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133 Cards in this Set
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define ANS
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autonomic nervous system is a network of peripheral nerves involved in regulating the activity of glands, smooth muscle, and certain aspects of metabolism
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what is the potential of the autonomic nervous system?
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alter a wide variety of functions that involve a number of different systems in the body
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what is the function of clonidine?
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antihypertensive agent that stimulates adrenergic receptors in the CNS
lowers SNS tone which decreases blood pressure and effectively alleviates HTN |
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in what situations is clonidine useful?
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emergency hypertension
stimulates adrenergic receptors in inhibitory center -> decreases SNS outflow |
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what is the ultimate source of ANS activity?
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CNS stimulatory and inhibitory centers
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what peripheral autonomic nervous system fibers are myelinated?
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preganglionic fibers (both sympathetic and parasympathetic)
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what peripheral autonomic nervous system fibers are not myelinated?
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postganglionic fibers (both sympathetic and parasympathetic)
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how many neurons are in series for the peripheral sympathetic nervous system? the peripheral parasympathetic nervous system? the peripheral somatic nervous system?
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sympathetic - two neurons in series
parasympathetic - two neurons in series somatic - one neuron to the effector |
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where are the ganglia of the sympathetic nervous system?
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along the spinal cord
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where are the ganglia of the parasympathetic nervous system?
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intramural (within the wall of the organ)
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what are the relative lengths of the pre- and postganglionic fibers of the sympathetic nervous system?
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preganglionic sympathetic fibers are short
postganglionic sympathetic fibers are long |
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what are the relative lengths of the pre- and postganglionic fibers of the parasympathetic nervous system?
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preganglionic parasympathetic fibers are long
postganglionic parasympathetic fibers are short |
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what are the two synapses of the ANS outside of the CNS?
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ganglia
junction of postganglionic fiber at the effector organ |
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what is the neurotransmitter from the preganglionic fibers of the sympathetic nervous system?
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acetylcholine
preganglionic fiber is cholinergic |
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what is the neurotransmitter from the postganglionic fibers of the sympathetic nervous system?
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norepinephrine
postganglionic fiber is adrenergic |
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what is the neurotransmitter from the preganglionic fibers of the parasympathetic nervous system?
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acetylcholine
preganglionic fiber is cholinergic |
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what is the neurotransmitter from the postganglionic fibers of the parasympathetic nervous system?
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acetylcholine
postganglionic fibers are cholinergic |
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what is the neurotransmitter from somatic neurons?
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somatic neurons release acetylcholine at the neuromuscular junction
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what is the effect of the sympathetic nervous system on the eye?
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stimulates the pupil dilator muscle (iris) -> dilation (mydriasis)
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what is the effect of the sympathetic nervous system on glands associated with the eye, nasal cavity, and oral cavity?
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no direct effect
stimulation of SNS causes vasoconstriction of the arteries supplying the glands, which indirectly decreases secretion |
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what is the effect of sympathetic stimulation on the respiratory system?
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stimulation of sympathetic nervous system -> bronchial dilation
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to what adrenergic stimulus does the respiratory system respond?
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responds to circulating epinephrine from adrenal glands
no receptors for norepinephrine in the respiratory system |
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what is the effect of sympathetic nervous stimulation on the heart?
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stimulation of sympathetic nervous system -> increased heart rate, increased AV conduction, increased contractility
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what is the effect of sympathetic nervous stimulation on the digestive system?
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stimulation of sympathetic nervous system -> decrease GI tone and motility
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what is the effect of sympathetic nervous stimulation on the urinary system?
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sympathetic nervous stimulation -> relaxation of bladder wall
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by what division of the autonomic nervous system is total peripheral resistance controlled (and therefore blood pressure)?
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sympathetic nervous system
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by what division of the autonomic nervous system are arterioles innervated?
