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Introduction to Autonomic Pharmacology Dr. Mohammed Samir Hussein BCs of Pharmaceutical Science, MD of Clinical Pharmacology
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Introduction to Autonomic Pharmacology Anatomical considerations of Parasympathetic Nervous system and Sympathetic Nervous System Neuro-humoral transmission & Co transmission Types of neurotransmitters and receptors Cholinergic and adrenergic receptors and its functions
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NERVOUS SYSTEM INTRODUCTION The nervous system contains more than 10 billion neurons (complexity). The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback.
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NERVOUS SYSTEM INTRODUCTION The nervous system exerts its influence by the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells, which specifically respond to the release of neuro=mediator substances. Chemical transmission occurs between nerve cells and their effector cells (transmitter substances). By using drugs that mimic or block the actions of chemical transmitters, we can selectively modify many autonomic functions.
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The nervous system can be divided into two parts: 1. central nervous system (CNS), the brain and spinal cord 2. The peripheral nervous system (PNS), consisting of the cranial and spinal nerves - The Afferent: transfer impulses from Organs (peripheral receptors) to CNS. - The Efferent : transfer impulses from CNS to the periphery organs ÷d to i: -The somatic NS are involved in voluntarily controlled functions such as contraction of the skeletal muscles in locomotion (movement). -The Autonomic system functions involuntarily to regulate everyday needs and requirements out the conscious participation of the mind (smooth muscle, cardiac- muscle, and exocrine glands). Visceral functions such as cardiac output, blood flow to various organs, vascular tone, pupillary constriction, sweating, salivation, which are necessary for life. - ANS is divided into Sympathetic: fight /flight system, Parasympathetic system: rest and digest. and the enteric nervous system (involuntary) controlling the gut
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3 REFLEX ARC Reflex arcs: Excitation or stimulation of specific sensory cells that are directly connected to motor neurons.
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Autonomic nervous system is a part of Peripheral Motor Nervous System which control Involuntary organs and subdivided into Sympathetic , Parasympathetic, and Enteric nervous systems
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1. Somatic nervous system: differs from the ANS in that a single myelinated motor neuron, originating in the CNS, and Travels directly to skeletal muscle without the mediation of ganglia Somatic nervous system is under voluntary control Responses in the somatic division are generally faster than those in the ANS 2. The Autonomic nervous system carries impulses from CNS to effector organs by 2 neurons: a- The preganglionic neuron: Preganglionic neurons emerge from the brain stem or spinal cord and make a synaptic connection in ganglia. -These Ganglia (a group of nerve cells forming center out side CNS), b- The postganglionic neuron has a cell body originating in the ganglion, and terminates on effector organs such as smooth muscles of the viscera, cardiac muscle and the exocrine glands. N.B: Adrenal medulla, like sympathetic ganglia receives preganglionic fibers from sympathetic system, in response to stimulation it secrets the hormone epinephrine into the blood. 3. The Enteric Nervous System (ENS) Enteric nervous system is called as “brain of the gut” Nerve fibers that innervate the gastrointestinal tract, pancreas, and gallbladder This system functions independently of the CNS and controls the motility, exocrine and endocrine secretions, and microcirculation of the gastrointestinal tract
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7 Origination of Autonomic Nervous System 1 -The preganglionic neurons of the Sympathetic system come from Thoracic and Lumbar (THORACOLUMBAR) regions spinal cord. The preganglionic neurons are short than the postganglionic ones ganglia that run in parallel on each side of the spinal cord 2. The Parasympathetic preganglionic fibers arise from the Cranial and Sacral areas (CRANIOSACRAL) the ganglia close to or within the organ preganglionic fibers are long, and the postganglionic ones are short
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How neurons regulate other cells the basic steps in the process by which neurons elicit responses from other cells are
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Autonomic Neurotransmitters: Neurotransmitters is specific chemical signals released from the nerve terminals and Communicate between nerve cells and effectors organs The neurotransmitters rapidly diffuse across the synaptic cleft or gap (synapse) between nerve endings and combine with specific receptors on the postsynaptic (target) cell. 1- Cholinergic transmission: Acetylcholine (ACh) is the transmitter in A. all preganglionic B. autonomic ganglia and somatic nerve ganglia C. parasympathetic postganglionic, 2- Adrenergic Transmission : Nor Epinephrine (NE) is the transmitter In Sympathetic postganglionic 3- Co transmitters: These co transmitters may be localized in the same vesicles as the primary transmitter or in a separate population of vesicles. Includes: Epinephrine, Dopamine, Nitric oxide, Serotonin, Substance P, Glutamate, γ-aminobutyric acid Each of these binds to specific family of receptors.
