Adrenergic Antagonists

Where are beta 1 receptors located?

Give a beta 1 agonist and antagonist

B1 is in the heart

Agonist - Dobutamine

Antongist - Betaxolol

Where are beta 2 receptors located?

Give a beta 1 agonist and antagonist

B2 are in the lungs

Agonist - Albuterol

Antagonist - Butoxamine

Where is beta 3 located?

Provide a beta 3 agonist

Beta 3 is on the bladder and adipose tissue

Agonist - Mirabegron

Alpha 1 increases peripheral vasoconstriction. The agonist is phenylephrine. What is the antagonist? (2)

• Prazosin

• Tamsulosin (A1B)

Alpha 2 receptors decrease peripheral resistance and inhibit the release of NE.

Give the agonist and antagonist for alpha 2.

agonist - clonidine

antagonist - Yohimbine

What affect do beta blockers have on…

1. heartbeat

2. heart work load

3. lowering blood pressure

1. BB slow the SA-node which initiates heartbeat

2. slow heart rate allows the left ventricles to fill completely and lowers heart workload

3. BB dilate arteries, lowering BP

Describe a (1st generation) Non-selective beta blocker

• non-selective (hits B1 and B2 and blocks them)

• Blocking both B1 and B2 = decrease HR/BP and may cause bronchospasm, worsen peripheral vasoconstriction, mask hypoglycemia

• nadolol, pindolol, propranolol, timolol

Describe (2nd generation) B1 selective beta blockers

• blocking beta 1 receptor only

• mainly going to effect the heart; less bronchospasms risk than nonselective (first gen; safer for asthma/COPD or diabetics

• acebutolol, atenolol, bisoprolol, esmolol, metoprolol

Describe 3rd generation non-selective beta blockers

• beta blockers with additional actions

• blocking B2 with extra block on A1 that offer vasodilatory effects, reducing systemic vascular resistance and providing improved cardiovascular outcomes. They are often used for managing hypertension and heart failure.

• carvedilol and labetalol

Describe 3rd generation selective beta blockers

• beta blockers with additional actions

• B1 selective and spares B2 (better for airways) 

• Betaxolol and Nebivolol

What are the side effects of beta blockers?

BAD FISH

• Bradycardia/Bronchospasm

• AV block/Arrhythmias - affects AV node too much

• Dizzy/Depression

• Fatigue - unable to increase heart rate

• Impotence

• Signs of hypoglycemia masked

• Hypotension

What are the therapeutic uses for beta blockers?

• hypertension

• Angina, chronic stable

• arrhythmias

• heart failure

• anxiety (situational)

• hyperthyroidism

• glaucoma

• tremor

• migraine prophylaxis

The typical signs of hypoglycemia are shaking/trembling, fast heart rate, extreme hunger, sweating, confusion, and dizziness. A diabetic patient arrives to the clinic with concerns of sweating and low blood sugar. His medical history shows he is also on beta blockers for his heart. Why didn’t the other symptoms prevail concerning his hypoglycemia?

Because beta blockers can mask the typical signs of hypoglycemia, such as tachycardia and tremors, making it harder for the patient to recognize low blood sugar. Only sweating won’t be masked

Why is it dangerous to abruptly stop taking beta blockers?

Abrupt cessation of beta blockers can lead to rebound hypertension because the body will continue to make receptors.

Which of the (first generation) non-selective beta blocker is good for CNS penetration and why?

a. Nadolol

b. Pindolol

c. Propranolol

d. Timolol

c. Propranolol - lipid soluble making it able to cross the blood brain barrier

Which (first generation) non-selective beta blockers have black box warning?

a. Nadolol

b. Pindolol

c. Propranolol

d. Timolol

a. Nadolol

d. Timolol

What are the key differences between the (first gen) non-selective beta antagonists and (second generation) B1 selective antagonists

B1 Selective antagonists

• selectivity is lost at high doses

• same uses as first gen but more cardio-specific

• same ADE but more cardio specific

Which of the B1 selective (second gen) medications has a black box warning?

a. Atenolol

b. Metoprolol

c. Esmolol

d. Bisprolol

D. Acebutolol

a. Atenolol

Which of the B1 selective (second gen) medications is used in IV infusions for urgent settings?

