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249 Cards in this Set
- Front
- Back
adrenal medulla is most like what neurons?
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post-ganglionic
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sweat gland post-ganglionic neurotransmitter and receptor
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ach; muscarinic
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somatic motor neurons neurotransmitter and receptor?
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ach; nicotinic
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nicotinic receptor locations
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parasympathetic ganglia; skeletal muscle; sympathetic ganglia
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nicotinic receptors are what kind of receptors?
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ligand-gated ion channel
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muscarinic receptor locations?
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cardiac m., smooth m., glands
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muscarinic receptor types?
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M1-M5
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which muscarinic receptors activate Gq? where are these located? what are effects?
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M1, M3, M5; s. muscle and secretory glands
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which muscarinic receptors activate Gi? where located? effects?
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M2 and M4; heart; binding decreases activity (increased k permeability causes hyperpolarization, which decreases heart rate)
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which muscarinic receptors are the primary concerns?
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M2 and M3
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all adrenergic receptors are what kind of receptors?
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g-protein coupled receptors
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t or f: NE binds well to beta-2 receptors?
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f
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how is NE made?
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tyrosine->dopa->dopamine->vesicle enclosed NE
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possible fates of NE?
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1. binds to alpha-1 or beta receptors postsynaptically
2. binds to alpha-2 receptors presynaptically 3. taken back to nerve terminal for reuse (70%) |
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when NE binds to beta receptors, what is downstream effect?
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depolarization
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what enzyme degrades NE?
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MAO or COMT
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how is EPI made?
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tyrosine->dopa->dopamine->NE->pnmt->EPI
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where does EPI bind?
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alpha or beta receptors
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what is the downstream effect when EPI binds to beta receptor?
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depolarization
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t or f: EPI has high affinity for beta-2 receptors
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t
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on blood vessels, what receptors are present? which does EPI prefer?
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beta-2 and alpha-1
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low dose of EPI effect on blood vessels? high dose?
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low dose binds beta-2 and causes vasodilation; high dose binds beta-2 receptors first, then alpha-1 receptors, causing increased PVR
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how is ach formed?
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glucose->acetyl coa + choline->CAT used to make vesicle
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downstream effect of ach binding to m-receptor? n-receptor?
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opens ion channel; increased na influx and k efflux, depolarizing membrane
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how is ach degraded?
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acetylcholinesterase breaks into acetate and choline; choline is recycled
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what is main mechanism of inactivation of NE? ach?
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recycling
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t or f: ach can travel easily
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f
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what are g-proteins attached to?
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7 transmembrane receptors
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what are the 3 g-proteins? what do they do?
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Gs-activates adenyl cyclase; Gi-inhibits adenyl cyclase; Gq-activates plc-beta
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what are the 4 signal transduction mechanisms?
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ligand regulated ion channels; membrane receptor linked via g-proteins; tyrosine kinase; intracellular receptors
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what are the 2 possible results of depolarization in ligand regulated ion channels?
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n-subclass-n increases firing; n-subclass-m increases contraction
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which receptors work by ligand regulated ion channels?
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nicotinic
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which receptors work by membrane receptor linked via g proteins? (hint:3 groups)
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1. alpha-1, M1, M3, and M5
2. alpha-2, M2, M4 3. beta-1, beta-2, beta-3 |
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steps involved in membrane receptor linked via g-proteins for alpha-1, M1, M3, and M5?
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ligand binds to 7 transmembrane receptor->GDP exchanged for GTP to form Gq-GTP complex->GTP binds to plc-beta->plc-beta cleaves pip2 into dag and ip3->ip3 binds to channels causing ca release->contraction/secretion occurs->ca binds with pkc->dag binds with pkc->phosphorylation of downstream proteins
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steps involved in membrane receptor linked via g-proteins for alpha-2, M2, and M4 receptors?
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same steps as for alpha-1, M1, M3, and M5 except that Gi-GTP complex inhibits adenyl cyclase->increased k permeability->decreased neurotransmitter release
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alpha-2 receptors can also be located where? what is their effect?
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cholinergic postganglionic neurons; decreased ach release
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what are the locations and effects of the three beta receptors?
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1. beta-1 is on the heart, causes increased rate and increased force of contraction
2. beta-2 is on the lungs and causes relaxation; skeletal muscle (causes tremors when EPI binds); and on the liver and causes glucose production 3. beta-3 is located in adipose tissue and causes lipolysis |
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what is the signal transduction for beta receptors?
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same as alpha-1, M1, M3, M5, alpha-2, M2, and M4 except that the Gs-GTP complex binds to adenylate cyclase->atp converted to camp->pka activation->downstream phosphorylation
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steps in tyrosine kinase signaling?
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transmembrane protein is bound to tyrosine kinase->ligand binds to receptor and activates it->cell signaling
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steps to intracellular receptor signaling?
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agonist is lipid soluble (NO, steroids)->transported to nucleus->activates translation and transcription
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alpha-1 agonist effects on bp? effect on glands?
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contraction of blood vessels->increased pvr->increased bp; glands will secrete
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what happens when you increase k permeability on the cardiac myocyte?
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hyperpolarization that slows heart rate
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what are the affinities of EPI and NE for adrenergic receptors?
