Autonomic Pharmacology (Sketchy Information)

Epinephrine (high dose)
Family: Sympathomimetics (alpha> beta agonist)
Action: bronchodilation, decrease DBP, increase CO, HR
Treatment Use: Anaphylaxis

Nicotinic Receptors
-Autonomic ganglion, skeletal muscles, adrenal glands
-Act as ion channel

Muscarinic Receptors
-Autonomic effector organ
-Coupled to G-protein
-M1, M2, M3

M1
-Location: CNS/ Enteric
-G-protein subtype: Gq (IP3- DAG -> increase intracellular Ca2+)

M2
-Location: Atrium, SA, AV node
-G-protein subtype: Gi ( decrease intracellular cAMP)

M3
-Location: Glands, Bladder, Eyes
-G-protein subtype: Gq (IP3- DAG -> increase intracellular Ca2+)

M3 Activation (Vascular effects)
-Normal: M3 activation in intact endothelium causes a release of NO which causes a increase in cGMP and vasodilation of smooth muscle
-Atherosclerosis: when there is damaged endothelium M3 agonist act directly on smooth muscle which cause vasoconstriction

Bethanocol
Family: Cholinomimetics
Action: Increase secretory and motor activity of the gut (M1)
Treatment Use: Non-obstrucutive urinary retention

Pilocarpine
Family: Cholinomimetics
Action: Increases salivation and contraction of the ciliary muscle and accommodation of lens, increase aqueous humor outflow, activates sphincter papillae muscle to cause pupillary constriction
Treatment Use: Glaucoma, Acute-angle closure glaucoma

Carbachol
Family: Cholinomimetics
Action: Constriction of pupil
Treatment Use: Glaucoma

Methacholine
Family: Cholinomimetics
Action: Contract bronchial smooth muscle which may exacerbate asthma or COPD
Treatment Use: Pulmonary testing

Varenicline
Family: Cholinomimetics
Action: nicotinic partial agonist
Treatment Use: smoking cessation

Cholinesterase Inhibitors
Indirect cholinomimetics by inhibiting acetylcholinesterase thus increasing the Ach concentration in the synapse

“stigamine”
drug suffix for acetylcholinesterase inhibitors

Quaternary Amines
Synthetic compounds that are positively charged and are thus unable to cross the blood-brain barrier

Tertiary Amines
Compounds that are uncharged and thus unable to cross the blood-brain barrier

Pyridostigamine
Family: Cholinesterase Inhibitors
Quaternary
Action: increase the Ach in the synapse
Treatment Use: long term treatment of Myasthenia Gravis to outcompete antibodies at the NMJ

Neostigamine
Family: Cholinesterase Inhibitors
Quaternary
Action: increase the Ach in the synapse
Treatment Use: long term treatment of Myasthenia Gravis to outcompete antibodies at the NMJ, long lasting, reverse the actions of non-depolarizing neuromuscular blocking agents, bladder retention

Edrophonium
Family: Cholinesterase Inhibitors
Quaternary
Action: transient increase the Ach in the synapse
Treatment Use: Tensilon test to determine if a Myasthenia Gravis patient is receiving adequate treatment

Non-depolarizing Neuromuscular Blocking Agent
-Inhibit Ach at the NMJ, causes flaccid paralysis
-Reversed with Neostigamine

Succinylcholine
Depolarizing NMJ blocking agent (N-Ach agonist) which causes a Phase I block
-the administration of Neostigamine would cause potentiate flaccid paralysis by flooding the synapse with Ach

Physostigamine
Family: Cholinesterase Inhibitors
Tertiary
Action: increase the Ach in the synapse
Treatment Use: Atropine Overdose

Organophosphates (Thiols)
Family: Cholinesterase Inhibitors
Tertiary
Action: increase the Ach in the synapse
Treatment Use: None
-used as insecticides, herbicides, nerve agents
-cause cholinergic toxicity
-reversed using pralidoximine for PNS symptoms, Atropine for CNS symptoms

Cholinergic Toxicity
DUMBBELS
1. Diarrhea
2. Urination
3. Miosis
4. Bronchospasm
5. Bradycardia
6. Excessive sweating
7. Lacrimation
8. Salivation
-Possible flaccid paralysis due to the flooding of Ach at the NMJ

Galantamine
Family: Cholinesterase Inhibitors
Tertiary
Action: increase the Ach in the synapse
Treatment Use: Alzheimers

Rivastigamine
Family: Cholinesterase Inhibitors
Tertiary
Action: increase the Ach in the synapse
Treatment Use: Alzheimers

Donepezil
Family: Cholinesterase Inhibitors
Tertiary
Action: increase the Ach in the synapse
Treatment Use: Alzheimers

