Autonomics Flashcards
A more appropriate name for anticholinergic drugs is
antimuscarinic drugs
The Autonomic Nervous System:
◼Located in both the ___ & ___
◼Coordinates and maintains a steady state among the _____________ organs
◼Neurons
- _____________ (myelinated)
- _____________ (unmyelinated)
◼Two divisions classified anatomically (often physiologic antagonists) = _____________ & _____________
CNS & PNS visceral (internal) Preganglionic Postganglionic Sympathetic & Parasympathetic
SNS “Fight or Flight” - Sympathetic innervation:
◼ Preganglionic neurons cell bodies located in ?, within the ?
T1 - L2-3 of spinal cord
Intermediolateral horn of grey matter
SNS “Fight or Flight” - Sympathetic innervation:
Post ganglionic neuron cell bodies are located in ?
◼ _____________ chains (either side spinal column)
◼ _____________ ganglia (i.e. celiac, superior, inferior mesenteric ganglia in abdomen)
ganglia
Paravertebral
Prevertebral
SNS “Fight or Flight” - Sympathetic innervation:
◼______ preganglionic neurons, ______ post
Short, long
PSNS “Rest and Energy Restoration” - Parasympathetic innervation:
Pre-ganglionic neurons arise in
◼ Cranial (medullary)…….
◼ Sacral (spinal) regions……
CN 3,7, 9, 10
S2-4
PSNS “Rest and Energy Restoration” - Parasympathetic innervation:
Post-ganglionic neurons cell bodies located in:
◼ Target ______
◼ Discrete ganglia in the _____ and _____ (i.e. ciliary ganglia)
organs
head and neck
PSNS “Rest and Energy Restoration” - Parasympathetic innervation:
◼ _____ preganglionic neurons, _____ post
Long, short
SLIDE 7, review/know
review/know
Summary of ANS Functions:
◼Often SNS & PSNS actions are ___________ of one another
◼SNS = self __________: most important function is maintenance of ___________
◼PSNS = ____ for the organism but “________” visceral functions such as digestion
antagonistic
preservation, vasomotor tone
rest, excitatory
Summary of ANS Functions (cont): ◼ Many organs have innervation by both SNS and PSNS - Examples = ◼ Exceptions to this rule however: - Only innervated by SNS = ◼ Only innervated by PSNS =
bladder, cardiac muscle, GI
Sweat glands & Blood vessels (Muscarinic receptors present though)
Ciliary muscle of the eye & Bronchial smooth muscle (B2 receptors present though ~ Epi from Adrenal Medulla)
◼ Important! Receptors can be present in a tissue and NOT be innervated. If this is the case….. that receptor will only respond when something is circulating in the blood (drug or hormone)
SNS:
◼ __________ response with diffuse innervation
◼ ________ changes
◼ ________
◼ ___________ massive response- fight or flight
Amplification
Postural
Exercise
Emergency
PSNS:
◼ discrete and narrowly _______ responses
targeted
SNS and PSNS:
Both systems exhibit “baseline tone”at rest
◼ __ = vagal predominance
◼ _________ = SNS tone
HR
Blood vessels
SLIDE 11, review!
Fig 9-2 Range and Dale: Note receptor types & where Ach and NE (NA) released
Receptors in the Peripheral Nervous System:
◼ Cholinergic Receptors =
◼ Adrenergic receptors =
- Nicotinic Ach receptors (Nm and Nn)
- Muscarinic Ach receptors (M1-5)
- alpha (1,2)
- beta (1, 2, 3)
◼ Disclaimer: When we discuss receptor types and affinities this is an oversimplification… For example, there are at least 3 subclasses of alpha 1 & 3 subclasses of alpha 2 receptors! Also many co-transmitters are released with NE and Ach
Receptors in the Peripheral Nervous System: 3 major anomalies (exceptions to the rule) are
◼ ____________ (acts like a ganglia but releases NE and Epi as HORMONES)
- Norepi __%
- Epi __%
◼ ____________
- Innervated anatomically by ____
- Post ganglionic nerve releases Ach onto a _________ Ach receptor
- Thus … “sympathetic cholinergic fibers”
**EXAM QUESTION
◼ Blood vessels
- No innervation by ____
- However, there are __________ Ach receptors present on the blood vessels (activate NO with eventual vasodilation if you had a situation with circulating Ach)
**EXAM QUESTION
Adrenal medulla, Norepi 20%, Epi 80%
Sweat glands, SNS, muscarinic
PSNS, muscarinic
SLIDE 14, review, memorize, KNOW!!!
