Adrenoceptor Agonists (Sympathomimetics) Flashcards by amanda kastel

drugs that mimic the actions of epinephrine or norepinephrine have been termed….

sympathomimetic drugs

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adrenergic agonists can be direct acting, mixed acting, or indirect acting.

what are epinephrine and norepinephrine? also explain their selectivity**

DIRECT ACTING adrenergic agonists

they are nonselective

epinephrine binds a1,a2,b1,b2

norepinephrine binds a1,a2,b1

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name 2 adrenergic agonist that is mixed acting

ephedrine, pseudoephedrine

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name 4 types of indirect acting adrenergic agonists

releasing agents
uptake inhibitor
MOA inhibitor
COMT inhibitors

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why does a beta blocker used for hypertension have to be selective?

blocking b1 only is the goal.

blocking b1 binding will prevent vasoconstriction and thus lower hypertension

however, if b2 is blocked as well, the lungs cannot relax and they will constrict - preventing breathing

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name 3 INDIRECT acting adrenergic agonists

amphetamine
cocaine
tyrosine

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albuterol is a ____ acting adrenrgic agonist

direct acting

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Name 6 direct acting adrenergic agonists, aside from epinephrine and norepinephrine

albuterol
dobutamine
dopamine
isoproteronol
terbutaline
salmeterol

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recap: name the 4 things that can block something in the synthesis of norepineprhine

metyrosine blocks tyrosine hydroxylase and dopamine cannot be formed from tyrosine

reserpine stops the packaging of NE/dopamine into vesicles

cocaine and tricyclic antidepressants prevent the reuptake of NE through NET and it thus stays in the synaptic cleft for longer

bretylium and guanethidine prevent the release of NE by blocking SNAPs and VAMPS

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what is a direct acting adrenergic agonist

binds and activates adrenergic receptors.
true agonist

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explain the mechanism of Tyramine

indirect acting adrenergic agonist

it displaces the stored catecholamines from the adrenergic nerve ending

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what has the same MOA as tyramine?

amphetamine

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mechanism of cocaine
what else has this same mechanism?

cocaine + tricyclic antidepressants

prevent the reuptake of catecholamines that have already been released

indirect acting adrenergic agonist

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what prevents the enzymatic metabolism of norepineprhine?

MAO inhibitors
monoamine oxidase

COMT inhibitors
catechol-o-methyltransferase

INDIRECT ACTING adrenergic agonists

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what enzyme(s) is responsible for catecholamine metabolism in the brain

COMT and MAO

drugs that prevent them from metabolizing NE and E are indirect acting adrenergic agonists

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true or false

COMT is a phase 2 biotransformation enzyme

true

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** rank the following according to their affinity for the alpha adrenoceptor:

norepinephrine, isoproterenol, and epinephrine

highest affinity or equal: epinephrine
norepinephrine is either equal or less than epinephrine

lowest affinity by far is isoproterenol

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rank the following according to their affinity for the beta adrenoceptor

norepineprhine
isoproterenol
epinephrine

isoproterenol has the highest affinity
epinephrine
norepinephrine is less than or equal to epinephrine

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name a factor that can contorl the response of an indirect acting adrenergic agonist

the underlying sympathetic activity

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true or false

the route of administration of adrenergic agonists does not control the response

false - it does

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adrenoreceptors are what kinf of receptors?

GPCRs

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the alpha 1 receptor uses what class of g protein?
also explain the mechanism

agonist binds to a1 receptor, alpha subunit of gq protein dissocitates and binds GTP (instead of GDP) and binds phospholipase c

phospholipase c increases DAG and IP3

DAG activates PKC

IP3 releases stored calcium to become FREE CALCIUM which activates calcium dependent protein kinase and second messengers (IP3,PKC, DAG ETC)

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in alpha 1 receptors, what releases the stored calcium?

