Pharmacodynamics

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Contents of pharmacodynamics

The pharmacodynamics is the study on the effect of drugs in the body and a branch of pharmacology . It deals with various aspects such as the profile of action, the dose-effect relationship, the mechanism of action and the interactions of a drug with other molecules.

While pharmacodynamics describes the effect on the body, pharmacokinetics deals with distribution and metabolism in the body.

Action profile

The action profile is determined by the type and location of the action of a drug (which effects occur? Which organs / structures or biological functions are influenced?).

Most active ingredients have a specific effect . Their effect is largely dependent on the molecular structure , i. H. bound to certain chemical, functional structures. Therefore, due to their partially similar structure , analogous compounds can have similar effects. Active ingredients usually work in low doses or concentrations and at a precisely defined target. The presence of multiple effects in one drug is known as pleiotropy . Few active ingredients are unspecific . Despite their different chemical structures, they have similar effects. They are more likely to be effective in high doses or concentrations. In the course of an active ingredient design , the properties of an active ingredient are specifically adapted.

Dose-response relationship

Against the background of the effectiveness and safety of a drug, the dose-effect relationship is of central importance (which doses are ineffective? At which doses do effects occur? How strong are the effects depending on the dose? Which doses are toxic?).

For example, a double dose does not necessarily have twice the effect. One then speaks of a non-linear dose-effect relationship.

Some drugs have a narrow therapeutic index . This means that the effective dose is close to the toxic dose. The effects of such drugs must therefore be carefully monitored. The usefulness of such ordinances must generally be critically questioned.

Mechanism of action

Selection of molecular mechanisms of pharmacological agents

The mechanism of action explains how the effect occurs on a biochemical or biophysical level. The structure-activity relationship is particularly informative for understanding the mechanism of action . In addition to the chemical formula, the spatial arrangement of the atoms in the molecule can also determine the mechanism of action. Substances are known which have different effects depending on their isomeric form.

Almost all drug effects are based on a few mechanisms of action, which can be classified as follows:

Interaction with receptors

Receptors are cell structures that, through binding with a ligand (e.g. a neurotransmitter ), trigger a signal transduction according to the lock and key principle , which in turn causes a certain effect. A distinction is made between intracellular ( i.e. localized in the cytoplasm or cell nucleus ) and membrane-based receptors. By stimulating or blocking such a receptor with a substance or structure similar to the natural ligand, an effect can be generated or suppressed.

Examples: blockade of adrenoceptors by sympatholytics ( alpha blockers , beta blockers ), stimulation of adrenoceptors by sympathomimetics , blockade of histamine receptors by antihistamines Active ingredients can be classified as agonist , partial agonist , antagonist by their effect on the receptor . With multiple ligands there are often changes in the extent of an effect due to interactions, e.g. B. in the form of a synergy , a Loewe additivity , a bliss independence or an antagonism.

Influencing enzyme activity

Another mechanism of action that is frequently encountered is the activation or inhibition of an enzyme activity . In addition to the catalysis of numerous biochemical reactions in the organism, enzymes are also responsible for regulation, e.g. B. protein kinases .

Examples: lowering the concentration of angiotensin II by ACE inhibitors (with the aim of vasodilation and thus diuretic effect); Inhibition of bacterial gyrase by gyrase inhibitors such as the fluoroquinolones ( antibiosis ).

Influence of voltage-dependent ion channels

Ion channels enable the transport of ions such as B. sodium , potassium , calcium and chloride through the cell membranes . They can be activated by various mechanisms. In addition to the receptor interaction ( see above: interaction with receptors), influencing by changing the membrane potential is possible.

Examples: Reduction of intracellular calcium concentrations by blocking the absorption carriers or channels with calcium channel blockers (lowering of the heart load due to reduced oxygen demand and lower blood pressure); Reduction of the sodium ion concentration in axons by local anesthetics (disturbance of the transmission of stimuli or failure of painful sensations dependent on it, see also local anesthetic # mechanism of action ).

Influencing transport systems

Medicinal substances can also develop their effects by influencing ion pumps or carrier systems.

Example: Inhibition of the proton potassium pump by proton pump inhibitors (suppression of hydrochloric acid production in the stomach )

Inhibition of biosynthesis in microorganisms

A large number of anti-infective therapies are based on the disruption of the pathogen's biosynthesis .

Examples: inhibition of bacterial cell wall synthesis by β-lactam antibiotics , disruption of bacterial folic acid synthesis by sulfonamides , inhibition of bacterial protein synthesis by macrolides , inhibition of mycotic ergosterol synthesis by azole antimycotics

literature

  • E. Mutschler, G. Geisslinger, HK Kroemer, P. Ruth, M. Schäfer-Korting: Mutschler - drug effects, textbook of pharmacology and toxicology; Basic knowledge of pharmacology / toxicology. With introductory chapters on anatomy, physiology and pathophysiology , WVG Stuttgart 2005, ISBN 3-8047-2251-2 .
  • Philipp FW Vogt: Textbook of Pharmacodynamics , Giessen 1821 (first single work on pharmacodynamics).

Individual evidence

  1. ↑ Aktories, Klaus ; Förstermann, Ulrich; Hofmann, Franz; Starke, Klaus (Ed.): General and special pharmacology and toxicology. (Founded by W. Forth, D.Hentschler and W. Rummel). 10th edition. Urban & Fischer, Munich / Jena 2009, ISBN 978-3-437-42522-6 , pp. 2, 5, 7f.
  2. ↑ PJ Yeh, MJ Hegreness, AP Aiden, R. Kishony: Drug interactions and the evolution of antibiotic resistance. In: Nat Rev Microbiol. (2009), Volume 7, No. 6, pp. 460-466. doi : 10.1038 / nrmicro2133 . PMID 19444248 ; PMC 2855488 (free full text).