Beta Blockers - Dawes

Question 1

Indications

Answer 1

Hypertension 
Angina 
Heart failure 
Arrhythmias (atrial fib and flutter, SVT) 
Thyrotoxicosis 
Migraine prophylaxis 
Anxiety --> get big sympathetic drive

Question 2

Act on what receptors

Answer 2

Beta 1 and 2,

Question 3

Over time taking beta blockers??

Answer 3

Will attenuate and change activity of the kinases associated with Beta receptors. This change in kinase activity may mediate some of the long term effects of beta blockers.
They also increase the population density of beta blocks on postsynaptic membranes

Question 4

MoA

Answer 4

antagonise Beta adrenoreceptors

Question 5

Mixed agonists

Answer 5

antagonise alpha and beta = labetalol, carvedilol

Question 6

Beta1&raquo_space;»> beta2 selectivity

Answer 6

metoprolol, atenolol

Question 7

beta1 = beta2

Answer 7

propranolol, nadolol

Question 8

Water soluble vs lipid soluble beta blockers

Answer 8

water sol:

• eliminated by the kidneys
• have longer half life

Lipid sol:

• Absorbed rapidly so use slow release capsule
• mainly excreted and metabolised in the liver, can pass the blood brain barrier therefore central mechanism

Question 9

Metoprolol properties

Answer 9

Beta 1 blocker

Lipid soluble, hepatic

Question 10

atenolol

Answer 10

beta 1

polar, renal

Question 11

propanolol

Answer 11

beta 1 and 2, lipid soluble, hepatic

Question 12

carvedilol

Answer 12

beta 1 and 2
alpha blocker, antioxidant
commonly used in HF

Question 13

Labetalol

Answer 13

beta 1 and 2
alpha blocker
good at controlling hypertension during pregnancy, not teratogenic

Question 14

Esmolol common use

Answer 14

rapidly changes BP, niche use for intensive care

Question 15

sotalol

Answer 15

also has antiarrythmic properties

Question 16

Blood pressure lowering effects

Answer 16

MoA unclear 
Reduce CO (HR, Cardiac work) 
reset baroreceptors 
Renin inhibition therefore dec RAAS 
central actions (reduce sympathetic activity) 
Presynaptic actions - TPR 
Negative chronotropic, SAN affects, AVN transmission 
Inotropic effects 
- Negative (acute/short term) 
- Positive (chronic / long term)

Question 17

What to do when patient presents in emergency with acute HF

Answer 17

Sit him up
Give frusemide diuretics –> wan to get rid of extra fluid before you initiate beta blockers
Nitrates to vasodilate, decrease preload (starlings law of the heart)
The watch the patients weight everyday, once the crackles in the chest have gone, and peripheral edema gone, initiate beta blocker at tiny dose and gradually titrate up.

Question 18

Drug interactions

Answer 18

verapamil –> marked negative chronotropic effect. contraindication, both do same thing.
Diltiazem, caution but acceptable
Amiodarone
anti diabetics - hypoglycaemia awareness

Question 19

Partial agonists

Answer 19

Oxprenolol, pindolol

• intrinsic sympathomimetic activity
• offset full antagonism
• theoretically less likely to cause extreme side effects not important in clinical practise

Question 20

Vasodilating beta blockers

Answer 20

celiprolol
beta 1 antagonist
beta 2 agonist –> VSM dilator

nebivolol

• beta 1 antagonist
• Increases NO bioavailability

Question 21

Pharmacologic differences between beta blockers

Answer 21

selective vs non selective 
lipophilic vs hydrophilic 
Additional properties 
- alpha adrenergic blocking properties 
- antioxidant / NO enhancing 
- Intrinsic / sympathomimetic activity 
Inverse agonism: metoprolol > carvedilol 
receptor up regulation: dec carvedilol

Question 22

The significance of the ratio of Beta2 and alpha1 adrenergic receptors in the damaged heart

Answer 22

In the failing heart the amount of postsynaptic beta1 receptors decrease, suggest that chronic beta blockade might change overtime the beta receptor population in a failing heart and bring it back to normal.

Question 23

Other uses of beta blockers

Answer 23

Thyrotoxicosis (crisis)
propranolol
blocks T4-T3 conversion
Versus tachycardia, AF, tremor, agitaiton

Migraine
Propranolol,
Via action on central Beta1 receptors

Question 24

Adverse side effects?

Answer 24

Can trigger asthma attack in asthmatics, because of the antagonism of the beta2 receptor in bronchial smooth muscle.