PRINT!!!
SLIDES 16-19, review Table 11.1 Range and Dale
Per Dr. B!!!!
alpha 1: Most vascular smooth muscle; (i.e blood vessels, sphincters & bronchi) = (action) Iris (radial muscle) = Pilomotor smooth muscle = Prostate and Uterus = Heart =
contraction Contraction (dilates pupils= mydriasis) Erects Hair Contraction Increases force of contraction (B-1 more important though)
alpha 2: Platelets = (action) Adrenergic & cholinergic nerve terminals *presynaptic = Vascular smooth muscle = GI tract = CNS =
Aggregation
Inhibits transmitter release (decrease BP and HR)
Contraction (postsynaptic) OR Dilation (pre-synaptic, CNS)
Relaxation (presynaptic)
Sedation and analgesia via ↓SNS outflow from brain stem
beta 1:
Heart Kidneys = (action)
↑ force & rate of contraction Stimulation of renin release
beta 2: Respiratory, uterine, vascular, GI, GU (visceral smooth muscle) = (action) Mast Cells = Skeletal muscle = Liver = Pancreas = Adrenergic Nerve Terminals =
Promotes smooth muscle relaxation ↓ Histamine release Potassium uptake, dilation vascular beds, tremor, ↑speed contraction Glycogenolysis ↑ Insulin secretion ↑release of NE
beta 3:
Fat cells = (action)
Activates lipolysis; thermogenesis
D1:
Smooth muscle = (action)
Post-synaptic location; Dilates renal, mesenteric, coronary, cerebral blood vessels
D2:
Nerve endings = (action)
Pre-synaptic - Modulates transmitter release; nausea and vomiting (anti N/V or causes?)
SNS Pharmacology: Overview of Drug Classes
Endogenous catecholamines =
Epi, Norepi, Dopa
SNS Pharmacology: Overview of Drug Classes
Synthetic catecholamines =
Isoproterenol, Dobutamine
SNS Pharmacology: Overview of Drug Classes
Synthetic non-catecholamines
- Indirect acting =
- Direct acting =
Ephedrine, mephentermine, amphetamines
- sledge hammer; acting on release of NT, not receptor stimulation
Phenylephrine, Methoxamine
SNS Pharmacology: Overview of Drug Classes
Selective Alpha-2 agonists =
Clonidine, dexmedetomidine
SNS Pharmacology: Overview of Drug Classes
Selective Beta-2 adrenergic agonists =
Albuterol, terbutaline, ritodrine
SNS Pharmacology: Overview of Drug Classes used in Anesthesia
◼ Direct Agonists – varied affinities for………
◼ Indirect Agonists =
Alpha 1, Alpha 2, Beta 1, Beta 2
↑ release of neurotransmitters
Overall activity of these drugs is governed by their affinity, efficacy and selectivity with respect to different types of adrenoreceptors.
All ___________________ are Beta-phenylethylamine derivatives.
◼ An _________ group side chain
◼ _________ group on the 3,4 carbons of benzene ring→catechol (Maximal _____ and _____ receptor activity)
◼ Thus the name _________________
sympathomimetics amine (NH2) Hydroxyl alpha and beta catechol-amine
Sympathomimetics: Mechanism of Action
Activation of G-protein coupled receptor (D,beta,alpha)
◼ _______ = the drug increases endogenous norepinephrine release from post-ganglionic SNS nerves which then activates the receptor
◼ _______ = the drug binds to the receptor and activates the Gprotein itself
Indirect
Direct
Sympathomimetics: Mechanism of Action
◼ _________ will activate or inhibit an intracellular enzyme (adenylate cyclase→cAMP, phospholipase C) or will open or close an ion channel
◼ Usually the __________ “cascade” has an eventual positive or negative effect on the amount of intracellular Calcium = physiological effect we see clinically
G-protein
G-protein
Sympathomimetics: Mechanism of Action
◼Different parts of the body have different types and densities of _________ (skeletal muscle VS venous smooth muscle VS myocardium VS bronchial smooth muscle etc.)
