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Autonomic Nervous System Pharmacology Shan Nanji
+ANS – Parasympathetic & Sympathetic Basics
n Parasympathetic - “CHOLinergic”
n Craniosacral, cGMP n MUSCARINIC - Most n NICOTINIC: Located at _______ and _______
n Sympathetic – “adreNErgic” n Thoracolumbar, cAMP
n NICOTINIC – Most n MUSCARINIC – _______ and _______
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+ANS – Parasympathetic & Sympathetic Basics
n Parasympathetic - “CHOLinergic”
n Craniosacral, cGMP n MUSCARINIC - Most n NICOTINIC: Located at NMJ and
Ganglia
n Sympathetic – “adreNErgic” n Thoracolumbar, cAMP
n NICOTINIC – Most n MUSCARINIC – Sweat Glands
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+Parasympathetic System
- Cholinergic
n M1 – CNS/ENS
n M2 – Heart
n M3 – EG MP AC BB n _________Exocrine Gland Secretion n Increases _________ n Miosis via Pupillary sphincter
n Accommodation via Ciliary n Broncho_________ n Bladder _________
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+Parasympathetic System
- Cholinergic
n M1 – CNS/ENS
n M2 – Heart
n M3 – EG MP AC BB n Increases Exocrine Gland Secretion n Increases Gut Motility
n Miosis via Pupillary sphincter
n Accommodation via Ciliary
n Bronchoconstriction n Bladder constriction
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+Parasympathetic System
- Cholinergic
n M1 – CNS/ENS
n M2 – Heart
n M3 – EG MP AC BB n Increases Exocrine Gland Secretion n Increases Gut Motility
n Miosis via Pupillary sphincter
n Accommodation via Ciliary
n Bronchoconstriction n Bladder constriction
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+CHOLinergics
n BethanaCHOL – Post op and neurogenic ileus and urinary retention
n CarbeCHOL – Glaucoma, pupillary contraction, and relief of IOP, also for Post op urinary retention
n MethaCHOLine – Induces bronchospasm used in ______________
n Pilocarpine –Cystic Fibrosis Sweat Test; “PiloCHOLpine”
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+ Anti-ACh-Esterases MOA: Prevent degradation of ACh increasing endogenous AcH
- More ACh (acetylCHOLine) so more CHOLinergic!
n Edrophonium – Dx __________________, used to differentiate it from cholinergic crisis
n NeoSTIGmine/PyridoSTIGmine – Rx Myasthenia Gravis (No BBB)
n Rx – Myasthenia Gravis, Ileus, Urinary Retention, Reversal of NMJ Blockage
n PhysoSTIGmine – Rx for __________________ (Will cross BBB), also for glaucoma
n Ecothiophate – For Glaucoma
n Donepezil – For Alzheimer’s disease - Lipid Soluble
n Tacrine – Lipid Soluble – Rx – Alzheimers
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+ Anti-ACh-Esterases MOA: Prevent degradation of ACh increasing endogenous AcH
- More ACh (acetylCHOLine) so more CHOLinergic!
n Edrophonium – Dx Myasthenia Gravis, used to differentiate it from cholinergic crisis
n NeOstigmine/PyridoSTIGmine – Rx Myasthenia Gravis (No BBB)
n Rx – Myasthenia Gravis, Ileuis, Urinary Retention, Reversal of NMJ Blockage
n PhysoSTIGmine – Rx for Atropine Overdose (Will cross BBB), also for glaucoma
n Ecothiophate – For Glaucoma
n Donepezil – For Alzheimer’s disease - Lipid Soluble
n Tacrine – Lipid Soluble – Rx – Alzheimers Shan Nanji - [email protected]
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+ Anti-ACh-Esterases MOA: Prevent degradation of ACh increasing endogenous AcH
- More ACh (acetylCHOLine) so more CHOLinergic!
n Edrophonium – Dx Myasthenia Gravis, used to differentiate it from cholinergic crisis
n NeOstigmine/PyridoSTIGmine – Rx Myasthenia Gravis (No BBB)
n Rx – Myasthenia Gravis, Ileus, Urinary Retention, Reversal of NMJ Blockage
n PhysoSTIGmine – Rx for Atropine Overdose (Will cross BBB), also for glaucoma
n Ecothiophate – For Glaucoma
n Donepezil – For Alzheimer’s disease - Lipid Soluble
n Tacrine – Lipid Soluble – Rx – Alzheimer's Shan Nanji - [email protected]
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+Anti-ACh – Anti-Cholinergics MOA:
So, if cholinergics agonize M3… ……………an Anti-ACh will ANTAGONIZE M3.
Antagonizing M3 will cause: n Decrease Exocrine Gland Secretions n Decrease Gut Motility n No Miosis so – Mydriasis n No Accommodation so – loss of accommodation n Bronchodilation n Bladder relaxation
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+Anti-ACh – Anti-Cholinergics MOA:
So, if cholinergics agonize M3… ……………an Anti-ACh will ANTAGONIZE M3.