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arterioles are innervated exclusively by the sympathetic nervous system; sympathetic tone to the arterioles controls peripheral resistance and therefore blood pressure
(only a small degree of PS innervation; not important) |
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what are the two exceptions to norepinephrine as the sympathetic nervous system postganglionic neurotransmitter?
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adrenal medulla - secretes 80% epinephrine (not norepinephrine)
sweat glands - receive a postganglionic sympathetic neuron that releases acetylcholine |
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where do the postganglionic sympathetic neurons for the adrenal medulla project?
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the adrenal medulla is an example of a sympathetic ganglion that doesn't project anywhere
cells that receive neurons release their product into circulation |
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what is the sympathetic neurotransmitter received by sweat glands from postganglionic neurons?
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acetylcholine
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what is the effect of parasympathetic stimulation on the eye?
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parasympathetic stimulation
-> focal adjustment -> miosis (constriction of pupil) |
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what is the parasympathetic ganglion that innervates the eye?
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ciliary ganglion
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what is the parasympthetic ganglion that innervates the lacrimal gland?
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sphenopalatine ganglion
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what is the parasympathetic ganglion that innervates the glands of the head?
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otic ganglion
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what is the effect of parasympathetic stimulation on the glands of the head?
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parasympathetic stimulation -> copious secretions
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what are the four large parasympathetic ganglia of the head? what do they innervate?
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ciliary ganglion - eye
sphenopalatine ganglion - lacrimal gland otic ganglion - glands of the head submandibular ganglion - submandibular glands |
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what is the effect of parasympathetic nervous stimulation on the respiratory system?
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parasympathetic nervous stimulation
-> mucous production -> bronchiole constriction |
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what is the effect of parasympathetic nervous stimulation on the heart?
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parasympathetic nervous stimulation
-> decreased heart rate -> decreased AV conduction |
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what is vagal dominance?
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parasympathetic stimulation easily overwhelms sympathetic stimulation at the heart
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what is the effect of parasympathetic nervous stimulation on the digestive system?
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parasympathetic nervous stimulation -> increased GI tone and motility
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what is the effect of parasympathetic nervous stimulation on the urinary system?
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parasympathetic nervous stimulation -> emptying bladder
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what are the effects of the autonomic nervous system on the pupil?
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sympathetic - dilation (mydriasis)
parasympathetic - constriction (miosis) |
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what are the effects of the autonomic nervous system on the ciliary muscle?
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sympathetic - no effect
parasympathetic - contraction (near vision) |
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what is the effect of the ANS on the nasal gland?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on lacrimal glands?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on the parotid glands?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on the submaxillary glands?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on the gastric glands?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on the pancreatic glands?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on the bronchial glands?
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sympathetic - vasoconstriction of arterioles -> decreased blood flow to gland -> indirect decrease of secretions
parasympathetic -> copious secretions, rich in enzyme |
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what is the effect of the ANS on the sweat glands?
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sympathetic - direct stimulation of copious secretions
parasympathetic - no effect |
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what is the effect of the ANS on the heart?
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sympathetic - increase heart rate, increase contractility, increase AV conduction velocity
parasympathetic - decrease heart rate, decrease AV conduction velocity |
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what is the effect of the ANS on the bronchi?
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sympathetic - dilated
parasympathetic - constricted |
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what is the effect of the ANS on the lumen of the gut?
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sympathetic - decrease peristalsis and tone
parasympathetic - increased peristalsis and tone |
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what is the effect of the ANS on the sphincter of the gut?
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sympathetic - increase tone
parasympathetic - decrease tone |
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what is the effect of the ANS on the liver?
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sympathetic - increased glycogenolysis -> increased blood glucose
parasympathetic - no effect |
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what is the effect of the ANS on the kidney?
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sympathetic - decreased output; increased renin secretion -> inc. angiotensin II -> inc. TPR
parasympathetic - no effect |
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what is the effect of the ANS on the bladder detrusor muscle?
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sympathetic - relaxation
parasympathetic - contraction |
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what is the effect of the ANS on the bladder trigone?
