8. Adrenergic Antagonists - Adrenergic Receptor Blockers

Front 1

What are adrenergic receptor blockers?

Back 1

Agents that produce their major actions by inhibiting alpha and beta receptors

Front 2

What can adrenergic receptor blockers block?

Back 2

Both exogenous AND endogenous catecholamines

Front 3

What else may adrenergic receptor blockers affect?

Back 3

The release of NE from sympathetic neurons

Front 4

what are the 3 specific alpha adrenergic blockers? What is their receptor selectivity?

Back 4

Phenoxybenzamine - a1/a2
Phentolamine - a1/a2
Prazosin - a1

Front 5

What type of antagonist is Phenoxybenazmine? How does it affect the dose-effect curve of norepinephrine?

Back 5

Irreversible antagonist
-Reduces Emax
-No change in EC50

Front 6

What is needed to overcome the antagonist effects of Phenoxybenzamine? How long does its effects last?

Back 6

-New receptor synthesis
-Effects last for days

Front 7

What is the physiological effect of blocking both a1 and a2 receptors with Phenoxybenzamine? Why?

Back 7

Vasodilation - there is normal basal sympathetic tone in our vessels; lack of a1 means the vessels vasodilate

Front 8

What type of antagonist is Phentolamine? How does this affect its duration of action?

Back 8

-Reversible competitive
-Shorter duration of action

Front 9

How can Phentolamine be surmounted?

Back 9

By increasing the agonist concentration

Front 10

What are Phentolamine and Phenoxybenzamine used to treat?

Back 10

-Pheochromocytoma
-Raynaud's disease (vasoconstr)
-HTN in patients with pheochromocytoma

Front 11

What effect does blocking a1 and a2 receptors have in light of the fact that B1 receptors are not blocked?

Back 11

-Blocks vasoconstriction (a1)
-Blocks neg feedback inhibition (a2)so NE release continues
-Overstimulates B1

Front 12

What are 3 side effects of Phenoxybenzamine and phentolamine as a result of overstimulation of B1 receptors?

Back 12

-Tachycardia
-Salt/water retention
-Orthostatic hypotension

Front 13

What is the most clinically important alpha blocker?

Back 13

Prazosin

Front 14

What alpha blockers does Prazosin block?

Back 14

alpha-1

Front 15

What is the good thing about only blocking a1 receptors with Prazosin?

Back 15

It doesn't block neg feedback inhibition of NE release via a2 receptors, so there is minimal tachycardia

Front 16

Why do Phenoxybenzamine and Phentolamine stimulate water/salt retention?

Back 16

Remember that overstimulation of B1 receptors affects the heart AND increases renal renin release

Front 17

And what is the result of Prazosin only being selective for a1 receptors?

Back 17

Little increase in heartrate, no retention of water/salt

Front 18

What are the 2 major effects of Prazosin?

Back 18

1. Decreased tone in arterioles and veins - decreases bp
2. Relaxes the urinary sphincter and prostate

Front 19

What is another unexplained effect of Prazosin?

Back 19

Favorable lipid profile

Front 20

What is the bad thing about Prazosin?

Back 20

It is subject to significant FPE

Front 21

What are the 3 major clinical uses of Prazosin?

Back 21

-Hypertension
-Short term txmt of CHF
-Benign prostatic hypertrophy

Front 22

Why is Prazosin used to treat CHF in the short term?

Back 22

It reduces both preload and afterload

Front 23

Why is Prazosin used to treat BPH?

Back 23

It relaxes the a1-mediated prostate contraction and bladder neck which otherwise cause resistance to urine flow

Front 24

What are 3 major side effects of Prazosin?

Back 24

1. First dose phenomenom
2. Orthostatic hypotension
3. Salt-water retention

Front 25

What is the first dose phenomenon?

Back 25

Hypotension and syncope 30-90 min after the first dose

Front 26

How is the first dose phenomenon of Prazosin avoided?

Back 26

By administering it during bedtime

Front 27

What are the major Beta receptor adrenergic antagonists?

