Week 3: Adrenergic agonists (sympathetic nerves)

Question 1

What are the steps of synthesis of norepinephrine?

Answer 1

Tyrosin –> DOPA –> Dopamine –> Norepinephrine (which can be converted into epinephrine)

Question 2

What two routes of adrenergic amine uptake accounts for the concentration gradient inside vesicles?

Answer 2

Axoplasmic (50x) and granular uptake (200x)

Question 3

How are adrenergic amines released normally?

Answer 3

stimulation of nicotinic receptors on post-synaptic surface of post-ganglionic nerve

Question 4

How are adrenergic amines released via indirectly-acting sympathomimetics (amphetamine, tyramine, ephedrine)?

Answer 4

Can induce the release of norepi without the dopamine beta hydroxylase, basically reverse the pump on the cell membrane

Question 5

What is the effect of cocaine and imipramine on adrenergic amines?

Answer 5

inhibit the axoplasmic pump to potentiate sympathetic responses (inhibits reuptake)

Question 6

What is the effect of reserpine on adrenergic amines?

Answer 6

Inhibts granular pump accumulating catecholamines in vesicles which results in depletion

Question 7

What is the effect of guanethidine on adrenergic amines?

Answer 7

induce release of vesicles of norepi slowly, depleting the stores; reduces response to sympathetic stimulation

Question 8

What are the effects of MAOIs? (i.e. pargyline)

Answer 8

Inhibit the breakdown of catecholamines, increasing their effects

Question 9

What is the breakdown product of epinephrine/norepinephrine?

Answer 9

Vanillylmandelic acid (VMA)

Question 10

What amines interact with alpha 1 receptors from most to least?

Answer 10

epinephrine >= norepinephrine&raquo_space; isoproterenol

Question 11

What amines interact with alpha 2 receptors from most to least?

Answer 11

epinephrine >= norepinephrine&raquo_space; isoproterenol

Question 12

What is the effect of alpha1 agonist?

Answer 12

mediates smooth muscle contraction via GCPR (Gq)

Question 13

What is the effect of an alpha 2 agonist?

Answer 13

inhibits neural norepi release by binding to G-alpha-i proteins

Question 14

What toxin binds to Gi proteins and irreversibly inhibits them?

Answer 14

Pertussis toxin

Question 15

What amines interact with beta 1 receptors from most to least?

Answer 15

isoproterenol > epinephrine = norepinephrine

Question 16

What amines interact with beta 2 receptors from most to least?

Answer 16

isoproterenol > epinephrine&raquo_space; norepinephrine

Question 17

What is the effect of beta 1 agonists?

Answer 17

adrenergic cardiac effects, renin release

Question 18

What is the effect of beta 2 agonists?

Answer 18

relaxation of smooth muscle and metabolic (glycogenolytic) effects - Mostly in lungs and somewhat in blood vessels

Question 19

What toxin binds to beta 2 receptors?

Answer 19

Cholera

Question 20

What drug is a beta 1 agonist?

Answer 20

Dobutamine

Question 21

What is the effect of dobutamine?

Answer 21

Beta1 agonist, positive inotrope

Question 22

What are the effects of dopamine?

Answer 22

positive inotrope, vasodilation in renal and mesenteric vasculature at low dose, vasoconstrictor (alpha 1) at high dose

Question 23

What drug is an alpha 1 agonist?

Answer 23

Phenylephrine

Question 24

What are the effects of phenylephrine?

Answer 24

Used to reverse hypotension or to treat paroxysmal atrial tachycardia, topical vasoconstrictor and mydriatic. Decreases tachycardia due to reflex bradycardia

Question 25

What drugs are beta 2 selective agonists?

Answer 25

metaproterenol, terbutaline, albuterol, ritodrine, salmeterol

Question 26

What are the effects of beta 2 agonists?

Answer 26

bronchodilation, delay labor. Major side effects: tachycardia and palpatations

Question 27

What is the effects of isoproteronol?

Answer 27

Beta2: vasodilation, Beta1: tachycardia

Question 28

What does isoproteronol do to blood pressure? Explain.

Answer 28

Decreases it. It does affect CO, but because radius is raised to the 4th power in the TPR equation, it will affect that significantly more.

Question 29

What are the cardiovascular actions of norepinephrine? What receptors do they interact with to do this?

Answer 29

Vasoconstriction (alpha1), increased heart rate and force (beta 1), reflex reduction in heart rate (vagus nerve)

Question 30

What are cardiovascular actions of epinephrine? And what are the receptors that mediate this?

Answer 30

Vasoconstriction (alpha 1), vasodilation (beta 2), heart rate and force increase but reflexes to the elevation in blood pressure can suppress heart rate (vagal stimulation)

Question 31

What is the effect of amphetamine?

Answer 31

releases norepinephrine, increasing BP

Question 32

What is the effect of ephedrine?

Answer 32

Releases norepinephrine (which interacts with alpha 1 and beta 1 receptors to vasoconstrict, but also interacts with Beta 2 receptors to vasodilate)

Question 33

What is the effect of pseudoephedrine?

Answer 33

Releases norepinephrine (raises BP via alpha 1 and beta 1, lowers via beta 2)

Question 34

What is the MOA of pargyline?

Answer 34

MAOI- potentiates sympathetic responses

Question 35

What are the effects of guanethidine and guanadrel?

Answer 35

releases NE from vesicles, depleting it.