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Steps of Synaptic Transmission ACh synthesis and degradation In cholinergic neurons acetylcholine is synthesized from choline. 1. Synthesis : Acetyl-CoA + Choline (CAT)→ Acetylcholine (Blocked by Hemacholinum) 2. Storage : Vesicular Ach transporter ( Blocked by Vesamicole) 3. Release : By depolarization of Ca ion (blocked by botulinum ) 4. Hydrolysis : Acetylcholinesterase (AChE) NE synthesis and degradation Choline acetyltransferase (ChAT) In the adrenergic neurons Norepinephrine is synthesized from Tyrosine. 1. Synthesis : Tyrosine → L-Dopa → Dopamine → Norepinephrine (Blocked by Metyrosin) 2. Storage :Vesicular NE transporter ( Blocked by Reserpine ) 3. Release : By depolarization of Ca ion ( Blocked by Guanethidine ) 4. Degradation: Monoamine Oxidase MAO, Catecholamine-o-methyl transferase (COMT) 5. Uptake : NE transporter (Blocked by Cocaine or TCA)
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Autonomic Receptors Dopamine R : D1, D2, D3, D4, D5 Other receptors (receptors for NANC transmitters, e.g. nitric oxide, vasoactive intestinal peptide, neuropeptide Y)
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Autonomic Receptors
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ADRENERGIC RECEPTORS (ADRENOCEPTORS) Epinephrine → high affinity for alpha (α) Isoproterenol → high affinity for (β) CHOLINERGIC RECEPTORS (CHOLINOCEPTORS) Muscarine → high affinity for Muscarinic Nicotine → high affinity for Nicotinic
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Sympathetic Nervous System FIGHT, FLIGHT RESPONSE Stressful, Emergency Situations Trauma, fear, hypoglycemia Parasympathetic Nervous System Rest & Digest Situations Function of Autonomic System
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FUNCTION OF SYMPATHETIC (FIGHT OR FLIGHT) Increase heart rate and blood pressure, to mobilize energy stores of the body. Increase blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs Dilation of the pupils and the bronchioles. Activated during emergency stress response. FUNCTION OF Autonomic Nervous system FUNCTION OF PARASYMPATHETIC (REST AND DIGEST ) Maintains essential bodily functions Responsible for “rest and digest” responses Digestive processes and elimination of wastes Oppose or balance the actions of the sympathetic division
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Innervation by the autonomic nervous system Dual innervation: Most organs in the body are innervated by both divisions of ANS Parasympathetic innervation slows the heart rate, and sympathetic innervation increases the heart rate. Organs receiving only sympathetic innervation: Some effector organs, such as the adrenal medulla, kidney, pilomotor muscles, and sweat glands, receive innervation only from the sympathetic system. The control of blood pressure is also mainly a sympathetic activity UN innervated receptors : Some receptors respond to autonomic transmitters & drugs receive no innervations , These inclua- Muscarinic receptors on the endothelium of blood vessels b- Some presynaptic receptors c- Adrcnoceptors on sweat glands and adrenoceptors in some blood vessels.
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: ANS activity Integration of autonomic function The autonomic nervous system is a motor system; it does require sensory input from peripheral structures to provide information on the state of affairs in the body. 1- Systemic Reflux (Reflex arcs) The control of BP by the Baroreceptor neural reflex EX. Decrease in blood pressure caused by hemorrhage causes increased SNS 2- Local Feedback Inhibition Release of NE from nerve endings is modulated by norepinephrine acting on presynaptic alpha2 3. Emotions and the autonomic nervous system: Stimuli that evoke feelings of strong emotion, such as rage, fear, or pleasure, can modify ANS activity
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