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Flashcards in ANS Deck (145):

What is the ANS? What does it do? What does it consist of

  • Located in CNS and PNS
  • Coordinates and maintains steady state among the visceral organs
  • Neurons
    • preganglionic (myelinated)
    • postganglionic (unmyelinated)
  • 2 division classified anatomically
    • sympathetic
    • parasympathetic


Characteristics of SNS innervation?

  • Preganglionic neurons cell bodies located in T1-L2/3
  • Post ganglionic neuron cell bodies in ganglia
    • paravertebral chain
    • prevertebral ganglia (celiac, superior, inferior, mesenteric)
  • Short pre, long post


What is characteristics of PSNS?

  • Pre-ganglionic neurons arise from
    • cranio (medullary CN 3,7, 9. 10)
    • Sacral (spinal cord S2-S4) regions
  • Post ganglionic neuron cell bodies in
    • target organs
    • descrete ganglia in head/neck
  • LONG pre, short post



What is main role SNS?

  • Self preservation;: mst important function is maintenance of vasomotor tone


What is main function PSNS?

Rest for organism but excitatory visceral functions such as digestion


Many organs have innervation by SNS and PSNS. WHat are exceptions to the rule?

  • Only innervated by SNS
    • sweat glands 
    • Blood vessels (however muscarinic are present at blood vessels)
  • Only innervated by PSNS
    • Ciliary muscle of the eye (accomodate eye for near vision)
    • bronchial smooth muscle (B2 receptors present though)

Receptros can be present in a tissue and NOT be innervated. In this case, receptor will only respond when something is circulating in blood


What is major role of SNS?

  • Amplicfication resposne with diffuse innervation
    • controls:
      • postural changes
      • excercie (world class marathon runner won't want to take beta blocker)
      • Emergency massive response


PSNS exhibits ___ and ____ targeted resposnes

discrete; narrolwy targeted


Which baseline tones do both systems (SNS, PSNS) exhbiit at rest?

HR- Vagal predominance

Blood vessels- SNS tone


What is NT released/receptor at skeletal muscle?

ACh at nicotinic receptor (Nm)


Pre/post NT/receptor for blood vessels?

  • Pre ACh at Nic (Nn)
  • Post Norepinephrine @ adrenergic


Pre/post NT/receptor for sweat glands?

  • Pre: Ach at Nicotinic (Nn)
  • Post Ach at Muscarinic (exception to rule)


What is preganglionic for adrenal medulla?

Ach on nicotinic, adrenal medulla acts like post ganglionic


What is pre/post NT/receptor for parasympathetic system

  • Pre Ach at nicotinic
  • Post ach at muscarinic (salivary glands, etc)


What are receptors on cholinergic receptors?

  • Nicotinic Ach receptors
    • Nm and Nn
  • Muscarinic Ach receptors
    • M1-M5


What are adrenergic receptors?

  • alpha 1,2
  • Beta 1,2,3


What does adrenal medulla release?

Norepi 20%

Epi 80%


What are 3 major anomalies to SNS?

  • Adrenal medulla acts like ganglia but releases NE and Epi in 20/80 ratio
  • Sweat glands
    • sympathetic cholinergic fibers
    • Post ganglionic Ach onto muscarinic Ach receptor
  • Blood vessels
    • no innervation PSNS
    • there are muscarinic Ach on blood vessels, activate NO with eventual vasodilation if you had circulating Ach



Receptor, signal, 2nd messenger, physio response?

  • Receptor: Gαq
  • Signal: excitatory CNS, modulatory at ganglia
  • 2nd messenger: 
    • 1. PLC activated
    • 2. IPC & DAG increase
    • 3. PKC and increased free Ca, decreased K conductance= contraction!
  • Physiologic response
    • CNS activity, modulation at ganglia
    • located CNS and stomach



Receptor? Signal? 2nd messenger? Physiologic response?

  • Receptor Gαi
  • Signal: inhibitory cardiac
  • 2nd messenger:
    • 1. inhibit adenylate cyclase
    • 2. decrease cAMP
    • 3. increase K conductance
  • Physiologic effect
    • decreased cAMP slows HR and decreases contractility



Receptor, signal, 2nd messenger, physiologic?

  • Receptor: Gαq
  • Signal: excitatory smooth muscle, glands
  • 2nd messenger
    • 1. PLC activated
    • 2. IP3 and DAG increase
    • 3. PKC and increased free Ca
  • Physiologic response: smooth muscle contraction


Nn receptor?

Signal, 2nd messenger, physiologic response?

  • Receptor: ligand gated ion channel
  • Signal: excitatory ganglia CNS
  • 2ND messenger: Na and K permeability
  • Physiologic resposne: depolarization



Receptor? Signal? 2nd messenger? Phsyiologic response?

