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55 Cards in this Set
- Front
- Back
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Is the ANS a network of central nerves, peripheral nerves, or both?
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Peripheral nerves that are overridden by the CNS
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Name an antihypertensive agent that works by stimulating an inhibitory center in the CNS, leading to decreased sympathetic output.
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Clonidine (0.2mg)
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Name the parasympathetic neurotransmitter and receptor type that innervate the few arterioles that it does.
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ACh; Orphan receptors
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Which four cranial nerves provide PSNS fibers, what are their corresponding nuclei, what is their ganglion, and what is their target organ?
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III (Edinger-Westphal; Ciliary ganglion; pupilary constrictor), VII (Superior Salivatory; Sphenopalatine (lacrimal gland); Submandibular (Submandibular gland/Sublingual gland), IX (Inferior Salivatory; Otic ganglion; Parotid gland), X (Dorsal vagal nucleus; all the way down to splenic flexure)
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Which two structures respond to high pressure flow, resulting in the baroreceptor reflex?
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Pressorreceptor fibers of aortic arch and the carotid sinus
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Tyrosine is taken up into the SNS varicosity with which ion?
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Na+
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What is the progression from Tyrosine to Epinephrine?
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Tyrosine to DOPA to Dopamine to Norepi to epi
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Name two agents that inhibit the reuptake of Norepi from the junctional cleft.
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Cocaine and TCAD
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Dopamine is taken up into a mature vesicle by exchange for which ion?
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H+
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The uptake of dopamine and NE into mature vesicles is blocked by which pharamacological drug?
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reserpine
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Which enzyme converts dopamine into NE?
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DBH (Dopamine Beta-Hydroxylase)
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Name two drugs that block the release of NE vesicles at the varicosities.
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GUANETHIDINE and bretyllium
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Which enzymes convert the following: Tyrosine to DOPA, DOPA to Dopamine, Dopamine to NE, NE to Epi?
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Tyrosine hydroxylase, DOPA decarboxylase, Dopamine Beta-Hydroxylase, Phenylethanolamine-N-methyltransferase
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Why is NE converted to Epi only in the adrenal medulla?
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Phenylethanolamine-N-methyltransferase is only located here.
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Which two neurotransmitters accumulate in patients taking monoamine oxidase inhibitors (MAOIs)?
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tyramine (also in diet) and octopamine
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What is the RLS in NE synthesis from tyrosine?
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Tyrosine Hydroxylase
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Name a drug that is used in treating pheochromocytomas, and what is its MOA?
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Metyrosine (alpha-methyl-p-tyrosine); competitively inhibits tyrosine hydroxylase
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What does AAADC and DBH stand for, and what can they form?
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Aromatic amino acid dopa decarboxylase; Dopamine Beta-Hydroxylase; False neurotransmitters (alpha-methyl norepinephrine and octopamine)
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Why, when given an I.V. bolus of Guanethidine, do they initially experience a short-term increase in BP, followed by a long-term fall in BP?
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Initially, Guanethidine causes a displacement of NE from the varicosity into the synaptic cleft (causes increase in BP), but its main function is to block Calcium-induced exocytosis of NE granules (long-term fall in BP).
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What are three "side effects" of Guanethidine?
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Orthostatic hypotension (no reaction to baroreceptor action), excessive GI stimulation (unopposed PSNS), and INHIBITION OF EJACULATION (Point and Shoot)
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Guanethidine's action of displacing the NE from nerve terminals upon I.V. bolus administration is know as what type of action?
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Indirect Sympathomimetic Action
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What are three methods that drugs are targeted to decrease adrenergic function?
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1) Biosynthesis (e.g. metyrosine C.I. of Tyrosine Hydroxylase), 2) Storage and release (e.g. Guanethidine and Reserpine), and 3) Signal termination (e.g. Cocaine and Tricyclic Antidepressants (TCADs)
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What is the main action of, and what are some "side effects" of Reserpine?
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Main action: Inhibit ATP-dependent NE/Dopamine uptake carrier present in vesicles.
Side effects: Sedation, Lethargy, Nightmares, and DEPRESSION!!! |
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What is the main mechanism by which adrenergic stimulation is terminated?
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Reuptake of catecholamines!!
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Can biotransformation of catecholamines by MAO (Monoamine Oxidase) and COMT (Catechol-O-Methyltransferase) terminate an adrenergic signal?
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No! These biotransformations occur after the catecholamines are taken up into the presynaptic and/or postsynaptic membranes.
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Where is the location of action and method of reaction for MAO and COMT?
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MAO: mitochondrial enzyme that turns alpha-carbon into carboxylic acid (removes amino group: NH2)
COMT: cytoplasmic enzyme that methylates the left, distal hydroxyl group. Both reactions inactivate the catecholamine! |
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What three catecholamine breakdown products are detected within the urine?
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Metanephrine (COMT action), Normetanephrine (COMT action), and 3-Methoxy-4-Hydroxy-Mandelic Acid ("VMA")
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What is the fate of many "false transmitters" before even reaching presynaptic vesicles? What substance can enhance the action of "false transmitters"?
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They are often chewed up by MAO.
Administration of MAOIs allow accumulation of "false transmitters" like Octopamine (converted from Tyramine by DBH) which can displace the NE and prevent postsynaptic stimulation. |
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What was the original function of MAOIs, and what is the MOA?
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Antihypertensive. They allow accumulation of "false neurotransmitters" in the presynaptic vesicles.
