Transcript 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 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."
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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.
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”;
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Introduction parenteral;
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Introduction “per rectum”;
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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.
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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
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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.