PHARMACOLOGY OF PERIPHERAL NERVOUS SYSTEM AUTONOMIC NERVOUS SYSTEM Department of Pharmacology Copyright notice The presentation is copyrighted work created by employees of Masaryk university. Students are allowed to make copies for learning purposes only. Any unauthorised reproduction or distribution of the presentation or individual slides is against the law. Nervous system Central nervous system Peripheral nervous system Somatic nervous system Autonomic nervous system afferent system central part HYPOTHALAMUS MEDULLA OBLONG. efferent system vegetative nerves + ggl. SYMPATHETIC NERVOUS SYSTEM PARASYMPATHETIC NERVOUS SYSTEM Autonomic nervous system peripheral part - non - myelinized fibers - pain perception - visceral perception Main functions of ANS • contractions and relaxations of smooth muscles • function of all exocrine and some of endocrine glands • heart functions • metabolic functions ANS Sympathetic = adrenergnic system • thoracolumbal s. • fight or flight • noradrenaline(NA) •  a ß receptors Parasympathetic = cholinergnic system • craniosacral s. • rest and digest • acetylcholine • N a M receptors 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 Note: ggl. S a PS NN receptors neuromusc. plate NMreceptors Autonomic nervous system Autonomic acting pharmaceuticals On the basis of mechanism of action - drugs: 1. binding to the receptors for Ach or NA: ⚫ a) starting reaction = agonist - DIRECT MIMETICS ⚫ b) receptor blockade = antagonist – DIRECT LYTICS ..................................................................................... 2. changing the synaptic concentration of NT – intervene in the fate of the Ach or NA (affect the synthesis, storage, release from nerve endings, inactivation); do not bind directly to receptors on the effector organs ⚫ a) increase of NT effect = INDIRECT MIMETICS ⚫ b) decrease of NT effect = INDIRECT LYTICS sympathotropic drugs sympatomimetics sympatolytics direct indirect alfa beta alfa1 alfa2 beta1 beta3 indirect direct alfa beta alfa1 alfa2 beta1 beta3 beta2 beta2 Vegetative acting drugs 2. sympatotropic Vegetative acting drugs 2. cholinotropic cholinotropic drugs cholinomimetics direct N M indirect cholinolytics indirect direct N M cholinotropic drugs cholinomimetics direct NN M indirect cholinolytics indirect direct NN M parasympatomimetics choline derivatives acetylcholinesterase (ACHE) inhibitors parasympatolytics ganglioplegics neuromuscular-blocking drugs NM Vegetative acting drugs 2. cholinotropic ANS RECEPTORS cholinergic receptors NICOTINE: N -skeletal muscle NM -vegetative ganglia NN -(CNS) MUSCARINIC: M1, M2, M3, M4, M5 adrenergic receptors  1 2  1 2 3 organ receptor sympathetic parasympathetic system system heart ß1 M + chrono, dromo, - chrono, dromo bathmo, inotropic bathmo, inotrop. eye 1 M 2 mydriasis miosis acomodation into the distance acom.to close respiratory tract (1) M 2 bronchoconstriction bronchoconstriction bronchodilatation secretion blood vessels 1 M (2) 2 vasoconstriction dilatation vasoconstr. dilatation (coronary, blood vessels in skeletal muscles) organ receptor sympathetic parasympathetic system system GIT 1 M 2 2>1 M ↓ motility and tone ↑ motility sphincter contraction sphincter relaxation secretion inhibition secretion stimulation ↑ gastr. secretion urinary bladder 1 M3 2, 3 sphinct. contraction sphinct. relaxation relax. of the bladder contract. of the wall bladder wall kidney 1>2 ↑ renin secretion uterus 1 2 contraction relaxation-tocolysis organ receptor sympathetic parasympathetic system system liver 1,ß2 glycogenolysis gluconeogenesis pancreas 2 2 insulin secretion insulin secretion sexual organs 1 M ejaculation erection glands 1 M 2 sparse secretion sparse significantly viscous secretion increased secretion Note: HEART positive chronotropic effect positive inotropic effect positive dromotropic effect positive bathmotropic effect Adrenergic receptors • metabotropic • 1, 2 a 1, 2 a 3 • stimulated by noradrenaline (norepinephrine) Receptor 1 stimulation: • vasoconstriction (skin, mucous membranes, splanchnic area,..) • mydriasis (+ ↓ intraocular pressure) • contraction of pregnant uterus • ejaculation • urinary bladder sphincter contraction, GIT sphincter contraction • glycogenolysis and gluconeogenesis stimulation • (reduce secretion of bronchial glands) • (presynaptic) increased NA release (espec. in CNS) • stimulation of platelet aggregation • vasoconstriction in local application, otherwise the influence of stimulation of central receptors to reduce sympathetic tone and BP • hypotensive effect of central mechanism • inhibition GIT secretion • inhibition of lipolysis, increased fat storage Receptor 2 stimulation: heart: •  HR (+ chronotropic effect) SA node •  automaticity (+ bathmotropic) AV node, ventricles •  force of heart contraction (inotropic effect) •  conduction (dromotropic effect) •  oxygen consumption kidney: •  renin secretion Receptor 1 stimulation : • vasodilatation, espec. in skeletal muscles ("preparation for fight or flight"),  diastol. BP, vasodilatation in coronar blood vessels • bronchodilatation • relaxation of uterus (indic. in impending preterm birth) • intestine wall relaxation • intestinal passage decrease • urinary bladder wall relaxation • glycogenolysis - ↑ glycemia, increased insulin secretion • blockade of mast cells degranulation Receptor 2 stimulation: • lipolysis • urinary bladder wall relaxation (m. detrusor) Receptor 3 stimulation: MUSCARINIC: M1(„neural“) – CNS, peripheral neurons,parietal cells of stomach, (glands with external secretion) M2 („heart“) - heart (SA, atria, AV, ventricles), (smooth muscle (GIT), neuronal tissue), presynapt. neur.endings M3 – glands, blood vessels (smooth muscle, hl. sval, endothelium), smooth muscles: bronchial muscles, GIT, urinary bladder, eye M4 – salivary glands, GIT (muscles), eye, CNS M5 – lungs, CNS Cholinergic receptors Cholinergic receptors • M – metabotropic • stimulated by acetylcholine • N – coupled with ion channels • stimulated by nicotine