general pharmacology
special pharmacology

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
















Aspirin_03 aspirin1



BASICS OF PHARMACODYNAMICS















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

Hypersensitivity
üincerase of receptor sensitivity/counts after chronic anatagonist exposure

Rebound phenomenom
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
ü
•Regulation of receptor sensitivity and counts

•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

•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 classification



Katzung BG, 2001
rcpt_sys_nic_ag1


auto1



Image50 insulin-receptor-GLUT4_w500









BASICS OF PHARMACOKINETICS















obrazek lepsi2
čas
Oral administration
AUC

•
•Effects of different bioavailability (F) on the
pharmacokinetics

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

http://icp.org.nz/icp_t3.html?htmlCond=0

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

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