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sympathetic - constriction
parasympathetic - relaxation |
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what is the effect of the ANS on the penis?
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sympathetic - ejaculation
parasympathetic - erection |
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what is the effect of the ANS on the vasculature?
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sympathetic - constriction of abdominal and skin vasculature, dilation of muscle vasculature
parasympathetic - no effect |
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what is the effect of the ANS on the adrenal cortical secretion?
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sympathetic - increases cortisol secretion
parasympathetic - no effect |
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what is the effect of the ANS on the adrenal medullary secretion?
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sympathetic - increases release of NE/epinephrine
parasympathetic - no effect |
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what is the main example of a glucocorticoid?
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cortisol
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what type of adrenergic receptor is responsible for the vasodilation of muscle vasculature?
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beta-2 adrenergic receptors
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where are the baroreceptor fibers and what are their jobs?
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carotid sinus
pickup degree of stretch in arterial wall |
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what is the cycle of the baroreceptor reflex?
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inc. BP
-> inc. stretch of baroreceptors -> inc. firing of afferents -> inc. PSNS output -> dec. HR -> dec. SNS output -> dec. HR -> dec. TPR -> return to normal BP |
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what happens to baroreceptors when MAP is increased?
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baroreceptor firing is increased
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what are the effects of sympathetic nervous system stimulation?
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inc. peripheral vascular resistance
inc. heart rate inc. contractile force inc. venous tone |
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how does contractile force affect cardiac output?
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inc. contractile force
-> inc. stroke volume -> inc. CO |
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how does venous tone affect cardiac output?
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inc. venous tone
-> inc. venous return -> inc. stroke volume -> inc. CO |
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what is the hormonal feedback loop of the ANS and the cardiovascular system?
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inc. MAP
-> inc. renal blood flow/pressure -> dec. renin -> dec. angiotensin II -> dec. TPR -> dec. aldosterone -> dec. blood volume -> dec. venous return -> dec. stroke volume -> dec. cardiac output -> dec. MAP |
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how is typrosine transported into the noradrenergic varicosity?
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carrier that is linked to sodium uptake
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what is the action of reserpine?
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inhibits the transporter that carries dopamine into storage vesicles in the sympathetic varicosities
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how is dopamine carried into the vesicles in sympathetic varicosities?
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countertransport with hydrogen ions
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how is NE transported into vesicles in the sympathetic varicosities?
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countertransport with hydrogen ions
same transporter as dopamine |
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how is dopamine converted to norepinephrine?
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catalytic action of dopamine-B-hydroxylase (DBH)
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what is the function of dopamine-B-hydroxylase (DBH)?
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convert dopamine to norepinephrine
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describe the process between action potential and exocytosis of neurotransmitter in the sympathetic varicosities
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action potential is conducted to the varicosity by the action of voltage-sensitive sodium channels
depolarization of the varicosity memrane opens voltage-gated calcium channels and results in an increase in intracellular calcium elevated calcium facilitates exocytotic fusion of vesicles with the surface membrane and expulsion of NE, ATP, and some of dopamine-B-hydroxylase |
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what is the action of reserpine?
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blocks amine (dopamine/NE) countertransport with hydrogen ions in sympathetic varicosities
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what is the effect of cocaine on the sympathetic varicosity?
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blocks the reuptake pump on presynaptic cells, so that NE is not taken back up into the presynaptic cells
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how can nonvesicular NE be released?
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tyramine and a variety of the other indirectly acting adrenergic agonists
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what is the action of guanethidine?
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prevents calcium-induced exocytosis
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what receptors inhibit further release of NE from sympathetic varicosities?
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alpha-2 receptors on the presynaptic cell bind NE and inhibit further NE release
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what are the mechanisms that stop the action of NE?
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uptake into presynaptic cell (most important)
uptake into postsynaptic cell diffusion away from cleft |
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what is COMT?
