Beta Blockers - Dawes Flashcards
Indications
Hypertension Angina Heart failure Arrhythmias (atrial fib and flutter, SVT) Thyrotoxicosis Migraine prophylaxis Anxiety --> get big sympathetic drive
Act on what receptors
Beta 1 and 2,
Over time taking beta blockers??
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
MoA
antagonise Beta adrenoreceptors
Mixed agonists
antagonise alpha and beta = labetalol, carvedilol
Beta1»_space;»> beta2 selectivity
metoprolol, atenolol
beta1 = beta2
propranolol, nadolol
Water soluble vs lipid soluble beta blockers
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
Metoprolol properties
Beta 1 blocker
Lipid soluble, hepatic
atenolol
beta 1
polar, renal
propanolol
beta 1 and 2, lipid soluble, hepatic
carvedilol
beta 1 and 2
alpha blocker, antioxidant
commonly used in HF
Labetalol
beta 1 and 2
alpha blocker
good at controlling hypertension during pregnancy, not teratogenic
Esmolol common use
rapidly changes BP, niche use for intensive care
sotalol
also has antiarrythmic properties
Blood pressure lowering effects
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)
What to do when patient presents in emergency with acute HF
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.
Drug interactions
verapamil –> marked negative chronotropic effect. contraindication, both do same thing.
Diltiazem, caution but acceptable
Amiodarone
anti diabetics - hypoglycaemia awareness
Partial agonists
Oxprenolol, pindolol
- intrinsic sympathomimetic activity
- offset full antagonism
- theoretically less likely to cause extreme side effects not important in clinical practise
Vasodilating beta blockers
celiprolol
beta 1 antagonist
beta 2 agonist –> VSM dilator
nebivolol
- beta 1 antagonist
- Increases NO bioavailability
Pharmacologic differences between beta blockers
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
The significance of the ratio of Beta2 and alpha1 adrenergic receptors in the damaged heart
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.
Other uses of beta blockers
Thyrotoxicosis (crisis)
propranolol
blocks T4-T3 conversion
Versus tachycardia, AF, tremor, agitaiton
Migraine
Propranolol,
Via action on central Beta1 receptors
Adverse side effects?
Can trigger asthma attack in asthmatics, because of the antagonism of the beta2 receptor in bronchial smooth muscle.