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1. EPI: alpha-1=alpha-2; beta-1=beta-2
2. NE: alpha-1=alpha-2; beta-1>beta-2 |
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is the iris sphincter parasympathetic or sympathetic innervation?
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parasympathetic
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is the iris radial parasympathetic or sympathetic?
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sympathetic
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what are the neurotransmitter, receptor, and effect of the iris sphincter?
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ach binds to M3 receptor to cause contraction and miosis
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what are the neurotransmitter, receptor, and effect of the iris radial?
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NE binds to alpha-1 receptor to cause contraction and mydriasis
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how are lacrimal glands innervated? how are they stimulated?
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parasympathetics; ach binds to M3 to increase secretion
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what is the effect of the ciliary muscle relaxing? contracting?
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far vision; near vision
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how are the ciliary muscles innervated? how are they stimulated?
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parasympathetics; ach bind to m-receptors to contract muscle, which will change the lens to short and fat for near vision
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what causes open angle glaucoma? closed angle glaucoma?
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1. open-blocked aqueous outflow
2. too little space between cornea and iris |
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what are 2 ways to induce mydriasis?
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1. give M3 antagonist (blocks m-receptors)
2. give alpha-1 agonist |
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if an m-antagonist is given to dilate pupil, what happens to their vision?
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m-antagonist decreases near vision by relaxing ciliary muscle
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will an alpha-1 agonist cause blurry vision?
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no, because near/far vision is regulated by m-receptors
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what drugs could you give to help with trouble breathing?
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1. beta-2 agonist to vasodilate and thus bronchodilate
2. M3 antagonist to block mucus secretion and bronchoconstriction |
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what 3 things do the parasympathetics do to GI tract? which receptor?
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1. increase secretion, relax sphincters, increase contractions
2. M3 |
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what 2 things do the sympathetics do to GI tract? which receptors?
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1. contract sphincters-alpha-1
2. relaxation-alpha-2 and beta-2 |
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if a patient has too much gastric acid secretion, what drug can be given?
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M3 antagonist
|
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what are the parasympathetic receptors on the bladder? what are their effects?
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1. M receptors
2. Contract the detrusor and relax the trigone |
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what are the sympathetic receptors on the bladder? what are their effects?
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1. beta-2 receptor relaxes the detrusor
2. alpha-1 receptor contracts the trigone |
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what drug can be given for urinary incontinence?
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M-blocker because it will relax the detrusor and contract the trigone
|
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what are the parasympathetics and sympathetics of erection and ejaculation?
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1. erection-parasympathetic-M receptors
2. ejaculation-sympathetic-alpha-1 receptors |
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what are the effects of muscarinic receptors on blood vessels?
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1. activation of M3 receptors on endothelial cells induces NO
2. NO diffuses to vascular smooth muscle and activates guanylyl cyclase 3. guanylyl cyclase increases production of cgmp 4. cgmp causes smooth muscle relaxation and vasodilation |
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how do parasympathetics and administration of a m-agonist differ in their effects on pvr?
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1. parasympathetics don't change pvr because they don't innervate blood vessels
2. an m-agonist on blood vessels will cause NO release and end up with smooth muscle relaxation and vasodilation (lowers pvr) |
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which blood vessels are innervated by the parasympathetics?
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salivary glands, GI glands, erectile tissue
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which receptors are on blood vessels? what are their effects?
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1. alpha-1 receptors on most blood vessels (vasoconstriction)
2. beta-2 receptors on liver and skeletal muscle (vasodilation) |
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what are the autonomics of the heart?
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1. parasympathetics- M-receptors (decrease HR, force of contraction, and conduction velocity)
2. sympathetics- beta-1 receptors (do the opposite) |
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stimulation of which receptor will cause greatest increase in CO?
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beta-1
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what is a side effect of a m-blocker?
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dry mouth
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which glands do the parasympathetics work on? which receptors?
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1. salivary and nasopharyngeal
2. M3 |
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which glands to sympathetics work on? which receptors?
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1. sweat glands
2. M3 (thermoregulatory) and alpha-1 (palms) |
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what is a possible side effect of beta-blockers on diabetics?
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blocking beta-2 receptors leads to decreased gluconeogenesis and glycogenolysis
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describe autonomics to the endocrine glands. what is the predominant effect of EPI on insulin release?
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1. pancreas- alpha-2 decreases insulin release and beta-2 increases insulin release
2. kidney- beta-2 increases renin release 3. EPI inhibits insulin release |
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what happens to bp when EPI is given in high doses? low doses?
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1. increased bp->as response wanes->decreased bp
2. little or no effect on bp |
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why is there little or no effect on bp when EPI is given in low doses?
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increased bp from increased heart rate and increased contractility is countered by tpr decrease from vasodilation that occurs when EPI acts preferentially to beta-2 receptors
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explain bp pressor and depressor effects of high dose EPI
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1. pressor-due to increased heart rate, contractility, and vasoconstriction in vascular beds
2. depressor effects due to beta-2 activation, which vasodilates (not seen initially due to alpha-1 vasoconstricting effects) 3. effects of alpha-1 wane, but effects of beta-2 remain |
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what is epinephrine reversal?
