Adrenergic Receptors 2

Question 1

What are the general local risks with alpha-agonists?

Answer 1

localized ischemia, extravasation, weaning down the dose is required

Question 2

What are ergot alkyloids?

Answer 2

Lycergic acid compounds from a rye grass fungus that affect a variety of neural systems (LSD comes from here!)

Question 3

What family contains ergonovine and ergotamine? Where is their action?

Answer 3

Ergots; alpha agonists

Question 4

What is the indication for ergonovine?

Answer 4

Post partum bleeding

Question 5

What is the indication for ergotamine?

Answer 5

acute migraine treatment

Question 6

What are the general side effects of alpha agonists?

Answer 6

hypertension or headache, local ishemia, withdrawal symptoms including dramatic BP drop, nervousness, anxiety, and insomnia

Question 7

What is the mechanism of action of a2 agonists such as clonidine?

Answer 7

post-synaptic a2 receptors in the solitary tract of the midbrain are activated, decreasing CNS sympathetic outflow and tone

Question 8

What is the major difference between a-methyl dopa and clonidine?

Answer 8

a-methyl dopa is a prodrug while clonidine is innately active

Question 9

What is the major indication of B1 agonists?

Answer 9

cardiac stimulation (according to Dr. Brown this is of limited effect due to pre-existing unfixable heart damage)

Question 10

What is the major indication of B2 agonists?

Answer 10

Smooth muscle relaxation including in asthma and uterine relaxation (i.e. to halt premature labor)

Question 11

Which beta adrenergic receptors are found in the heart?

Answer 11

B1, B2, and very low levels of B3

Question 12

What are the side effects of beta agonists?

Answer 12

cardiac arrhythmia (B1 activation) and vasodilation (B2-selective) leading to tachcardia

Question 13

What are the 3 classes of adrenergic blockers?

Answer 13

alpha, beta, and nerve-ending blockers

Question 14

Name the two first generation beta blockers. What is their selectivity?

Answer 14

Propranolol (most important) and Timolol; B1 and B2 non-selective

Question 15

Why are B1 blockers more desirable than B2 blockers?

Answer 15

B1 blockers have heart-specific effects, but a B2 blocker can induce an asthma-like attack

Question 16

What are the two second generation beta blockers? What is their selectivity?

Answer 16

Atenolol and Metoprolol; B1 selective

Question 17

What is the meaning of ‘third’ generation beta blockers?

Answer 17

additional actions are seen beyond beta blocking (B1/B2 or B1 only)

Question 18

List additional properties of third generation beta blockers.

Answer 18

NO production, B2 agonism, a1 antagonism, Ca entry blockers, K channel openers, antioxidants

Question 19

What are the two major 3a generation beta blockers? What is the major additional action?

Answer 19

Labetalol and Carvedelol; B1/B2 non-selective with a1 antagonism

Question 20

Why do beta blockers help hypertension?

Answer 20

Who knows? Possible actions on renin (antagonist), norepinephrine control, NO production, a1 blocking, Ca entry blocking, K channel opening (Note that the JGA produces renin and beta blockers always work in patients with high renin levels)

Question 21

What is the effect of activation of pre-synaptic beta receptors?

Answer 21

Increase in norepinephrine release (a beta blocker would inhibit this effect)

Question 22

What major disease etiologies are treated with beta blockers?

Answer 22

hypertension, arrhythmia, angina, glaucoma, migraine, stage fright, congestive heart failure

Question 23

Are beta blockers contraindicated or first line therapy for heart failure patients?

Answer 23

Both. By weaning in a beta blocker, you can slow down the hypersympathetic tone and reduce stress on the heart. The dose must be titrated, but if done properly it is highly effective.

Question 24

Which beta blockers should be used in heart failure patients?

Answer 24

second and third generation only to limit general beta blocking effects

Question 25

What considerations must be made in tapering off beta blockers?

Answer 25

Cardiac depression, (fatigue/nausea/depression), and bronchoconstriction in susceptible individuals

Question 26

What are the two classes of alpha blockers? What are the major members of these classes?

Answer 26

Non-selective: phenoxybenzamine and phentolamine; Selective: Prazosin

Question 27

What makes Phenoxybenzamine stand out from other adrenergic blockers?

Answer 27

It is a nitrogen mustard and thus covalently binds to alpha receptors, not competitively as the other blockers do, thus increasing its lifetime and effective duration

Question 28

What are major side effects of alpha blockers?

Answer 28

Orthostatic hypotension (fainting when you stand up) and tachycardia

Question 29

Where in the synapse are a1 and a2 receptors?

Answer 29

a1 is post-synaptic, and a2 is pre-synaptic

Question 30

How do a2 receptors decrease sympathetic tone?

Answer 30

They are pre-synaptic and activation exerts an inhibitory effect on norepinephrine release

Question 31

What are the major indications for alpha blockers?

Answer 31

Hypertension, Peripheral Vascular Disease (only small effect), Raynaud’s Syndrome, Frostbite

Question 32

What is the difference between vasoconstriction in Raynaud’s Syndrome and Atherosclerosis that allows an alpha blocker to be more effective in Raynaud’s?

Answer 32

The vessels are still healthy in Raynaud’s, so there is more ability of the vessels to undergo normal vasoconstriction or vasodilation

Question 33

What are secondary uses of alpha blockers?

Answer 33

Frostbite sequelae, Pheochomocytoma (with beta blockers pre-surgery), shock, benign prostatic hyperplasia

Question 34

What is the major nerve-ending blocker?

Answer 34

alpha-methyl tyrosine; it blocks tyrosine hdroxylase; major treatment for non-surgical pheochomocytoma

Question 35

What is the mechanism of action for Reserpine? Why is it rarely used?

Answer 35

It empties the vesicles of norepi and epi; it leads to frequent suicide

Question 36

What is the mechanism of action for guanethidine? What is its major indication?

Answer 36

It displaces norepi from the vesicles, and is used in hypertension