Muscarinic Antagonist
Reversible block muscarinic receptor, block DUMBBELS via a block of Ach effects

Atropine
Family: Muscarinic Antagonist
Action: nonselective anatomist of M1, M2, M3; cause mydriasis, cycloplegia, block parasympathetic activation of the atriums, SA and AV nodes thus increasing HR and AV conductance
Treatment Use: to reverse shock, bradycardia in cardiac emergencies, AV node block

Scopolamine
Family: Muscarinic Antagonist
Action: cross BBB and inhibit central M1 receptors
Treatment Use: Motion sickness/ vestibular nausea with transdermal application

Ipratropium
Family: Muscarinic Antagonist
Action: M3 antagonist of the smooth muscle of the bronchial tree and secretion of airways, causes bronchial dilation and reduced secretion
Treatment Use: COPD

Tiotropium
Family: Muscarinic Antagonist
Action: M3 antagonist of the smooth muscle of the bronchial tree and secretion of airways, causes bronchial dilation and reduced secretion, longer lasting than Ipratropium
Treatment Use: COPD

Oxybutynin
Family: Muscarinic Antagonist
Action: M3 antagonist, causes relaxation of the smooth muscle of the bladder causing slower voiding
Treatment Use: Overactive bladder, bladder spasm after surgery

Tolterodine
Family: Muscarinic Antagonist
Action: M3 anagonist, cause relaxation of the smooth muscle of the bladder causing slower voiding
Treatment Use: Urinary Inconsistence

Benztropine
Family: Muscarinic Antagonist
Action: M1 receptor antagonist, reduces tremors and (cogwheel) rigidity, re-establishing the dopamine-Ach balance
Treatment Use: Parkinson’s Disease, extrapyramidal side effects of anti-psychotic medications (dystonia, akathisia, parkinsonia)

Trihexyphenidyl
Family: Muscarinic Antagonist
Action: M1 receptor antagonist, reduces tremors and (cogwheel) rigidity, re-establishing the dopamine-Ach balance
Treatment Use: Parkinson’s Disease, extrapyramidal side effects of anti-psychotic medications (dystonia, akathisia, parkinsonia)

Muscarinic Antagonist Toxicity (10 symptoms)
1. Increased HR
2. Hyperthermia (due to decrease sweating)
3. Dry Mouth (decrease salivation)
4. Dry Eyes (decreased lacrimation)
5. Blurred Vision (Mydriasis, Cycloplegia)
6. Acute-angle closure glaucoma
7. Sedation
8. Agitation
9. Hallucinations
10. Coma (in the elderly)

alpha-1 receptor
-Location: Vasculature, Urethral, Prostate Sphincter
-G-protein subtype: Gq (IP3-PAG, increases intracellular Ca2+)
-Function: Vasoconstriction (increase SVR), Mydriasis, Urethral/ Prostate constriction

alpha-2 receptor
-Location: Preganglionic Sympathetic Neurons, Pancreatic Inlet Cells, Lipid Cells, Lacrimal Gland
-G-protein subtype: Gi (decrease intracellular cAMP)
-Function: Inhibit NT release and thus act to decrease sympathetic tone, decrease Insulin releases, decrease lipolysis and FA release, decrease aqueous humor production in the eye

beta-1 receptor
-Location: Myocytes, SA node, AV node, Juxtaglomerular Cells
-G-protein subtype: Gs (increase intracellular cAMP)
-Function: Increase SA conduction thus HR, increase contractility, increase cardiac output, increase Renin release

beta-2 receptor
-Location: Bronchial smooth muscle, Coronary and Skeletal Vasculature, Pancreatic Inlet Cells, Lacrimal Gland, Lipid Cell, Liver, Most Cells
-G-protein subtype: Gs (increase intracellular cAMP, thus increase protein kinase A and relax smooth muscle)
-Function: vasodilation (decrease SVR), decrease diastolic BP, increase lipolysis and FA release, increase Insulin release, increase gluconeogenesis, increase aqueous humor production, drive K+ into cells which causes a hypokalemia

Brimonidine
Family: Sympathomimetics (alpha-2 agonist)
Action: decrease the production of aqueous humor
Treatment Use: open angle glaucoma

Phenyleprine/ Oxymetazoline
Family: Sympathomimetics (alpha-1 agonist)
Action: vasoconstriction, increase MAP, SBP, DBP, mydriasis, causes reflex bradycardia
Treatment Use: nasal congestion, eye dilation, hypovolemic shock, septic shock

Norepinephrine
Family: Sympathomimetics (alpha> beta agonist)
Action: vasoconstriction, increase MAP, SBP, DBP, increase contractility (SV, CO), increase PP
Treatment Use: hypovolemic shock, septic shock

Dobutamine
Family: Sympathomimetics (beta-1 > beta-2 agonist)
Action: increase HR, CO, minimal decrease in SVR, increase PP (increase SBP and decrease DBP)
Treatment Use: refractory heart failure, cariogenic shock, stress testing for those that cannot exercise (via increase in cardiac oxygen demand)

Isoproterenol
Family: Sympathomimetics (beta-1 > beta-2 agonist)
Action: increase HR, CO, decrease SVR, DBP, MAP, and SBP stays relatively the same
Treatment Use: bradycardia, heart block (?)