  • Receptor: ligand gated ion channel
  • Signal: excitatory @ NMJ
  • 2nd messenger: increase Na and K permeability
  • Physiologic: depolarization



Receptor, signal, 2nd messenger, physiologic resonse?

  • Receptor: Gαq
  • Signal: Excitatory blood vessels
  • 2nd messenger:
    • 1. PLC acticated
    • 2. IP3 and DAG increased
    • 3. PKC and increased free Ca
  • physiologic response: smooth muscle vasoconstriction



Receptor, signal, 2nd messenger, pysiologic reponse?

  • Receptor: Gαi
  • Signal: inhibitory BV @ pre, CNS @post
  • 2nd messenger:
    • 1. inhibit adenylate cyclase
    • 2. decrease cAMP
    • 3. Increase K conductance
  • Physiologic
    • decreased cAMP increases smooth muscle contraction (post)
    • hyperpolarization with increase K 


B 1,2,3

Receptor, signal, 2nd messenger, physiologic?

  • Receptor: Gαs
  • Signal: excitatory or inhibitory depends on cAMP actions
  • 2nd messenger
    • 1. activate adnylate cyclase
    • 2. increase cAMP
  • Physiologic
    • increased cAMP causes smooth muscle relaxation
    • stimulates cardiac contractility and increases rate


Where are α1 found? Actions?

  • Most vascular smooth muscle (blood vessels, sphincters, bronchi)->>> causes contraction
  • Iris--> contraction, dilates pupils
  • pilomotor---> erects hair
  • prostate and uterus--> contracts
  • heart---> increases force of contraction (B1 more important though)

Remember, α1 causes activation PLC--> IP3 & DAG--> PKC and increased free Ca causing contraction!


Where are α2 receptors found? Actions?

  • platelets--> aggregation
  • adrenergic and cholincergic nerve terminals **presynaptic**--> inhibits transmitter release (decrease HR and BP)
  • Vascular smooth muscle--> contraction (post synaptic) and dilation (pre-synaptic, CNS)
  • GI tract--> relaxation (presynpatic)
  • CNS---> sedationa nd analgesia via decrease CNS outflw from brain stem


Remember, alpha 2 causes inhibition of adenylate cyclase--> decrase cAMP--> increase K conductance


Where are beta 1 receptors found? Actions?

  • Heart--> increase force and rate of contraction
  • Kidney--> stimulate renin release

Remember Beta 1 (all betas) is Gαs causing increase adenylate cyclase, increase cAMP, and causing smooth muscle relaxation


Where are B2 receptors found, actions?

  • Respriatory, uterine, vascular, GI, GU--> promotes smooth muscle relaxation
  • Mast cells--> decrease histamine release
  • Skeletal muscle--> potassium uptake, dilation of vascular beds, tremor, increase speed of contraction
  • Liver--> glycogenolysis
  • Pancrease--> increase insulin secretion
  • adrenergic nerve terminals --> increase release NE


Remember Beta 2 is Gαs causing increase adenylate cyclae, increase cAMP, and causing smooth muscle relaxation, but also cAMP increase force/rate of contraction in cardiac muscle. 


Where are beta 3 receptors found? Action?

Fat cells--> activate lipolysis, thermogenesis


Where are D1 receptors found, actions?

  • Tissues- Post synaptic location: dilates renal, mesenteric, coronary, cerebral blood vessels


Where are D2 receptors found, actions?

  • Nerve endings- presynpatic: modulates transmitter release; nausea and vomiting


What are endogenous catecholamines?

Epi, Norepi, Dopamine


What are synthetic catecholamines?




What are synthetic non-catecholamines?

  • Indirect acting
    • ephedrine
    • mephentermine
    • amphetamines
  • Direct acting
    • phenylephrine
    • methoxamine


What are selective alpha-2 agonists




What are selective beta-2 adrenergic agonists?





What are direct agonists?

Varied affinities for alpha 1, alpha 2, beta1, beta 2


What are indirect agonists?

Increase the release of neurotransmitters by stimulating nerve endings

Dnagerous to give long term, because you're depleting nerve endings of neurotransmitters


How to choose right drug for right situation?

  • All sympathomimetics are not created equal, have differing affinities for various types of adrenergic receptors
  • need to consider all particular drug effects before giving it
  • example phenylephrine vs ephedrine
    • phenyl is direct
    • ephedrine indirect


All sympathomimetics are ___

beta-phenylethylamine derivatives


What makes something a catecholamine?

  • Amine group side chain
  • hydroxyl group on 3,4 carbon of benzene ring--> called catechol (maximal alpha nad b receptor activity)
  • thus names catechol-amines


What is doa of catecholamines vs non-catecholamines?

Catecholamines are very short DOA, more potent

Non- catecholamines are longer acting and may not be as potent as local agonists


What is pathway for creation of epinephrine?


