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143 Cards in this Set
- Front
- Back
The circadian rhythm of autonomic function originates where?
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suprachiasmatic nucleus (SCN) in the hypothalamus
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The circadian rhythm of autonomic function is entrained by light falling on what?
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melanopsin-containing retinal ganglion cell dendrites (not rods or cones) in the eye
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stretch-sensitive mechanoreceptors in the carotid arteries transmit information via what nerve?
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glossopharyngeal
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sretch sensitive mechanoreceptors in the aorta transmit information via what nerve?
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vagus
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stretch sensitive receptors transmit information to where in CNS?
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nucleus tract solitarii (NTS) in the posterior medulla.
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Excitatory neurons from the nucleus tract solitarii (NTS) innervate what?
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the dorsal motor nucleus
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Inhibitory neurons of the nucleus tract solitarii (NTS) innervate what?
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Excitatory neurons innervate the dorsal motor nucleus of the vagus, where parasympathetic outflow is regulated.
Inhibitory neurons, using gamma- aminobutyric acid (GABA) as neurotransmitter, innervate areas in the ventrolateral medulla from which sympathetic outflow is regulated. The most important such site is the rostral ventrolateral medulla (RVLM). |
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Destruction of the NTS or its afferent input can lead to what?
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the syndrome of baroreflex failure--acute period of dramatic hypertension, followed by wide swings in blood pressure
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Efferent parasympathetic outflow to the cardiovascular system goes through what nerve?
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vagus nerve.
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Glossopharyngeal neuralgia?
(glossopharyngeal syncope) |
disorder post 9th cranial nerve damaged
Paroxysms of severe throat pain with hypotension and bradycardia occur. Attacks are due to massive spontaneous afferent discharges of the glossopharyngeal nerve, providing excessive input into the NTS, and eliciting parasympathetic activation and sympathetic withdrawal. |
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Efferent sympathetic outflow from the RVLM travels in the ____tract to the intermediolateral column of the spinal cord.
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bulbospinal
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The primary neurochemical mediator of both sympathetic and parasympathetic preganglionic neurons is what?
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acetylcholine (ACh).
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The primary mediator of sympathetic postganglionic fibers is usually ____, but at least some sympathetic postganglionic fibers to sweat glands are ____
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norepinephrine (NE), cholinergic (acetylcholine).
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Neurotransmitter of parasympathetic postganglionic fibers is what?
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acetylcholine.
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Epinephrine is found in the ____, the central nervous system and the ____
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adrenal medulla
para-aortic bodies (organs of Zuckerkandl). |
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____ is a neurochemical mediator in the central nervous system and probably also in some neurons in the superior cervical ganglion and the kidney.
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Dopamine
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name the catecholamines
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Norepinephrine, epinephrine and dopamine
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sympathomimetic amines
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norepinephrine, epinephrine, adrenaline plus drugs that resemble them
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what is cotransmission ?
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multiple neurotransmitters commonly exist within one neuron, and they may be differentially released
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P2 receptor
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ATP acts directly on receptor (purinergic)
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P1 receptor
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adenosine acts on receptor (ATP post metabolism)
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Acetylcholine (ACh) is synthesized by what?
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choline acetyltransferase
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choline acetyltransferase catalyzes what reaction?
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the transfer of an acetyl group from acetylcoenzyme A to choline
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What is the rate limiting step of ACh synthesis?
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the choline transporter into the neuron
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botulinum toxin acts by what biochemical mechanism
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blocking the release of acetylcholine
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hydrolysis of ACh into choline and acetic acid is catalyzed by which enzyme
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acetylcholinesterase
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acetylcholinesterase (true cholinesterase) is found where?
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near cholinergic neurons and in red blood cells
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non-specific cholinesterase (pseudocholinesterase or butyrylcholinesterase) is found where?
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in plasma and in some organs but not in the red blood cell or the cholinergic neuron.
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clinical effect of pseudocholinesterase deficiency
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some drugs such as succinylcholine (used during anesthesia) which are normally broken down by pseudocholinesterase, are very poorly metabolized by this variant enzyme. Such patients may have prolonged muscle paralysis from succinylcholine
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the rate-limiting step in NE synthesis and is located in which cell compartment?
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the cytoplasm
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the rate limiting step of NE synthesis is what reaction & enzyme?
