“ Biological and exogenic factors”

1. “Biological and exogenic factors” Lecture 3

2. 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.

3. 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 inter-individual 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."

4. 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 (inter-individual 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.

5. Amount of medicinal substance which gets in a system blood stream at the different ways of introduction, differs: While parenteral introduction of the medicinal substance the bioavailibility is equal 100 % At other ways of introduction (“per os”, “per rectum”, intramuscularly etc.) is less than 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.

6. Pharmaceutical factors and their classification Physical state of medicinal substance Medicinal form and ways of application PHARMACEUTICAL FACTORS Auxiliary substances (their nature, physical state and quantity) Simple chemical updating of medicinal substance Technological process

7. Therapeutical activity of medicinal substances depends on: Optical properties Among optical isomers there is no chemical distinction, but each of them revolves the plane of polarization ray in certain direction. In spite of the fact that the chemical analysis fully confirms the presence of the same substance in medicine with different isomers, they will not be therapeutically equivalent. Depending on concentration of hydrogen ions the medicinal substances can be in the ionized or unionized form. pH index influences also on the solubility, coefficient of distributing of medicinal substances, membrane potential and superficial activity. Degree of ionization The waterless medicinal substances and crystallohydrate has a different solubility that causes change of their pharmacological action. For example, the waterless forms of caffeine, ampicillin, teophylline dissolve quickly, as compared to their crystallohydrate and consequently is quickly sucked. Contain in molecul crystalline water

8. Many factors are responsible for the entry of a drug into the body and then into biophase. These factors include the route of administration; the dosage form; the liberation rate of the drug from the dosage form; dissolution; penetration and permeation of the drug through biomembranes; its distribution within the body fluids and tissues; the type, amount and rate of biotransformation; and recycling processes and elimination. In addition to these factors, pharmacogenetics and certain pathophysiological conditions also affect the above process. The entire process can be described as the LADMER (liberation, absorption, distribution, metabolism, elimination and response) system showing that liberation, absorption, distribution, metabolism and elimination are involved to elicit the response. One can subdivided this approach according to the scheme shown in fig.

9. Many factors are responsible for the entry of a drug into the body and then into biophase. These factors include the route of administration; the dosage form; the liberation rate of the drug from the dosage form; dissolution; penetration and permeation of the drug through biomembranes; its distribution within the body fluids and tissues; the type, amount and rate of biotransformation; and recycling processes and elimination. In addition to these factors, pharmacogenetics and certain pathophysiological conditions also affect the above process. The entire process can be described as the LADMER (liberation, absorption, distribution, metabolism, elimination and response) system showing that liberation, absorption, distribution, metabolism and elimination are involved to elicit the response. One can subdivided this approach according to the scheme shown in fig.

10. 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.

11. 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; • disruption caused by other war and violence.