Principles of Pharmacology an der RWTH Aachen

= Development & application of (modern) chemical tools for the investigation of biological processes & phenomena.

- drug = heterogeneous chem. Substance, influence on biol. processes (except nutrients, O2, endogenous metabolites,...)

- toxicology = study of harmful effects

- generic drug name = INN, globally recognized name for active ingredient (acetylsalicylic acid)

- trade name = Commercial name by the company (Aspirin)

- Morphine: extraction from opium -> milk sap extracted from poppy plants (varying proportion, isolation relevant in terms of medication).

- Opium components: morphine, codeine, noscapine, papaverine

- small molecules drugs = micromolecular "weight class" (< 800 g mol-1); take up a large proportion of active ingredients -> e.g. acetylsalicylic acid

- biologicals (protein drugs) = produced by biologic systems (incl. recombinant proteins); macromolecular "weight class" -> insulin

- Other: Ions (Li+), noble gases (Xe), specific Carbohydrates (Heparine), ...

- Drug Receptor Concept: development of the understanding of the term receptor

- Ehrlich: bound bodies act together - Changeux: site of action of a pharmaceutical - today: receptor = endogenous molecular target (protein, o.a. DNA) that binds the drug and mediates its effect

Pharmacodynamics = study of the effect of the active ingredient on the organism.

- receptors

- Signal transduction proteins (e.g. phosphodiesterase)

- (effector) enzymes (e.g. glycogen phosphorylase)

Pharmacokinetics = investigation of the effect of the organism on the active substance

- Transport proteins (e.g. monoamine transporters)

- Drug-metabolizing enzymes (e.g. ADH)

- Binding proteins (e.g. albumin)

- druggability = functional regulation of proteins via drugs

- Affected: Receptors (activation o. blockade), transporters/ion channels (blockade), enzymes (inhibition, allost. activation), protein-protein WW if applicable.

BC/phys. Receptors = for endogenous chemical signals

- G protein-coupled receptor (GPCR), also 7-transmembrane or heptahelical receptors -> e.g. adrenergic (responding to [nor]adrenaline) receptors

- Ligand-gated ion channels (LGIC), also ionotropic receptors -> nicotinic acetylcholine receptor, GABA_A-R.

- Enzyme-linked receptors, protein kinase or guanylate cyclase activity -> insulin receptor

- Nuclear receptors, ligand-regulated transcription factors -> glucocorticoid receptor

Pharmacolog. Receptors = drug targets

- Enzymes: acetylsalicylic acid acts on cyclooxygenase

- Transporters: Paroxetine acts on monoamine transporter

- Ion channels: Menthol acts on TRP channels

- other targets: Heparin acts on antithrombin III

- Agonist = fixes active conformations, full agonists elicit max. signal at the interrogated pathway (e.g. endogenous ligands)

- (neutral) antagonist = no effect on receptor, blocks binding site for agonist (no change in equilibrium, alpha = 0)

- Inverse agonist = fixes inactive conformation, decreases receptor activity

intrins. activity = effect size mediated by the drug (D) receptor (R) complex.

alpha 0:

- D does not bind o. irreversibly R

- D = antagonist

- D = 0 mM

- K_D = 0 mM

- (Experimental) pharmacology = branch of biology, the science of interaction between substances and living beings.

- The use of a chemical agent (morphine) on an organism (human) is intended to produce an effect (sleep induction) on the desired target (organ, cell, receptor)

- Areas: Molecular pharmacology, chemotherapy, biochemical pharmacology, ...