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pretreat person with alpha adrenergic blocker and only the beta-2 vasodilation effects are seen, decreasing tpr and bp
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which has a lower threshold to activation by low dose EPI, alpha-1 or beta-2 receptors?
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beta-2 receptors
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what happens during stage fright? what drug can help this?
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1. excess EPI binds to beta-2 receptors, causing skeletal muscle contractions
2. beta-2 blocker |
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how does EPI work on a beta-2 receptor? in what condition can this mechanism be advantageous?
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1. EPI binds to beta-2 receptor, causes k influx into skeletal muscle
2. hyperkalemia |
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generally speaking, what do alpha-1 receptors do? alpha-2 receptors?
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1. smooth muscle contraction
2. presynaptic regulation of neurotransmitter |
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generally speaking, what do beta-1 receptors do? beta-2 receptors?
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1. cardiac stimulation
2. smooth muscle bronchodilation and skeletal muscle vasodilation |
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potency rank for alpha-adrenergic receptors?
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EPI>NE>isoproterenol
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potency rank for beta-adrenergic receptors beta-1? beta-2?
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1. iso>EPI=NE
2. iso>EPI>NE |
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what is the formula for bp?
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SV x HR X TPR
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NE binds to which receptors?
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alpha-1=alpha-2; beta-1>beta-2
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EPI binds to which receptors?
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alpha-1=alpha-2; beta-1=beta-2
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isoproterenol binds to which receptors?
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beta-1=beta-2; beta>alpha
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effect of low dose EPI, NE, and ISO on bp?
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1. no change
2. increase 3. decrease |
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effect of low EPI, NE, and ISO on hr?
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1. increase
2. decrease 3. increase |
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effects of low dose EPI, NE, and ISO on tpr?
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1. decrease
2. decrease 3.increase |
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how do we calculate mean arterial pressure?
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map=co x tpr
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how do we calculate stroke volume?
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sv=end diastolic volume-end systolic volume
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activation of what receptors will result in increased tpr?
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alpha-1
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activation of what receptors will result in increased co?
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beta-1
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how are EPI and NE given?
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parenterally due to low oral bioavailability
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why do NE and EPI have low oral bioavailability?
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high amounts of mao and comt in gut and liver
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EPI vs. NE in binding to alpha-1, beta-1, and beta-2 receptors?
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1. E >/= N
2. E=N 3. E>>N |
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what are the overall effects of EPI and which receptors are activated?
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1. increase systolic pressure via beta-1 on heart
2. vasodilation in vascular bed of skeletal muscle via beta-2 3. vasoconstriction of vascular bed in kidney via alpha 4. increases coronary blood flow 5. increases aqueous humor drainage via alpha 6. dilates the pupil via alpha 7. relaxes bronchial smooth muscle via beta-2 |
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what are the overall effects of EPI and which receptors are activated?
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1. increases tpr and diastolic pressure more than EPI because it can't vasodilate via beta-2 receptors like EPI
2. increases systolic pressure 3. directly stimulates heart |
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what is dipivefrin? what are the effects? how is it given?
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1. prodrug converted to EPI
2. ophthalmic agent 3. topical |
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what kind of a drug is dopamine? what receptors does it activate? what are its effects on these receptors?
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1. catecholamine
2. alpha, beta-1, and dopamine 3. increases hr and contractility via beta-1 4. reduces arterial resistance and increases blood flow via dopamine |
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what are the effects of dopamine at low doses? high doses?
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1. increases systolic pressure
2. vasoconstriction |
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what can be given in treatment of minor hemorrhage? mechanism of action?
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EPI will activate alpha-1 receptors to vasoconstrict blood vessels in the area
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what can be given in treatment of anaphyaxis? mechanism of action?
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1. angioedema-high dose EPI activates alpha-1 to constrict capillaries
2. bronchoconstriction-EPI activates beta-2 to bronchodilate 3. pruritus-activates b-receptors on mast cells to suppress mediator release 4. hypotension-activates alpha-1 and beta-2 receptors to vasoconstrict and raise bp |
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does high dose EPI cause reflex bradycardia?
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no
|
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what can be given to stop premature labor?
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terbutaline will activate beta-2 receptors, causing uterine smooth muscle relaxation
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why is NE not drug of choice in anaphylaxis?
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EPI has better affinity for receptors needed to stop reaction; NE doesn't bind to beta-2 to stop the bronchoconstriction
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what are the 3 therapeutic effects of phenylephrine?
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nasal congestion, hemorrhoids, and psvt
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how does phenylephrine work?
|
activates alpha-1 to vasoconstrict blood vessels, increasing bp->activates baroreceptors->increased parasympathetics to heart->activation of m-receptors on av node, slowing it->stops arrythmia
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what are side effeccts of phenylephrine?
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shrinks mucosa when not needed
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what would be used for av block?
