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Sympathetic Nervous System. Nervous System. CNS. PNS. Brain Spinal Cord. Autonomic NS. Somatic NS. Sympathetic. Parasympathetic. CNS. ACh. C. M. N. ACh. T. ACh. 1. NE. N. L. NE. 1. 2. S. ACh. SM. N. CNS. ACh. C. M. N. ACh. T. ACh. 1. NE. N. L. NE.
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Sympathetic Nervous System
Nervous System CNS PNS Brain Spinal Cord Autonomic NS Somatic NS Sympathetic Parasympathetic
CNS ACh C M N ACh T ACh 1 NE N L NE 1 2 S ACh SM N
CNS ACh C M N ACh T ACh 1 NE N L NE 1 N EPI ACh 2 S ACh SM N
CNS ACh C M N ACh T ACh 1 NE N L NE ACh 1 N SG ACh M 2 S ACh SM N
Sympathetic Nervous System CNS (-) 2 C M T ACh 1 NE N L NE 1 N EPI ACh 2 S
Dual Innervation Exceptions (only sympathetic) - blood vessels (only parasympathetic) - bronchioles (only parasympathetic) - ciliary muscles Predominant Tone Primarily parasympathetic NS Exceptions - blood vessels (sympathetic) - sweat glands (sympathetic cholinergic)
Denervation Supersensitivity + Effect +++ Effect NT NT Before Denervation After Denervation
Catecholamines NE EPI DA
PRESYNAPTIC POSTSYNAPTIC NE - predominately removed from synapse via ‘re-uptake 1’ Metabolic Removal Re-uptake 2 Re-uptake 1 NE synthesis COMT MAO NE / Action NE MAO (-) 2 Receptor Binding
Adrenergic Receptors 1, 2, 1 NE 1, 2, 1, 2 EPI
Adrenergic Receptors 1, 2, 1 NE 1, 2, 1, 2 EPI 1, 1, DA1 DA
EFFECTS OF STIMULATING ADRENERGIC RECEPTORS SITEEFFECT HEART TACHYCARDIA and INCREASED CONTRACTILITY (1) VASCULATURE VASODILATION VASOCONSTRICTION (1, 2) (2) BRONCHORELAXATION (2) AIRWAYS IRIS MYDRIASIS (1) BLADDER DECREASED URINATION (2) GI TRACT DECREASED GI MOTILITY and SECRETIONS (2) UTERUS RELAXATION (2)
contractile force heart rate 1 renin release vasodilation, TPR 2 vasoconstriction TPR 1, 2
CNS Adrenergic Agonists ACh C M N ACh T ACh 1 NE N L NE 1 N EPI ACh 2 S ACh SM N
MIXED ADRENERGIC AGONISTS • Norepinephrine 1, 2, 1 • Epinephrine 1, 2, 1, 2 Dopamine DA1, 1, 1
HR BP TPR
MIXED ADRENERGIC AGONISTS • Norepinephrine (1, 2, 1) • Epinephrine (1, 2, 1, 2) Tx: ● Asthma (but there are better drugs) ● Anaphylactic shock ● Cardiogenic shock ● Prolong action of local anesthetics ● Topical hemostatic agent Dopamine (DA, 1, 1) Tx: ● CHF
ALPHA AGONISTS - Phenylephrine (1) - Methoxamine (1) • - Oxymetazoline (1 and 2 in periphery) - Tetrahydrozoline (1) - Naphazoline(1) - Ephedrine/Pseudoephedrine (1) • - Clonidine (2, Tx site of action is CNS)
Tx uses for ALPHA AGONISTS • Alpha-1 agonists Tx: ● Nasal decongestion ● Used in eye drops to ‘get the red out’ ●Hypotensive states Alpha-2 agonists Tx: ● Hypertension
BETA AGONISTS and Tx uses Non-selective 1/2 - Isoproterenol Selective 1 • - Dobutamine Selective 2 • - Albuterol Tx: Cardiac stimulant • - Metaproterenol • - Terbutaline Tx: COPD, Asthma • - Isoetharine • - Bitolterol Tx: Inotropic agent • - Ritodrine Tx: Uterine relaxation