a. Atenolol

b. Metoprolol

c. Esmolol

d. Bisprolol

D. Acebutolol

c. Esmolol

Which beta blocker group are Carvedilol and Labetaolol found in?

non-selective - 3rd generation

Which B1 selective 3rd gen BB is membrane stabilizing via calcium entry blockade and therefore used for HTN and glaucoma?

a. Nadolol

b. Nebivolol

c. Metroprolol

d. Betaxolol

d. Betaxolol

Which B1 selective 3rd gen BB provides vascular relaxation by enhanced NO production and therefore used in HTN?

a. Nadolol

b. Nebivolol

c. Metroprolol

d. Betaxolol

b. Nebivolol

Explain BB with Intrinsic Sympathomimetic Activity

• the BB partially stimulate beta receptors while still blocking them from full activation by catecholamines = partial agonists

  • the binding to beta receptors causes mild activation limiting full sympathetic stimulation

• Useful because BB usually cause bradycardia and reduce heart contraction and ISA BB cause less bradycardia

  • overall this is better for patients with already low heart rate

Which of the following beta antagonists also show alpha antagonist activity?

a. Propranolol

b. Atenolol

c. Labetaolol

d. Nebivolol

c. Labetaolol

• Labetalol binds to α₁ receptors as a competitive antagonist, preventing NE from activating them.

• This blocks the vasoconstrictor signal, so arterioles relax → vasodilation → decreased blood pressure.

• common misconception is it is a 3rd generation non-selective because it blocks alpha 1, but this is the exception

What are the alpha receptor antagonists?

• non-selective - blocks alpha 1 and alpha 2

• A1 selective - block arteriolar and venous vasodilation which will decrease peripheral resistance and blood pressure

• A2 selective - increase release of NE increasing BP and HR

What are the uses of non-selective alpha antagonists?

• acute control hypertension

• treat HTN and related to pheochromocytoma

• treat extravasation (the leakage of fluid or medication from a blood vessel into the surrounding tissue)  of alpha agonist (Epi and phenylephrine)

Phenoxybenzamine and Phentolamine are agents of ______

non-selective alpha antagonists - blocking alpha 1 and alpha 2

What are the therapeutic uses for Phentolamine?

• control BP in pheochromocytoma (a rare tumor that develops in the adrenal glands, producing excessive amounts of hormones called catecholamines (epinephrine and norepinephrine)

• reverse local vasoconstriction

• Tyramine reactions

• Withdrawal hypertension from clonidine 

• pulmonary HTN in newborns

Which non-selective alpha antagonist has irreversible binding?

Phenoxybenzamine

What are the effects of phenoxybenzamine?

• CV effects

• vasodilation

• hypotension

• tachycardia

• venous pooling (edema)

• anticholinergic effects

• antihistamine and anti-serotonin effects

What are the ADE of phenoxybenzmine?

• severe postural hypotension - due to vasoconstriction in the legs

• nasal stuffiness

• marked tachycardia

• anticholinergic effects

• sexual dysfunction

What are the ADE of Phentolamine?

• hypotension

• sexual dysfunction

• tachycardia and cardiac arrhythmia

• nasal stuffiness

• GI stimulation (only different one from phenoxybenzamine)

What are the indications for using Phentolamine?

• hypertensive crisis - occurs when abruptly stopping clonidine (A2)

• tyramine containing food given with MAOI

• Diagnosis of pheochromaocytoma - a rare tumor that develops in the adrenal glands, producing excessive amounts of hormones called catecholamines (epinephrine and norepinephrine)

• Mydriasis - dilation of the pupils

• reversible binding

What are the indications of phenoxybenzamine?

• HTN associated with pheochromocytoma

• irreversible binding

What are the alpha 1 selective antagonists medications?

• Prazosin - short acting

• Terazosin 

• Doxazosin - long acting

Receptors A1A receptors on the bladder for:

• Tamsulosin (flomax)

• Alfuzosin (uroxtral)

What are the indications of selective alpha-1 antagonists indications?

Benign Prostatic Hyperplasia (BPH)

treat HTN

• all are reversible

Which of the following alpha 1 antagonists would be a poor choice for someone with hypertension?

a. Doxazosin

b. Terazosin

c. Prazosin

d. Alfuzosin

d. Alfuzosin - effects the bladder and prostate