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beta-1 agonist to increase av conduction (EPI or ISO)
|
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compare phenyleprhine, xylometazoline, oxymetazoline, ephedrine, and pseudoephedrine in the treatment of nasal congestion
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1. phenyleprhine-short duration (topical, oral)
2. xylometazoline-long duration (topical) 3. oxymetazoline-long duration (topical) 4. ephedrine-indirect effect through release of NE; has NO REBOUND EFFECT 5. pseudoephedrine-indirect effect through release of NE; less side effects than ephedrine |
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what is the problem with chronic activation of alpha-1 receptor in nasal mucosa?
|
downregulation of receptor->once stopped, insufficient NE to activate receptors (rebound nasal congestion)
|
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compare beta-2 agonists, ephedrine, atropine, and ipratropium bromide in treatment of asthma and copd
|
1. short and long-acting beta-2 agonists cause bronchodilation
2. ephedrine-seldom used for this due to cardiac and cns 3. atropine-blocks M3, which reverses bronchoconstriction and secretion 4. ipratropium bromide is short acting, inhaled, works like atropine, which is how copd is reversed (less side effects than beta-agonists) |
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which beta-2 agonists are short acting?
|
1. albuterol
2. metaproterenol 3. bitolterol 4. pirbuterol 5. terbutaline |
|
which beta-2 agonists are long acting (at least 15 minutes)
|
1. salmeterol
2. formoterol 3. arformoterol |
|
compare treating asthma with ipratropium vs. beta-2 agonist
|
asthma may have minimal bronchoconstriction caused by parasympathetics, which means beta-2 agonist works better
|
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compare treating copd with ipratropium vs. beta-2 agonist
|
copd may have significant bronchoconstriction caused by parasympathetics, which means that ipratropium works just as well as beta-2 agonists
|
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what is the advantage of giving albuterol vs. EPI/isoproterenol to treat asthma?
|
albuterol only targets beta-2 receptor, EPI/ISO also affects beta-1 receptors
|
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compare phenylephrine, atropine, scopolamine, and tropicamide in dilatint the pupil
|
1. phenylephrine-alpha-1 agonist on iris radial smooth muscle->contracts iris radial smooth muscle, dilating pupil without cycloplegia
2. atropine-blocks m-receptors on iris sphincter smooth muscle (long-acting) 3. scopolamine-same as atropine 4. tropicamide-same mechanism as atropine, but is short-acting |
|
what is cycloplegia?
|
paralysis of the ciliary muscle
|
|
what are side effects of adrenomimetics on alpha-1 receptors? beta-1 receptors? beta-2 receptors?
|
1. alpha-1 effects on blood vessels->vasoconstriction->cv problems/ischemia at site
2. alpha-1 effects on nasal mucosa->rebound nasal congestion 3. alpha-1 effects on pupils->photophobia or narrow angle glaucoma 4. beta-1 effects on heart->increased heart rate->heart problems 5. beta-2 effects on liver->hyperglycemia 6. beta-2 effects on skeletal muscle->tremors |
|
contraindications of adrenomimetics?
|
1. cv disease (alpha-1 effects)
2. hyperthyroidism (heart is sensitive to catecholamines in hyperthyroidism patients->exaggerated effect) 3. diabetes (beta-2 effects) |
|
what is the action of mao inhibitors?
|
blocks mao->indirect acting adrenomimetics are not metabolized->buildup leads to increased NE release
|
|
what is the interaction between mao inhibitor and tyramine?
|
1. tyramine comes from gut bacteria
2. if not metabolized->tyramine travels to synaptic nerve terminal->buildup leads to increased NE release |
|
what is the effect of an mao inhibitor on a patient who eats a lot of cheese and drinks a lot of beer?
|
hypertensive reaction due to buildup of tyramine, which increases NE release
|
|
describe ephedrine and pseudoephedrine mixed effects
|
1. ephedrine-acts directly on alpha and beta receptors; indirectly releases NE
2. pseudoephedrine-acts directly on alpha and to a lesser extent beta receptors; indirectly releases NE |
|
t or f: ephedrine crosses the bbb?
|
t
|
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what receptors does ephedrine act on in the cns?
|
alpha and beta receptors
|
|
what are the therapeutic effects of ephedrine?
|
asthma and copd (beta-2), and nasal congestion (alpha-1)
|
|
does ephedrine show rebound effect on alpha-1 receptors when used in treating nasal congestion?
|
no
|
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what is the route of administration for ephedrine and pseudoephedrine?
|
1. oral
2. nasal |
|
what drug has replace pseudoephedrine? why?
|
phenylephrine; pseudoephedrine was used in meth labs
|
|
why is ephedrine seldom used for asthma?
|
cv and cns adverse effects
|
|
what class of drugs can be used to treat nasal congestion in general?
|
alpha-1 selective agonists
|
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what are the therapeutic uses of the alpha-1 selective, reversible antagonists?
|
1. prazosin-htn, bph, raynaud's disease
2. teazosin-htn/bph 3. doxazosin-htn/bph 4. tansulosin-bph 5. alfuzosin-bph |
|
what is the mechanism of action in alpha-1 blockers?
|
blocking the alpha-1 receptor prevents binding of EPI/NE
|
|
how do alpha-1 blockers treat raynaud's disease? which is drug of choice? which would not be used?
|
1. alpha-1 blockers prevent vasospasm in digits
2. prazosin 3. tamsulosin |
|
what are the actions of muscarinic agonists?