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Describe the MOA in "Wine and Cheese Syndrome"
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Certain foods (wine, cheese, beer, caviar) are high in Tyramine. Individuals taking MAOIs (no active MAO in liver/gut) that spent the night fine dining on wine and cheese built up tyramine in their systoms, which was then converted to octopamine in the adrenergic nerve terminals. This huge influex of octopamine displaces a huge amount of NE, resulting in an EXTREME indirect sympathomimetic action, resulting in death!
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What are ergot alkaloids?
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They are a complex of naturally occuring compounds from wheat rust (mold on wheat). They are used in "Epi Reversal" where upon their administration, followed by Epi. administration, you get a decrease in BP (reversal of normal action).
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Explain the Epi Reversal phenomenon as show by Dale in 1906.
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Upon administration of Epi, you get a rise in BP. If you first administer ergot alkaloids, followed by Epi again, you get a rebound decrease in BP. The same method with NE results in NO rebound decrease in BP (actually results in no action at all).
This shows that their must be two populations of adrenergic receptors (alpha and beta). This also shows that Epi works on both receptors, and that the ergot alkaloids block the adrenergic receptor shared by NE and Epi. |
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What was the main findings with the Alquist Study as far as Epi/NE/Isoproterenol MOA.
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The order of potency of these three adrenergic agonists depended on the tissue being studied.
Epi>NE>>ISO with alpha receptor (vasoconstriction, uterus contraction, pupillary dilation, and GI inhibition) ISO>Epi>NE with beta receptor (vasodilation, uterus inhibition, myocardial stimulation) Therefore, Isoproterenol is a pure Beta-agonist! |
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What did the Land Study of 1967 show concerning beta receptors?
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NE acts at only one of the two beta receptors (Beta 1 only)
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What receptor type does Isoproterenol stimulate?
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Pure Beta-agonist!
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What is the function of Ergot Alkaloids?
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It blocks the alpha response, allowing the beta response to be seen.
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Renin secretion is stimulated by which sympathetic receptor?
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Beta 1 (Epi, NE, and Isoproterenol all work here)
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What are two responses to Beta-2 agonists (e.g. Epi).
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Vascular dilation in muscles (Epi only), and Bronchiolar relaxation
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Why, upon administration of Ergot Alkaloids, do you not see a decrease in BP like you do with Epi?
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The Ergot Alkaloids block the alpha response (vasoconstriction), leaving only the beta response. Since NE only has the Beta-1 response, you don't really see any increase, and definitely not a decrease in BP. Since Epi has both Beta-1 and Beta-2 action, you get a decrease in BP due to the Beta-2's vasodilation in the skeletal muscles.
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Does NE have both alpha and beta adrenergic stimulation?
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Yes, but less so than Epi. Epi is the bind all.
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Which adrenergic receptor type (alpha or beta) will win in the vasculature?
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ALPHA!!! Show by Epi reversal: NE binding alpha-receptors results in increased BP, but upon blocking the alpha-receptors by ergot alkaloids, you get nothing!
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What is the difference between high and low doses of Epi upon alpha-1 versus beta-2 stimulation.
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At low [Epi], you get more beta-2 response (vasodilation).
At higher [Epi], you get more alpha-1 response (vasoconstriction) |
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What happens to HR, BP, and TPR upon administration of: 1) NE, 2) Epi, and 3)Isoproterenol
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1) decrease (baroreceptor reflex on heart because no way to decrease TPR); increase; increase (no beta-2 reaction)
2) increase; slight increase; big decrease (at low Epi dose) 3) increase; decrease; biggest decrease |
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What are two functions of alpha-2 receptors? Beta-2 receptors?
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Inhibit NE release, inhibit insulin release (from beta-cells of pancreas)
Bronchodilation, increased glucagon release (from alpha cells of pancreas) |
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Why do you administer Epi in conjunct to local anesthetics? Where do you not want to administer Epi and for what reason?
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It acts through alpha-1 receptors to cause vasoconstriction, allowing the anesthetic to remain in origin of action.
You do not want to administer Epi to places with weak blood supply (nose, ears, penis, fingers, toes). |
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What is the issue with the heart upon excess Epi administration?
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Too much beta-1 stimulation can lead to changes in conduction of electrical impulse across the heart.
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Why can't you give catecholamines orally?
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Poor absorption and first pass effect by liver (MAO) destroys them
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What is one of the few clinically useful properties of NE?
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Treat shock, but dopamine would be better because it will not reduce renal blood flow (actually renal vasodilation)
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What is the difference between high and low doses of dopamine on beta-1 and alpha receptors?
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Low doses target beta-1
High doses target alpha-1 |
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Increasing the size of the alkyl substituents on the amino group of Beta-phenylethylamine results in what receptor affinity?
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Beta-receptor activity (e.g. NE to Epi by methylation; or isopropyl substitution for isoproterenol)
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Removal of hydroxyl group(s) from the catechol group result in which adrenergic receptor affinity?
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Alpha-receptors (also no longer a catecholamine, so it isn't broken down by COMT anymore, and it has a longer half life). Two examples are phenylephrine and methoxamine
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Methylation of alpha carbon on "catecholamine" backbone results in what?
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Decreased MAO action, leading to increased half life
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Complete removal of ring systituents of catecholamine backbone results in what added function, and name two examples.
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Increased CNS penetration and oral availability.
Ephedrine and Amphetamine |
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What is the MOA of amphetamine?
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Since it is an alpha substituted drug, it is not degraded by MAO (just like taking an MAOI). It displaces NE from adrenergic nerve terminals (indirect sympathomimetics).
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Name three direct alpha agonists.
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Oxymetazoline, Phenylephrine, and Methoxamine
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