E2: Beta Adrenergic Antagonists

Question 1

Nonselective beta-blocker (which receptors)
Lipophilicity

Answer 1

Propranolol-Inderal
ß1,ß2
high lipophilicity ( ↑ CNS penetration)

Question 2

Cardio selective beta-blocker (which receptors)

Answer 2

Atenolol-Tenormin
ß1

Question 3

mixed adrenergic antagonist
selective and vasodilating beta-blocker (which receptors)

Answer 3

Carvedilol-Coreg, Labetelol-trandate
ß1>ß2, α1 antagonist

Question 4

Cardio selective beta-blocker w/unique vasodilating properties (which receptors)

Answer 4

Nebivolol-Bystolic
ß1 (stimulate eNOS, nitric oxide producing)

Question 5

8 indications of beta blockers

Answer 5

1. Open angle glaucoma
2. Hypertension (Not first line agents)
3. Cardiac arrhythmias
4. Ischemic heart disease: angina and MI (Decrease work demands on the heart (by ↓ CO and HR))
5. Migraine prophylaxis
6. Stage fright/phobias
7. Essential tremor
8. Heart Failure (↓ hospitalizations/mortality)

Question 6

Dosing beta-blockers in HF and why

Answer 6

must TITRATE doses, can’t be started in conventional doses because negative inotropic and chronotropic effects can worsen HF initially

Question 7

General info of pharmacologic effects of beta blockers in all organs (2)

Answer 7

all have competitive reversible action on Beta receptors
Cardioselectivity is lost w/increasing doses

Question 8

pharmacologic effects of beta blockers in eye

Answer 8

↓ IOP by 25-30%
–↓aq production by ciliary epithelium
–outweighs the blockade of trabecular network outflow (ß2)

Question 9

pharmacologic effects of beta blockers in blood vessels (arteries/veins)

Answer 9

A. acute ↑ in vasoconstriction
1) blockade of ß mediated vasodilatory effects
2) especially non-selectives
delayed fall in TPR in arteries

B. over time and overall effect is to ↓ BP when on beta blockers
1)↓tonic sympathetic outflow to the periphery from the CNS
2) blockade of renal renin release

Question 10

what are the causes of renal renin release

Answer 10

1. ↓AngII, ↓Aldosterone
2. ↓TPR, ↓BP
3. ↓water loss, Na+ loss, ↓vasoconstriction

Question 11

cardiac pharmacologic effects of beta blockers

Answer 11

1) overall ↓ force of contraction (neg. inotropic)
2) ↓ SA and AV nodal impulse conduction (neg. chronotropic) to ↓ HR
3) when sympathetic tone is high, these agents work best (little effect on resting HR)
4) some agents act as partial agonists/ intrinsic sympathomimetic activity (ISA)

Question 12

what agent acts as a partial agonist/intrinsic sympathomimetic activity (ISA)

Answer 12

labetalol-Trandate

Question 12

which beta blockers are Class I antiarrhythmic agents and what are their pharmacological effect

Answer 12

-Labetalol-Trandate, Metoprolol-Lopressor, propranolol-Inderal
-local anesthetic/membrane stabilizing action (MSA)
1) Additional blockade of Na channel dependent depolarization in heart muscle
2) may aid in antiarrhythmic actions to ↓ action potential generation therefore delaying muscle contraction

Question 12

what is intrinsic sympathomimetic activity (ISA)

Answer 12

stimulate receptors when NE, EPI low
1. prevents bradycardia
2. potential benefit in patients w/severe peripheral arterial disease, dyslipidemia
3. ↓ precipitation of asthma, ↓ rebound symptoms upon discont

Question 12

which beta blockers are Class II antiarrhythmic agents and what are their pharmacological effect

Answer 12

All beta blockers
delay action potential generation

Question 12

-What class antiarrhythmic agent are beta blockers

Answer 12

Class II antiarrythmic agnets
or
Class I

Question 13

pharmacologic effects of beta blockers in ischemic heart disease

Answer 13

1. ↓HR, ↓contractility, –> ↓O2 demands –> ↓ ischemia in heart
2. beta blockers produce a fall in O2 consumption

Question 14

beta blockers that have ISA have been show to _____ _________ in angina and MI patients
Drug ex