|
parasympathetic effects: decreased hr, vasodilation via NO, ciliary contraction, miosis, increased gi activity, and micturition
|
|
why are muscarinics used often?
|
many side effects
|
|
what are some problems with ach usage?
|
very non-specific and is metabolized quickly by gi enzymes
|
|
what disease can be treated with muscarinic agonists?
|
sjogren's syndrome
|
|
describe moa of pilocarpine and cevimeline in treating sjogren's syndrome
|
1. oral->m-receptors->salivation
2. more selective for salivary glands only; longer lasting; fewer side effects than pilocarpine |
|
which m-receptor is found on salivary glands?
|
M3
|
|
compare moa of bethanechol, neostigmine, alpha-1 antagonists, and muscarinic antagonists in treating urinary retention or incontinence
|
1. treats non-obstructive urinary retention->m-agonist->stimulates bladder (used for post-op)->given orally or sc
2. treats urinary retention->indirect psns->inhibits ache->increases ach->stimulates bladder 3. treats urinary retention->blocks alpha-1 trigone contraction->relaxes trigone->stimulates bladder 4. treats urinary incontinence->relaxes ureter and bladder->constricts urinary sphincter->sedates bladder |
|
can bethanecol be used to treat bph?
|
no, because bph is a form of urinary obstruction and bethanecol can only be used to treat non-obstructive urinary retention
|
|
what is the drug of choice in treating bph? why? moa?
|
1. tamsulosin
2. greater affinity for the alpha-1-a receptors in the prostate 3. blocks alpha-1-a receptor->relaxes smooth muscle in base of bladder and prostate->improved urine flow |
|
where are alpha-1-b receptors located?
|
vascular smooth muscle
|
|
what are side effects of muscarinic agonists?
|
1. excessive salivation
2. excessive sweating 3. intestinal cramps, nvd, increased gastric acid production 4. vasodilation via M3 receptors->increased hr and force of contraction 5. bradycardia (common) via m2 receptors, reflex tachycardia 6. bronchoconstriction, dyspnea, asthma attack 7. contracts ciliary muscle and iris sphincter |
|
describe the effects of baroceptor reflex vs. drug action
|
if a drug causes a change in pvr, but also works directly on the heart, the reflex reaction wins over the direct heart effect
|
|
poisoning by mushrooms can have effects similar to which drug class?
|
muscarinic agonists
|
|
what is the advantage of using ipratropium bromide instead of atropine?
|
atropine crosses bbb and causes cns side effects; ipratropium bromide does not cross the bbb
|
|
what is the advantage of using a muscarinic blocker prior to surgery?
|
they help to reduce secretions, create amnesia, and induce sedation
|
|
why does atropine have no effect on ventricular arrythmias?
|
1. because it only works on muscarinic receptors in the atria (m-receptors normally decrease hr)
2. beta-2 receptors are in the atria and ventricles (b-2 normally increases hr) |
|
would atropine work better on asthma or copd? why?
|
1. atropine is an m-blocker, and would work better on copd because it is caused mostly by psns problems; asthma is not usually caused by psns problems
2. atropine->blocks bronchoconstriction and mucus secretion |
|
why can an m-blocker be used for acute rhinitis?
|
because it blocks m-receptors on nasopharyngeal glands to reduce mucus secretion
|
|
what are the thereapeutic uses of m-blockers?
|
1. hyperactive carotid sinus syndrome
2. vagal-induced heart block (prevents av block and bradycardia) 3. gi tract-gi spasm 4. motion sickness-vestibular apparatus signals to vomit center can be blocked 5. urinary incontinence-ach is blocked from activating bladder |
|
what are dicyclomine and hyoscyamine used for?
|
gi spasm
|
|
can m-blockers be used in ulcers? ibs?
|
1. too many side effects
2. questionable efficacy |
|
what drug treats motion sickness?
|
scopolamine
|
|
which m-blockers can be used to treat urinary incontinence?
|
1. tolterodine
2. oxybutynin chloride 3. darifenacin 4. solifenacin 5. trospium chloride |
|
what are some adverse effects of m-antagonists?
|
cns effects
|
|
rate the side effects for scopolamine, atropine, and ipratropium
|
scopolamine>atropine>>ipratropium
|
|
contraindications for m-antagonist?
|
narrow angle glaucoma
|
|
what is nicotine? what does it do?
|
1. ganglionic stimulant
2. stimulates cns, autonomic ganglia, adrenal medulla, and neuromuscular junction |
|
what are some ganglionic blockers? what is their moa?
|
1. trimethaphan
2. mecamylamine 3. moa-nicotinic receptor antagonist |
|
physostigmine, neostigmine, pyridostigmine, and organophosphates: which crosses bbb
|
physostigmine and organophosphates
|
|
which alpha-1 antagonists treat htn?
|
prazosin, terazosin, doxazosin
|
|
what 3 drugs treat pheochromocytoma?
|
phentolamine, phenoxybenzamine, and propranolol
|
|
what should be used in conjunction with an alpha-blocker in the treatment of htn due to pheochromocytoma?
|
beta-antagonist
|
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how does propranolol affect pheochromocytoma?
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beta-blocker blocks beta-1 on kidneys->decreases blood pressure
|
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what happens if beta-blocker is given without an alpha blocker in treatment of pheochromocytoma?