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catechol-O-methyl transferase
enzyme which catalyzes the degradation of catecholamines such as dopamine, epinephrine, and norepinephrine |
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what is the chain of reactions from tyrosine to epinephrine?
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tyrosine
-(tyrosine hydroxylase)-> DOPA -(Aromatic Amino Acid Decarboxylase)-> dopamine -(dopamine-beta-hydroxylase)-> norepinephrine -(phenylethanolamine-N-methyltransferase)-> epinephrine |
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what is phenylethanolamine-N-methyltransferase? where is it found?
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enzyme which catalyzes the conversion of NE to epi
found in the adrenal medulla |
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what enzyme is required to convert tyrosine to dopamine?
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tyrosine hydroxylase
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what is the function of tyrosine hydroxylase?
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hydroxylates tyrosine to make DOPA
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what is the function of aromatic amino acid decarboxylase (aka DOPA carboxylase)?
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decarboxylates DOPA to make dopamine
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what enzyme is required to convert DOPA to dopamine?
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aromatic amino acid decarboxylase (aka DOPA decarboxylase)
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what enzyme is required to convert dopamine to norepinephrine?
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dopamine-beta-hydroxylase
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what is the function of dopamine-beta-hydroxylase?
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hydroxylates the carbon in the beta position to the amino group of dopamine to make norepinephrine
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what enzyme is required to convert norepinephrine to epinephrine?
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phenylethanolamine-N-methyltransferase
(methylates the nitrogen) |
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what molecules accumulate in patients treated with monoamine oxidase inhibitors?
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tyramine
octopamine |
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what is the rate-limiting step of epinephrine/norepinephrine synthesis?
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tyrosine hydroxylase catalyzed hydroxylation of tyrosine to make DOPA
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for what is metyrosine used to clinically treat?
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pheochromocytoma
acts to decrease catecholamine synthesis by the tumor as a competitive inhibitor of tyrosine hydroxylase |
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what is a pheochromocytoma?
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a catecholamine-producing tumor of the adrenal medulla
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what is the pathophysiology of pheochromocytoma?
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hyperactivity of the SNS exhibited symptomatically as severe hypertension and associated complications
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what two enzymes in the synthesis of epi/NE are "promiscuous enzymes"?
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aromatic amino acid decarboxylase
dopamine-beta-hydroxylase react with endogenous tyramine and exogenous (alpha-methyldopa) substances to form false transmitters |
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what are promiscuous enzymes?
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enzymes that are nonspecific for their substrates
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what is a false transmitter?
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a compound that enters presynaptic storage vesicles and replaces the normal neurotransmitter
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how does the postsynaptic activity of a false transmitter compare to that of the normal transmitter?
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can have the same, less, or even greater postsynaptic activity
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what is alpha-methyl DOPA (aldomet) used to treat?
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hypertension (has a central action)
decreases SNS outflow from CNS |
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what is the pathway by which alpha-methyl norepinephrine is made from alpha-methyl DOPA?
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alpha-methyl DOPA
-(aromatic amino acid decarboxylase)-> alpha-methyl dopamine -(dopamine-beta-hydroxylase)-> alpha-methyl norepinephrine |
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what is the pathway by which octopamine is made from tyramine?
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tyramine
-(dopamine-beta-hydroxylase)-> octopamine |
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what is the effect of octopamine?
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octopamine is a false neurotransmitter with no postsynaptic activity
it replaces NE in the vesicles of the sympathetic varicosities and subsequently decreases total peripheral resistance |
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what is the effect of alpha-methyl norepinephrine?
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replaces NE in the vesicles of the sympathetic varicosities and stimulates postsynaptically as well as NE
metabolized much slower than NE, so its effect is enhanced, causing greater stimulation of inhibitory center of medulla |
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what are the functions of presynaptic vesicles?
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storage of neurotransmitter
protection from cytoplasmic enzymes |
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what are the two effects of an I.V. bolus of guanethidine?
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short-term initial increase in b.p.
long-term decrease in b.p. |
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why does guanethidine I.V. bolus cause an initial increase in b.p.?
