooding into internal organs (cerebrum) and paralysis of arms and legs, in some cases to death. Alcohol influence on the absorption and changing of hormonal medicines. It promote the activity of insulin and other syntetic medicines for treatment of diabetes, thet cause to coma and twitch. Antibiotics, vitamines (B1, B6, PP, B12, C, A, pholic acid) reduce the activity while alcohol application. While simultaneously application of such medicines as ephedrine, mezaton, vazopressin promoting a bloody pressure, sunnarizing of both alcohol and these medicines effect comes to bloody pressure rises to the high numbers, up to development of hypertensive crisis with the dangerous effect for life. Influencing of the magnetic field and meteorological factors on organism Bioavailability substantially changes both decreasing and increasing side. Mans are more sensitive to magnetic field of Earth than women. Especially sensitive to magnetic storm in atmosphere of Earth are patients with a disease of nervous and cardiac-vessel systems. While magnetic storm they have aggravation of disease and crying out: - hypertonic crisis, - dysfunction of cardiac rhythm, - attack of pectoris, - decreasing of ability to work hard etc. For example, the lowering of atmospheric pressure in limits 10-12 mm m. col. can cause to vessels dysfunction. Raining weather is cause to depression. Storms influence on the intensification of hard work, breathing, blood pressure etc. High concentration of positive ions cause to depression, breathlessness, giddiness, hypotonia, fatigue and fainting fit. High concentration of negative ions is cause to the better psychical state and mood. Obviously, they are break off the formation of serotonin. It is a transmitter connected with a pain transferring. The state of central nerve system, general tonus of organism is regulated intensifies of blood circulation in different organs and tissues and intensivity of medicinal substances biotransformation in metabolites. It described in changes of absolute and relative bioavailability of medicines. Absolute humidity of air Meteorological factors Elasticity of blood Atmospheric pressure vessels are affect on Direction and strength of wind Average daily temperature Viscosity and time of blood coagulation Medical diet for prophylaxis of side effects for some medicines Medicines Necessary diet Butadion Poor of sodium chloride Hexabarbital Rich of vtamines Dichlorthiazid, Rich of potasium (potatoes, aprocot and carrot cardiac glycosides, uregit juice, nuts, apples, peaches, figs etc) Corticotropine Rich of vegetables, fruits (potassium), proteins Anabolic medicines Rich of proteins and foodstuffs calcium (milk products) Nicotinic acid Rich of methionin (curd cheese) Paracetamol Rich of proteins Polymixin M Poor of attendant substances Limitation of usage a products for the prophylaxix of side reactions of medicines Medicines Amynasine, antidiabetic biguanid, antipyrine, tetracycline Anticoagulants Hypotensive medicines Glybutid, diakarb, salicylates, nitrophurane Isoniasid Tiroxin, tireoidine, iodine medicines Urographin, bilimin Food which should be eliminated Sausage, ham and other smoked products, vegetables Lettuce, spinach, green tomatos, fresh liver, cabbage and other products contents vitamin K Strawberry, viburnum, rowan berry, beetroot Fruit juices contents acids Cod Cabbage, radish Milk products, fruits, vegetables, smoked products, lettuce, black bread Peculiarities of medicines application taking into account time and food composition Medicine Peculiarities of application Avisan After meals, using a big amount of water Adelphan After meals Adonis-brom After meals Aevit After meals Allochol After meals Almagel 15-30 min before meals Amizon After meals, do not chewing Aminolon 30-60 min before meals, do not chewing Ampicilline 30-60 min before meals, using a big amount of water Analphen After meals Aspirin After meals, using a big amount of water Atropine sulphate 30-40 min before meals or 1 hours after Aeron 30-60 min before departure Barbital 30-60 min before sleeping, alcoholic drink is excepted Bisakodil 30 min before meals or before sleeping, using a milk for wash down Biseptol After or during meals Peculiarities of medicines application taking into account time and food composition Calcium salts Before meals; do not wash down by milk Codein 30-60 min before meals Bromcamphora After meals Butadion After or during meals Dekamevit After meals Diasolin After meals Diakarb Before meals; fruit juice is excepted Dibazol 1-2 hours before or 2 hours after meals Digitoxin Dimedrol 30-60 min before meals; medicines of potassium is used simultaneously After meals Doxicycline hydrochloride After meals Ibuprophen 30-60 min after meals; wash down by warm water or tea Hexavit After meals Heptavit 20-30 min before meals, after meals it is possible Griseophulvine During meals, using a big amount of water; alcohol is forbidden Kanamycine 30-60 min before or between meals Influencing of age and sex of person For young patients the highest data of absorption, elimination, smallest time of achievement