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Transcript
Autonomic Nervous System Pharmacology 1. Describe the anatomical differences in the sympathetic and parasympathetic nervous system. CNS Brain & spinal cord Integrative and control centre PNS Cranial and spinal nerves Communication between CNS and the rest of the body Motor (efferent) division Sensory (afferent) division Somatic & visceral sensory nerve fibres Conducts impulses from receptors to the CNS Motor nerve fibres Conducts impulses from CNS to effectors (muscles & glands) Autonomic Nervous System Somatic Nervous System Involuntary (visceral motor) Conducts impulses from CNS to cardiac mm, smooth mm & glands Sympathetic division Mobilises body systems during emergency situations Flight or fight Voluntary (somatic motor) Conducts impulses from CNS to skeletal mm Parasympathetic division Conserves energy Promotes non-emergency functions Anatomical and Physiological Differences between the Sympathetic and Parasympathetic Systems Reference: Marieb & Hoehn (2004) Characteristic Origin Location of ganglia Parasympathetic Craniosacral outflow: brain stem nuclei of cranial nerves III, VII, IX and X; spinal cord segments S2 – S4 Ganglia in (intramural) or close to visceral organ served Relative length of pre and postganglionic fibres Rami communicantes Long preganglionic; short postganglionic None Degree of branching of preganglionic fibres Functional role Minimal Neurotransmitters All fibres release ACh (cholinergic fibres) Maintenance of functions; conserves and stores energy Sympathetic Thoracolumbar outflow: lateral horn of grey matter of spinal cord segments T1-L2 Ganglia within a few cm of CNS: alongside vertebral column (chain or paravertebral ganglia) and anterior to vertebral column (collateral or prevertebral ganglia) Short preganglionic; long postganglionic Grey and white rami communicantes. White rami contain myelinated preganglionic fibres; grey contain unmyelinated postganglionic fibres Extensive Prepares body to cope with emergencies and intense muscular activity All preganglionic fibres release Ach; most postganglionic fibres release norepinephrine (adrenergic fibres); postganglionic fibres serving sweat glands and some blood vessels of skeletal mm release Ach; neurotransmitter activity augmented by release of adrenal medullary hormones (norepinephrine and epinephrine). 2. Describe autonomic tone Autonomic tone describes the state of the body that the sympathetic and parasympathetic systems keep. There is sympathetic tone and parasympathetic tone. The sympathetic nervous system controls most of the vascular system. The sympathetic fibres keep the blood vessels in a continual state of partial constriction called sympathetic tone or vasomotor tone. When faster blood delivery is needed, these sympathetic fibres deliver rapid impulses causing blood vessels to constrict and BP to rise. BP can also be decreased to allow vasodilatation when required. α blocker drugs that interfere with these vasomotor fibres are used to treat hypertension. The parasympathetic nervous system dominates the heart and the smooth mm of the digestive and urinary tract organs. This is referred to as parasympathetic tone. The parasympathetic tone ensures that the heart beats at a low, normal rate and dictates the normal activity levels of the digestive and urinary organs. Drugs that block parasympathetic nerve fibres increase HR and causes faecal and urinary retention. Except for the adrenal gland, most glands and sweat glands of the skin are also under parasympathetic control. 3. Describe autonomic neurotransmitter control of the heart, gut and bladder, including thermoregulation and food intake. Neurotransmitter – along with electrical signals, are the language of the nervous system. Allows communication between neurons. In the ANS there are 2 types of neurotransmitters: Acetylcholine (ACh) and Norepinephrine (NE) ACh is released by: 1) all ANS preganglionic axons and 2) all parasympathetic postganglionic axons Fibres that release ACh are called cholinergic fibres. NE: Most sympathetic postganglionic axons release NE and are called adrenergic fibres. Exceptions are sympathetic postganglionic fibres innervating sweat glands, some blood vessels in skeletal mm and external genitalia. These fibres secrete ACh. Cholinergic: 2 types of receptors that bind ACh. Nicotinic receptors – always stimulatory Muscurinic receptors – can be either stimulatory or inhibitory Adrenergic: 2 major classes α and β receptors α (2 subclasses) – mostly stimulatory β (3 subclasses) – mostly inhibitory. Exception is heart mm where it stimulates the heart into more vigorous activity. Cholinergic and Adrenergic Receptors Reference: Marieb & Hoehn (2004) p. 543 Neurotransmitter Receptor Type Major Locations Acetylcholine Effect of Binding Cholinergic Nicotinic All ganglionic neurons; adrenal medullary cells (also neuromuscular junctions of skeletal mm) Excitation Muscurinic All parasympathetic target organs Excitation in most cases; inhibition of cardiac mm Selected sympathetic targets: Norepinephrine (and epinephrine released by adrenal medulla) eccrine sweat glands blood vessels in skeletal mm Activation Inhibition (causes vasodilation Adrenergic β₁ Heart and coronary blood vessels predominantly, but also kidneys, liver, and adipose tissue Increases heart rate and strength; dilates coronary arterioles; stimulates rennin release by kidneys β₂ Lungs and most other sympathetic target organs; abundant on blood vessels serving the heart Stimulates secretion of insulin by pancreas; other effects mostly inhibitory: dilation of blood vessels and bronchioles; relaxes smooth muscle walls of digestive and urinary visceral organs; relaxes pregnant uterus. β₃ Adipose tissue Stimulates lipolysis by fat cells α₁ Most importantly blood vessels serving the skin, mucosae, abdominal viscera, kidneys and salivary glands; but virtually all sympathetic target organs Constricts blood vessels and visceral organ sphincters; dilates pupils of the eyes except heart α₂ Membrane of adrenergic axon terminals; blood platelets Mediates inhibition of NE release from adrenergic terminals; promotes blood clotting Thermoregulation Under control of sympathetic NS Heat blood reflexive dilation of blood vessels activation of sweat glands to cool the body skin becomes flushed with warm Cold vital organs reflexive constriction of blood vessels blood restricted to deeper, more 4. Describe cholinergic and noradrenergic recept or transmission and second messenger systems See Q.3 above. Second Messenger Systems Adrenergic receptors are associated with specific second messenger systems. They are coupled with various substances that help to produce an effect. Second messengers and effectors α₁ α₂ β₁ β₂ β₃ Phospholipase C activation ↓cAMP ↑cAMP ↑cAMP ↑cAMP Increased cardiac rate and force Bronchodilatation, lipolysis vasodilation, relaxation of visceral smooth mm, hepatic glycogenolysis ↑inositol triphosphate ↑diacylglycerol ↓Calcium channels ↑Potassium channels ↑Ca²⁺ Effects Vasoconstriction, relaxation of GI smooth mm, salivary secretion, hepatic Inhibition of transmitter release (including noradrenalin and acetylcholine glycogenolysis release from autonomic nerves), platelet aggregation, contraction of vascular smooth mm, inhibition of insulin release and mm tremor 5. Describe ganglia and co-transmitters Ganglia Clusters of neuronal cell bodies Ganglia associated with afferent nerve fibres contain cell bodies of sensory neurons (dorsal root ganglia) Ganglia associated with efferent nerve fibres mostly contain cell bodies of autonomic motor neurons. Co-transmitters There are other transmitters apart from ACh and NE (NAd). This means that autonomic transmission is not completely blocked by ACh and NE antagonists. The main co-transmitters are: NO (nitric oxide), VIP (vasoactive intestinal peptide, parasympathetic), ATP and neuropeptide Y (NPY, sympathetic). The presence of these co-transmitters means that the autonomic nervous system cannot be completely blocked; there may still be autonomic effects if an autonomic antagonist drug is administered.