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Tyrosine hydroxylase (tyrosine to dopa)
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During increased sympathetic stimulation, dopa production is increased in what ways?
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a) more enzyme is synthesized, and b) the physical properties of the enzyme are altered (allosteric activation) so that affinity for tyrosine is increased and affinity for end products like NE is reduced
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what is a clinically useful inhibitor of tyrosine hydroxylase? Why significant enzyme?
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metyrosine (a-methyl-p-tyrosine).
rate limiting step of NE synthesis |
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Dopa decarboxylase "aromatic-L-amino acid decarboxylase" (dopa to dopamine) is found in what cell compartment of what tissues?
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cytoplasm of many nonneural as well as neural tissues
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carbidopa clinical usefulness
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Peripheral (non-neuronal) dopa decarboxylase inhibition when one is trying to prevent formation of peripheral dopamine during dopa therapy of Parkinsonism
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Dopamine-ß-hydroxylase catalyzes what reaction? what metal contained by enzyme?
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dopamine to norepinephrine
copper |
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treatment of Dopamine-ß-hydroxylase deficiency
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dihydroxyphenylserine (DOPS), which is decarboxylated directly into norepinephrine by dopa decarboxylase, thus restoring the appropriate neurotransmitter
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symptoms of Dopamine-ß-hydroxylase deficiency
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lifelong orthostatic hypotension, and ptosis of the eyelids. Their sympathetic neurons contain large quantities of dopamine, but little or no norepinephrine.
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Phenylethanolamine-N-methyltransferase (norepinephrine to epinephrine) is restricted to where?
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adrenal medulla, the brain and the organ of Zuckerkandl
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inhibition and stimulation of Phenylethanolamine-N-methyltransferase (norepinephrine to epinephrine)
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inhibited by physiological concentrations of epinephrine
Glucocorticoid increases enzyme activity. |
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monoamine oxidase (MAO) breaks down what neurotransitter?
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norepinephrine
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acetylcholine stimulates release of NE from postganglionic neuron via what receptor
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nicotinic receptor
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nicotinic receptor function in sympathetic system?
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accepts acetylcholine from preganglionic sympathetic neuron.
Stimulates release of norepinephrine |
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a2-receptors
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reduce release of additional norepinephrine
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b2-receptors
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increase release of norepinephrine
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which modulatory receptor reduces release of additional norepinephrine?
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presynaptic a2-receptors
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Which modulatory receptor increases release of additional norepinephrine?
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b2-receptors
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substances that increase norepinephrine release in selected tissues via a nicotinic receptor
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angiotensin, and acetylcholine
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substances that decrease norepinephrine release via a muscarinic receptor in selected tissues
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1 dopamine
2 histamine 3 serotonin 4 adenosine 5 PGD2 6 PGE2 7 acetylcholine |
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uptake I
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reuptake of catecholamines into the neuron via norepinephrine transporter
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uptake II
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uptake of catecholamines into extraneuronal tissue
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inhibitors of monamine oxidase
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pargyline, tranylcypromine, and selegiline (Deprenyl®)
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Monoamine oxidase function, location
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converts catecholamines to their corresponding aldehydes
located in the outer membrane of mitochondria as well as extraneuronally |
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Catechol-o-methyltransferase (COMT) function and location
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converts NE into normetanephrine and epinephrine into metanephrine
found especially in liver and kidney. |
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intervention which results in acetylcholine precursor transport blockade?
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hemicholinium
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interventions which promote acetylcholine release?
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choline, black widow spider venom (latrotoxin)
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intervention which prevents acetylcholine transmitter release?
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botulinum toxin
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intervention which prevents ACh storage?
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vesamicol
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Interventions which result in cholinesterase inhibition?
