Martin - Adrenergic Agonists/Antagonists

Question 1

What is the primary NT released from presynaptic neurons in the sympathetic ganglia? What receptor type does it act on?

Answer 1

ACh released from presynaptic neurons in sympathetic chain ganglia.

Acts on nicotinic receptors

Question 2

What is the primary sympathetic NT released from postsynpatic neurons onto cardiac and smooth mm cells?

Answer 2

Norepinephrine

Question 3

What is the major effect of dopamine in the periphery? Through which receptors does it achieve this effect?

Answer 3

Dilates renal afferent blood vessels via activation of D1 receptors, thus increasing renal blood flow

Question 4

What is the effect of norepinephrine on peripheral vascular resistance? Through what receptors does it elicit this effect?

Answer 4

Increased peripheral resistance via stimulation of α1 receptors

Question 5

What is the effect of increased peripheral resistance caused by norepinephrine?

Answer 5

Decreased heart rate due to increased baroreceptor reflex activity

Question 6

What effect does low dose epinephrine have on peripheral resistance?

Answer 6

Low dose epi will mildly decrease peripheral resistance

Question 7

What type of drug is Isoproterenol?

Answer 7

Pure β agonist

Question 8

What effect will isoproterenol have on peripheral resistance?

Answer 8

Isoproterenol will cause a major decrease in peripheral resistance

Question 9

What effect will isoproterenol have on heart rate?

Answer 9

Reflex tachycarda due to decrease in peripheral resistance and drop in MAP

Question 10

What is the difference between low dose and high dose epinephrine?

Answer 10

At low doses, epi will cause decreased peripheral resistance via β2 receptors, but at high doses it will cause a marked increase in peripheral resistance due to higher affinity α1 stimulation

Question 11

What type of drug is phenylephrine?

Answer 11

α1-adrenergic agonist, also know as a pressor agent

Question 12

What does the term “mixed acting α agonist” imply?

Answer 12

The drug (i.e. Metaraminol) will directly stimulate α1 receptors, but will also stimulate norepinephrine release

Question 13

What are the effects of phenylephrine?

Answer 13

Vasoconstriction leading to increased peripheral resistance and overall BP, which can cause reflex bradycardia

Question 14

What agent can be used to block the reflex bradycarda caused by phenylephrine?

Answer 14

Atropine

Question 15

What is phenylephrine used for?

Answer 15

Maintain BP in hypotensive states such as spinal anesthesia

Induce the baroreceptor reflex and slowing of the heart in conditions like paroxysmal atrial tachycardia

Nasal decongestant

Question 16

What are the vascular effects of dopamine? Through what receptor are these effects achieved?

Answer 16

Vasodilation of renal, coronary, and mesenteric vascular beds via stimulation of D1 receptors. Main goal is to increase renal blood flow.

Question 17

What caution must be taken when administering dopamine?

Answer 17

BP must be monitored because it will cause α1-mediated vasoconstriction at high concentrations, resulting in end-organ ischemia

Question 18

What is the order of peripheral receptor activation by increasing concentrations of dopamine?

Answer 18

D1 > β1 > α1

Question 19

What is dopamine used for?

Answer 19

Increases cardiac output and renal blood flow in cases of shock or CHF

Question 20

What kind of drug is Dobutamine?

Answer 20

β1-selective agonist with some α1 agonist/antagonist effects

Mostly has β1 effects

Question 21

What are the effects of Dobutamine?

Answer 21

Increased inotropy and some increase in heart rate
Increased cardiac output
Little vascular effect

ONLY USED SHORT TERM

Question 22

What are potential adverse effects of Dobutamine?

Answer 22

May increase size of infarct
May cause potential arrhythmias
Increases the work/O2 requirement

Question 23

What is the primary use of α1-selective antagonists?

Answer 23

2nd or 3rd line treatment for essential HTN

Usually used in combination with other agents from different drug classes

Question 24

What are the main effects of α1-selective antagonists?

Answer 24

Decreased peripheral vascular resistance, venous return, and preload
Usually do not increase HR or CO
No α2 blockade so no increased release of norepi
Lipids: Decreases LDL and TGL, increases HDL

Question 25

What are the main adverse effects of α1-selective antagonists?

Answer 25

Postural hypertension and syncope, orthostatic hypotension

Question 26

What is the prototypical α1-selective antagonist?

Answer 26

Prazosin

Question 27

What is the prototype nonselective β receptor antagonist (1st generation β blocker)?

Answer 27

Propranolol (Inderal)

Question 28

What does it mean if a drug has intrinsic sympathomimetic activity?

Answer 28

It is a partial agonist

Question 29

What are some drugs classified as nonselective β receptor antagonists?

Answer 29

``` Propranolol Timolol Nadolol Pindolol Carteolol Sotalol ```

Question 30

What are the common β1-selective antagonists (2nd generation β blockers)?

Answer 30

Atenolol Metoprolol Esmolol Bisoprolol

Question 31

What is the main use and advantage of Esmolol?

Answer 31

Used during surgery to control heart rate. | Very short acting, so effects diminish rapidly after stopping infusion.

Question 32

What are the characteristics of the 3rd generation β blockers?

Answer 32

Designer drugs that have other activity beyond β blockade: Combination α and β blockers like Carvedilol and Labetalol Vasodilators like Betaxolol and Carteolol

Question 33

What are the effects of β blockers when used for HTN?

Answer 33

Decreases CO | Produces SLOW decrease in peripheral resistance

Question 34

Clinical uses of β blockers

Answer 34

HTN Ischemic heart disease (angina, MI, ACS) Thyrotoxicosis

Question 35

Why are β blockers beneficial in pts with ischemic heart disease?

Answer 35

Increased catecholamine release during MI increases cardiac work and O2 demand. β blockers decrease the overall work of the heart and O2 consumption.

Question 36

Role of β blockers in MI and post-MI prophylaxis

Answer 36

Reduce risk of arrythmia | Limits spread of infarct size

Question 37

What is the role of β blockers in thyrotoxicosis?

Answer 37

Hyperthyroid pts have increased β receptor sensitivity | β blockers reduce the severity of β stimulation, especially in cases of thyroid storm

Question 38

What are the pharmacological effects of β blockers on the heart?

Answer 38

``` Decreases in OHAIRE: O2 demand Heart rate AV nodal conduction Infarct size Rate of ectopic pacemaker depolarization Exercise tolerance ```

Question 39

What are the effects of β blockers on renin release?

Answer 39

Catecholamines stim β1 receptors in JGA of kidney to increase renin release. β-blockers inhibit this catecholamine stimulation, thereby decreasing renin release

Question 40

What is a general complication of β blocker use in diabetics?

Answer 40

β antagonists block compensatory responses to hypoglycemia

Question 41

What happens if a pt on long-term β-blocker therapy suddenly withdraws from the medication?

Answer 41

Pt will have rebound HTN and possibly an infarct due to induced hypersensitivity to β-agonists

Question 42

What do clinical trials show about bisoprolol?

Answer 42

Dramatic benefits for CHF pts

Question 43

What type of drug is clonidine and what is its general mechanism?

Answer 43

α2 receptor agonists that works centrally to decrease sympathetic outflow

Question 44

What is the result of sudden withdrawal of clonidine?

Answer 44

May cause hypertensive crisis that can be life-threatening