◼The specific effect depends on the ____ of receptor stimulated, receptor ________ in a given tissue, and what the __________________ activate at a molecular level in the cell.
◼Receptors will ____ or ____ regulate based upon plasma concentrations of sympathomimetic
receptors
type, density, second messengers
up or down
Termination of effect/Metabolism of Sympathomimetics:
Catecholamines
◼REUPTAKE I
- Uptake I = __________ reuptake
- Uptake II = __________ uptake
◼MAO & COMT are responsible for catecholamine ___________ in the _____ removing them from reuse
◼_____
*metabolism of Catecholamines < or > that of Non-catecholamines because of __ group
neuronal extraneuronal catabolism, brain Lungs >, OH?
Termination of effect/Metabolism of Sympathomimetics:
Non-catecholamines
◼___
◼______________________
MAO Urinary excretion (unchanged) ~ polar
How would MAO inhibitors cause a problem in terms of NE and beta 1?
Inhibition of MAO metabolism of NE, leaving an elevated reuptake storage of NE (presynaptic) available for release upon next stimulation. When this excessive storage of NE is released, along with NE from post - ganglionic nerves, Injected Drugs and Epinephrine/ Norepinephrine excreted from the adrenal medulla circulating in the blood stream can result in excessive concentrations of NT.
*Remember the exception is B2 which NE cannot activate (but epi can).
How would MAO inhibitors cause a problem in terms of serotonin?
MAO inhibitors elevated the levels of NE, SEROTONIN, and dopamine. When given a drug, like Demerol, that blocks presynaptic serotonin reuptake, this can result in serotonin hyperstimulation.
*MAOIs used in treatment of depression and parkinson’s
Selectivity of Adrenoreceptor Agonists:
◼ alpha-agonists
Phenylephrine - alpha _ > alpha _»_space;»> beta (0 clinical effect)
Clonidine - alpha _ > alpha _»_space;»> beta
◼ Mixed alpha- and beta-agonists
NE* - alpha _ = alpha _; beta _»_space;»»> *beta _
Epinephrine - alpha _ = alpha _; beta _ = beta _
*(remember this is what is released by post-ganglionic nerves in the SNS – now does it make sense why B2 receptors are present in many tissues but NOT innervated…)?????????????????????????????????
alpha 1 > alpha 2
alpha 2 > alpha 1
alpha 1 = alpha 2; beta 1»_space;»»> *beta 2
alpha 1 = alpha 2; beta 1 = beta 2
Selectivity of adrenoreceptor agonists: ◼ beta-agonists Dobutamine - beta _ > beta _ >>>> alpha Isoproterenol - beta _ = beta _ >>>> alpha Terbutaline/albuterol - beta _ >> beta _ >>>> alpha ◼ Dopamine agonists Dopamine D_=D_ >> \_\_\_\_ >> \_\_\_\_ Fenoldopam D_>>D_
beta 1 > beta 2»_space;» alpha
beta 1 = beta 2»_space;» alpha *Chem pacemaker
beta 2»_space; beta 1»_space;» alpha *EX: beta 1 comes in to play upon extended use of nebulizer
D1=D2»_space; beta»_space; alpha
D1»D2
Endogenous Catecholamines:
Epinephrine = _____________**
◼ Many physiological functions (acts on all 4 Adrenergic receptors)
◼ Most potent activator = ______ receptors
◼ Routes: __ or __
◼ Very ______ lipid soluble = _____ CNS effect
◼ Onset: (SQ) ____ min (IV) ____ min
◼ Duration: ____ min
◼ Indications:
The prototype alpha SQ or IV poorly, little (SQ) 5-10 min (IV) 1-2 min 5-10 min
Bronchial asthma
*if servere and give after beta 2 agonist
Acute allergic reaction
Cardiac arrest, asystole
Electromechanical dissociation
V.fib. unresponsive to initial defibrillation
Infusion to increase myocardial contractility
- beta 2 = peripheral vasodilation
- beta 1 = contraction
Epinephrine dosing:**
◼ Standard bolus dose for resuscitation is _______ IV
◼ Can start with _-_mcg/kg
◼ Need infusion – with single bolus dose CV effects dissipate after _-_min? So if no dissipation, cont. infusion?