Antagonizing M3 will cause: n Decrease Exocrine Gland Secretions n Decrease Gut Motility n No Miosis so – Mydriasis n No Accommodation so – loss of accommodation n Bronchodilation n Bladder relaxation
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+Anti-ACh – Anti-Cholinergics MOA:
So, if cholinergics agonize M3… ……………an Anti-ACh will ANTAGONIZE M3. Antagonizing M3 will cause:
n Decrease Exocrine Gland Secretions n Decrease Gut Motility
n No Miosis so – Mydriasis n No Accommodation so – loss of accommodation n Bronchodilation n Bladder relaxation
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+Anti-ACh
n Atropine – Mydriasis w/Cyclopegia, Management of Anti-AChE “poisoning”
n Benztropine/Trihexyphenidyl– Lipid Soluble (CNS Entry) for __________________, and EPS Symptoms due to antipsychotics
n Ipratropium – Safe to use in ________and __________
n Glycopryrrulate, Oxybutinin – Reduce urgency in mild cystitis and reduce bladder spasms
n Scopolamine – Motion Sickness
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+ANS – Parasympathetic & Sympathetic Basics
n Parasympathetic - “CHOLinergic”
n Craniosacral, cGMP n MUSCARINIC - Most n NICOTINIC: Located at NMJ and Ganglia
n Sympathetic – “adreNErgic” n Thoracolumbar, cAMP
n NICOTINIC – Most n MUSCARINIC – Sweat Glands
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+Alpha 1 Receptor
n __________________ n __________________ n Mydriasis via radial (dilator muscle)
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+Alpha 1 Receptor Pharmacology
Alpha 1 Agonists n EpinephRINE/NorepinephRINE
n __________________/ __________________ – Incontinence in the elderly
n __________________ – Neurogenic shock, pupillary dilation, vasoconstriction, nasal decongestion
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+Alpha 1 Receptor Pharmacology
Alpha 1 Agonists
n EpinephRINE n Causes Decreased Production of Aqueous Humor
n Vasoconstriction n Clinical Use:
n Hypotension n Asthma n Anaphylaxis n Open Angle Glaucoma
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+Alpha 1 Receptor Pharmacology
Alpha 1 Agonists
n NorepinephRINE n Clinical Use:
n Hypotension (Decreased Renal Blood Flow)
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+Alpha 1 Receptor Pharmacology
Alpha 1 Antagonists
n __________________ – Dx Pheochromocytoma, also for patients on MAOi that ate tyramine
n __________________ – Rx Pheochromocytoma
n Yohimbine – Impotence
n Prazocin – Rx HTN but assoc. with __________________
n Terazocin/Doxazocin – First line for BPH, also for HTN
n Tamsulosin
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+Alpha 2 Receptor
n Decrease __________________ (makes you less “adrenergic” AKA less SYMPATHETIC and MORE Parasympathetic)
n Decreases __________________
n Promotes platelet aggregation
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+Alpha 2 Receptor Pharmacology
Alpha 2 Agonists
n Clonidine – __________________, associated with rebound HTN
n Alpha-Methyl Dopa – Rx HTN, safe in pregnancy but can cause __________________.
n Guanabenz
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+Alpha 2 Receptor Pharmacology
Alpha 2 Antagonists
n Mirtazapine – Rx __________________, S/E – Increased appetite, Increased serum cholesterol, increased sedation
n “mirSADzapine”
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+Beta 1 Receptor
n Increases Heart Rate
n Increases Contractility
n Promotes __________________ Release
n Increases __________________ Release n Increases Lipolysis
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+Beta 2 Receptor
n Increases Contractility
n __________________ – DECREASES: TPR, Diastolic Pressure, and Afterload
n __________________ of the Uterus
n Broncho __________________ n Increases __________________.
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+Trouble Remembering β Receptors?
n So, #1 comes BEFORE #2 and
n Letter G comes BEFORE letter I Alphabetically
n β1 = Increase Glucagon
n β2 = Increase Insulin
n Get it! Got it! Good!
n 1 BEFORE 2 and G BEFORE I
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+Beta Receptor Pharmacology Beta 1 Agonists n __________________ (__> __) – Congestive Heart
Failure n Isoproterenol (B1=B2) Bronchospasm, Heart
block and Bradyarrhythmias n S/E – Flushing, Angina, Arrhythmias
Beta 2 Agonists n Albuterol – Asthma – short half life n __________________ – Asthma – short half life,
Premature labor treatment n Ritodrine – Premature labor treatment n Salmeterol – Asthma – Long term treatment
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+Beta Receptor Pharmacology Beta Receptor Antagonists
n Propanolol – Long half life, used in TH storm – prevents peripheral T4-T3 conversion
n Esmolol – Short half life
n Acebutolol, Atenolol, Pindolol – __________________
n Labetalol & Carvedilol = Has ______ Antagonistic Activity, used in HTN emergency
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+Beta Receptor Pharmacology Beta Receptor Antagonists
n Nadalol – In liver failure; decrease variceal
bleeding
n Timolol/Butexalol __________________ – Decreases secretion of Aqueous humor
n Carvedilol & Metoprolol – Decrease post MI mortality
n Sotolol – __________________ Channel Activity, will increase the QT Interval
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