a maximal concentration of medicines; For elderly persons is typical the highest data of period semi-elimination of medicines; While prescribing medicines for child till 1.5 years the bioavailability of medicines is not differed from adults in “per os” application. But their absorption (both active and passive) is carrying out very slowly. As a result the smallest concentration is form in blood, which is not enough for pharmacological effect. Child has a sensitive, easily irritative mucous of rectum. Reflex cause to quickly empty of intestinal and decreased a bioavailability of medicines which are introduced per rectum. While inhalation method of introduction the mucous of breath way easily irritated and connected with a secret. It cause to swelling and makes a difficult for absorption of medicines. The absorption of any medicines trough the skin of children is carrying out easily. The time of setting a medicine in women organism is longer than for man. So, the concentration of medicinal substances in women’s blood is higher. It is connected with a biggest content of “inert” fatty tissue in women, which is play a role of depot. Influencing of biorhythms The increasing of physiological functions (cardiac contract, arterial pressure, body temperature, oxygen usage, sugar content in blood etc.) in day time and decreasing at high are characterized for human. Biorhythms are classified according to periods: - ancient, - annual, - seasonal, - monthly, - weekly, - daily. During a day the different sensitivity of organism to optimal and toxic doses of medicines is carrying out (fig. ). For example, tranquillizers have a maximal toxicity in active day time. Their minimal toxicity is shown at night. Acute toxicity for adrenaline hydrochloride, ephedrine hydrochloride, mezaton are increased in day time and decreased at night. Acute toxicity for alkaloids is higher at night than in day. At evening the sensitivity to the sedative and narcotic substances is bigger. For anesthetic in dentistry the better time for usage is 2-3 o’clock. Daily variation is typical for absorption, transportation and decomposition of some medicinal substances. For example, the time of semi-decomposition of prednisolon at morning in 3 times more than at evening. It is connected with a periodicity of enzyme system of liver and kidney function. Chronopharmacology is a science which studied questions of action a medicinal substance on the organism depending to the time and season. It established a principles and rules of rational application of medicines. The important role in daily changes of pharmacokinetics plays the intensively of exchange reaction and complex interaction of glands internal secretion. In connection with a periodic absorption, transformation, elimination of medicines and sensitivity, the actual question is the synchronous of time and high activity of medicine. When these maximums are agree the efficiency of medicine will be increased significantly. Patterns of alcohol use and the human body Alcohol Abuse Refers to patterns of problem drinking that have resulted in detrimental effects on both social and health problems. Alcohol can have negative effects on the social well-being and physical health of the problem drinker. Alcohol Dependence • Often referred to as Alcoholism. • Refers to a disease characterized by compulsive alcohol-seeking behavior that leads to the inability to control drinking. Differences between Abuse and Dependence Alcohol dependency and alcohol abusers experience many of the same harmful effects of drinking. Critical difference is the physical dependence displayed by alcoholics and their lack of ability to regulate their consumption of alcohol. Alcoholics will continue to drink in spite of severe negative consequences of their drinking. Warning Signs of Problem Drinking • Frequently drinking to state of intoxication. • Using alcohol to seek relief from problems and cope with stress. • Engaging in antisocial behavior during and after drinking. • Going to work intoxicated or decline in job performance. • Experiencing family or economic problems. • Driving a car under the influence of alcohol. • Sustaining injuries as a result of intoxication. • Seeking out places where alcohol is available and avoiding places where it is not. • • • • • • • Tobacco smoking and the human body The most damaging compounds in tobacco smoke include: Tar – this is the collective term for all the various particles suspended in tobacco smoke. The particles contain chemicals including several cancer-causing substances. Tar is sticky and brown and stains teeth, fingernails and lung tissue. Tar contains the carcinogen benzo(a)pyrene that is known to trigger tumour development (cancer). Carbon monoxide – this odourless gas is fatal in large doses because it takes the place of oxygen in the blood. Each red blood cell contains a protein called haemoglobin – oxygen molecules are transported around the body by binding to, or hanging onto, this protein. However, carbon monoxide binds to haemoglobin better than oxygen. This means that less oxygen reaches the