Autonomic Nervous System Pharmacology - … Nervous System Pharmacology Shan Nanji + ANS – Parasympathetic & Sympathetic Basics ! Parasympathetic - “CHOLinergic” ! Craniosacral,

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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 _______

Shan Nanji - [email protected]

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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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- 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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- 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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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 Tacrine – Lipid Soluble – Rx – Alzheimers Shan Nanji - [email protected]

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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 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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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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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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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 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 Agonists

n NorepinephRINE n Clinical Use:

n Hypotension (Decreased Renal Blood Flow)


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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 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 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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Autonomic Nervous System Pharmacology - … Nervous System Pharmacology Shan Nanji + ANS – Parasympathetic & Sympathetic Basics ! Parasympathetic - “CHOLinergic” ! Craniosacral,