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physostigmine, neostigmine
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intervention which inhibits tyrosine hydroxylase
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metyrosine, used to treat pheochromocytoma
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intervention which inhibits dopa decarboxylation
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carbidopa
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intervention which inhibits Dopamine-ß-hydroxylase
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disulfiram
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interventions which inhibit monamine oxidase
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pargyline, tranylcypromine, selegiline
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intervention which prevents norepinephrine storage
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reserpine
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interventions which cause initial release of NE leading to depletion of catecholamine
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guanethidine, guanadrel
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intervention which blocks NE release
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bretylium
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intervention which block the norepinephrine transporter
(Uptake I) |
cocaine, tricyclic antidepressants
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intervention which inhibits Catechol-o-methyltransferase
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entacapone
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intervention which blocks uptake II of catecholamine
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glucocorticoids
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motor neuron -< skeletal muscle
Name: neurotransmitter/receptor type of skeletal muscle |
ACh
nicotinic |
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pregang symp -< postgang symp
Name: neurotramsmitter and receptor type |
ACh
nicotinic |
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Medulla Oblongata a2
NE what response? |
Reduced sympathetic outflow
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Pupil a1
--NE what response? |
Mydriasis (radial muscle contraction)
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Heart b1
NE what response? |
Acceleration, contractility increase
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Arterioles a1,a2
NE what response? |
Constriction
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Arterioles b2
NE what response? |
Dilation
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Veins a1,a2
NE what response? |
Constriction
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Bronchial Muscle b2
NE what response? |
Relaxation
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Uterus b2
NE what response? |
Relaxation
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Bladder Sphincter a1
NE what response? |
Contraction
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Platelet a2
NE what response? |
Aggregation
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Salivary Glands a1,a2
NE effects? |
Viscous secretion
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Pilomotor Muscles a1
NE effects? |
Contraction (horripilation, "chill bumps")
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Gastrointestinal Muscle a1,a2,b2
NE effects? |
Relaxation
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Spleen Capsule a1
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Contraction
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Pancreas a2
NE effect? NE effects? |
Reduced insulin
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Pancreas ß2
NE effect? |
Increased insulin
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Liver a1, b2
NE effect? |
Hyperglycemia
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Adipose Tissue b1, b3
NE effect? |
Lipolysis
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Adipose Tissue a2
NE effect? |
Reduced lipolysis
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Adipose Tissue b3
NE effect? |
Heat production
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Kidney a2
NE effect? |
Sodium conservation, reduced renin
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White Blood Cells b2
NE effect? |
Demargination
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Norepinephrine is especially potent at which adrenoreceptors.
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a1 and at b3
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Epinephrine has relatively more activity at which adrenoreceptors than does norepinephrine.
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b2
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a1-agonists
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phenylephrine, methoxamine, norepinephrine
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eccrine sweat glands are stimulated by what neurotransmitter
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ACh
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Bladder sphincters are contracted by stimulation of what receptor
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a1-stimulation
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Phenylephrine (Neosynephrine®) and methoxamine are far more potent in stimulating which receptors
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a1-receptors
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How are Phenylephrine (Neosynephrine®) and methoxamine used clinically?
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hypotensive states
locally to cause mydriasis nasal congestions Phenylephrine is occasionally used to restore paroxysmal atrial tachycardia to normal sinus rhythm (via baroreceptor-mediated enhancement of vagal tone). |
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how does Norepinephrine differs from phenylephrine in receptor stimulation
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greater capacity to stimulate b1-adrenoreceptors as well as a1-adrenoreceptors
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Epinephrine clinical use
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to support blood pressure, especially during anaphylaxis
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a1-blockers, 4
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1 prazosin
2 phentolamine 3 tolazoline 4 phenoxybenzamine |
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prazosin receptor stimulation
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selectively block the a1- receptor
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Phentolamine clinical use
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competitive nonselective alpha adrenergic receptor antagonist
used to determine whether a given level of hypertension is catecholamine-mediated. helpful in diagnosing pheochromocytoma at the bedside. |
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Phenoxybenzamine clinical use
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medical management of pheochromocytoma.
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Phentolamine mechanism
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competitive, short-acting a-antagonist.
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Phenoxybenzamine mechanism
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noncompetitive, long-acting a-antagonist
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Prazosin mechanism
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selective blocks a1-receptors without blocking the a2-receptors that mediate feedback inhibition of norepinephrine synthesis/release
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Prazosin clinical use
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hypertension and in congestive heart failure.