What is mechanoism of action for sympathomimetics?

  • Activation of g-protein coupled receptr (D, beta, alpha)
    • indirect= drug increases endogenous NE release form post-ganglionic SNS nerves which then activates receptor
    • direct= directly stilumates the receptor and activates G-protein itself
  • G-protein will activate or inhibit an intracellular enzyme (adenylate cycale--> camp--> plc) or will open or close ion channel
  • Usually g-protein cascade has an eventual positive or negative effect on amount on intracellular ca= physiologic effect we see clinically


What does specific effect of sympathomimetics depend on?

  • Receptor stimulated
  • receptor density in a given tissue
  • what second messengers activate at a molecular level in the cell

Receptors will up or down regulate based upon plasma concentrations of sympathomimetic


How do we terminate effect of catecholamines?

  • Reuptake
    • uptake I- neuronal reuptake
    • upatke II- extraneuronal uptake
  • MAO
  • COMT
  • Lungs


Need infusion because it is short acting


How do we terminated effect of non-catecholamines?

  • MAO
  • Urinary excretion (unchanged)


What is it a bad idea to administer sympathomimetics to people taking MAOIs?

  • MAO is in presynpatic terminal in order to break down norepinephrine
  • If this is inhibited, then you aren't metabolizing NE as much, and will have even more NE release with subsequent stimulation


What is selectivity of receptor for phenylephrine?

alpha 1> alpha 2>>>>> Beta


What is receptor selectivity of clinidine?

alpha 2> alpha 1>>>>>> B


What is receptor selectivity for norepinephrine?

alpha 1=alpha 2; B1>>>>>>>>>>> B2 (no clinical effect)


What is receptor selectivity for epinephrine?

alpha 1= alpha 2; b1=b2


Selectivity of B-agonist recpeotrs?




Dobutamine B1>B2>>>>> alpha

Isoproterenol B1=B2>>>ALPHA

Terbutaline/albuteral B2>>B1>>>> ALPHA


What is receptor selectivity of dopamine agonists?

Dopamine D1=D2>>B>>ALPHA

Fenoldopam D1>>D2


Route, duration, dosages, indication for epinephrine?

  • Route: SQ (onset 5-10 min), IV (1-2 min onset)
  • Duration 5-10 min
  • Dosages
    • standard bolus dose 10 mcg/kg IV
    • Start 2-8 mcg/kg
    • 1-2 mcg/min IV- beta 2<
    • 4-5 mcg/min IV- beta 1
    • 10-20 mcg/min IV- alpha and beta
  • Indication
    • bronchial asthma
    • acute allergic reaction
    • cardiac arrest, asystole
    • electromechanical dissociation
    • vfib unresponsive to intial defibriallation
  • Poorly lipid soluble- little CNS effect


CV effects epinephrine?

  • ALPHA 1:
    • vasoconstriction- Increase BP, Increase CVP, Increase cardiac work
    • skin, mucosa, hepatic, renal constriction
  • alpha 2: negative feedback (decreaes BP) keeps sympathetic tone in check
  • B1: Increased contractility, HR, CO, increae BP
  • B2: 
    • peripheral vasodilation (decrease BP)
    • Skeletal muscle dilation, increase K uptake, increase glucose

With moderate epi dose, SBP increases (B1, Alpha 1) DBP tends to decrease (B2), map stays same


Cerebral effects epinephrine?

  • At clinically relevant doses, minimal vasoconstriction of artieroles in
    • cerebral vasculature
      • increase cerebral blood flow in general (even with normal BP secondary to redistribution of flow)
    • Coronary vasculature
    • pulmonary vasculature


Ocular effects of epinephrine?

  • Acoomodation for far vision
    • alpha 1- mydriasis (dilation of eyes)
  • Regulation of ocular pressure
    • alpha 1, alpha 2- increase humoral outflow
    • B1- increase produciton of aqueous humor


Respiratory effects of epinephrine?

  • Dilate smooht muscles of bronchial tree
    • B2
  • Decreased release of vasoactive mediators (histaomine) in bronchial vasculature
    • B2
  • Reduce mucosal secretion- decongestion
    • alpha 1


GI effects of epinephrine?

  • Decreased digestive secretions
    • alpha 2
  • decreased peristalsis
    • alpha 2, b2- direct smooth muscle relaxation
  • decreased splanchnic blood flow
    • alpha 1- blood flow drasitcally reduced even if BP relatively normal


GU effects of epinephrine?