IP3

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in alpha1 receptors, what activates PKC (protein kinase c)

DAG

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What g protein does alpha 2 adrenoceptors work through

what g protein do Beta receptors work through

explain the mechanism of agonist binding to alpha 2 receptors

agonist binds, alpha i(nhibitory) subunit binds GTP and disociates from b and y subunits alpha subunit bound to GTP does NOT bind adenylyl cyclase and cAMP is not produced cAMP levels decrease

explain the mechanism of agonist binding to beta receptor

as subunit binds GTP and dissociates from by subunits as binds Adenylyl cyclase which causes ATP to increase cAMP

name an alpha1 agonist what will it cause when binds to alpha 1?

phenylephrine vasoconstriction

alpha 1 antagonist what will be the effect when binding to alpha1?

prazosin will block vasoconstriction and cause vasodilation

name an alpha 2 agonist what will happen upon binding to alpha 2 receptor?

clonidine will cause vasodilation

name an alpha 2 antagonist

yohimbine - not used clinically anymore

true or false when an alpha 2 agonist binds to it, IP3 and DAG will increase

FALSE this is alpha 1 mechanism alpha 2 will decrease camp levels

true or false a1 receptor works through Gq

true

name a nonselective beta agonist what happens upon binding?

isoproterenol increased cAMP levels - works through Gs increased heart rate and relaxes bronchial smooth muscle

name a nonselective beta antagonist what happens upon binding?

propanolol decreased heart rate and possible bronchoconstriction

general effect of beta receptor binding

works through Gs, so increased cAMP levels

explain what receptor selectivity means

the drug preferentially binds to a certain subgroup of receptors however, only at low concentrations. selectivity is not absolute because at higher concentrations the drug also interacts with related classes of receptors

the effects of a drug depend on the selectivity for certain subtypes and also....

the expression of these receptor subtypes in a given tissue

where is the B3 receptor

adipose tissue

name 2 alpha agonists that are most selective for alpha 1

phenylephrine and methoxamine a1>a2>>>>>>>>>>B

name 2 alpha agonists that are most selective for A2

clonidine and methylnorepinephrine a2>a1>>>>>>>>>B

name 2 mixed alpha and beta agonists

epinephrine and norepinephrine

explain the selectivity of both epinephrine and norepinephrine

both have equal affinity for alpha1 and alpha2 epinephrine has equal affinty B1=B2 also norepinephrine has more affinity for B1 than B2 B1>>B2

isoproterenol selectivity

B1=B2 >>>>>>>>>>>>>>a

albuterol/terbutaline/metaproterenol/ritodrine selectivity

B2>>B1>>>>>>a

dobutamine selectivity

B1>B2>>>>>A

What happens if a potent drug continually binds to a receptor?

desensitization

what is heterologous desensitization? how can it happen?

the desensitization of receptors that were NOT exposed to the agonist 2nd messengers like PKC and PKA phosphorylate different receptors and decrease their activity ex: PKA phosphorylates the b2 receptor and changes its preference from Gs to Gi

what does biased agonists mean? give an example

a receptor can have many effects for example, binding to B1 incresed the heart rate and cardiac workload through the GPCR mechanism BUT also has non-GPCR arrestin-mediated efects biased agonists for heart attack work through non-GPCR pathway

NET reuptakes norepinephrine breakdown where it takes the NE

reuptakes 90% NE into heart synapses and about 60% into other synapses there, it enters vesicles and undergoes metabolism by MAO and COMT

explain how amphetamine works

an indirect acting adrenergic agonist instead of NET reuptaking the NE in the cleft, the transporter is reversed and more NE comes out into the cleft

explain how cocaine works

indirect acting adrenergic agonist blocks the reuptake of NE by NET so it stays in the synaptic cleft longer

effect of alpha 1 binding on most vascular smooth muscle

contraction

effect of alpha1 binding on the eye

contracts the pupillary dilator muscle (which dilates the eye)

effect of alpha1 binding on pilomotor smooth muscle

hair gets erected

effect of alpha 1 on prostate

contraction

effect of alpha 1 on heart

increased force of contraction

effect of alpha 2 binding on fat cells

inhibitis lipolysis

effect of alpha 2 on platelets

causes them to aggregate

effect of alpha 2 on adrenergic/cholinergic nerve terminals

inhibits the release of neurotransmitter

effect of B1 on the heart and on juxaglomerular cells

increased force and rate of contraction of the heart increases release of renin (body retains fluid, increased BP)

effect of B2 on smooth muscle

smooth muscle relaxation

true or false b2 binding causes bronchodilation and vasodilation

true

effect of b3 binding on fat cells

activates lipolysis

true or false alpha 2 agonists cause lipolysis

FALSE inhibits lipolysis B3 agonists cause lipolysis

explain how the cardiovascular effects of adrenergic agonists can vary

there is a widespread distribution of alpha and beta receptors in heart/blood vessels/neural/hormonal systems that are all involved in BP regulation thus, the effects depend on whether the agonist acts on alpha, beta, or both