Adrenergic

Question 1

1. What is the parent compound of the sympathomimetic amines?

Answer 1

B-phenylethylamine (adrenergic agonist)

Question 2

2. What is a catecholamine?

Answer 2

A catecholamine is a sympathomimetic amine with a hydroxyl substitution in the aromatic ring. NE, E, Dopamine, Isoproterenol all have –OH substituted at position 3 and 4 of the benzene ring.

Question 3

3. What receptors are activated by Epinephrine?

Answer 3

a and B receptors are activated by epinephrine which is released by the adrenal medulla.

Question 4

4. What is the difference in cardiovascular effects of epinephrine at large and small doses?

Answer 4

Large dose → increase in blood pressure due to (1) increased ventricular contraction (B1 effect), (2) increased HR (B1 effect) which MAY be opposed by baroreceptor reflex, (3) vasoconstriction (a1 effect)
Low dose → No increase in mean blood pressure (MAP) b/t (1) peripheral resistance decreases b/c B2 receptors (which are in blood vessels of muscles and when activated relax) are more sensitive to epinephrine than a1 receptors (diastolic falls), (2) systolic pressure increases due to increased cardiac contractile force (B1), (3) HR increases (B1)
**the effects of epinephrine are dose dependent (high vs low) the ratio of a1 to B2 response is in the vascular beds is what determines the blood pressure changes

Question 5

5. What is the effect of epinephrine on the respiratory system?

Answer 5

Epinephrine activates the B2 receptors in the lungs causing bronchodilation

Question 6

6. What is the effect of epinephrine on body metabolism?

Answer 6

1. Increased glycogenolysis in liver (B2 effect)

2. Increased lipolysis (B3 effect)

Question 7

7. What are the clinical uses of epinephrine?

Answer 7

1. Anaphylactic shock
2. Asthmatic attacks – acute treatments
3. Cardiac arrest – to restore cardiac rhythm in pts with cardiac arrest
4. In local anesthetics – epinephrine increases duration of local anesthetics by producing local vasoconstriction at the site of injection thereby keeping the anesthetic

Question 8

8. What receptors are activated by norepinephrine?

Answer 8

NE is a potent agonist at a1, a2, and B1 receptors. There is very little action on the B2 receptors.

Question 9

9. What is the effect of norepinephrine on the cardiovascular system?

Answer 9

1. vasoconstriction and increased peripheral resistance– a1 effect
2. increase in systolic and diastolic blood pressures (B1 and a1 activated and increase systolic and diastolic)
3. no change in cardiac output due to baroreceptor reflex

Question 10

10. What is the baroreceptor reflex with vasoconstriction of the blood vessels?

Answer 10

1. vasoconstriction → increase in blood pressure
2. activation of carotid sinus to stimulate parasympathetic activity and inhibit sympathetic activity
3. stimulated parasympathetic activity activates the vagal centers which decreases the HR
4. inhibition of sympathetic centers lead to decrease in HR and decreased force of contraction

Question 11

11. What is the baroreceptor reflex with vasodilation of the blood vessels?

Answer 11

1. vasodilation → decrease in blood pressure
2. stimulation of carotid sinus to stimulate the sympathetics and inhibit the parasympathetics
3. inhibition of parasympathetic activity decreases vagal centers which increases HR
4. stimulation of sympathetic activity increases HR and increase force of contraction

Question 12

12. What is the effect of pre-treatment atropine prior to NE on the Cardiovascular system?

Answer 12

If atropine is given before NE, then NE causes tachycardia b/c there is an inhibition of the parasympathetics therefore baroreceptor reflex

Question 13

13. What are the clinical uses of norepinephrine?

Answer 13

Treat shock b/c it increases vascular resistance and therefore blood pressure. On a side note, dopamine is better to treat shock b/c it doesn’t decrease blood flow to the kidneys as NE does.

Question 14

14. What receptors are activated by dopamine?

Answer 14

B and a receptors → D1 more than B1 more than a1 [as dose of dopamine increases, the next receptor in line is activated – low dose D1 activated, moderate dose D1 and B1 activated, etc] There is negligible activation of B2 receptors by dopamine.

Question 15

15. What is the response of the cardiovascular system on dopamine?

Answer 15

Dose dependent
Low dose → dopamine activates D1 receptors in renal and other vascular beds causing vasodilation, increased GFR, increased renal blood flow, increased sodium excretion
Intermediate dose → dopamine activates B1 receptors in the heart causing an increased CO AND dopamine causes release of NE from nerve terminals contributing to cardiac effects (increased systolic blood pressure, unaffected diastolic blood pressure)
High dose → dopamine activates vascular a1 receptors leading to vasoconstriction and a rise in blood pressure, increase in TPR

Question 16

16. What is the clinical use of dopamine?

Answer 16

1. treat severe CHF

2. treat cardiogenic and septic shock [intermediate to high rates]

Question 17

17. What is isoproterenol? (mechanism, actions on CV and lungs, uses)

Answer 17

This is a non-selective B-adrenergic agonist that stimulates B1 and B2 adrenergic receptors. It does not effect a-receptors.
CV → increase HR and force of contraction (reflex?? and B1), dilates arterioles of skeletal muscle (B2) causing decreased peripheral resistance
Pulmonary → bronchodilation (B2 effect)
Uses → emergencies to stimulate heart rate in patients with bradycardia or heart block

Question 18

18. What is Dobutamine? (mechanism, use)

Answer 18

B1-selective adrenergic agonist. It is composed of a racemic mixture…
(-) → a1 agonist and weak B1 agonist
(+) → a1 antagonist and potent B1 agonist
Clinical Mechanism → selective B1 agonist b/t the a1 effects cancel each other out
Dobutamine has greater iontropic than chronotropic effects. It increased CO, contractility and HR. PVR and BP are not significantly affected. This drug has a significant effect over other sympathomimetic drugs due to no significantly elevating oxygen demand of the myocardium.
Uses → management of acute heart failure and cardiogenic shock

Question 19

19. What are Terbutaline and Albuterol?

Answer 19

Short acting B2 adrenergic agonists used to treat asthma. Because it is short acting it is used prn (only when needed).

Question 20

20. What are Salmeterol and Formoterol?

Answer 20

Long acting B2 adrenergic agonists that is used to treat asthma. They have a prolonged duration of action of 12 hrs. It does have slow onset of action so is not suitable for relief of breakthrough attacks of bronchospasm and should be taken on a consistent basis.

Question 21

21. What are the adverse effects of B2-adrenergic agonists?

Answer 21

Tremor, restlessness, apprehension, anxiety, tachycardia – these effects are less likely with inhalation compared to parenteral and oral therapy

Question 22

22. What is Phenylephrine?

Answer 22

Phenylephrine is an a1-selective adrenergic agonist used to cause vasoconstriction. By effecting a1 only there is an increase in peripheral resistance, a decrease in HR due to reflex and increase in blood pressure. Phenylephrine is used as a nasal decongestant, mydriatic, increase blood pressure in hypotension resulting from vasodilation in septic shock or anesthesia and to increase blood pressure and terminate supraventricular tachycardia.