Good

1. Pharmacodynamics
Pharmacodynamics is a part of general
pharmacology which studies drug
effects and mechanisms of their
development.
Pharmacodynamics studies drug
pharmacological effects, their
localization, strength and mechanisms
of the effect development.

2. Pharmacological effects
Pharmacological effect is the final
result of a drug action on an organism

3. There are two groups of
pharmacological effects:
Main (basic)
effects
Adverse (side)
effects
They are effects providing
therapeutic (curative)
action of a drug
for the sake of which
the drug is used
in medical practice
They are the rest of effects
developing in an organism
after a drug administration.
Adverse effects
are
unwanted (unfavorable)
for an organism.

4. Kinds of pharmacotherapy
Etiotropic therapy
This is administration
of a drug acting on
the cause of a disease
(e.g. staphylococcal pneumonia
is treated by antibiotics).
Pathogenetic therapy
This is administration of a drug influencing
on pathogenesis of a disease.
Pathogenetic therapy is directed on
a weakening of mechanisms of
the disease development.
(e.g antiischemic drug Nitroglycerin
is capable to arrest attacks
of angina pectoris,
but it does not eliminate
the cause of the disease)

5. Kinds of pharmacotherapy
Symptomatic therapy
It only eliminates
some symptoms of a disease
(analgetics)
Replacement
(substitutive)
therapy
It is used in deficiency of
natural hormones,
enzymes
(e.g. deficiency of pepsin or insulin)

6. Possible mechanisms of drug action
Receptor mechanism
a majority of modern drugs
have the mechanism
Enzymatic mechanism
Drugs can act on enzymes as their inducers
(inductors) or as inhibitors (blockers)
(e.g. neostigmine, nialamide).
Influence on ion channels
Action potential does not appear in case of absence of ion transport.
Smooth muscles do not contract in case of absence
of calcium ion flow
(e.g. blockers of calcium channels result in relaxation of
smooth muscles of vessels)

7. Influence on transport systems
There are great number of transport systems in living organisms
for movement of enzymes, hormones, etc.
(HCl is produced from H+ and Cl- in parietal cells of the stomach
with the help of special hydrogen pump.
Omeprazole inhibits the pump and production of HCl is decreased).

8. Characteristics of receptor
action of drugs
Types of receptors
Membranous
Cytoplasmic
(cytosolic)
Nuclear

9. Families of receptors
1. Ligand-gated ion channels
Examples: Cholinergic nicotinic receptors, GABAA-receptors,
NMDA-receptors
2. G protein-coupled receptors
Examples: α- and β-adrenoceptors, cholinergic muscarinic receptors
3. Enzyme-linked receptors
Examples: Insulin receptors
4. Intracellular receptors
Examples: Steroid receptors

11. Receptors are very dynamic structures.
A majority of receptors can be
changed under the influence of drugs.
There are specific mediators
(endogenous ligands)
for receptors in an organism.
Drugs acting on receptors similarly endogenous ligands
are called mimetics (agonists)
Drugs acting oppositely endogenous ligands are called
lytics (antagonists) or blockers

12. A medicinal substance can interact with a
receptor in case of existence of affinity
(relation).
The more affinity, the drug action is more
selective and directional.
The main task of modern pharmacology is
search of drugs with a high degree of
selectivity of their action.

13. Pharmacological effects
depend on various factors:
External (environmental) factors
Medicinal preparation
properties
Internal factors
(an organism condition)

14. Drug properties
I. Chemical structure
1. Activity 2. Solubility
3. Ability to pass
via
biological barriers
4. Ability to combine with
enzymes
depend on presence of some chemical groups
in a drug chemical formula.

15. II. Stereoisomerism
A drug can have a few stereoisomers –
e.g. laevorotary stereoisomers of
adrenaline and camphor are more
active then dextrorotatory ones.
Racemates are mixture of equal quantities of two
enantiomers, substances whose molecular
structures are mirror images of one another

16. Pharmacological activity of a drug
depends also on:
Its aggregative state
Solubility
pH of medium Polarity
Temperature

17. All drugs have adverse (unwanted)
effects worsening a life quality of
patients.
A drug must not be administered until all
adverse effects will be determined
(e.g. antipsychotics eliminate psychosis
but decrease amount of sex hormones in
patients).

18. CLASSIFICATION OF ADVERSE EFFECTS
(offered by World Health Organization)
4 groups:
Type A – adverse effects which depend
on pharmacodynamics of drug.
Such reactions are predictable.
A drug should be carefully studied in clinical
trials before its incoming to pharmaceutical
market.
All noted adverse effects are listed in an
annotation (instruction for drug use). A
doctor must know them and must prevent
them.