  • Renal vasculature
    • Alpha 1- renal blood flow drastically reduced even if BP relatively normal
      • 2-10x more potent than NE for decreasing renal vascular resistance
    • Beta 1- in kidney increaes renin release--> cause angiotensin II vasoconstriction as well
  • Bladder
    • alpha 1- contraction urethral spincter- urinary continence
    • Beta 2- decreases urinary output
  • Erectile tissue
    • alpha 1- facilitates ejacluation
  • Uterus
    • beta 2- relaxation- inhibits labor


Metabolic effects of epinephrine

  • Increased liver glycogenolysis  and promotion of insulin release
    • B2
  • Increased adipose tissue lipolysis
    • B3
  • Inhibition of insulin release (more minor effect because opposed by B2)
    • alpha 1
  • May also cause mild hypokalemia d/t activation of Na-K pump and transfer of K into cells



Dose, effects?


  • Dose for hypotension 4-16 mcg
  • Peripheral IV admin dnagerous if IV infiltation
  • Potent alpha  and beta effect, minimal beta 2
    • intense vasoconstriciton skeletal muscle, liver, kidney, cutaneous tissue (at risk for metabolic acidosis)
    • increased SBP, DBP, MAP
    • Baroreceptors activated
      • decreased HR (vagal induced effect, ach on sa node)
      • Decreased respiration
  • Decreased venous return, CO, HR (despite B1 effect) Make sure you look and see if baroreceptors would be involved to potentially change expected effect!!!!
    • ​CO decreases d/t intense vasoconstriction
      • also why venous return decreases


Dopamine highlights? Dosing?

  • Endogenous precursor of NE
  • Stimulates all adrenergic receptors including dopamine receptors
  • Dangerous IV infiltrate
  • Concurrently, increases myocardial contractiliy, renal blood flow, UO gfr
  • increase endogenous NE release- dopa may not work as well with depleted catechol stores
  • synergistic with dobutamine to reduce afterload and improve CO
  • inhibitory at carotid bodies
  • increaed intraocular pressure
  • dosing guidelines
    • 1-3 mcg/kg/min- dopa 1 stimulation dominates ("renal dose")
    • 3-10 mcg/kg/min- Beta 1 receptor dominate
    • >10 mcg/kg/min- alpha receptor dominate




Isoproterenol highlights?

B1=B2>>>> alpha

  • Synsthetic catecholamine
  • Selective B1 and B2 agonist
  • increases HR, contractility with decreased SVR (increase SBP,. decrease DBP, decrease MAP)
  • "Chemical pacemaker"
    • 1-5 mcg/min for heart block and bradydysrhythmias
  • Rapid metabolism by COMT
  • What kind of patient is at risk with this drug?
    • CAD pt, increase demand, decreased supply, setting up for failure


Dobutamine highlights?

B1>B2>>>> alpha

  • Synthetic catecholamine
  • Dose 2-10 mcg/kg/min
  • B1 selective <5 mcg/kg/min (weak activity at SA node)
  • Weak alpha 1 >5mcg/kg/min
    • very weak compared to dopamine
  • Improves CO without increasing HR or BP substantially (good for CHF)
  • Is coronary artery vasodilator (B2 effect)


Highlights ephedrine?

  • Indirect acting non-catecholamine
    • Some direct agonist
  • Weak epinephrine (misleading, 10x longer laster)
  • Given PO, IM, IV
  • Dose 10-25 mg IV; 10-50 mg IM
  • Tachyphylaxis with repeated dosing
    • NE depletion at nerve terminals
    • Receptor occupation long 1/2 life- CV compensation
  • Excreted unchanged in urine (about 40%) and slowly metabolized by MAO and conjugated in liver; E 1/2 t 3 hours


Phenylephrine highlights?


alpha 1> alpha 2>>>>>>> b

  • Direct acting non catecholamine
  • primarily alpha 1
  • venonconstricitons > arterial constriction
  • less potent and longer lasting than norepinephrine
  • dose
    • 50-200 mcg IV
    • infusion 20-50 ug/min
  • Increases MAP, SBP, DBP, SVR
  • Decreases HR, CO


What's the worst drug you could give to correct overdose phenyl/epi?

Beta blocker. You'll loose contractility that you so despeartely need to combat increased BP

Give alpha antagonist instead!



Actions of Selective Beta 2 Agonist

  • Relax bronchiole smooth muscle
  • relax uterine smooth muscles
  • sustained DOA d/t different placement of their hydroxyl groups on benzene ring
  • Routes : PO, inhalation, SQ, IV
  • Useful in premature labor, asthma, COPD
  • Side effects: tremor (B2 in skeletal muscle), reflex tachycardia (vasodilation and B2 in heart) 
    • reflex tachycardia baroreceptor mediated d/t profound vasodilation
  • Hypokalemia


Albuterol highlights?

