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adrenergic agonists

UVa med pharmacology block 2

Norepinephrine α1 > β1 α2 used for hypotension/shock neural transmission - postgang symp fibers, certain CNS tracts short acting admin'd by injection Met'd by MAO/COMT in liver, kidney etc CI: hypotension, hypovolemic
Epinephrine LOW dose β1, β2 HIGH dose α1, β1, β2 hemostasis of skin/mucous membs, w/local anesthetics, conduction/reverse A-V block, cardiac arrest, hypotension, allergic attack, anaphylactic shock, asthma, WA glaucoma met'd like NE short acting injeciton
Dopamine β1 (α1 at high dose) Direct acting adrenergic agonist inotropic for heart failure, preserves kidney function in cardiogenic shock short acting injection - met'd like NE Side fx: vasodilates kidney via DA receptors
Isoproterenol β1, β2 direct agonist improves conduction & reverses A-V block, bronchospasm Injection or inhaled CI: tachyarrhythmia
Dobutamine β1 direct agonist inotropic for heart failure short acting (2 min) by IV admin side fx: incr HR/BP, hypersensitivity rxns
Phenylephrine α1 direct agonist arrhythmia (reflex cardiac effect of vasopressor drugs), fundus exam, WA glaucoma IV admin
Clonidine α2 direct agonist hypertension (e.g. opiate withdrawal) long lasting (12-16hrs) oral admin Excreted by kidney (50% met'd by liver)
Terbutaline beta-2 direct agonist bronchospasm, delay premature delivery T1/2 = 3-4hrs oral, injection, inhaled excreted by kidney side fx: minimal CV effects when inhaled
Albuterol beta-2 direct agonist bronchospasm short acting inhaled or oral delivery side fx minimal when inhaled
Ritodrine beta-2 direct agonist delays premature delivery oral, IV admin
Tyramine indirect presynaptic NE release by exchange Found in cheese, red wine and beer does not affect adrenal medullary chromaffin cells (no uptake system) side fx: hypertensive crisis in px's taking MAO inhibitors
Amphetamine alpha/beta mixed acting causes presynaptic NE release and some intrinsic adrenergic activity ADHD, narcolepsy, widely abused primary systemic actions on heart (beta1) and Blood volume (alpha1) side fx: stims heart & bv's, CNS, resp cent cerebrospinal axis
Ephedrine alpha/beta mixed acting causes presynaptic NE release & epi like direct effects (longer duration of action) ortho hypotension, bronchospasm, muc memb decongestion, fundus exam, hypersens rxn side fx: CNS effects
Where are catecholamines produced and from what amino acid? What molecules degrage them? - Produced in neural tissue and adrenal medulla - from Tyrosine - degraded by Monoamine Oxidase (MAO) and Catechol-o-methyltransferase (COMT)
What drugs are used to delay delivery in premature labor? Ritrodine and terbutaline
Why are cardiovascular adrenergic response the most complex? They are a SUM of actions at many sites, and the response is modified by baroreceptor and vagal reflexes
How do alpha 2 receptors carry out their effects? Coupled to various intracellular effectors (adenylate cyclase, ion channels, etc.
What is the use of Ergot alkaloid post-partum? profound uterine contraction via a1 to prevent bleeding and promote uterine involution
In GENERAL, where are alpha-2 receptors found what is the response? found presynaptic adrenergic nerve terminal and CNS inhibition of NE release and CNS outflow
What are the intermediates between Tyrosine and Epinephrine? Tyrosine --> Dopa --> Dopamine --> Norepi --> Epi
What are the main side effects of the B2 agonists used for both asthma and premature labor? Cardiovascular side effects
How do Beta receptors carry out their effects? Stimulation of adenylate cyclase which activates cAMP-dependent kinase and stimulates cell-specific intracellular pathways
What is the only difference betweent he cardiovascular effects of phenylephrine and norepinephrine? Why? Norepinephrine may cause arrythmias to appear a1 effects cause a reflexive decrease in heart rate that trumps the B1 effect. However, there is still the increase automaticity of the myocardium due to B1stimulation, so arrythmias may appear.
What are site of drug actions affecting the catecholamine life cycle? Inhibition of synthesis Blockade of storage Displacement of Transmitter and Block of NE release Mimic of Block action post-synaptically Blockade of reuptake Inhibit NE metabolism Action of presynaptic alpha-2 receptor