19. Type B – adverse effects of immuno-
allergic character.
They are genetically predetermined reactions
and depend on individual features of a person.
They are not predictable.
Allergic reactions develop as a result of
hypersensibility of an organism.
Hypersensibility is redundantly (excessively)
increased sensitivity of a person to a
substance (including drugs).
Idiosyncrasy is a perverted (unnatural)
immune reaction.
Allergy and idiosyncrasy make up about
25% of all adverse effects.

20. Type C - adverse effects which develop
in long-term pharmacotherapy.
They have a toxic character
(e.g. ototoxicity, hepatotoxicity)
These effect can be accumulated.
Type D - delayed adverse reactions.
They appear in some months and even in
some years after discontinuation of a
drug administration.

21. Drug use during pregnancy can be
unsafe for antenatal development of a
fetus. Drugs can have embryotoxic,
teratogenic, fetotoxic and mutagenic
actions.
Embryotoxic action is a damage of
unimplanted blastocyst resulting in its
death. Toxic drug action on an embryo
develops in first days and weeks (1-3
weeks) from the beginning of
fertilization.

22. Teratogenic action is a result of a
drug administration mainly from 3 to
10-12 weeks of pregnancy.
Process of organogenesis occurs in this
period.
Drug administration can result in
disturbance of tissue differentiation.
Infants can be born with different
abnormalities of their development
(with malformations).

23. Fetotoxic action is negative effect of a
drug directed on ripening (maturing) fetus.
Fetal period lasts from 3-4 month to the end
of pregnancy.
Drug administration in the latter
half of pregnancy without
physician’s control can result in
negative action on a fetus.

24. Adverse reactions can be determined by
pharmacokinetics of drugs
e.g. sulfanilamides excreted through
kidneys with urine can form urinary
sediment (crystals) consisting of
their salts
Crystalluria

25. Reactions of an organism in
repeated drug administration
Tolerance is a decrease of a drug effect
in consequent administration.
(e.g hypnotics, antihistaminic drugs)
Tachyphylaxis is acute tolerance.
(e.g ephedrine)
Tolerance can be overcame by change of
causal drug.

26. Cumulation
Material cumulation is accumulation
of a drug in an organism.
(barbiturates are accumulated in the
adipose tissue, cardiac glycosides are
accumulated in the myocardium)
Functional cumulation is observed
when a drug is eliminated, but its
effects are accumulated.
(e.g. ethyl alcohol)

27. Drug dependence (abuse)
It develops in administration of drugs with a
psychotropic action. Narcotic substances are
capable to cause euphoria, propensity
(addiction).
Drug addiction develops in repeated
administration of the drugs.
Euphoria is a feeling of great happiness or
well-being

28. Mechanism of euphoria development is related
with endorphin- enkephalinase system
(hormones of happiness).
Drug dependence (abuse) is manifested by:
Physical dependence Psychic dependence
For the most of psychotropic drugs the reactions are sequential.

29. Physical dependence is more serious
condition than psychic dependence.
Different disorders of functioning of internal
organs (an increase in ABP, intermittences in
the heart work), endocrine system, etc. are
observed.
In such condition, a drug addict is ready for
any action.
In case of absence of a narcotic, abstinence
(withdrawal) syndrome develops in
persons with physical and psychic
dependence.
Dependence to toxic substances is called
toxicomania.

30. Reactions of an organism in sudden
discontinuation of drugs
Some drugs must not be abolished suddenly.
After their discontinuation, a withdrawal
syndrome can occur (sharp exacerbation of
disease symptoms).
E.g. sudden discontinuation of β-adrenergic
blocker and clonidine administration can
result in a severe increase in ABP.
Discontinuation of hypnotic administration can
result in sleeplessness.

31. Interaction of medicinal substances in
their simultaneous administration
Interactions of medicinal substances can be divided into:
pharmacodynamic pharmacokinetic pharmaceutical
Pharmaceutical interaction is an interaction of
medicinal substances during manufacturing of drugs.
Pharmacokinetic interaction is an interaction of drugs
in routes of administration, absorbtion, metabolism
and excretion.
Pharmacodynamic interaction is an interaction
of drugs at the place of their action.

32. In pharmacodynamic interaction between two
drugs synergism or antagonism can occur.
Synergism can be summarized and potentiated.
Summarized synergism is such interaction of
medicinal substances when common pharmacological
effect is equal sum of effects of two components.
Potentiated synergism is such interaction of medicinal
substances when common pharmacological effect of
two drugs exceeds sum of their effects.
It means that one substance intensifies (potentiates)
action of the another substance.
Synergism is unidirectional action of two or
a few medicinal substances.