  • Prototype for selective Beta 2 agonist
  • preferred choice for bronchospasm due to asthma
  • Dose
    • MDI 100 mcg/puff, 2 puffs q 4-6 hours
    • max 16-20 puffs
    • Nebulization for life threatensing asthma 15 mg/hr for 2 hours
  • Tachycardia and hypokalemia with large doses



Oral, SC (0.25 mg) or puffs

For premature labor or asthma



  • MDI, DOA >12 HOURS
  • otherwise, similar ot albuterol
  • lots of attention lately for causing sudden death in asthmatics



  • FOr treatmnet of premature labor
  • some beta 1 activity, thus increase HR and CO
  • Can cause pulm edema d/t decreased excretion of Na, K and h2o


Direct acting, non catecholamines your patient may be taking that are alpha agonists?

  • Midodrine- postural hypotension
  • Oxymetazoline (afrin),Tetrahydrozoline, xylometazoline
    • all nasal and ocular decongestants


Alpha 2 agonists your patient might be taking?

  • Clonidine (partial)D
  • Dexmedetomidine (full agonist)
  • methyldopa (BP in pregnant women)
  • Decreased SNS output from CNS
    • decreases BP
    • sedation and analgesia


Indirect-acting sympathomimetics your patient might be taking?

  • Amphetamine
    • increase release NE, 5HT, dopamine
    • blocks reuptake
    • blocks vesicular transport
    • inhibitor MAO
  • Methamphetamine
    • similar to amphetamine but higher CNS effects
  • Methylphenidate (Ritaline)
  • Pemoline (Cylert)
  • Amphetamine variants- ADHD


What are the actions of amphetamines?


  • increase release NE, 5HT, dopamine
  • blocks reuptake
  • blocks vesicular transport
  • inhibitor MAO


Which drugs are inhibitors of catecholamine storage and reuptake?

  • Reserpine (originalyl developed as anti HTN)
    • vesicles lose ability to store NE, 5HT, dopamine
    • MAO breaks down excess except in high doses
      • hypotension and psych depression common
  • Cocaine
    • prevents reuptake of catechols (NE, DA, 5HT)
    • Interferes with catecholamine transport


Which drugs are our alpha antagonists?

  • Prazosin, terazosin, doxazosin
    • alpha 1>>>> alpha 2
  • Phentolamine
    • alpha 2= alpha 1
  • Yohimbine, tolazoline 
    • alpha 2>> alpha 1


Which drugs are mixed alopha and beta antagonist?

  • Labetalol, carvedilol
    • B1=B2>alpha 1> alpha 2


Which drugs are mixed B antagonist?

  • Metoprolol, atenolol, esmolol
    • B1>>> B2
  • Propanolol, nadolol, timolol
    • B1=B2
  • Butoxamine
    • B2>>> B1


What are CV effects of alpha-1 antagonism?

  • Decreases PVR and lowers BP
    • also causes tachycardia via baroreceptor mediated reaction
  • Postural hypotension due to failure of venous vasoconstriction upon standing


What are effects of alpha 2 antagonism?

  • Increases NE release from nerve terminals
  • Blocking the negative feedback mechanism


Non-selective alpha agonists ___ blood pressure ___ significantly

drop; more


GU , eye effects, nasal effects of alpha antagonists?

  • GU effects
    • blockade in prostate and bladder cause muscle relaxation and ease micturation
  • Miosis
    • pupillary constriction
  • Increased nasal congestion (generally a negative)


MOA of alpha antagonist?

  • Bind selectively to alpha receptors and interfere with ability of catecholamine to cause reposne
    • some competitive
      • phentolamine, prazosin, yohimibine
    • others bind covalently and are non competitive
      • phenoxybenazmine


What is phentolamine?

Causes? Dose? Uses?

  • Nonselective alpha blocker
  • causes: vasodilation, decrease BP, increase HR and CO
  • Used in:
    • hypertensive emergencies
      • pheochromocytoma or autnomic dysreflexia
      • nice drug for correcting immediate vasoconstrictions. very short acting
  • Dose:
    • 30-70 mcg/kg IV
    • Onset 2 min
    • DOA 10-15 min
  • Local infiltation also for accidental extravascular admin of sympathomimetics
    • 2.5-5mg in 10 mL


What is phenoxybenazmine?

  • Binds covalently
  • will be stuck with this decision
  • Alpha 1 activity >alpha 2
    • decrease SVR, vasodilation
  • Pro-drug with 1 hour onset time; long acting (E1/2t of 24 hours)
  • Preop for pts with pheochormocytoma, can be used for pts with raynaud's dx
  • 92


    • Contorl BP in pheochromocytome
    • selective alpha 1 blocker
    • minimal alpha 2
    • less reflex tachycardia (remember alpha 2 is inhibitory to NE releae)


    What is yohimibine?

    • Alpha 2 selective blocker
    • increases the release of NE form post-synaptic neuron
      • inhibits + feedback so more NE present
    • used with orthostatic hypotension, impotence


    WHat are terazosin and tamulosin?

