Preliminary Outline

Endogenous Catecholamines          Norepinephrine          Epinephrine          Dopamine Synthetic Catecholamines          Isoproterenol

Medical Pharmacology Topics   

Adrenergic Receptors

In general, adrenergic receptors can be classified as alpha and beta. The main adrenergic neurotransmitter is norepinephrine. Epinephrine from the adrenal medulla also acts on postsynaptic adrenergic receptors. Dopamine acts on a few sites of the adrenergic system at D1 receptors.

Effects of Catecholamine

Alpha adrenergic receptors (a) respond stronger to epinephrine than to norepinephrine, and are less responsive to isoproterenol (a synthetic catecholamine). In general, their activation leads to contraction of smooth muscle, glucose production (glycogenolysis and gluconeogenesis) and GI inhibition.

Alpha-1 receptors (a1) mediate vasoconstriction, pupillary dilation, localized sweating, GI sphincters contraction, trigone contraction (urinary inhibition), eyaculation, and contraction of piloerector muscles. Alpha-2 receptors (a2) mediate prejuctional inhibition of norepinephrine release and GI motility inhibition.

Beta adrenergic receptors (b) respond stronger to isoproterenol than to epinephrine, and are less responsive to norepinephrine. In general, their activation leads to relaxation of smooth muscles, lypolisis and myocardial and skeletal muscle stimulation.

Beta-1 receptors (b1) mediate cardiac stimulation and renin secretion. Beta-2 receptors (b2) mediate vasodilation, bronchodilation, uterine relaxation, GI motility inhibition, detrusor relaxation (urinary inhibition) and skeletal muscle contractions. The b2 receptor is much less sensitive to norepinephrine than the b1 receptor, so it seems to be there for the figth-or-fligth response mediated by epinephrine.

Dopamine is a neurotransmitter catecholamine that stimulates D1 receptors in renal blood vessels, producing vasodilation. It also acts on the pituitary gland (CNS) to inhibit prolactin secretion through action on D2 receptors in lactotrophs of the pituitary. 

Adrenergic Control of Cardiac Function

Both a and b receptors act on cardiovascular function to yield a net response. Norepinephrine will act directly on a1 receptors (vasoconstriction) to elevate periferal resistance and blood pressure. Although norepinephrine will have some effect on the heart via b1 receptors, it is a lesser effect that will be overcomed by the baroreceptor reflex and vagal dominance (triggered by the incresed blood pressure). The net effect of norepinephrine on cardiovascular function is an increase in blood pressure and a decrease in heart rate.

Epinephrine acts mostly on b2 receptors to decrease diastolic blood pressure (vasdilation), but also stimulates b1 receptors in the heart, increasing systolic pressure as well. Alpha receptors are also stimulated but at a lesser extent. The effects of epinephrine combine to increase heart rate, while only slightly increasing blood pressure. In the presence of an a receptor blocker, epinephrine will decrease blood pressure.

Clinically, epinephrine is an "all purpose" catecholamine. It is a potent agonist of all adrenergic receptors, although its effects on b2 are more significant. It is used in the treatment of acute anaphylaxis because its action on alpha receptors increase tissue perfussion, and its action on b2 receptors has a bronchodilator effect.

Epinephrine is also used to treat cardiac arrest because of increased heart rate by b1 activation. It may be administered with local anesthetics because of its vasoconstricting effects through a1 receptors, keeping the anesthesia local and prolonging its action. Only IV doses are effective because of fast MAO and COMT degradation. Since it is not very receptor specific, epinephrine coadministration may produce many side effects.

At high concentrations, dopamine acts on b1 receptors and causes the release of norepinephrine (indirect sympathomimetic), and acts on vascular a1 receptors. At higher than normal physiological concentrations, dopamine increases heart rate and blood pressure. Dopamine is used to treat shock and in selected congestive heart failure patients (IV only).

Isoproterenol, a synthetic catecholamine, is a pure beta agonist. It acts on b1 receptors to increase heart rate, while its action on b2 receptors decreases blood pressure (vasodiation), further increasing heart rate through the vagal reflex. Its mayor clinical use is as a bronchodilator.

Continue to "Adrenergic Agonist Drugs" or take a quiz: [Q1].

Need more practice? Answer the review questions below (after sponsor).

1- Name the main adrenergic neorotransmitter of the autonomic nervous system.

2- List the 3 main catecholamines that act on a-adrenergic receptors, from more to less response.

3- List 3 general effects mediated by a-adrenergic receptors

4- List 7 specific effects are mediated by a1-adrenergic receptors.

5- List 2 specific effects of a2-adrenergic receptors.

6- List the 3 main catecholamines that act on a-adrenergic receptors, from more to less response.

7- List 4 general effects of b-adrenergic receptors.

8- List 2 specific effects are mediated by b1-adrenergic receptors.

9- List 7 specific effects are mediated by b2-adrenergic receptors.