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The major problems in prazosin use
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prazosin syncope," fainting that occasionally occurs on standing 2-4 hours after the first oral dose
tendency toward reduced efficacy with chronic use |
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a2-agonists
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clonidine, guanabenz, guanfacine, and a-methylnorepinephrine
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The most important effects of a2-agonists
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presynaptic a2- stimulation mediates feedback-inhibition of norepinephrine release
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intracellular effect of activation of beta-adrenoreceptor
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synthesis of cAMP by adenylyl cyclase
**The hormone-receptor ("liganded receptor") interacts with a stimulatory guanine nucleotide-binding regulatory protein (Gs), which then activates the adenylyl cyclase. |
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intracellular effect of activation of alpha-2 receptor (M2 receptor)
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inhibition of adenylyl cyclase
**regulatory protein (Gi) also binds to GTP interaction of Gi leads to inhibition of adenylyl cyclase. The Gi regulatory protein sometimes also interacts with ion channels to activate (K+ channels) or inhibit (voltage-gated Ca++ channels) them |
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intracellular receptor for cAMP
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cyclic AMP-dependent protein kinase (protein kinase A)
When activated by cyclic AMP, the kinase phosphorylates a variety of cellular proteins and regulates their activities. |
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intracellular effect of alpha 2 receptor activation
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Ca++ release-> calmodulin-dependent enzyme activation
DAG--> protein kinase C **activation of a membrane-bound phospholipase C (PLC). Phospholipase C hydrolyzes a membrane phospholipid, phosphatidylinositol-4,5-biphosphate (PIP2), resulting in the formation of diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). IP3 causes the release of Ca2+ |
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what drug stimulates brainstem a2 receptors and binds to imidazoline receptors and reduces sympathetic outflow to cardiovascular system?
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Clonidine
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reason for methyldopa use as antihypertensive
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its metabolite, a-methylnorepinephrine, stimulates a2 receptors
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Causalgia
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pain syndrome that develops in the joints especially after nerve injuries
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only widely available, relatively specific a2-antagonist
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yohimbine
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mechanism of yohimbine
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By blocking a2-adrenoreceptors in the medulla, it increases sympathetic outflow
By blocking presynaptic a2-adrenoreceptors in the periphery, it enhances norepinephrine release |
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Isoproterenol mechanism
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stimulates both b1- and b2-receptors
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clinical uses of beta2 agonist (none is perfectly selective)
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asthma and cessation of premature labor
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dobutamine mechanism
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relatively selective b1-agonist
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dobutamine clinical uses
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cardiac stimulation
such as in pulmonary edema, coronary bypass post-op |
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b3 adrenoreceptor funciton
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mediates heat production and energy expenditure in adipose tissue.
sensitive to norepinephrine, not easily blocked |
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Propranolol mechanism
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competitive inhibitor of sympathomimetic amines at both the b1- and b2- receptor
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propranolol affects on heart rate, contractility, and BP
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In persons on no medication, propranolol reduces heart rate, contractility and blood pressure
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propranolol affect on AV conduction
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slowed
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propranolol effect on bronchial tone
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increased
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propranolol contraindications
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in asthmatics and in patients with chronic obstructive pulmonary disease.
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propranolol use
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to reduce heart work in patients with angina pectoris and
treat ventricular arrhythmias antihypertensive agent probably by reducing renin production. produces subjective improvement in thyrotoxicosis subjective improvement in certain anxiety states |
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Metoprolol mechanism
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relatively selective blocker of the b1-receptor
|
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Atenolol mechanism
|
relatively selective blocker of the b1-receptor
|
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timolol clinical use
|
eye drops are used in glaucoma patients to reduce intraocular pressure
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Atenolol clinical use
|
given once daily in managing hypertension.
|
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Fenoldopam mechanism
|
specific for D1
|
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D1 receptors effects
|
mediate vasodilatation in the coronary, cerebrovascular, renal, and mesenteric vascular beds
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D2 receptors effects
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cause emesis and inhibition of prolactin
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Tyramine mechanism
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enters noradrenergic neurons via the norepinephrine transporter and displaces NE from the "labile pool" (non-stored NE) and into the synaptic cleft onto postsynaptic receptors
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foods which are dangerous for patients on inhibitors of monoamine oxidase
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patients on inhibitors of this enzyme (e.g., pargyline) may have profound hypertension from over-indulgence in tyramine-containing foods.
--such as cheddar cheese, certain wines, marmite, country ham, and broadbeans (fava beans). |
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diagnosis and localization of Horner's syndrome
|
documenting that an a1-adrenoreceptor agonist (phenylephrine) will dilate the patient's constricted pupil.
Hydroxyamphetamine, a tyramine-like agent, will also dilate the pupil if the neuron innervating the iris is intact (that is, if the lesion is more central). If the most peripheral nerve is the damaged one, hydroxyamphetamine will not work. |