general pharmacology
special pharmacology

(molekulární, buněčné, orgánové i na úrovni celého organismu)
















Aspirin_03 aspirin1



BASICS OF PHARMACODYNAMICS






NON-SPECIFIC MECHANISMS OF ACTION



NON-SPECIFIC MECHANISMS OF ACTION



NON-SPECIFIC MECHANISMS OF ACTION



NON-SPECIFIC MECHANISMS OF ACTION
•ADSORBENTS
•
•
•SUBSTANCES WITH LARGE SURFACE BINDING (ADSORBING) OTHER SUBSTANCES, TOXINS, ETC. - CHARCOAL
•

NON-SPECIFIC MECHANISMS OF ACTION



SPECIFIC MECHANISMS OF ACTION
•
1.RECEPTORS
2.ION CHANNELS
3.ENZYMES
4.CARRIERS







lock and key image






Image48









Antagonism
Competitive
üligands compete for the same binding site
ü c of antagonist decreases agonist effect and inversely
üthe presence of antagonist incerases the amounts of agonist needed to evoke the effect
Non-competitive
üallosteric antagonism
üirreverzible bounds
ü c of agonist does not interrupt the effect of antagonist

ANTAGONISM
Physiological antagonism
a)
Two different ligands act on different target structures and their opposite effects occur in the
same organ.
Histamine x norepinephrine (affecting of vessels).
Affecting of bronchioles.
http://pulmonaryintmed.com/c/Portals/1/Pictures/Bronchiole_Normal_vs_Asthmatic.jpg
¥ (H1)
¥ (β2)
histamine (bronchoconstriction)
salbutamol
(bronchodilatation)

•HYPERSENSITIVITY - INCERASE OF RECEPTOR SENSITIVITY/COUNTS AFTER CHRONIC ANTAGONIST EXPOSURE
•
•REBOUND PHENOMENON
•AFTER DISCONTINUATION OF LONG-TERM ADMINISTERED DRUGS RETURN TO ITS ORIGINAL STATE OR ↑ INTENSITY
OF THE ORIGINAL CONDITION (HYPERSENSITIVITY OF RECEPTORS TO ENDOGENOUS LIGANDS → UP-REGULATION)
•EXAMPLE: CHRONIC ADMINISTRATION OF Β BLOCKERS

    Up regulation of β-receptors following long-term therapy
-
-abrupt cessation of therapy may lead to excessive stimulation of β-receptors
    thereby exacerbating the symptoms
Figure 3. Representation of beta-receptor density changes as a result of chronic beta-antagonist
therapy. A. Representation of beta-receptor density on cardiac myocyte prior to initiation of
beta-antagonist therapy. B. Reduction in beta-receptor stimulation after initiation of beta
antagonist. C. Receptor upregulation as a result of chronic beta-receptor blockade. D.
Supersensitivity of cardiac myocyte following abrupt withdrawal of beta-antagonist therapy.
A.Representation of beta-receptor density on cardiac myocyte prior to initiation of beta-antagonist
therapy.
B.
B. Reduction in beta-receptor stimulation after initiation of beta antagonist.

C. Receptor upregulation as a result of chronic beta-receptor blockade.

D. Supersensitivity of cardiac myocyte following abrupt withdrawal of
    beta-antagonist therapy.
rebound phenomenon !

•DESENSITIZATION – REDUCED RECEPTOR SENSITIVITY/COUNTS AFTER CHRONIC AGONIST EXPOSURE
•TOLERANCE –  REDUCED SENSITIVITY TO THE ACTIVE SUBSTANCE, ARISING FROM THE REPEATED ADMINISTRATION
OF THE DRUG (DAYS – WEEKS) → DOWN-REGULATION
•EFFECT REQUIRES INCREASINGLY HIGHER DOSES
•THE ORIGINAL REACTIVITY RETURNS A CERTAIN PERIOD OF TIME AFTER DISCONTINUATION OF THE DRUG
•EX. OF TOLERANCE – OPIOIDS ADMINISTRATION







Receptor clasification



Katzung BG, 2001
rcpt_sys_nic_ag1


auto1



Kinase-linked receptors
Insulin receptor
tyrosine kinase activity
glucose transporter
glucose
↑cell metabolism
↑phospho-
 rylation
of proteins




http://cdn.pharmacologycorner.com/wp-content/uploads/2009/01/types-of-drug-receptors.jpg



BASICS OF PHARMACOKINETICS















          AUCpo
F =   -----------
          AUC iv
http://icp.org.nz/icp_t6.html?htmlCond=1

obrazek lepsi2
čas
Oral administration
AUC

Presystemic elimination
First pass effect
intupta
http://icp.org.nz/icp_t6.html

3l –plazma, 12l –extracel. tekutina, 42l –celk.těles.tek., 1000l – depo!



The apparent volume of distribution, Vd, is defined as the volume that would contain the total body
content of the drug at a concentration equal to that present in the plasma
http://icp.org.nz/icp_t3.html?htmlCond=0

Příklad léčiva s nízkým distribučním objemem



Příklad léčiva s vysokým distribučním objemem



http://icp.org.nz/icp_t2.html



More hydrophilic compounds, sometimes active metabolites



http://icp.org.nz/icp_t1.html



polocas1
http://icp.org.nz/icp_t4.html

biologický poločas