Pharm Jan 18, 2007

Jan 18, 2007  Go to www.naturopathicdoctor.ca/BAS208/ to get notes o Good NPLEX study charts!!!  Autonomic Nervous System o SNS and PNS o Somatic not part of ANS, but put there as a comparison o Fight or flight o SNS o In most case norepiepherine or epinephrine released o Released at adrenergic receptor sites o Alpha 1 and alpha 2 – found in peripheral organs o Beta 1 and beta 2 – found in heart and lungs  Beta 1 in heart (one heart)  Beta 2 in lungs (2 lungs) o SNS  Mostly norepinepherine, except medulla which binds epinephrine and sweat glands where acetylcholine binds and not adrenergic receptors, but nicotinic receptors • Still part of ANS  Axons are likely myleinated  Adrenergic receptor sites  Beta 2 • When norepinephrine binds here get bronchodilation • Want to suck in as much oxygen as possible • Drugs will be used for bronchodilation in asthma  Alpha 1 • Primarily binds epinephrine or norephinephrine • Vasoconstrictor of vessels • Important in terms of hypertension • Result in vasodilation by decreasing binding o PNS  Calming nervous system  Acetylcholine  Muscarinic or nicotinic receptors that bind acetylcholine  SNS - Norepinephrine and Adrenergic  Parasympathetic nervous system – acetylcholine and muscarinic receptor sites  SNS o Stops digestion in favour of blood going to the limbs o Nervous system that you can think of as the  Exercise  Excitement  Emergency

 Embarrassment o Eyes – pupil dilation. Need to see better o Bronchodilation  Norepinephrine binding to beta 2 receptors o Heart  Uses norephinephrine binding to beta 1 receptors o Blood divereted to muscles o Decreased urine output o Increases sweating  PNS Resting and digesting Promotes squirting of glands Facilitates digestion Has to do with the  Digesting  Defecating  And dyuresis Each of the two nervous systems are subdivided into two other categories so that the drugs effect the SNS or PNS Sympathetic o Anticholinergic  Anitaceytlcholine  Block parasympathetic acetylcholine o Sympathomimetics  Mimics sympathetic nervous system  Promote sympathetic norepinephrine Parasympathetic o Cholinergic agonists  Agonists – promotes end result o Acetylcholinesterase inhibitors  Promotes the action of acetylcholine by keeping it in the synaptic space  esterase clean up enzymes Anticholinergics – sympathetic norepinephrine and adrenergic (muscarinic receptors) o Block the binding of acetylcholine at muscarinic sites o Block the intended parasympathetic effect of acetylcholine o Result is sympathetic o o Possible uses  Dilate pupils  Decreases urination, so may use it for incontinence  Contraindicated in benign prostatic HTN o Side effect o o o o

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Facial flushing without sweating • Sweating controlled by acetylcholine not norepinepherine and these drugs block acetylcholine  Do not produce a euphoric state!!! o Atropine  Not specifically in the NPLEX blueprints, but works the same  Some impact at nicotinic sites at sweat glands that stop sweating  If someone takes too much of anticholenergic inhibitors then give them a shot of atropine to overcome that.  Antispasmotic • Sooth spasm in bronchi and GI  Envoking a sympathetic effect, so will stop disorders that have more blood fluid going to the area  Remember side effects • C/I o Peptic ulcers  Think that should use it for peptic ulcers, but need to look up why you don’t o Glaucoma  b/c cause pupil dilation  already have a problem with drainage and pressure  become more painful o Oxybutynin  Sympathetic reaction  antispasmodic reaction  not as strong as atropine, but has fewer side effects  has more of one action than the other  main use in MS induced incontinence  similar SE and C/I • important – gastric retention • Peptic ulcer o stops digestion, not an all or nothing response o people take these drugs and continue their ordinary lives with eating and drinking o if there is slow gastric emptying, people who have sluggish digestion it sits in their ST o in shifting their state to a sympathetic state the food, digestive juices, will keep everything in the ST and irritate an existing peptic ulcer  cleared through the LIV o Tolterodine  Similar to others 

 Muscarinic receptor antagonist  Cleared through LIV  Sympathomimetics o Symp, norepinepherine, adrenergic receptors o Catecholamines  Act directly at the SNS at adrenergic, alpha1/alpha2 or beta1/beta2  With LU • Bronchodilation  With HT • Increases rate and force of HT beat, so use for MI  Anapnyactic shock • SNS sending blood to vessels  Hypotension  Decongestions • Result is vasoconstriction that will dry up the nose  Norepinephrine is a potent vasoconstrictor  Side effect • Can produce a state of euphoria o Noncatecholamines  Methylphenidate • Blocks the reuptake of norepinephrine • Stays in synaptic space longer and does its thing longer • Don’t know why it calms overactive children down. • Similar to amphetamines • Side effect o MAOI  Results in certain hormones sticking in the synaptic space for longer  Careful using these with cyclic antidepressants   Amphetamines • Increase the release of those chemicals o Dopamine, norepinepheine • Block norepinephrine and potentially increasing the release of it • Used in ADHD o Mechanism of reaction in this disease is unknown o Seems counterintuitive, something that brings about a stimulative state in ADHD  Oxymetazoline • Visine or Dristan

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Constriction of blood vessels leads to drainage, b/c not having continuous flow of blood and macrophage • Vasoconstriction allows the area to dry out • Other sympathomimetics are very addictive • When use too often becomes habit forming • C/I o If have HTN stay away from decongestants o BPH  Vasoconstriction  Will do all of the things that sympathomimetics will do too Psudoephedrine • Has peripheral effects (nasal decongestant) • Has some CNS effects that are expected with sympathomimetics, but less effect • Oral nasal decongestant • Review amphetamine SE as well • Look at the similarities of all these drugs • Figure out what are the key aspects

 Choliergic Agonist o PNS, acetylcholine and muscarinic receptors o Agonist – promotes something o Like sympathomimetics o Act at muscarinic receptors, and induce PNS effects o Used to induce calm relaxed state o Used to promote bladder function, digestion o PNS state, bronchoconstriction o Direct  Nicotine • Nicotinic agonist • When nicotine binds to nicotinic receptor it is stimulated • Binding of acetylcholine to nicotinic receptor is always stimulatory, but that doesn’t’ mean the body is stimulated. Overrides what normally happens • Acetylcholine binding to other sites either stimulates or activates or shuts down the receptor • First cigarette of the day causes the most profound reaction, with continued smoking throughout the day there is a steady stream of nicotine in the body o Indirect  Acetylcholinesterase Inhibitor • Block reuptake of acetycholine once it’s been released • Donepezil

o Parasympathetic effects o used in the treatment of early alzheimer’s disease and down syndrome o www.txtwriter.com/onscience/articles/addictingkids o give atropine of acetylcholinesterase poisoning o may also cause bladder outflow obstruction  Hypertension  Antihypertensives o Adrenergic blockers  Beta 1 and Beta 2 blocker • Propranolol o Used to treat migraines o Blocking beta 2 receptors that normally cause bronchodilation, so becomes a problem in asthmatics  Beta 1blockers • Used primarily in the treatment of HTN • Used to decrease HT rate and output, lowering pressure • At correct doses don’t have to worry about beta 2 blockage but at high doses you do • Atenolol and Metoprolol o Used in acute MI o Don’t use propranolol in an actue MI, b/c blocks delivery of Oxygen o At high doses A and M will inhibit beta 2 receptors o