Beta blockers

Question 1

Beta 1 adrenergic receptor mechanism of action

Answer 1

• The beta 1 receptor is a G protein-coupled receptor
• When the G protein is in it’s stimulatory form it links the beta receptor to adenylyl cyclase.
• Adenylyl cyclase produces cAMP from ATP
• cAMP is the intracellular second messenger of beta 1 stimulation

1. Positive inotropic effect: opening of calcium channels to increase the rate and force of contraction
2. Positive lusitropic effect: increased reuptake of cytosolic calcium into the SR
3. Positive chronotropic effect: Pacemaker current is increased
4. Positive dromotropic effect: Increased rate of contraction

Question 2

Non-selective beta blockers

Answer 2

First generation beta blockers: propranolol, sotalol

Block beta 1 (cardiac) and beta 1 (bronchial and vascular smooth muscle).

Tend to cause pulmonary complications such as bronchospasm

Question 3

Beta 3 receptors

Answer 3

Endothelial, = vasodilation via nitric oxide

Carvedilol (blocks beta 1, beta 2 and alpha)

Question 4

What can happen during a continued infusion of dobutamine?

Answer 4

tachyphylaxis = clinical beta receptor down regulation during prolonged beta agonist therapy (progressive loss of decrease of therapeutic efficacy)

Question 5

Effect of beta blockers on coronary flow

Answer 5

The longer diastolic filling time, due to the decreased HR during exercise, leads to better diastolic myocardial perfusion

Question 6

What are the 5 effects of beta blockers?

Answer 6

1. Negative chronotropic
2. Negative dromotropic
3. Antiarrhythmic
4. Negative inotropic
5. Anti-ishemic

Question 7

Does beta blockade increase or decrease oxygen demand of the heart?

Answer 7

Decrease

Question 8

What is the ultrashort-acting beta blocker that can be used for SVT?

Answer 8

Esmolol: very short half life of 9 minutes

Question 9

What’s a non-cardiac reason for a beta blocker?

Answer 9

Thyroid storm

Question 10

Second generation (selective) beta blockers

Answer 10

• Block mainly beta 1 (cardiac) receptors
• Atenolol
• Less bronchospasm

Question 11

Class II and class III antiarrhythmic?

Answer 11

Sotalol

Question 12

Propranolol

Answer 12

• Historic gold standard
• Non-cardioselective
• Half life of 3 hours
• Eliminated by the liver, first pass effect
• Highly protein bound

Question 13

Sotalol

Answer 13

• Non-cardioselective
• Longer half life
• Eliminated by the kidneys

Question 14

Atenolol

Answer 14

• Cardioselective
• Longer half life
• Eliminated by the kidneys

Question 15

Carvedilol

Answer 15

• Blocks: beta 1, beta 2 and alpha
• Vasodilatory, nonselective
• Highly protein bound
• Eliminated by the liver

Question 16

4 side effects of beta blockers

Answer 16

1. Smooth muscle spasm (ie. bronchospasm)
2. Bradycardia, heart block, excess negative inotropic effect
3. CNS penetration (insomnia, depression)
4. Metabolic (increased risk of new diabetes)

Question 17

Treatment for beta blocker overdose

Answer 17

• Atropine
• Glucagon (stimulates formation of cAMP by bypassing the beta receptor)
• Phosphodiesterase inhibitor (Pimo??)
• Dobutamine at high doses