Alpha Blockers (Sweatman)

Question 1

Of the alpha blockers, which have a higher affinity for alpha-1 receptors?

Answer 1

Doxazosin
Terazosin
Prazosin
* the -azosins have a1 affinity*

Question 2

Of the alpha blockers, which have a balanced affinity for alpha-1/alpha-2 receptors?

Answer 2

Phentolamine
Phenoxybenzamine
the -amines have balanced affinity

Question 3

Tell me about Alfuzosin and its applications.

Answer 3

Alfuzosin has a higher affinity for alpha-1a receptors found in the bladder neck and prostate than other Alpha-1 blockers. This lends it to use in improving urine flow rate in BPH by relaxing the internal sphincter’s SM.
Remember, alpha agonists could cause urinary retention so it makes sense that an alpha-blocker would ease similar symptoms.

Question 4

Alpha-1b and alpha-1d receptors are involved in smooth muscle contraction found where?

Answer 4

vasculature

Question 5

Alpha-1a receptors represent 70% of alpha-receptors found where?

Answer 5

prostate

Question 6

Describe alpha receptors’ relationship with skin and splanchnic vessels.

Answer 6

Agonism of alpha receptors in the BVs of the skin and splanchnics causes vessel contraction –> reduced blood supply to these organs.
Antagonism will restore blood supply to the skin and splanchnics (visceral organs).

Question 7

Describe the locations of alpha-1 and alpha-2 receptors on the pre/post-synaptic nerve membranes.

Answer 7

Alpha-1 found on post

Alpha-2 found on pre (autoreceptor, terminates further release of endogenous NE)

Question 8

What are the ADEs of alpha-2 agonists?

Answer 8

bradychardia, hypotension

Question 9

Blockade of alpha-1 receptors will produce what effect and why?

Answer 9

Hypotension, by preventing NE-stimulated SM contraction in the vasculature.

Question 10

What would happen if you pre-treated with a Alpha-blocker and then administered epinephrine to raise BP?

Answer 10

BP would drop, ironically. Because Epi has effects on a-1, a-2, B-1, B-2 receptors, and you blocked the alpha receptors, only its B function would make a change. And that change happens to be mediated by B-2 receptors on the heart and lungs that actually reduce BP even further!

Question 11

Given their effects, alpha blockers would be used to treat what?

Answer 11

Hypertension

Question 12

What are ADEs of alpha blockers in general?

Answer 12

First dose orthostatic hypotension
*Most prominent with Prazosin
Sinus tachycardia (angina, palpitations), syncope, vertigo

Question 13

Which are more likely to produce tachycardia and why:

Alpha-1 selective or non-selective agents?

Answer 13

Non-selective, by virtue of the action augmenting the release of endogenous NE.

Question 14

Describe the difference in action of NE at low and high doses.

Answer 14

At low doses, you get cardiac stimulation.

At high doses, you get vasoconstriction. (think of it as a weak epi, as far as vasoconstriction is concerned)

Question 15

What effect does Phenoxybenzamine have on alpha-1/2 receptors and what effect does this have physiologically?
What are its indications?

Answer 15

Binds covalently LONG LASTING to both A1/A2
Alpha-1: antagonizes circulating Epi and NE effect on vascular smooth muscle
Alpha-2: increases presynaptic NE release (negative feedback blocker) –> vasodilation–> Lowers BP
Indications: pheochromocytoma (adrenal gland tumor that produces too much Epi–> sympathetic overstimulation)
Off label use: for poor circulation (Raynaud’s).

Question 16

Describe the indications, effects, and ADEs of Phentolamine.

Answer 16

Short-acting, competitive antagonist at a-1/2 receptors.
Indications: pheochromocytoma & hypertensive emergency
Antagonism at a-2 increases circulating levels of NE due to loss of -ive feedback.
Small doses: Raises BP (positive inotropic effect)
Larger doses: Lowers BP (peripheral vasodilation)
ADE: postural hypotension, reflex tachycardia, cardiac arrhythmias (these effects severely limit use for essential hypertension)

Question 17

Are alpha blockers used as extensively as they were before to treat HTN?

Answer 17

No. There drugs with more efficacy in use more often now.

Question 18

Describe the location and physiological role of alpha-adrenergic receptors in CV tissues.

Answer 18

Alpha receptors located in vessel SM of skin/splanchnics, prostate, and urinary bladder.
Agonism causes decreased flow to skin/splanchnics leading to dry/possible necrotic skin and decreased GI peristalsis and increased contraction of prostate and urinary bladder SM leading to urinary retention

Question 19

Contrast the effect of a- and B-receptor blockade on EPI and NE induced change in BP and HR.

Answer 19

Alpha-1: Decrease EPI and NE effect on post-synaptic receptor–> Lower BP
Alpha-1/2: Same as 1 and also increase NE release from pre-synaptic terminal due to loss of -ive feedback inhibition.
Not sure about Beta yet, check that deck.