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Queen's University
Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Physiological and Pharmacological Aspects of the Autonomic Nervous System Organization of the Nervous System Sensory and Motor Neurons • sensory neurons: recognize change in the envmt ◦ carry signals to the CNS from sensory organs • motor neurons: respond to changes in the envmt ◦ carry signal from CNS to areas that control the activities of muscles and glands ▪ ie move muscle or secret chemicals Organization of the Nervous System Somatic Nervous System • controls voluntary movements by activating skeletal muscle • CNS stimulates release of the neurotransmitter acetylcholine (ACh) • ACh interacts with nicotinic receptors on skeletal muscle • Synapse is called the neuromuscular junction Neuromuscuular Junction Neuromuscular Blocking Agents • few drugs target skeletal muscle • drugs interfere with neurotransmission at the neuromuscular junction • two therapeutic indications ◦ surgical Procedures ◦ produce muscle paralysis (adjuncts to anesthetics) ◦ reduce spasticity ◦ muscle relaxants (chronic back pain, fibromyalgia) • natives of South America used “curare” to kill animals → competes w/ curare for nicotinic receptors (competes w/ACh) ◦ causes skeletal muscle paralysis (in particular to the respiratory tract) Autonomic Nervous System (ANS) • controls involuntary responses by influencing organs, glands and smooth muscle breathing, heart rate, etc. • maintains a stable internal environment • large number of drugs affect this system ANS: Parasympathetic & Sympathetic • parasympathetic division ◦ “Rest and Relax” response ◦ Activated under non-stressful conditions ◦ Anabolic “conserves energy” ◦ Craniosacral: where nerves originiate from (spinal cord) • Sympathetic Division ◦ “Fight or Flight” response ◦ Activated under conditions of stress ◦ Catabolic “burns energy” ◦ Thoracolumbar: neurons derive in thorassic and co-- Many organs are innervated by both parasympathetic and sympathetic nerves Fromadrenal gland, 80% epinephrine and 20% norepinephrine Parasympathetic NS: Neurotransmitters and Receptors Neurotransmitters • acetylcholine (ACh) ◦ stored in vesicles in the presynaptic neuron ◦ released into synaptic cleft when an action potential arrives • acetylcholinesterase (AChE) is an enzyme in the synaptic cleft that breaks downACh ◦ terminates its activity Receptors • receptors that bind ACh are called cholinergic receptors • two types: muscarinic (called muscarinic b/c first compound known to bind → muscarin; found in mushrooms) and nicotinic (also in somatic nervous system) Cholinergic Receptors Parasympathetic NS: Organization • two neurons required to reach target organ • first neuron’s cell body in CNS, second neuron’s cell body in ganglia • ganglia = mass of nerve cell bodies • neuron before the ganglia = preganglionic • neuron after the ganglia = postganglionic • long preganglionic fibers releaseAch, binds to N receptors • short postganglionic fibers releaseACh at the target organ, binds to M receptors (vs somatic: only one neuron that releasesACh and binds to nicotinic receptors) Cholinergic Receptor Summary • all autonomic ganglia have nicotinic receptors • all target organs of the parasympathetic nervous system have muscarinic receptors • direct acting agents: interfere with N or M receptors • indirect acting agents: block metabolism ofACh, increasing the concentration ofAch Cholinergic Drugs *Stimulate the parasympathetic nervous system (produce characteristics of “rest and relax”) • not widely used because they can adversely slow heart rate and constrict respiratory passages • clinically, most widely used cholinergics exert effects on theACh receptors in skeletal muscle or the CNS • includes toxic nerve gas! (serin) ◦ excess ACh: constrictd pupils, salivating w/out control, urinating and defecating, die b/c lungs constricts too much ◦ antidote: ▪ paladoxin help break downACh ▪ attripine: muscarinic antagonist, even if have too muchACh can't bind • acute poisoning can be lethal Anticholinergic Drugs *Inhibit the parasympathetic nervous system (thus they produce characteristics of “fight or flight”) • inhibition by blocking muscarinic receptors • cause dilation of pupil, increase heart rate, dilation of bronchi • high incidence of side effects has limited their clinical use Two in particular: 1) Tachycardia (fast heart rate) 2) Urinary retention in men with prostate disorders Sympathetic Nervous System: Neurotransmitters Norepinephrine (NE), Epinephrine (Epi) • referred to as catecholamines or adrenergics • work in similar ways • Stored in vesicles in the presynaptic neuron until release • Activity is terminated by reuptake followed by enzyme degradation within the neuron by: ◦ Monoamine oxidase (MAO) ◦ Catechol-O-methyltransferase (COMT) •
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