E2: Beta Adrenergic Antagonists Flashcards
Nonselective beta-blocker (which receptors)
Lipophilicity
Propranolol-Inderal
ß1,ß2
high lipophilicity ( ↑ CNS penetration)
Cardio selective beta-blocker (which receptors)
Atenolol-Tenormin
ß1
mixed adrenergic antagonist
selective and vasodilating beta-blocker (which receptors)
Carvedilol-Coreg, Labetelol-trandate
ß1>ß2, α1 antagonist
Cardio selective beta-blocker w/unique vasodilating properties (which receptors)
Nebivolol-Bystolic
ß1 (stimulate eNOS, nitric oxide producing)
8 indications of beta blockers
- Open angle glaucoma
- Hypertension (Not first line agents)
- Cardiac arrhythmias
- Ischemic heart disease: angina and MI (Decrease work demands on the heart (by ↓ CO and HR))
- Migraine prophylaxis
- Stage fright/phobias
- Essential tremor
- Heart Failure (↓ hospitalizations/mortality)
Dosing beta-blockers in HF and why
must TITRATE doses, can’t be started in conventional doses because negative inotropic and chronotropic effects can worsen HF initially
General info of pharmacologic effects of beta blockers in all organs (2)
all have competitive reversible action on Beta receptors
Cardioselectivity is lost w/increasing doses
pharmacologic effects of beta blockers in eye
↓ IOP by 25-30%
–↓aq production by ciliary epithelium
–outweighs the blockade of trabecular network outflow (ß2)
pharmacologic effects of beta blockers in blood vessels (arteries/veins)
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
what are the causes of renal renin release
- ↓AngII, ↓Aldosterone
- ↓TPR, ↓BP
- ↓water loss, Na+ loss, ↓vasoconstriction
cardiac pharmacologic effects of beta blockers
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)
what agent acts as a partial agonist/intrinsic sympathomimetic activity (ISA)
labetalol-Trandate
which beta blockers are Class I antiarrhythmic agents and what are their pharmacological effect
-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
what is intrinsic sympathomimetic activity (ISA)
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
which beta blockers are Class II antiarrhythmic agents and what are their pharmacological effect
All beta blockers
delay action potential generation
-What class antiarrhythmic agent are beta blockers
Class II antiarrythmic agnets
or
Class I
pharmacologic effects of beta blockers in ischemic heart disease
- ↓HR, ↓contractility, –> ↓O2 demands –> ↓ ischemia in heart
- beta blockers produce a fall in O2 consumption
beta blockers that have ISA have been show to _____ _________ in angina and MI patients
Drug ex
↑ mortality
Labetalol-Trandate
beta blocker indication in heart failure
- in HF, cardiac remodeling observed (heart becomes larger, more globular)
- Beta blocker: slow/reverse the detrimental effects resulting from chronic endogenous adrenergic stimulation
- ↓ SNSA, ↓tachycardia
- ↓ arrhythmia potential
5.↑ LVEF w/long term therapy - ↓RAAS
ADR of beta blockers
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»_space;cardioselectives)
DI of beta blockers
CI of beta blockers
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
Warnings/Precautions of Beta blockers
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)
What can happen to the # of post-synaptic receptors w/LT use of beta blocker’s? What must be done to combat this?
supersensitization (↑ number of post-synaptic receptors
Taper dose upon withdrawal
4 components of the ß blocker SAR
Aryl
Oxy
Propranol
Amine
Substitution off amine leads to ____ receptor binding over _____ receptors for beta blockers
beta binding over alpha
most beta antagonists contain ______ bridges
oxymethylene
ß1 selective agents have ________ ________ _______
1 aromatic ring; para substituent
ß1ß2 non-selective antagonists have ______ ______ ______
2 aromatic rings
________ adrenergic antagonists tend to be more hydrophillic
selective B1 adrenergic antagonists
Atenolol-Tenormin
Class
Use
Chemistry
Class: beta-1 selective adrenergic antagonist
Use: angina, post MI, HTN
Chemistry: hydrophyllic, doesn’t cross BBB
Esmolol-Brevibloc IV
Class
Pharmacokinetics
Uses
Class: beta-1 selective antaongist
Pharmacokinetics: ultra short acting, hydrolysis of plasma esterases excreted as zwitteronic metabolite
Use: perioperative HTN and antiarrhythmic
Metoprolol tartrate-Lopressor
Class
Use
Class: beta-1 selective (cardioselective) adrenergic antagonists
Use: HTN, hyperthyroidism, arrythmia, MI
Metoprolol succinate- Toprol XL
Class
Use
Pharmacology
DIs
beta-1 selective cardioselective adrenergic antagonist
Use: Heart failure, arrythmia, HTN, hyperthyroidism
Pharmacology: antiarrythmic w/MSA
Metabolized by CYP26, inhibited by diphenhydramine, fluoxetine-Prozac
Nebivolol-Bystolic
Class
Indication
MOA
Important pharmacology
Warning
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
Labetalol-Trandate
Class:
Indication:
MOA:
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
Carvedilol-Coreg
Dosing:
Class:
Indication:
MOA:
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