    Long acting selective alpha-1a particularly effective in prostatic smooth muscle relaxation


    How do beta-adrenergic antagonists work, effects?

    • Prevent sympathomimetic (via competitive antagonism) from provoking a beta response on:
      • heart
        • improve O2 supply and demand balance
      • Airway
        • can provoke bronchospasm
      • blood vessels
        • vasoconstriction in skeletal muscle
        • PVD symptoms increae
      • Juxtaglomerular cells
        • decreae renin release- indirect way of decreasing BP
      • Pancreas
        • decreased stimulation of insulin release by epi/NE at b2 and then masked symptoms of hypoglycemia B1


    MOA of beta adrenergic receptor antagonist?

    • Slective binding to beta receptors (influence inotropy, chornotropy)
    • Competitive and reversible inhibiton- large doses of agonists will completely overcome antagonism
    • chronic use is associated with increase in # receptors (up-regulation)
      • cannot stop these suddenly. will make patients have profound increase HR and contractility


    Beta adrenergic receptor antagonists are all derivatives of ____


    some may act more like partial agonist


    Classifications of beta adrenergic receptors?

    • Non selective (beta 1&2)
      • propranolol, nadaolol, timolol, pindolol
      • beta-2 is nearly always negative
    • Cardioselective (beta 1 only)
      • metoprolol, atenolol, acebutolol, betaxolol, esmolol
      • large doses lose selectivity
        • this occus in all meds


    What is propranolol?

    • Non selective
      • equal B1 and B2
    • Lacks sympathomimetic activity thus it is a pure antagonist (no partial agonist present)
    • Administered in stepwise manner until goal of 55-60 achieved


    Cardiac effects of propranolol?

    • Decreased HR (more with exercise, not so much resting HR), Contractility, decreased CO
      • Above effects especially prominent during exercise and sympathetic outflow
    • Blockade of B2
      • increased PVR, increased coronary vascular resistance
    • However due to decreased HR and CO, oxygen demand is lowered opposing the above effects
    • Sodium retention due to renal system respone to drop in CO


    Pharmacokinetics of propranolol?



    Significance  r/t LA? Opioids?

    • Goes through significant first pass effect (90-95%)
      • oral dose much larger than IV dose
      • 0.05 mg/kg IV or 1-10mg (give slowly q 5 min)
    • Protein bound (90-95%)
      • unique amoung beta blockers
    • Metabolized in liver
      • e1/2 t= 2-3 hours
        • prolonged in low hepatic blood flow states
    • Decreases clearance of amide LA due to drop in hepatic blood flow/metabolism inhibition
    • decrease pulmonary first pass effect of fentanyl
      • more fent will be in system, increasing effects


    What is timolol?

    • Non-selective beta blocker
    • used to tx glaucoma- decreases intraocular pressure by decreasing production of aqueous humor
    • eye drops can cause decerase BP, HR and increase airway resistance


    What is nadolol?

    • Non selective beta blocker
    • no significant metabolism (renal/biliary elimination)
      • excreted unchanged
    • E1/2 t of 20-40 hrs taking 1x dialy
      • longer lasting


    What is metoprolol?

    • Selective beta 1 blockers
    • prevents inotropy and chronotropy
    • selectivity is dose related
    • about 60% goes through first pass effect
      • po 50-400 mg
      • IV 1-15 mg
    • E1/2 t of 3-4 hours
      • extensive hepatic metabolism
      • crosses BBB easily b/c lipid solubility
        • CNS depression
        • lethargy/fatigue


    What is atenolol?

    • Most selective beta 1 antagonist and thought to have least CNS effects
    • E1/2 t= 6-7 hours
    • Not metabolized in liver, excreted via renal system, therefore E1/2T is increased markedly in pts with renal dx
    • very useful in cardiac pt with CAD


    What is betaxalol?

    • Cardioselective beta 1 blocker
    • e1/2 t 11-22 hours
      • slightly less concernign if patient doesn't take in AM
    • Single dose daily for HTN
    • Topically for glaucoma
    • less risk of bronchospasm as seen with timolol, so good alternative choice in asthmatics with glaucoma


    What is esmolol?

    • Selective beta 1 antagonist
    • rapid onset, short acting
    • typical dose of 0.5 mg/kg IV (10-180 mg IV)
      • DOA <15 min
      • infusion 50-300 mcg/kg/min
    • Effects HR without decreasing BP sig in small doses
      • great for blunting short lived noxious stimuli in OR or for controlled hypotension
      • be careful of admin if patient has profound sympathetic mediated vasoconstriciton b/c can precipitate CV collapse
      • great for young pt where you want HR control or cardiac pt who needs lower HR to allow filling time
    • In doses used, it does not occupy sufficient beta receptors to cause negative inotropy


    E 1/2t of esmolol? Metabolized by?