- 1-2mcg/minute IV = _____
- 4-5mcg/min IV = _____
- 10-20mcg/min IV = ___________
10mcg/kg IV 2-8mcg/kg 1-5min? Beta-2 *asthma Beta-1 Alpha & Beta
Cardiovascular Effects of Epinephrine:**
Epinephrine stimulates all adrenoreceptors
Major role - BP regulation:
◼ alpha 1 =
◼ alpha 2 =
◼ beta 1 =
◼ beta 2 =
◼ **With moderate epinephrine doses: ___ tends to increase ~ beta _, alpha _; ___ tends to decrease ~ beta _, & ___ stays the same*
◼ alpha 1 = vasoconstriction = ↑ BP, ↑ CVP, ↑ Cardiac work
* skin, mucosa, hepatic, renal
◼ alpha 2 = negative feedback = ↓ BP
◼ beta 1 = increased contractility, HR, CO – ↑ BP
increase in phase 4 depolarization = arrhythmias in older pts
◼ beta 2 = peripheral vasodilation = ↓ BP
skeletal muscle
◼ **With moderate epinephrine doses: SBP tends to increase ~ beta 1, alpha 1; DBP tends to decrease~ beta 2, & MAP stays the same*
Cerebral Effects of Epinephrine:**
At clinically relevant doses minimal vasoconstriction of arterioles in:
◼ _________ vasculature (__________ cerebral blood flow in general, even with normal __ secondary to redistribution of blood flow)
◼ _________ vasculature
◼ _________ vasculature
◼ Makes sense doesn’t it? ~ Fight or Flight!
Cerebral, increase, BP
Coronary
Pulmonary
Ocular Effects of Epinephrine:**
Accommodation for far vision
◼ alpha 1 = mydriasis (pupil dilation)
Regulation of intraocular pressure
◼ alpha 1, alpha 2 = increase _______ outflow
◼ beta 1 - increase production of _____________
alpha 1 = mydriasis (Contraction of radial muscles of the eye = pupil dilation) humoral (body fluid) aqueous humor (clear fluid filling space in front of eyeball between lens and cornea) *EX: BB for glaucoma!
Respiratory Effects of Epinephrine:**
◼Dilate smooth muscles of bronchial tree = ◼Decreased release of vasoactive mediators (histamine) in bronchial vasculature =
◼Reduce mucosal secretion - decongestant =
◼What are the anesthetic considerations here?
◼Dilate smooth muscles of bronchial tree = beta 2 ◼Decreased release of vasoactive mediators (histamine) in bronchial vasculature = beta 2
◼Reduce mucosal secretion - decongestant = alpha 1
◼***With a beta blocker you see the opposite effect that is why asthmatics do not get beta-blockers – even the selective B-1 types like esmolol can adversely impact bronchial tone. B-2 stim also decreases the release of vasoactive mediators associated with symptoms of bronchial asthma.
GI Effects of Epinephrine:**
◼ Decreased digestive secretions =
◼ Decreased peristalsis =
◼ Decreased splanchnic blood flow =
◼ Decreased digestive secretions = alpha 2
◼ Decreased peristalsis = alpha, beta 2- direct smooth muscle relaxation
◼ Decreased splanchnic blood flow = alpha 1 –blood flow drastically reduced even if BP relatively normal
GU Effects of Epinephrine:**
◼ Renal Vasculature (hint: Important!!!!!)
- alpha 1 = renal blood flow drastically ________ even if __ relatively normal
- beta 1 = kidney ________ renin release
** Hint: think about why beta blockers might decrease BP…
◼ Bladder
- alpha 1 = ___________ of urethral sphincter - urinary continence?
- beta 2 = _________ - decreases urinary output?
◼ Erectile tissue
- alpha 1 - facilitates __________
◼ Uterus
- beta 2 - relaxation - _______ labor
reduced, BP increase contraction relaxation ejaculation inhibits
***Epi is estimated to be 2-10X more potent than norepi for decreasing renal vascular resistance. Key point here – kidneys are going to take a big hit with epinephrine consider a vasodilator to accompany epi gtt.
