Download Lecture 3

“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 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."
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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.
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.
Pharmaceutical factors and their classification
Physical state of medicinal substance
PHARMACEUTIC
AL
Medicinal form
and ways of application
FACTORS
Auxiliary substances (their nature, physical state
and quantity)
Simple chemical updating of medicinal
substance
Technological process
Therapeutical activity of medicinal substances depends on:
Optical properties
Degree of ionization
Contain in molecul
crystalline
water
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.
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.
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.
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.
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:
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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.