    • E1/2 t= 9 min
    • rapidly hydrolyzed by plasma esterases
    • not same esterases as cholinesterases responsbile for metabolism of sux, therefore no effect on sux metabolism


    Side effects of beta-blockers

    • CV system- decreases HR, contractility, BP
    • Exacerbation of peripheral vascular disease
      • block beta2- vasodilation
    • airway resistance- bronchospasm
    • metabolism- alter carb and fat metabolism
      • masks hypoglycemia increase in HR
    • distrubtion of ECF potassium
      • inhibits uptake of potassium into skeletal muscle
    • interaction with anesthetics- may have decrease BP with IAs
    • nervous systm- fatigue, lethargy
    • nausea, vomiting, diarrhea


    What are relative contraindications of beta-blockers?

    • Pre-existing AV heart block or cardiac failure (acute only)
    • Reactive airway dx
    • diabetes mellitus (without BS monitoring)
    • hypovolemia


    Clinical uses of beta blockers?

    • Treatment of HTN
    • Management of angina (oxygen supply/demand issue in heart)
    • decrease mortality in treatment of post MI pts
      • slows remodeling process
    • used periop and preop for pt at risk for MI
    • Suppresion of tachyarrthmias
    • prevention of excessive sympathetic nervous system activity


    What is labetalol?

    Selectivity? Metabolism?

    E 1/2 T


    Can cause...

    • Selective at alpha 1 and beta 1 and 2
      • IV beta to alpha 7:1 ratio
    • Metabolism conjugation of glucuronic acid <5% in urine
    • E1/2 t 5-8 hours, prolonged in liver dx
      • max drop in BP 5-10 min after IV
    • Dose
      • 0.1-0.5 mg/kg
      • usually 5 mg at a time for mild hypertension in OR
    • Can cause orthostatic hypotension, bronchospasm, heart blcok, CHF, bradycardia


    Anticholingergic drugs are more appropriately called _______ drugs



    Where can ACh act on synapse?

    • Nicotnic ACh receptor post synapse
    • nicotinic ACh receptor pre synpatically
    • Muscarinic ACh (M1-M5) post synaptically
    • Muscarinic (m2, m5) pre synaptic
      • don't have meds that really specifically target pre-synaptically
      • you'll block pretty much all muscarinic receptors


    What are cholinergic receptor subtypes?

    • Nicotinic receptors
      • pentameric (5 subunit ) structures
      • funciton as ligand-gated ion channels
    • Muscarinic receptors
      • G protein coupled
        • M1, M3 M5, inositol phosphate pathway Gαq pathway
        • M2, M4, inhibit adenylyl cyclase reduce cAMP--> Gαi


    Where are each of the cholinergic receptors located?

    • M1- CNS, stomach
    • M2- cardiac muscle, CNS, airway smooth muscle (anitcholinergics cause dilation here)
    • M3- airway smooth muscle, glandular tissue
    • M4- CNS
    • M5- CNS
    • Nm- skeletal muscle at NMJ
    • Nn- autonomic ganglia, adrenal medulla, CNS
      • sledgehammer, fallen out of favor


    MOA and structure of antimuscarinic drugs?

    • Competitively antagonize ACh at muscarinic receptors only
    • Cation portion of the drug ifts into ACh place on anticholinergic receptor and reversibly inhibits ACH binding
    • Allow sympathetic response to predominate
    • competitive inhibition can be reversed if [ACh] increases
    • Natural antimuscarinics (atropine and scopolamine) are tertiary amines
      • alkaloids of belladonna plant
      • crosses BBB
    • Semi-synthetic (glyco/Robinal) are quaternary ammonium derivatives
      • does not cross BBB


    What is atropine's largest effect?

    • Mainly increase HR(+++)
    • Slight relax in smooth muscle(++)
    • some confusion and anti-sialogogue (+)
      • can occasionally cause patient to wake up confused


    Scopolmain comparative effects?

    • Sedation, mydriasis and motion induced nausea, as well as anti-sialagogue
      • (+++)
    • Minimal effect HR and relax smooth muscle (+)


    Gylcopyrrolate comparative effects?

    • Equal (++) on HR, Relax smooth muscle, and antisialagogue
    • 0 on sedation, mydriasis, and motion induced nausea


    What can scopalamine also be used for when patient unstable?

    • Also a sedative that decreases risk of recall when you can't utilize anesthesia gases
    • doesn't have huge impact on hemodynamic status


    If HR is <40 and BP not great, which would be best antimuscarinic to use? 

    If HR is around 40s and BP tolerating, which would be a better drug?

    Atropine (need that HR up quick!)