Back 27

Props to my boy tim who's a metrosexual eskimo
-Propanolol
-Timolol
-Metrolol
-Esmolol

Front 28

What are 3 ways that Beta blockers work?

Back 28

1. Block beta receptors selectively
2. Also partial agonists
3. Local anesthetic effects

Front 29

What is the prototypical non-subtype-selective Beta adrenergic receptor antagonist?

Back 29

Propanolol

Front 30

So what receptors does Propanolol act on?

Back 30

B1 and B2

Front 31

What type of an antagonist is Propanolol?

Back 31

Competitive reversible

Front 32

What are the important kinetic points about Propanolol?

Back 32

-FPE is significant (short t1/2)
-Sustained release preps allow it to be more long acting
-Its metabolite is active

Front 33

What are the 5 major therapueutic uses of Propanolol?

Back 33

CHAMPS
-Cardiac arrythmias
-HTN
-Angina
-Migraines
-Prevent recurrent MI

Front 34

What is the most important side effect of Propanolol?

Back 34

Bronchospasms

Front 35

For what other condition should care be taken if Propanolol is prescribed?

Back 35

Diabetes

Front 36

What can Propanolol do to diabetics?

Back 36

Mask the symptoms of hypoglycemia and augment the hypoglycemia induced by insulin

Front 37

What should care be given for when stopping Propanolol therapy?

Back 37

Withdrawal syndrome due to upregulated receptors

Front 38

What are 4 cardiovascular side effects of Propanolol?

Back 38

-Heart failure (tho its beneficial in low doses)
-Heart block
-Hypotension
-Bradycardia

Front 39

What is another nonselective B-blocker and what is it used to treat?

Back 39

Timolol - for wide angle glaucoma

Front 40

How does Timolol treat glaucoma?

Back 40

By decreasing aqueous humor formation from ciliary epithelium, reducing intraocular pressure

Front 41

Who should you be wary about giving Timolol? Why?

Back 41

Cardiac patients and Asthmatics; some can circulate systemically even if only applied to the eye

Front 42

What are Metoprolol and Esmolol selective antagonists of?

Back 42

B1 receptors

Front 43

What type of antagonist is Metoprolol?

Back 43

Competitive reversible

Front 44

What is a side effect of Metoprolol at high concentrations?

Back 44

It also can hit and block B2 receptors thus causing bronchoconstriction

Front 45

What are the kinetics of Metoprolol?
-absorption
-Halflife
-Metabolism
-Excretion

Back 45

-Rapid oral absorption, subject to significant FPE
-Short halflife
-Metabolized by the liver
-Excreted by the kidney

Front 46

What are the 3 major clinical uses of Metoprolol?

Back 46

-HTN
-Recurrent MI
-CHF

Front 47

Who should you be wary about giving Metoprolol due to its side effects?

Back 47

Asthmatics - it can cause bronchoconstriction at high enough doses

Front 48

And what is the receptor selectivity of Esmolol?

Back 48

B1

Front 49

How does the half life of Esmolol compare to the other Beta blockers?

Back 49

MUCH SHORTER - 10-20 min!

Front 50

Why is the half life of Esmolol so short?

Back 50

It has an ester group that is rapidly metabolized by plasma esterases in RBCs

Front 51

What is Esmolol used for clinically? (2 things)

Back 51

-Emergency treatment of sinus tachycardia and atrial flutter/fibrillation
-Facilitate intubation

Front 52

What are the 2 3rd generation Beta blockers that also are alpha antagonists?

Back 52

-Labetolol
-Carvedilol

Front 53

What receptors are blocked by Labetolol?

Back 53

Alpha1 and both Betas

Front 54

What is Labetolol used to treat
-orally
-IV

Back 54

Oral - chronic HTN
IV - Hypertensive emergencies

Front 55

What does Carvedilol block?

Back 55

a1, B1, B2

Front 56

What other properties does Carvedilol have?

Back 56

Antioxidant

Front 57

What does Carvedilol block at high doses?

Back 57

L-type calcium channels

Front 58

What is Carvedilol used to treat?

Back 58

-CHF
-HTN
-Recurrent MI - reduces CV mortality