Peripheral Nervous System Drugs Nervous System l l l l l Central Nervous System l l Brain Retina Spinal Cord Sensory Somatic Autonomic Enteric l Peripheral Nervous System l l l l l l l Parasympathetic Cholinergic Ach l Sympathetic Adrenergic NE EP Schematic of the Autonomic Nervous System Parasympathetic first neuron in brain stem and sacral region of spinal cord Sympathetic First neuron in CNS in brainstem or spinal cord then projects to periphery and makes a synapse in the autonomic ganglion second neuron carries it to the end organ Differentiating Between Parasympathetic and Sympathetic Nervous Systems Origin o PNS Cranio scaral o SNS Thoraco lumbar Structures Innervated Effector End Organs o PNS cardiac muscle smooth muscles glands viscera o SNS cardiac muscle smooth muscles glands viscera o PNS preganglionic long postganglionic short o SNS preganglionic short postganglionic long except adrenal Ganglia o PNS near effector end organ o SNS near CNS Length of Fibers Ganglionic Transmitter o PNS Acetylcholine o SNS Acetylcholine Ganglionic Neurotransmitter Receptors o PNS Nicotinic fast major response o SNS Nicotinic fast major response Postganglionic Transmitters o PNS Acetylcholine o SNS Norepinephrine most cases NE and epinephrine adrenal medulla acetylcholine sweat glands and skeletal muscle blood vessels Postganglionic Receptors o PNS muscarinic o SNS a1 a2 b1 b2 receptors muscarinic o Beta 1 located in heart and kidney Chemical Neurotransmission in Cholinergic Neurons Chemical Neurotransmission in Cholinergic Neurons Anticholinesterases Muscarinic Agonists mimic muscarinic effects of ACh Muscarinic Antagonists Nicotinic Agonists Nicotinic Antagonists block major ganglionic transmission or neuromuscular transmission in skeletal muscle Adrenergic Neurotransmission Relevant Drugs MAO Inhibitors o Selegiline increases NE in vesicles Catecholamine Pump Inhibitors antidepressants o Cocaine increase NE in synaptic cleft A or B agonists A or B antagonists Sympatholytics o Phenylephrine mimic effects of endogenous catecholamines o Propranolol block effects of endogenous catecholamines o Reserpine delete adrenergic nerve terminals of norepinephrine and or o Blocks the catecholamine pump in storage vesicles allowing the NE to block NE release leak out and be metabolized In General A Cholinergic usually parasympathetic o Innervation is responsible for housekeeping or vegetative functions in the body rest and digest o SPLUDD Effects o Salivation o Perspiration only sympathetic o Lacrimation o Urination o Digestion and Defecation B Adrenergic sympathetic o Innervation is response for fight or flight responses in body o Speeds heart rate increases contractile strength dilates pupil and bronchi o Increases metabolism availability of glucose and oxygen Cholinergic and adrenergic innervation in direct opposition o Yin yang or tug of war relationship Effector Organ Responses to Autonomic Nervous System Activation Agonists will mimic these effects Antagonists will counteract these effects Effector Organ SA Node AV Node Ventricles Responses to Cholinergic Para Decrease rate Decrease conduction velocity Arterioles Dilate or no effect Veins Smooth Muscles Glands GI Tract Sphincter Muscles Salivary Glands Exocrine Glands Urinary Bladder Detrusor Muscle Sphincter Iris Radial Muscle Iris Sphincter Muscle Ciliary Muscle Liver Pancreas Acini B Cells Lacrimal Glands Pilomotor Muscle Sweat Glands Constriction Increase secretion Increase motility Relax Dilation watery secretion Increase secretion Contraction Relax Contraction miosis Contraction near vision Increase Secretion None Increase secretion Increase secretion Penis Uterus Pregnant Erection Variable Reponses to Adrenergic Symp Increase rate Increase conduction velocity Increase conduction force and velocity A receptors cause constriction B2 or dopamine receptors cause dilation Constriction and dilation Relaxation Decrease secretion Decrease motility Contract Vicious secretion Decrease secretion Relaxation Contract Contraction mydriasis Relaxtion far vision Glycogenolysis Decrease Secretion Increase Secretion Contraction Increase secretion in palm only Ejaculation Relaction Contraction Adrenergic Receptor B1 B1 B1 A2 B2 B2 A B2 A a B2 a A1 B2 B2 a B2 a a a a Fat Cells Lipolysis B1 B3 Sympathomimetics Adrenergic Agonists Sympathomimetics stimulate end organs similar to activation by the sympathetic nervous system Directly acting sympathomimetics activate adrenergic receptors directly Mixed action drugs have both directly acting and indirectly acting Indirectly acting sympathomimetics sympathomimetic properties Epinephrine Nonselective Directly Acting Adrenergic Agonist Selected indications o Bronchial Asthma o Anaphylactic Shock o Adjunct with local anesthetics o Hemostatic agent to reduce bleeding o Used in glaucoma treatment o Used in cardiac arrest o Increase blood pressure tachycardia chills fever seizures o Overdose cerebrovascular accident tachyarrhythmia myocardial Side Effects ADRs infarction Drug Interactions o General Anesthetics sensitize heart for dysrhythmias or digitalis glycosides o Local Anesthetics when used in end artery areas fingers toes penis may cause ischemia and gangrene o MAO Inhibitors dysrhythmias tachycardia hypertension cocaine o Antidepressants Phenylephrine Isoproterenol Phenylephrine is a pure a agonist that is used only parentally or topically Phenylephrine will cause vasoconstriction and increases blood pressure Isoproterenol is a non selective B receptor agonist Isoproterenol is a potent bronchodilator and vasodilator increases cardiac contractile force cardiac conduction and cardiac automaticity Indications Given IV for cardiogenic shock or managing bradycardia More selective B1 agonists are more often used Isoproterenol is useful in asthma but largely supplanted by selective B2 agonists Side effects o CNS stimulation tachycardia and exacerbation of angina o Increases hyperglycemia in diabetics Effects of Beta Agonists and Dopamine Dopamine is used to treat shock usually to increase blood pressure Dopamine acts on dopamine receptors as well as a1 and b1 receptors Increases heart rate but has little effect on peripheral resistance also increases blood flow to kidneys Can cause tachycardia angina or cardiac arrhythmia Dopamine Fenoldopam Fendoldopam is a dopamine receptor type 1 agonist used to treat hypertension Causes vasodilation in the kidneys leading to decrease in blood pressure Use caution with beta