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1. beta-blocker will also block beta-2 on smooth muscle->vasoconstriction->htn
2. the alpha-blocker will block the vasoconstrictive effects on the blood vessels to lower bp |
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what are adverse reactions in alpha-antagonists?
|
1. orthostatic hypotension- 1st dose effect
2. reflex tachycardia- alpha-1 blockers decrease pvr->baroreceptor increases hr 3. nasal congestion 4. salt and water retention- decrease in bp will reduce kidney perfusion 5. inhibition of ejaculation- blocks alpha-1 on prostate, seminal vesicles, and vas deferens 6. h/a, weakness, vertigo- due to bp increase |
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baroreceptor reflex?
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1. inhibitory signals to m-receptors on heart->increase hr/force
2. excitatory signals to beta-1 receptors on heart->increase hr/force 3. excitatory to alpha-1 on blood vessels->vasoconstrict |
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why is venoconstriction important in baroreceptor reflex?
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blood would only pool in veins and never make it to heart to increase co
|
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what is the s-isomer of betaxolol?
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levobetaxolol
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how can you remember beta-1 selective, competititive, reversible antagonists?
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all begin with b, e, a, or m (take levo out of levobetaxolol)
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therapeutic uses of beta-blocker for cv disease?
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1. htn
2. ischemia 3. arrythmia 4. mi 5. heart failure |
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how are beta-blockers used in migraines?
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prophylaxis only
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2 theories of beta-blocker effects on migraines?
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1. if migraines are from dilated blood vessels, then beta-blocker will block beta-2, which will vasoconstrict vessels
2. beta blockers block beta-1 on kidneys->inhibit renin->decrease arachidonic acid and prostaglandins->might affect serotonin |
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how do essential tremors and parkinson's tremors differ?
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essential occurs in action; parkinson's occurs at rest
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can beta-blockers work on parkinson's tremors?
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no
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how do beta-blockers affect essential tremors?
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bind to beta-2 on red, slow-contracting skeletal muscle fibers->stops tremor
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what causes esophageal varices?
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1. portal hypertension
2. cirrhosis->portal htn |
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how can a non-selective beta-blocker prevent variceal bleeding? should you try to block beta-1 or beta-2?
|
1. reduction of blood into esophageal veins
2. you should try to block both beta-1 (to lower hr) and beta-2 (to vasoconstrict) |
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what are adverse effects of beta-blockers?
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1. cardiac- bradycardia, av block, decrease contractility
2. cns- nightmares, depression, insomnia (if this occurs, switch to non-lipid soluble form) 3. nvd 4. sexual dysfunction (placebo) 5. increases tg and lowers hdl 6. rebound htn- chronic therapy upregulates beta-receptors (withdrawal will cause rebound htn) |
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what is an adverse effect of propranolol?
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decreases hr/force->decreases co->decreases sv->hypotension
|
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contraindications for beta-blockers?
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1. diabetes- beta-blocker stops beta-1 on heart from increasing hr in hypoglycemia, which is a warning sign to eat
2. liver- beta-blocker stops beta-2 receptor from activating gluconeogenesis/glycogenolysis to increase glucose levels 3. bronchospasm- beta-blockers block beta-2->bronchoconstriction 4. atherosclerosis- beta-blockers cause unopposed vasoconstriction |
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how does propranolol affect exercise?
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1. normally, hr increases in exercise
2. patient on propranolol won't have hr increase->fatigue->exercise intolerance |
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non-selective and beta-1 selective blockers are contraindicated in what disease? why?
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1. asthma
2. high doses can block beta-2 receptors as well as beta-1 receptors |
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tetraethyl pyrophosphate is used for what?
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insecticide
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how are reversible ache inhibitors hydrolyzed?
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they bind to ache and are slowly hydrolyzed->impairs ability of ache to hydrolyze ach (30 minutes-6 hours, but clinical effects last 2.5-4 hours)
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what happens to ach in presence of neostigmine?
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neostigmine binds to ache and is slowly hydrolyzed->impairs ability of ache to hydrolyze ach->ach stays in synapse longer->increased ach activity
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what are therapeutic uses of neostigmine?
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1. lipid soluble->crosses bbb
2. miotic (topical) 3. glaucoma (topical) 4. reverses antimuscarinic effects from m-blocking plants and drugs |
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what non-selective, competitive, reversible beta-antagonists can treat migraines? what selective, competitive, reversible beta-antagonists can treat migraines?
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1. propranolol, nadolol, timolol
2. metoprolol and atenolol |
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what non-selective, competitive, reversible beta-antagonists can treat oag? what selective, competitive, reversible beta-antagonists can treat oag?
|
1. timolol, carteolol, and levobunolol
2. betaxolol an levobetaxolol |
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what happens with irreversible ache inhibitors that makes them dangerous?
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covalently change ache->perpetuating ach effects
|
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what are possible problems with physostigmine?
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1. sites of action are all cholinergic synapses->many side effects
2. asystole, respiratory problems, seizures |
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neostigmine and pyridostigmine act directly on which receptors?
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n-subclass-m receptors
|
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what are therapeutic uses of neostigmine and pyridostigmine?