In GENERAL, where are beta-2 receptors found? What is the response? Blood vessels, smooth muscle, metabolic function, glands - Relaxation of smooth musle, stimulation of metabolism, Gland secretion
In GENERAL, where are alpha 1 receptors found and what is the usual response? Blood vessels/smooth muscle --> Contraction, stimulation Glands --> secretion
How are adrenergic agonists used in the treament of shock? Anaphylactic shock -- Epinephrine ** vasopressor, cardiac ionotropy, stops mast cell degranulation Cardiogenic shock -- Dopamine reduces arterial resistance in the kidney to preserve kidney function
What are the adrenergic effects on the uterus? a1 causes contraction, B2 causes relaxation
a1 causes contraction, B2 causes relaxation Ephedrine or phenylephrine produce mydriasis (a1 effect) for fundus examination Ephedrine or phenylephrine reduce intraocular pressure via vasoconstriction and are used for WIDE ANGLE glaucoma
In GENERAL, where are beta-1 receptors found, what is the response? Atria, AV node, SA node, Ventricles --> increase rate/force of contraction JG cells in kidney --> Renin secretion
What are adrenal medullary chromaffin cells not affected by Tyramine? Because they have no uptake systems, so Tyramine can't exchange for NE
What are the metabolic effects of adrenergic agonists? When are they of concern? B -- raise blood glucose by acting on liver and muscle to promote glycogenolysis a2 -- inhibits insulin secretion
How do Amphetamines work? What is their primary systemic action? What is special about them? Promotes NE release, and also have alpha AND beta activity. They are orally effective. Primary systemic effects on the heart (B1) and vessels (a1).
What are the chief actions of norepi, epi, and dopamine as neurotransmitters? Norepi --> functions in CNS and is primary postganglionic sympathetic transmitter Epi --> primary agonist release by adrenal medulla in response to sympathetic stimulation Dopamine --> Extrapyramidal tracts of CNS
What are indirectly acting sympathomimetic agents and what is the prototypic drug? Indirectly acting agents exert their adrenergic function by stimulating NE release from presynaptic terminals Tyramine is the prototypic drug and it acts by exchanging with NE through neuronal transport mechanisms
What are some intermediates of degradation of catecholamines? Metanephrine, Normetanephrine, VMA
What is the therapeutic use of B1 agonists? - improve conduction and reverse AV block (epi and isoproterenol) - restart heart after cardiac arrest (epi if electroshock fails) - Dopamine and dobutamine are useful inotropic agents for the failing heart because they increase FORCE more than RATE
What cardiovascular response predominates at HIGH doses of Epinephrine? a1, B1, B2
What is ephinephrine reversal? epinephrine levels are HIGH when first injected. This means that at first you have a1, B1, and B2 effects which lead to an overall increase in MAP. When levels falls, you have only B1 and B2 which leads to an overall decrease in MAP
What cardiovascular response predominates at low doses of Epinephrine? B1 and B2
How does Ephedrine work? What is special about it? Promotes NE release and also have epinephrine-like effects. Is orally effective, has long duration of action, has CNS effects
What are mixed acting sympathomimetics? They have NE-releasing capability like Tyramine, but also have some intrinsic effect at adrenergic receptors
What is the B2 effect on Bronchi? What drugs are used as Bronchodialators? Bronchodilation. Terbutaline and Albuterol
How do alpha 1 receptors carry out their effects? stimulation of Phosphlipase C --> increase in Ca2+ and activation of PKC
What is the therapeutic uses of a1 agonists? a1 - constriction of blood vessels - hemostasis of skin - decongestion of mucous membranes - hypotension - Use with local anesthetics
What are the three major sites of sympathetic innervation? viscera, glands, blood vessels
What is the therapeutic use of a2 agonists? Treatment of hypertension and opiate abuse * Clonidine reduces vasoconstrictor sympathetic outflow. Reduces sympathetic activity in hypertensive states including during opiate withdrawal (to be covered more extensively in later lectures)
Created by: sam.mrosenfeld



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