33. Antagonism is opposite action of two drugs.
Antagonism is such interaction of medicinal
substances when full suppression or
weakening of a pharmacological effect of one
substance by another substance occurs.

34. Antagonism can be:
 direct (competitive)
 indirect (noncompetitive)
 one-sided
 double-sided

35. Direct functional (competitive) antagonism
develops in that case when medicinal substances
act on same cells or their receptors but in the
opposite direction.
E.g. a stimulator of muscarinic cholinoceptors
aceclidine and a blocker of these receptors
atropine act as direct functional antagonists.

36. Indirect functional antagonism occurs in case
when medicinal substances act as antagonists on
different receptors.
E.g. β2 – adrenoceptor agonist (salbutamol,
fenoterol) act as indirect antagonists in bronchial
asthma.
Bronchospasm is caused by a mediator of allergy
histamine which acts on histamine H1-receptors.
Salbutamol and fenoterol have bronchodilatory
action due to action on β2- adrenoceptors.

37. Pharmacological action of a medicinal
substance depends on its dose and
concentration.
Dose is amount of a drug for one administration – single
dose. Doses are noted in mass units (grams or parts
of gram).
Minimal (threshold) dose causes initial therapeutic
effect.
Average therapeutic dose determines average
pharmacological effect in most of patients.
Maximal therapeutic dose causes maximal
therapeutic effect. Maximal therapeutic dose is about
three average therapeutic doses.
Dose ranges from threshold up to maximal is called as
width of therapeutic action.

38. Ratio between maximal therapeutic effect and
threshold dose is called index of therapeutic
action.
The higher width of therapeutic action, the drug
is more safe.
Knock-out dose is used to provide
maximal concentration of a drug in the intestine
and blood plasma and to cause rapid and strong
effect.
Knock-out dose is usually doubled single dose.
After knock-out dose administration maintaining
dose is used.

39. Dose is one of the most important factors
determining rapidity, character, strength and
duration of a medicinal substance action.
Concentration of a medicinal substance in the blood and
intercellular space depends on its dose.
The more concentration of medicinal substance near
receptors, the more probability of its action on the
receptors
e.g. Pentobarbital in a certain dose range has hypnotic
effect.
When its dose is increased, narcosis can develop. In
further increase of its dose, toxic action and fatal outcome
occur.

40. It is necessary to remember, that dose-response
relationship is not always linear,
i.e. an increase in dose does not always result in equal
increase in therapeutic effect.
Linear Hyperbolic Parabolic
Sigmoid
It has been determined, that dose-response relationship
and concentration-response relationship can be

41. Influence of internal factors (individual
features of an organism) on drug action
 Age
 Sex
 Functional state of an organism,
different organs and systems
 Biological rhythms
 Genetic factors
 Hereditary enzymatic deficiency
 Abnormalities of functional activity
and dynamic topography

42. Administration of drugs to patients of
different ages (old people and young
children) requires a particular caution.
In elderly age, reactions on drug
administration are changed because of
“physiologic ageing” (senescence) of
organs, tissues and a decrease of
metabolic exchange.

43. Elderly patients suffer, as a rule, from a
few diseases.
Frequency of adverse effects on drugs is
increased with ageing.
Biotransformation rate is decreased, as a
result of slowing of drug metabolism.

44. Elimination rate is decreased, as a result of a
decrease of renal blood flow.
Quantity of functioning glomeruli is decreased on
30% up towards 65 year age. Tubular secretion
becomes slower.
Taking into account features of elderly age, it is
necessary to decrease a dose of most of drugs on
1/3 or ½ from average therapeutic doses for
adults.

45. In a child’s life, there are some periods
when pharmacokinetics and
pharmacodynamics of drugs essentially
differ from adult ones.
1. Antenatal
(before the birth)
2. Intranatal
(period of childbirth)
3. Neonatal
(up to 4 weeks after the birth
4. Period of infancy
(up to 1-year age)
5. Period of early childhood
(from 1-year up to 3-year age)
After 5-year age, clinical-pharmacological parameters
at children not much differ from adult ones.
At newborns, rate of oxidative reactions
with cytochrome P-450 is decreased in two times.

46. So, biotransformation of medicinal substances is
decreased. Kidney functions is decreased too.
Thereby, elimination of drugs is decreased, and
their half-life is increased.

47. Reactions of females on a drug
administration, in many respects, depend
on constitutional and hormonal features.
Hormonal background in females is
changed during a menstrual cycle.
Usually inactivation of xenobiotics in the
liver of females occur slower than at
males.

48. INFLUENCE OF EXTERNAL
(ENVIRONMENTAL) FACTORS ON DRUG
ACTION
 climate, environment
 social factors