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1. neostigmine treats post-op urinary retention and abdominal distension
2. neostigmine and pyridostigmine treat myasthenia gravis |
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how can muscle strength be increased in myasthenia gravis patients?
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inhibit ache->increase ach concentration in neuromuscular junction
|
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how does a reversible ache inhibitor work on myasthenia gravis?
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1. myasthenia gravis-antibodies to n-subclass-m receptors cause down regulation of receptor
2. this impaires action of ach on skeletal muscle->weakness 3. inhibiting ache in neuromuscular junction prolongs ach effect in junction |
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compare neostigmine, pyridostigmine, and edrophonium in treatment of myasthenia gravis
|
1. 2-4 hour duration (oral)
2. 3-6 hour duration (oral); 12 hour duration (time-release) 3. 3-4 minute duration (iv); less potent; used to determine if problem is myasthenic or cholinergic crisis and to test adequacy of treatment dose |
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explain myasthenic crisis and cholinergic crisis in patient with myasthenia gravis?
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1. disease flares up->shortness of breath and weakness
2. overexposure to med->overstimulation of ach->stimulation followed by depression of autonomics and skeletal muscle |
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how can too much neostigmine produce muscle weakness?
|
depolarization blcokade- insufficicent repolarization time
|
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toxicity potential and uses of echothiphate, dfp, parathion, malathion, and sarin gas
|
1. echothiphate-last resort drug for miotic pupils and glaucoma; will not cross bbb; not volatile
2. dfp- volatile, lipid soluble, highly toxic 3. parathion- insecticide easily absorbed that is major problem in accidental poisoning; more toxis than malathion 4. malathion- treats lice; low dermal absorption 5. sarin gas- nerve gas; irreversibly phosphorylates ache; very toxic; very volatile sarin>parathion>malathion |
|
adverse effects of ache inhibitors:
|
1. lens opacity
2. chronic neurotoxicity |
|
symptoms of cholinergic overstimulation/crisis:
|
1. stimulate m-receptors at effector organs
2. stimulate cholinergic receptors in cns 3. both 1 and 2 are followed by depression/paralysis of autonomics and skeletal muscle 4. miosis, salivation, bronchoconstriction, nvd, bradycardia, hypotension, urgency |
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what is the difference between neostigmine, physostigmine, and organophosphates?
|
1. neostigmine-reversible, does not cross bbb
2. physostigmine-reversible, crosses bbb 3. organophosphates-irreversible, most cross bbb (except echothiphate) |
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what is treatment for sarin gas exposure?
|
1. m-blocker (atropine) will prevent bronchoconstriction
2. cholinesterase reactivator (pralidoxime) will break bond between phosphate and oxygen->then ach can be broken down |
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compare atropine and pralidoxime in cholinergic crisis
|
1. atropine- m-blocker; has central and peripheral effector sites; used for reversible/irreversible ache inhibitors
2. pralidoxime- works in neuromuscular junction and autonomic ganglia; only peripheral sites; used only in organophosphate poisoning |
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what effect will pralidoxime have on neostigmine overdose?
|
none because it will not break the carbon-oxygen bond between neostigmine and ach
|
|
compare effects of m-agonists, ache inhibitors, and m-antagonists on cv system
|
1. m-agonists- hypotension, bradycardia, reflex tachycardia
2. ache inhibitors- bradycardia and hypotension 3. m-agonists- tachycardia and hypertension |
|
what are therapeutic uses for nm-blockers?
|
1. relax skeletal muscles for surgery or intubation
2. prevent fractures associated with ect 3. control muscle spasms of tetanus 4. sustained nm blockade in critically ill patients |
|
compare moa of non-depolarizing and depolarizing nm blockers in causing muscular paralysis
|
non-depolarizing- competitively inhibit the effect of ACh at the postjunctional membrane nicotinic receptor of the neuromuscular junction (prevent depolarization and AP propagation)
2. depolarizing- nicotinic receptor agonist that acts at the motor endplate of the neuromuscular junction to produce persistent stimulation and depolarization of the muscle, thus preventing stimulation of contraction by ACh |
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what is the order of flaccid paralysis due to nondepolarizing agents?
|
1. eyes and face
2. limbs 3. abdomen 4. intercostals 5. diaphragm 6. reversed in recovery |
|
how can you reverse the effects of pancuronium?
|
ache inhibitor
|
|
compare phase I and phase II (desensitizing) block in succinylcholine
|
phase I- depolarizes membrane by opening channel (same as ach)->succinylcholine binds to channel->na influx->resistance to ache allows longer duration->brief period of repetitive excitation may cause fasciculations->depolariztion block of neuromuscular transmission->flaccid paralysis
phase II- occurs with higher doses or continuous exposure; initial depolarization followed by gradual repolarization; this is like receptor desensitization; ache inhibtors may reverse |
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will neostigmine reverse the phase I block effecs of succinylcholine?
|
no, it acts in the same manner and will enhance phase I blocking
|
|
will neostigmine reverse phase II block of succinylcholine?