10- List 2 physiological functions of dopamine though D1 or D2 receptors.

11- What is the cardiovascular effect of NE action on a1-adrenergic receptors?

12- What is the cardiovascular effect of NE action on b1-adrenergic receptors?

13- What is the net cardiovascular effect of NE action on adrenergic receptors?

14- What is the cardiovascular effect of epinephrine action on b2-adrenergic receptors?

15- What is the cardiovascular effect of epinephrine action on b1-adrenergic receptors?

16- What is the net cardiovascular effect of epinephrine action on adrenergic receptors?

17- In the prescense of an a receptor blocker, what is the net cardiovascular effect of epinephrine action on adrenergic receptors?

18- What are the main clinical uses of epinephrine and why?

19- What are the effects of dopamine on peripheral adrenergic nerve junctions?

20- What is the net cardiovascular effect of dopamine action on peripheral adrenergic nerve junctions?

21- What are the clinical uses of dopamine?

22- What are the cardiovascular effects of isoproterenol action on adrenergic receptors?

Continue scrolling to answers below (after sponsor).

Hey! DON'T PEEK!!! Finish the questions fist!

1- Name the main adrenergic neorotransmitter of the autonomic nervous system.
norepinephrine

2- List the 3 main catecholamines that act on a-adrenergic receptors, from more to less response.
epinephrine
norepinephrine
isoproterenol

3- List 3 general effects mediated by a-adrenergic receptors
contraction of smooth muscle
glucose generation (glycogenolysis and glucogenesis)
GI inhibition

4- List 7 specific effects are mediated by a1-adrenergic receptors.
vasoconstriction
pupillary dilation
sweating
GI sphincters contraction
trigone contraction
eyaculation
contraction of piloerector muscles

5- List 2 specific effects of a2-adrenergic receptors.
inhibition of prejunctional NE release
GI inhibition

6- List the 3 main catecholamines that act on a-adrenergic receptors, from more to less response.
isoproterenol
epinephrine
norepinephrine

7- List 4 general effects of b-adrenergic receptors.
relaxation of smooth muscle
lipolysis
myocardial stimulation
skeletal muscle stimulation

8- List 2 specific effects are mediated by b1-adrenergic receptors.
cardiac stimulation
renin secretion

9- List 7 specific effects are mediated by b2-adrenergic receptors.
vasodilation
bronchodilation
uterine relaxation
GI inhibition
detrusor relaxation (urinary inhibition
skeletal muscle contractions

10- List 2 physiological functions of dopamine though D1 or D2 receptors.
vasodilation of renal blood vessels (D1)
inhibition of prolactin secretion by the pituitary (D2)

11- What is the cardiovascular effect of NE action on a1-adrenergic receptors?
Increase peripheral resistance, and therefore blood pressure.

12- What is the cardiovascular effect of NE action on b1-adrenergic receptors?
Although norepinephrine will have some effect on the heart via b1 receptors, it is a lesser effect that will be overcomed by the baroreceptor reflex and vagal dominance triggered by the incresed blood pressure (action on a1-adrenergic), decreasing heart rate.

13- What is the net cardiovascular effect of NE action on adrenergic receptors?
increase in blood pressure and decrease in heart rate.

14- What is the cardiovascular effect of epinephrine action on b2-adrenergic receptors?
Decreases peripheral resistance, therefore decreases diastolic blood pressure.

15- What is the cardiovascular effect of epinephrine action on b1-adrenergic receptors?
Increases heart rate, therefore increases systolic blood pressure.

16- What is the net cardiovascular effect of epinephrine action on adrenergic receptors?
Increases heart rate, and a slightly increases blood pressure.

17- In the prescense of an a receptor blocker, what is the net cardiovascular effect of epinephrine action on adrenergic receptors?
Increases heart rate, and decreases blood pressure.

18- What are the main clinical uses of epinephrine and why?
Acute anaphylaxis: action on alpha receptors increase tissue perfussion, and action on b2 receptors has a bronchodilator effect
Cardiac arrest: increased heart rate by b1 activation
Administered with local anesthetics: vasoconstricting effects through a1 receptors keep anesthesia local and prolonging its action.

19- What are the effects of dopamine on peripheral adrenergic nerve junctions?
At high concentrations, acts on b1 receptors, causes the release of norepinephrine (indirect sympathomimetic), and acts on vascular a1 receptors.

20- What is the net cardiovascular effect of dopamine action on peripheral adrenergic nerve junctions?
At higher than normal physiological concentrations, increases heart rate and blood pressure.

21- What are the clinical uses of dopamine?
used to treat shock and in selected congestive heart failure patients (IV only)

22- What are the cardiovascular effects of isoproterenol action on adrenergic receptors?
Acts on b1 receptors to increase heart rate, while its action on b2 receptors (vasodiation) decreases blood pressure, further increasing heart rate through the vagal reflex.