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Receptor theory of drug action.

Receptor theory of drug action. Receptor-effector system. = complex of processes extracelullar signal ------------- > intracell . signal cascade --------- > effector ( own effect ) receptor = protein, which interacts ligands involved in signal transduction

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Receptor theory of drug action.

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  1. Receptor theory of drug action.

  2. Receptor-effector system • = complexofprocesses • extracelullarsignal ------------->intracell. signalcascade--------->effector(owneffect) • receptor = protein, whichinteractsligands • involved in signaltransduction • effector = enzyme, ionicchanneletc. change in theactivityleads to theeffectofdrug • ligand(signalmolecule) = moleculeable to bind to specific receptor • endogenous - neurotransmitters, hormones • exogenous - xenobiotics

  3. Receptor-effector system • Affinity • ochota ligandu vázat se na příslušný receptor • 1/Kd • Instrinsicactivity • ability to evokeaneffectafterbinding to receptor • !!!the presence ofsufficientnumberof receptor fortheinductionofpharmacologicaleffectisessential as well as sufficientamountsofreceptor ligand!!!

  4. Receptor-effector system Relation between dose and effect

  5. Ligand classification • Agonist • FullagonistPartialagonist • IS= 1 - dualist • - IS in a rangefrom 0‹ to ›1 • Acts as antagonist in the presence offullagonist

  6. Ligand classification • Antagonist • IS = 0 • Blocksagonistbinding to receptor • Inverse agonist/superantagonist • IS = -1 • Stabilizesthe receptor in theconstitutiveactivity • Antagonism • competitive x non-competitive • Reversible x irreversible • on the receptor level x on theleveloffunction

  7. Antagonism • Competetive • ligandscompeteforthesamebindingsite •  c ofantagonistdecreasesagonisteffectandinversely • the presence ofantagonistincerasestheamountsofagonistneeded to evoketheeffect • Non-competitive • allostericantagonism • irreverziblebounds •  c ofagonistdoes not interrupttheeffectofantagonist

  8. Antagonism • Chemical • druginactivation by formingcomplexeswithothermolecules (protamine + heparin) • Physiologic • drugintereaction on theleveloffunction, drugsevokingoppositeeffects by differentmechanism (diuretics + vassopresin, nitrates + α1 agonists)

  9. Regulation of receptor sensitivity and counts • Desenzitization • decreaseof sensitivity to receptorsafterrepeatedexposition to agonists • interruptionofsignalcascade– tachyphylaxis (nitrates) • down-regulation, internalization - opioids

  10. Regulation of receptor sensitivity and counts • Hypersensitivity • inceraseof receptor sensitivity/countsafterchronicanatagonistexposure • βblockers

  11. PHARMACOLOGY OF THE PERIPHERAL NERVOUS SYSTEM PharmDr. Ondřej Zendulka, Ph.D.

  12. Peripheral nervous system Somatic • voluntary control • skeletal muscles Autonomic • smooth muscles • regulation of visceral organs • part of neurohumoral regulation

  13. Autonomic nervous system Afferent nerve fibre - non-myelinized - perception of pain - visceral perception - blood pressure regulation - breathing - heart rate Efferent neurons - vegetative neurons and ganglia - sympathetic n. - parasympathetic n. receptor stimulus Central part of ANS - medulla oblongata and hypothalamus organ, tissue

  14. Autonomic nervous system Efferent part of ANS • 2 neuronal pathway • preganglionic n. • postganglionic n. • chemical transmission of neural impulse- vegetative ganglia • fibres forms plexes – innervated area overlap • work in function uniformity

  15. Vegetativní nervový systém

  16. Autonomic nervous system Sympathetic = adrenergnic system • thoracolumbal s. • fight or flight • noradrenaline(NA), acetylcholine, (AcChol) •  a ß receptors Parasympathetic = cholinergnic system • craniosacral s. • rest and digest • acetylcholine • N a M receptors

  17. Cholinergnic receptors Nicotinic receptors • 3 types: muscular(NM), ganglionic(NG) and CNS (NB) • ligand-gated ion channels Muscular Rc • neuromuscular junction Ganglionální Rc • ANSganglionic transmission CNS Rc • in brain

  18. Cholinergnic receptors Nicotinic receptors • 3 types: muscular(NM), ganglionic(NG) and CNS (NB) • ligand-gated ion channels Muscular Rc • neuromuscular junction Ganglionální Rc • ANSganglionic transmission CNS Rc • in brain

  19. Cholinergnic receptors Nicotinic receptors • 3 types: muscular(NM), ganglionic(NG) and CNS (NB) • ligand-gated ion channels Muscular Rc • neuromuscular junction Ganglionální Rc • ANSganglionic transmission CNS Rc • in brain

  20. Cholinergnic receptors Nicotinic receptors • 3 types: muscular(NM), ganglionic(NG) and CNS (NB) • ligand-gated ion channels Muscular Rc • neuromuscular junction Ganglionální Rc • ANSganglionic transmission CNS Rc • in brain

  21. Cholinergnic receptors Nicotinic receptors • 3 types: muscular(NM), ganglionic(NG) and CNS (NB) • ligand-gated ion channels Muscular Rc • neuromuscular junction Ganglionální Rc • ANSganglionic transmission CNS Rc • in brain

  22. Cholinergnic receptors Nicotinic receptors • 3 types: muscular(NM), ganglionic(NG) and CNS (NB) • ligand-gated ion channels Muscular Rc • neuromuscular junction Ganglionální Rc • ANSganglionic transmission CNS Rc • in brain

  23. Cholinergic receptors Nicotinic receptor • all subtypes are pentamers • two binding sites for AcChol

  24. Cholinergnic receptors Muscarinic receptors • 5 types M1-M5, G-protein coupled • M1-M3 well characterized M1 • neural – CNS and ANS • membrane depolarization • decreased activity in brain = dementia • controls the production of gastric HCL

  25. Cholinergnic receptors M2 • cardial Rc • autoreceptors • inhibitory influence M3 • glandular/smooth muscle • stimulation of secretion and contraction/relaxation of smooth muscles M4,M5 - in CNS

  26. Cholinergnic receptors M4 a M5 • převážně v CNS • úloha není známa M1, M3, M5 –spojené s IP3 and DAG M2 a M4 –spojené s cAMP

  27. Adrenergic receptors

  28. 1 receptors

  29. 2, receptors:

  30. Autonomic nervous system The activity is mutually regulated • heterotropic interactions • homotropic interactions • most of visceral organs is inervated by both S and PS • opposite activity - bronchi, heart, bladder,,… • similar action – salivary glands • only S – blood vessels

  31. Pharmacology of autonomic nervous system Classification with regard to MofA: • ligands of adrenergic and cholinergic receptors • agonists - direct MIMETICS • antagonists – direct LYTICS ..................................................................................... • drugs changing the synaptic activity of neurotransmitters – influence the synthesis, storage, release or inactivation = INDIRECT PARASYMPATHOMIMETICS/PARASYMPATOLYTICS

  32. Pharmacology of autonomic nervous system

  33. Pharmacology of autonomic nervous system

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