brain, heart, muscles and other organs. Hydrogen cyanide – the lungs contain tiny hairs (cilia) that help to clean the lungs by moving foreign substances out. Hydrogen cyanide stops this lung clearance system from working properly, which means the poisonous chemicals in tobacco smoke can build up inside the lungs. Other chemicals in smoke that damage the lungs include hydrocarbons, nitrous oxides, organic acids, phenols and oxidising agents. Free radicals – these highly reactive chemicals can damage the heart muscles and blood vessels. They react with cholesterol, leading to the build-up of fatty material on artery walls. Their actions lead to heart disease, stroke and blood vessel disease. Metals – tobacco smoke contains dangerous metals including arsenic, cadmium and lead. Several of these metals are carcinogenic. Radioactive compounds – tobacco smoke contains radioactive compounds, which are known to be carcinogenic. Tobacco smoking and the human body Effect of tobacco smoke on the male body •Lower sperm count •Higher percentage of deformed sperm •Reduced sperm mobility •Changed levels of male sex hormones •Impotence, which may be due to the effects of smoking on blood flow and damage to the blood vessels. on the female body •Reduced fertility •Menstrual cycle irregularities or absence of menstruation •Menopause reached one or two years earlier •Increased risk of cancer of the cervix Greatly increased risk of stroke and heart attack if the smoker is aged over 35 years and taking the Influencing of pathological processes and individual peculiarities of organism Important role in reaction of organism on the medicine plays the initial state of patient. Pathological processes result in to the violation of barrier function of biological membranes • to the changing of permeability of biological barriers to the changing of electrolyte homeostasis of fabrics Firstly, pathological processes (which are promotes a oxidation of lipids), inflammatory processes (cause to activation of phospholypase, hydlolysis membrane phospholipids). General stress reaction of organism also cause to changing of properties of all biological barriers. It influence on the bioavailability of medicines and effectivity of medical therapy for patients. Influencing of pathological processes Stress causes to the changing of properties of all biological barriers, strengthens the processes of the excitement and loosens of a cephalic braking There is retarding of excretion at the diseases of kidneys At the diseases of gastricintestinal tract and liver the processes of absorbtion and distribution of medications are violated Environmental factors affecting health Environmental factors affect human health in important ways, both positive and negative. Positive environmental factors sustain health, and promoting them is preventive medicine. They include: - sources of nutrition (farming: soil quality, water availability, biodiversity/bio-integrity, genetically modified organisms (GMOs); hunting, fishing: wildlife, fish populations.) - water (drinking, cooking; cleaning / sanitation); - air quality; - ozone layer (protection from UV, cancers, etc); - space for exercise and recreation; - sanitation / waste recycling and disposal. Negative environmental factors are threats to health, and controlling them is public environmental health. They include: - environmental conditions favouring disease vectors (endemic and exotic vectors); - invasive biota (viruses, bacteria, etc), their hosts and vectors; - environmental disruptions: floods, droughts, storms, fires, earthquakes, volcanoes; - air quality: pollen and pollution leading to respiratory diseases or cancers; -water quality: biotic and abiotic contaminants; integrity of water transport and treatment infrastructure; - monitoring and management of municipal, agricultural, industrial outflows to the environment (gases, liquids, solid wastes); - human changes of the environment that create conditions that favour disease; - disturb and release noxious levels of previously bound chemicals (e.g. mercury released becomes poison) or biota (e.g. methane released from thawed peat contributes to climate change); - create temporary, intense, life-threatening heat islands (e.g. urban heat waves exacerbated by climate change); - result from nuclear, biological or chemical warfare or terrorism. At the World Summit on Sustainable Development, Canada announced $3 million to support the initiative Strengthening Health and Environment Linkages: from knowledge to action. The Initiative will bring together scientific, technical and socio-economic information on environment and health linkages, and transfer that knowledge to inform decision-making at the local, regional and national levels. Canada is principally concerned with the health of Canadians. This involves health factors in Canada and in biologically-shared health regions (shared geography or exposure through trade and travel). Canada also supports international health initiatives, such as determining health risks through environmental analysis of disease vectors in Africa or Asia.