    Gylcopyyrolate (will give that little HR booster that you need)


    What might be an undesired effect of glycopyyrolate?

    Can prevent elderly pt c BPH from urinaring.


    We can also use glycopyrrolate in



    Pharmacokinetics of IV atropine?

    • Onset 1 minutes
    • DOA 30-60 min
    • E1/2 t= 2.3 hours
      • 18% unchanged via urine, the rest undergoes hydrolysis


    Pharmacokinetics of glycopyrrolate

    • Onset 2-3 minutes
    • DOA 30-60 min
    • E1/2 t= 1.25 hours
    • 80% unchanged in urine
      • quaternary ammonia- caution in renal disease


    Pharmacokinetics scopolamine?

    • Extensively metabolized with 1% excreted unchanged in urine
      • very lipid soluble


    When might we use antimuscarinics?

    • Pre-op: Dry out mouth, sedation, nausea prevention
    • Treatment of bradycardia (especially vagally stimulated)
      • magnitude of effect dpeends on vaseline vagal tone
        • young pt= high tone= more tachycardia
        • elderly pt= less tone= less pronounced tachycardia
    • With anticholinesterase drugs always give antagonizing NMB
    • Promoting amnesia in unstable pt (scopolamine)
    • Bronchodilation (Ipratropium)
      • Ideally before sx
      • Dose MDI 40-80 2 PUFFS
      • 0.24-0.5mg via neb
      • Onset 30-90 min
      • Consider in asthmatics, COPD, and smokers prior to airway instrumentation
    • Mydriasis and cycloplegia (optho)
      • anticholinergics may be dangerous in pt with glaucoma
    • Reduce biliary and ureteral spasms r/t opioids


    Dose scopalamine?

    • 0.3-0.5 mg or 5 mcg/kg IM (preop)
    • 1.5 mg transdermal patch
      • 5mcg/hr x 72 hours for nausea


    Atropine doses?

    • 0.2-0.4 mg IV preop
    • 0.4-1 mg IV bradycardia
    • 2 mg in 5 mL NS via nebulizer
      • bronchodilator


    Glycopyrrolate doses?

    0.1-0.2 mg IV (preop and bradycardia)


    What is central anticholinergic syndrome? What can we give to treat it?

    • Mainly scopolamine and atropine
    • Restlessness, hallucination
    • Somnolence and unconsciousness
    • Delayed emergence/recovery in PACU
    • Physostigmine 15-60 mcg/kg IV repeated as needed q 1-2 hours
      • this is an antichoinesterase, so allows more ACh to stay in synapse
      • crosses BBB


    What med to you have to give with phsyostigmine?

    Atropine, some kind of anticholinergic

    Otherwise, we'll get excessive bradycardia, peristalsis etc


    What does ipratropium, tiotropium do?

    Bronchodilator for COPD


    What are oxybutynin (ditropan), tolterodine (detrol) 

    for overactive bladder

    nonspecific M-receptor


    What is darifenacin (enablex), solifenancin (vesicare) for?

    Overactive bladder

    M3 specific


    What do acetylcholinesterase inhibitors do?

    • Elevate concentraiton of endogenously released ACh in synapse by decreasing metabolism
      • increases transmission at Nm junction (reverses competitive NMB)
      • Increases parasympathetic tone
      • increases central cholinergic activity
        • only for those crossing BBB


    What are the indications of AChE inhibitors?

    • Useful in diseases of the Nm junction
      • myasthenia gravis- pyridostimgmine, neostigmine
    • Glaucoma
      • increases outflow of aqueous humor- physostigmine
    • Abdominal distention
      • increaes smooth muscle motility- neostigmine
    • AD and other forms of cognitiv dysfunction (first type of tranmission to fail in brain is ACh)
      • Tacrine (Cognex)
      • Donepezil (Aricept)
      • rivastigmine (exelon)
      • galantamine (razadyne)


    Adverse effects of ACHE?

    • Peripheral ACh effets on GI tract
      • n/v/d, anorexia, flatulence, abdominal cramping
      • dose dependent


    ACHe inhibitor contraindications?

    • Unstable or severe cardiac dx
    • uncontrolled epilepsy
      • placing more ACh in synapse can provoke sz prone area
    • active PUD
      • increases peristalsis


    What is methacholine?

    Used in dx of asthma


    What is carbachol?

    Decreases intraocular pressure, cause miosis


    What is bethanechol

    GI and urinary tract motility- postop and postpartum urinary retention, neurogenic bladder


    What is succinylcholine

    Continuous activation of nicotinic receptor channels result in depolarization blockade (depolarizing MR)


    What are non-depolarizing muscle relaxants?

    • Prevent endogenous ACh binding to nicotinic receptors an subsequent muscle cell depolarization
    • ex- pancuronium, cev, roc