NE EPI ISO HR BP TPR
Dose-response effects produced by dopamine at different receptors
CNS ADRENERGIC AGENTS • CNS : Tx antihypertensive effect • - Clonidine(2 agonist) - Guanabenz (2 agonist) - Guanfacine (2 agonist) - Methyldopa Converted in CNS to methylnorepinephrine (low efficacy 2 agonist)
Sympathetic Nervous System CNS (-) 2 C M T ACh 1 (-) NE N (-) L NE 1 N EPI ACh 2 S 2
CNS Adrenergic Antagonists ACh C M N ACh T ACh 1 X NE N L X NE 1 N EPI X ACh 2 S ACh SM N
ALPHA ANTAGONISTS and Tx uses Nonselective 1 and 2 receptor antagonists - Phenoxybenzamine Non-competitive action • - Phentolamine Competitive action Tx: - DOC for overdose of alpha agonists - Management of pheochromocytoma - Dental use for reversal of local anesthetic action Selective 1 receptor antagonists - Prazosin - Terazosin(water soluble) Tx: Antihypertensive agents, Management of benign prostatic hypertrophy
Adrenergic Influence on Vascular Smooth Muscle Tone VSMC 2 NE 1 NE Vasoconstriction (-) 2
Adrenergic Influence on Vascular Smooth Muscle Tone EPI VSMC 2 Vasoconstriction NE 1 NE Vasoconstriction (-) 2
Marked hypotensive response produced by dual 1 and 2 - Receptor Blockade on VSMC EPI VSMC X 2 Vasodilation X NE NE 1 Vasodilation (-) X 2 Phentolamine- 1 and 2 blockade
Moderate hypotensive response produced by dual 1 and 2 - Receptor Blockade 0n VSMC EPI VSMC 2 Vasoconstriction X NE NE 1 Vasodilation (-) 2 Prazosin- selective 1 blockade
BETA ANTAGONISTS ● Non-selective 1, 2 ● ‘Cardio’- Selective 1 • Atenolol • Propranolol • Metropolol Nadolol Esmolol Timolol Acebutolol(ISA) Pindolol ● Non-selective 1, 2, 1 Carteolol Intrinsic Sympathomimetic Activity Labetalol Carvedilol
Beta Blocker Tx Uses: ●Congestive heart failure ● Hypertension ● Myocardial infarction ●Angina ●Migrane ● Arrhythmias ●Anxiety ●Stage fright
INDIRECT ACTING ADRENERGIC AGONISTS Tyramine(dietary substance) Ephedrine Pseudoephedrine Amphetamine
Amphetamine PRESYNAPTIC POSTSYNAPTIC Re-uptake 1 NE / Action NE Receptor Binding
Amphetamine PRESYNAPTIC POSTSYNAPTIC Re-uptake 1 amphetamine NE NE (+) / Action Receptor Binding
Uptake Blockers • Cocaine • Tricyclic Antidepressants
Cocaine PRESYNAPTIC POSTSYNAPTIC Re-uptake 1 NE / Action NE Receptor Binding
Cocaine PRESYNAPTIC POSTSYNAPTIC Re-uptake 1 cocaine X NE NE / Action Receptor Binding
Neuronal Blockers • Reserpine Depletes NE stores by inhibiting vesicular uptake of NE; NE then metabolized by intra-neuronal MAO • Guanethadine Inhibits NE release, also causes NE depletion, and can damage NE neurons
Monoamine Oxidase (MAO) Inhibitors • Pargyline • Tranylcypromine Tyramine (or other drugs that promote NE release) may cause markedly increased blood pressure in patients taking MAO inhibitors