Autonomics

The Autonomics section provides High Yield information for the USMLE, COMLEX, Medical School, Residency, and in the future career as a Physician. Prepare and Learn Ahead!

Daniel Walsh and Alan Sved / CC BY-SA

Receptors

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 an increase in cGMP and vasodilation of smooth muscle
      
    • -Atherosclerosis: when there is damaged endothelium M3 agonist act directly on smooth muscle which causes vasoconstriction

Nicotinic Receptors

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

Cholinomimetics

Bethanechol

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

Carbachol

• Family: Cholinomimetics
  
• Action: Constriction of the pupil
  
• Treatment Use: Glaucoma

Methacholine

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

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

Varenicline

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

Cholinesterase Inhibitors

• “-stigamine”
  • drug suffix for acetylcholinesterase inhibitors
• Tertiary Amines
  • Compounds that are uncharged and thus unable to cross the blood-brain barrier
• Quaternary Amines
  • Synthetic compounds that are positively charged and are thus unable to cross the blood-brain barrier

Tertiary Amines

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 pralidoxime for PNS symptoms, Atropine for CNS symptoms

Physostigmine

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

Alzheimer’s Disease

Donepezil

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

Galantamine

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

Rivastigmine

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

Quarternary Amines

Myasthenia Gravis

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

Neostigmine

• 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

Pyridostigmine

• 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

Depolarizing NMJ Blocking Agent

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

Non-depolarizing Neuromuscular Blocking Agent

• -Inhibit Ach at the NMJ, causes flaccid paralysis
  
• -Reversed with Neostigmine

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

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

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

Scopolamine

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

Tolterodine

• Family: Muscarinic Antagonist
  
• Action: M3 antagonist, cause relaxation of the smooth muscle of the bladder causing slower voiding
  
• Treatment Use: Urinary Incontinence

COPD

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

Parkinson’s’ Disease

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 antipsychotic 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 antipsychotic medications (dystonia, akathisia, Parkinsonia)

Muscarinic Antagonist Toxicity

1. Increased HR
2. Hyperthermia (due to decreased 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)

Sympathomimetics Receptors

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

Sympathomimetics Agonists

Phenyleprine/ Oxymetazoline

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

Brimonidine

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

Epinephrine

• Family: Sympathomimetics (alpha> beta agonist)
• Low Dose
  • Action: increase SVR, MAP
    
  • Treatment Use: Anaphylaxis
• High Dose
  • Action: bronchodilation, decrease DBP, increase CO, HR
    
  • Treatment Use: Anaphylaxis

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, cardiogenic shock, stress testing for those that cannot exercise (via an 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 

Asthma

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

COPD

Indacaterol/Olodaterol

• Family: Sympathomimetics (beta-2 agonist)
  
• Action: bronchodilation, pseudo-irreversible
  
• Treatment Use: long term COPD

Vilanterol

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

Prevent Premature Labor

Terbutaline

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

Ritodrine

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

Sympathomimetics Antagonists

Esmolol

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

Hypertension

Bisprolol/ Metaprolol

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

Carvedilol

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

Labetalol

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

Midodrine

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

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

Pindolol

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

Propranolol/ Timolol

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