|
it can reverse the block in some circumstances
|
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ache inhibitor effects in reversing non-depolarizing and depolarizing nm-blockers
|
1. enhances initial phase I block by succinylcholine, but can reverse phase II block
2. ache inhibitors are administered for pharmacologic antagonism to reverse residual postsurgical muscarinic receptor blockade and avoid inadvertent hypoxia or apnea |
|
compare ability of ache in neuromuscular junction and butyrylcholinesterase in plasma and liver to metabolize succinylcholine
|
1. metabolizes succinylcholine more slowly than ach because of resistance to hydrolysis
2. rapidly metabolizes succinylcholine in plasma and liver (some genetics can prolong its effects causing poisoning and death) |
|
what is succinylcholine?
|
2 ach molecules together
|
|
what is important about all nm-blockers?
|
1. don't enter cns
2. don't affect sensory organs 3. not anesthetic or analgesic |
|
duration of action for succinylcholine and pancuronium?
|
1. (depolarizing) 5 minutes and eliminated in plasma
2. (non-depolarizing) 120-180 minutes and eliminated in kidney |
|
do we get depolarization blockade on cardiac muscle?
|
no, M2 receptors are not ligand-gated channels
|
|
what are side effects of non-depolarizing nm-blockers and cv effects?
|
1. posoperative muscle pain in high doses, hyperkalemia, malignant hyperthermia, prolonged paralysis
2. bradycardia, stimulates histamine release->vasodilation and bronchoconstriction |
|
what effect can a ganglionic blockade have on the cv system?
|
only one part of cv innervated by ans: blood vessels by sns->blocking this->vasodilation and tachycardia (from lack of psns regulation of resting tone)
|
|
what effect can muscarinic blockade have on cv system?
|
tachycardia
|
|
how can succinylcholine cause malignant hyperthemia nad hyperkalemia in some patients?
|
1. malignant hyperthermia- disorder of skeletal muscle->excessive calcium release->rapid hyperthermia and metabolic acidosis, tachycardia, muscle rigidity, accelerated muscle metabolism
2. hyperkalemia- loss of tissue potassium during depolarization->sodium influx->excitatory postsynaptic potential (risk high in burns, muscle trauma, and spinal cord transections)->can result in cardiac arrest or circulatory collapse |
|
what patients are contraindicated from receiving succinylcholine?
|
heart failure patients on digoxin or diuretics
|
|
what is drug to treat malignant hyperthermia?
|
dantrolene
|
|
atropine vs. ipratropium, which can pass through bbb?
|
atropine
|
|
compare use of atropine and scopolamine as pre-op med
|
both induce sedation, amnesia, and less oral secretions, but scopolamine is more potent than atropine
|
|
moa and use of atropine in cardiac disorders
|
1. blocks M2 on heart to prevent overstimulation
2. used for hyperactive carotid sinus syndrome and vagal induced heart block |
|
which anticholinergics are used to treat urinary incontinence?
|
1. tolterodine
2. oxybitynin chloride 3. darifenacin 4. solifenacin 5. trospium chloride |
|
m antagonist side effects
|
1. cns
2. dry mucus membranes 3. mydriasis, can't constrict pupil, cycloplegia 4. increased hr 5. decreased gut motility and acid secretion 6. can't micturate |
|
scopolamine can do what in therapeutic doses?
|
cns depression
|
|
rank in potency: scopolamine, atropine, and ipratropium
|
scopolamine>atropine>ipratropium
|
|
what are cns effects of scopolamine?
|
1. sedation or excitement
2. cns depression 3. cns problems |
|
why are adremomimetics and cholinolytics contraindicated in glaucoma?
|
in nag, these will cause dilation of the eye; this leads to increased intraocular pressure, which causes a nag attack
|
|
what is the moa and efficacy of beta-blockes, EPI, and alpha-2 agonists on oag?
|
1. beta-blockers and alpha-2 agonists decrease aqueous humor production by ciliary body->decrases introcular pressure
2. EPI is given as dipivefrin->increases aqueous humor outflow 3. beta-blockers>alpha-2 agonists>EPI |
|
moa of cholinomimetics in treatment of oag and nag?
|
1. oag-contracts ciliary muscle to open trabecular meshwork
2. nag-contracts iris sphincter muscle->moves iris->aqueous humor can flow out of tm |
|
compare use of pilocarpine, physostigmine, and echothiphate in treating glaucoma
|
1. pilocarpine (drug of choice)- contracts ciliary muscle->opens holes
2. physostigmine given 2nd 3. echothiphate given 3rd (more side effects) |
|
what are the alternative drugs for oag treatment?
|
1. alpha-2 agonists
2. EP 3. cholinomimetics |
|
why do you get blurred vision with pilocarpine but not betaxolol?
|
1. pilocarpine is m-agonist->activates m-receptors on iris sphincter muscle and ciliary muscle causing contraction
2. betaxolol is beta-1 selective blocker->blocks beta-1 receptors on eye muscles->prevents contraction |
|
describe moa of pilocarpine in treating nag
|
contracts iris sphincter muscle->induces miosis->pulls iris away from tm->increases aqueous humor outflow->decreases intra-ocular pressure
|
|
identify the drugs used to treat oag
|
1. non-selective beta-blockers: timolol, carteolol, levobunolol
2. beta-1 selective beta-blockers: betaxolol and levobetaxolol |