Terbutaline
Family: Sympathomimetics (beta-2 agonist)
Action: relax uterine smooth muscle
Treatment Use: prevent premature labor

Ritobrine
Family: Sympathomimetics (beta-2 agonist)
Action: relax uterine smooth muscle
Treatment Use: prevent premature labor

Albuterol/Terbutaline
Family: Sympathomimetics (beta-2 agonist)
Action: Bronchodilation
Treatment Use: Asthma

Formoterol/ Salmeterol
Family: Sympathomimetics (beta-2 agonist)
Action: Bronchodilation
Treatment Use: Asthma
*Long Lasting*

Epinephrine (low dose)
Family: Sympathomimetics (alpha > beta agonist)
Action: increase SVR, MAP
Treatment Use: Anaphylaxis

Indacaterol/Olodaterol
Family: Sympathomimetics (beta-2 agonist)
Action: bronchodilation, *pseudoirreversibile*
Treatment Use: long term COPD

Vilanterol
Family: Sympathomimetics (beta-2 agonist)
Action: bronchodilation
Treatment Use: COPD

Proprantol/ Timolol
Family: Sympatholytics (beta-1 and beta-2 antagonist)
Treatment Use: hypertension, angina pectoris, MI, tachycardia, situational anxiety

Pindolol
Family: Sympathomimetics (beta-1 and beta-2 partial agonist)
Treatment Use: hypertension, tachycardia

Bisprolol/ Metaprolol
Family: Sympatholytics (beta-1 antagonist)
Treatment Use: decrease Renin release, hypertension, angina pectoris, reduce mortality during cardiac failure

Esmolol
Family: Sympatholytics (beta-1 antagonist)
Treatment Use: intra-operative tachycardia, supra ventricle tachycardia, AFIB

Nebivolol
Family: Sympatholytics (beta-1 and beta-2 antagonist, partial beta-3 agonist)
Treatment Use: hypertension, stable heart failure, NO release via beta-3 and thus vasodilation

Labetolol
Family: Sympatholytics (beta-1 and beta-2 antagonist, partial beta-3 agonist)
Treatment Use: hypertensive crisis, hypertension in children, hypertension in pregnancy, vasodilation

Carvedicol
Family: Sympatholytics (beta-1 antagonist)
Treatment Use: hypertension, heart failure, left ventricular dysfunction following MI

Midrodrine
Family: Sympathomimetics (alpha-1 agonist)
Treatment Use: chronic orthostatic hypotension
*long lasting due to not being metabolized by COMT*

_________ cholinergic receptors are found on the autonomic ganglia/skeletal muscle NMRs while __________ cholinergic receptors are found on smooth muscle of the heart and glands (muscarinic/nicotinic) nicotinic; muscarinic _____________ cholinergic receptors are GPCRs and ____________ cholinergic receptors are ion channels …

parasympathethic nervous system decrease heart rate, nonvascular smooth muscle contracts (increase mobility of digestive muscles, increased bladder motility) sphincters relax eye ciliary muscles contract increase in exocrine gland secretion Sympathetic nervous system Fight or flight increase in HR increase in …

What components of the sympathetic nervous system are innervated by cholinergic fibers? adrenal medulla and sweat glands ACh acts are 2 types of receptors: nicotinic and muscarinic. What types of receptors are these? nicotinic ACh receptors are Na+/K+ channels muscarinic …

Two divisions of the Nervous System Central Nervous System (brain and spinal cord) Peripheral Nervous System (outside of brain and spinal cord) Two divisions of the Peripheral NS Efferent Division (consists of the neurons that carry signals AWAY from the …

alpha 1- found where? – vascular smooth muscle in skin and gut alpha 1- effect? – activates vasoconstriction – during flight or fight want reduced blood flow to skin and gut – End result: VASOCONSTRICTION at skin and gut WE …

Propranolol *Nonselective *Low dose-dependent bioavailability Negligible effects on alpha and muscarinic receptors *Nitric Oxide partial agonist activity at beta-receptors Metoprolol *Beta-1 selective (preferable in pts. with diabetes or PVD) Better for pts. who experience bronchoconstriction w/ propranolol but still use …

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