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it enters the pre-synaptic nerve terminal via NE reuptake pump and is pumped into transmitter vesicles
the guanethidine then displaces NE from granular binding sites, resulting in a high concentration of cytoplasmic NE not all of the cytoplasmic NE can be degraded and some leaks out into the cleft, where it interacts with post-synaptic receptors this elicits the initial sympathetic response of increased b.p. |
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what are the two actions of guanethidine?
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blocks physiologic release of NE
replaces NE in presynaptic vesicles |
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what is an indirect sympathomimetic?
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a drug that mimics the effects of transmitter substances of the sympathetic nervous system such as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc without directly stimulating the sympathetic post-synaptic receptors
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what is a direct sympathomimetic?
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a drug that mimics the effects of transmitter substances of the sympathetic nervous system such as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc by directly stimulating the sympathetic post-synaptic receptors
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from what does the secondary, long-lasting anti-hypertensive effect of guanethidine result?
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since guanethidine blocks the exocytosis of presynaptic vesicles, thereby blocking physiologic release of NE, it uncouples neuronal stimulation and NE release
since guanethidine replaces NE in the presynaptic vesicles, the NE stores in the nerve terminal are gradually depleted, and the nerve terminal is rendered ineffective |
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what are the side effects of guanethidine?
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1) orthostatic (postural) hypotension
2) excessive GI stimulation 3) inhibition of ejaculation 4) patients w/ pheos are especially sensitive |
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why do drugs that inhibit the SNS cause orthostatic (postural) hypotension?
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blood pools in the lower extremities upon rising from the supine position
SNS normally kicks in (baroreceptor reflex) to bring the blood pressure back up to prevent fainting SNS-inhibiting drugs prevent SNS from compensating and a patient will easily faint upon standing |
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why do SNS-inhibiting drugs cause diarrhea?
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excessive GI stimulation caused by unopposed parasympathetic nervous system activity/stimulation
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what is the major cause of non-compliance in patients on SNS-inhibiting drugs?
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inhibition of ejaculation causes a messed up sex life, and that leads to poor compliance
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what patients are especially sensitive to guanethidine's indirect sympathomimetic action?
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patients with pheochromocytoma
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how does guanethidine enter presynaptic vesicles?
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NE reuptake mechanism
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how does reserpine enter presynaptic vesicles?
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high lipid-solubility allows reserpine to enter storage vesicles by passive diffusion
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how does reserpine inhibit the SNS?
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passively diffuses into presynaptic vesicles and then inhibits the ATP-dependent NE/dopamine uptake carrier present in vesicles
NE is not displaced, the vesicle simply runs out of it |
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what is the monoamine theory of depression?
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depletion of NE in the CNS leads to depression, and possibly to suicide in already depressed patients
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what are the CNS symptoms caused by reserpine?
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sedation
lethargy nightmares **depression** |
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why is reserpine so good at causing CNS symptoms?
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it is very highly lipid soluble, and can cross the blood-brain barrier
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what is the primary means by which sympathetic signals are terminated?
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reuptake of NE into the presynaptic terminal
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what is the "classic" pharmacological agent to block reuptake of NE into presynaptic terminals?
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cocaine
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what drugs interfere with reuptake of NE into presynaptic terminals?
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cocaine (classic)
tricyclic antidepressants |
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why is guanethidine inhibited when cocaine and tricyclic antidepressants are administered?
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they block the NE/dopamine uptake carrier that guanethidine uses to enter presynaptic terminals
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how are direct sympathomimetics taken up into presynaptic cells?
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they act at the postsynaptic receptor and usually have a similar enough structure to NE that they are uptaken by the same uptake receptor as NE
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what happens to sympathomimetics when the NE/dopamine uptake pump is blocked?
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the sympathomimetics are usually taken up by the same uptake receptor as NE and when the receptor is blocked, the sympathomimetic sticks around longer and acts longer
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