Answer 14

↑ mortality
Labetalol-Trandate

Question 15

beta blocker indication in heart failure

Answer 15

1. in HF, cardiac remodeling observed (heart becomes larger, more globular)
2. Beta blocker: slow/reverse the detrimental effects resulting from chronic endogenous adrenergic stimulation
3. ↓ SNSA, ↓tachycardia
4. ↓ arrhythmia potential
   5.↑ LVEF w/long term therapy
5. ↓RAAS

Question 16

ADR of beta blockers

Answer 16

1) CNS: drowsiness, fatigue, depression (more likely w/lipophyllic B-blockers)
2) Cardiac: bradycardia, heart block
3) pulmonary (ß2): bronchospasm and asthma exacerbation (non-cardioselectives&raquo_space;cardioselectives)

Question 17

DI of beta blockers
CI of beta blockers

Answer 17

Calcium channel blockers w/cardio depressant effects
Verapamil-Calan, Diltiazem-Cardiazem

CI:
bronchospastic reactive disease
– mild: advantages > risks
–severe disease: selectives and non-selectives are CI

heart block, bradycardia

Question 18

Warnings/Precautions of Beta blockers

Answer 18

abrupt cessation can cause rebound angina/ischemic cardiac effect
1. FDA black-box warning
2. beta receptor supersensitivity may occur w/LT use (effector organs may ↑ receptor #s when antagonists given)
3. rebound effect more likely in drugs w/short t1/2 and pre-existing ischemic heart disease (propranolol, metoprolol tartrate-Lopressor)

Question 19

What can happen to the # of post-synaptic receptors w/LT use of beta blocker’s? What must be done to combat this?

Answer 19

supersensitization (↑ number of post-synaptic receptors
Taper dose upon withdrawal

Question 20

4 components of the ß blocker SAR

Answer 20

Aryl
Oxy
Propranol
Amine

Question 21

Substitution off amine leads to ____ receptor binding over _____ receptors for beta blockers

Answer 21

beta binding over alpha

Question 22

most beta antagonists contain ______ bridges

Answer 22

oxymethylene

Question 23

ß1 selective agents have ________ ________ _______

Answer 23

1 aromatic ring; para substituent

Question 24

ß1ß2 non-selective antagonists have ______ ______ ______

Answer 24

2 aromatic rings

Question 25

________ adrenergic antagonists tend to be more hydrophillic

Answer 25

selective B1 adrenergic antagonists

Question 26

Atenolol-Tenormin
Class
Use
Chemistry

Answer 26

Class: beta-1 selective adrenergic antagonist
Use: angina, post MI, HTN
Chemistry: hydrophyllic, doesn’t cross BBB

Question 27

Esmolol-Brevibloc IV
Class
Pharmacokinetics
Uses

Answer 27

Class: beta-1 selective antaongist
Pharmacokinetics: ultra short acting, hydrolysis of plasma esterases excreted as zwitteronic metabolite
Use: perioperative HTN and antiarrhythmic

Question 28

Metoprolol tartrate-Lopressor
Class
Use

Answer 28

Class: beta-1 selective (cardioselective) adrenergic antagonists
Use: HTN, hyperthyroidism, arrythmia, MI

Question 29

Metoprolol succinate- Toprol XL
Class
Use
Pharmacology
DIs

Answer 29

beta-1 selective cardioselective adrenergic antagonist
Use: Heart failure, arrythmia, HTN, hyperthyroidism
Pharmacology: antiarrythmic w/MSA
Metabolized by CYP26, inhibited by diphenhydramine, fluoxetine-Prozac

Question 30

Nebivolol-Bystolic
Class
Indication
MOA
Important pharmacology
Warning

Answer 30

3rd gen B1 cardioselective antagonist w/vasodilating properites
Indication: HTN, prevent arrythmias
MOA: cardioselective B1 adrenergic receptor antagonist
Important pcol: stimulate eNOS, suppression of renin
Warning: taper dose w/discont.; CYP2D6 metabolism

Question 31

Labetalol-Trandate
Class:
Indication:
MOA:

Answer 31

Non-selective beta blocker w/alpha-1 blockade (mixed alpha-1 + beta-1, beta-2 antagonist)
Indication: chronic HTN, hypertensive emergencies, HTN during PG
MOA: reversible blockade of a1,B1,B2 in competition w/NE or EPI

Question 32

Carvedilol-Coreg
Dosing:
Class:
Indication:
MOA:

Answer 32

Dose: Requires titration, take w/food
Indication: HTN, HF, Post-MI
MOA: net effect is reversible blockade of a1,B1,B2 in competition w/NE or EPI