BETA ADRENERGIC RECEPTOR ANTAGONISTS Flashcards by Colby Swank

What are the 4 Non-selective (first generation) beta adrenergic receptor antagonists?

Nadolol
Propranolol
Timolol
Sotalol

How well did you know this?

Not at all

Perfectly

4 B-1 selective Antagonists (Second Gen)

Atenolol
Bisoprolol
Esmolol
Metroprolol

How well did you know this?

Not at all

Perfectly

2 Non-selective 3rd generation Beta antagonists

Carvedilol
Labetalol

How well did you know this?

Not at all

Perfectly

Name 1 B1-selective (3rd gen.) antagonist

Nebivolol

How well did you know this?

Not at all

Perfectly

B1-receptor locations and what they affect

2 organs of interest

Heart
* Rate
* Contractility
* Automaticity
* Conduction velocity

Kidney (juxtaglomerular cells)
* Renin release

How well did you know this?

Not at all

Perfectly

B-2 receptor locations and functions

3 organs of interest

Lung
* Bronchorelaxation

Skeletal muscle
* Vasodilation
* Glycogenolysis

Liver
* Glycogenolysis
* Gluconeogenesis

How well did you know this?

Not at all

Perfectly

Identify some pharmacological properties of Beta receptor antagonists

Absorption (exceptions) / Distribution / Metabolism (exception)

Well absorbed after oral administration

Bioavailability is limited to varying degrees due to first-pass
metabolism
* Except for sotalol

Rapidly distributed and have large volumes of distribution

Most β antagonists have half-lives in the range of 3-10
hours
* Esmolol is a major exception, 10 min half-life

How well did you know this?

Not at all

Perfectly

Primary mechanisms of action of B-antagonists

Specifically block β adrenergic receptors

Differ in their relative affinities for β1 and β2 receptors

None are absolutely specific for β1 receptors
* Selectivity is dose-related

How well did you know this?

Not at all

Perfectly

Identify some secondary (variable) mechanisms of action. (when do they inhibit activation of B receptors, and when do they activate them).

Agonist / ISA / what can they help prevent

Secondary mechanisms (variable)
* Partial agonists as well
- Also referred as intrinsic sympathomimetic activity (ISA)
- Inhibit the activation of β receptors in the presence of high catecholamine concentrations
– but moderately activate the receptors in absence of endogenous agonists
* May help prevent profound bradycardia or negative inotropy
* Clinical significance is unclear

How well did you know this?

Not at all

Perfectly

Identify additional secondary mechanisms of action

anesthetic / what do they block / CV effects

Local anesthetic or membrane-stabilizing activity

Block α1 receptors (labetalol, carvedilol)

Additional cardiovascular effects (third generation β blockers)
* Vasodilator (nebivolol, carteolol)
* Antioxidant (carvedilol)

How well did you know this?

Not at all

Perfectly

B-adrenergic antagonists effects on the cardiovascular system. (HR, contractility, automaticity and conduction)

When are effects most evident?

Decreases most sympatheticallysupported cardiac functions
* Heart rate, contractility, automaticity and conduction

Depends on activity of sympathetic nervous system
* Modest effect when tonic stimulation is low
* Cardiovascular effects are most evident with exercise
- Attenuates expected rise in heart rate and contractility

How well did you know this?

Not at all

Perfectly

B antagnoist effects on BP, Cardiac Output, short term / long term effect on total peripheral resistance (TPR).

effect on presynaptic norepinephrine release / renin

Lowers blood pressure in patients with hypertension
* Generally do not lower blood pressure in normotensive patients

Mechanisms not fully understood
* Decreased CO
- Acute compensatory increase in TPR
- Reduction in TPR with long-term use

Block presynaptic β2 receptors that enhance NE release

Reduced β1-stimulation of renin release from juxtaglomerular cells

Additional vascular effects (e.g. vasodilation)

How well did you know this?

Not at all

Perfectly

B antagonist effects on the eye

Reduce intraocular pressure
Decreased aqueous humor
Useful for patients with chronic open-angle glaucoma

How well did you know this?

Not at all

Perfectly

Adverse effects on the CV-system

heart failure / Heart rhythm / Vascular / discontinuation / exercise

May cause or exacerbate heart failure
* Yet, extensive clinical evidence demonstrates that β blockers prolong the lives of heart failure patients

Bradyarrhythmias
* Particularly in patients taking other drugs that impair sinus or AV node function

Exacerbate peripheral vascular disease
* Raynaud’s phenomenon

Abrupt discontinuation
* Exacerbates angina
* Increased risk of sudden death

Exercise intolerance

How well did you know this?

Not at all

Perfectly

Adverse effects on pulmonary system

receptor / asthma / COPD / less likely / ischemic heart disease

Block β2 receptors in bronchial smooth muscle
* Little effect in normal individuals
* In patients with asthma or COPD, can cause life-threatening bronchoconstriction

Less likely with β1-selective antagonists or β antagonists with Intrinsic sympathomimetic activity
* Should still be used with great caution in patients with bronchospastic diseases
* Patients with COPD may tolerate β1- selective blockers
- Benefits for patients with concomitant ischemic heart disease may outweigh the risks

How well did you know this?

Not at all

Perfectly

Adverse effects on CNS

Study These Flashcards

Fatigue
Sleep disturbances (insomnia, nightmares)
Depression
No clear correlation with the incidence of CNS effects and
lipophilicity

Adverse Metabolic Effects

which ones less likely to affect metabolism?

Study These Flashcards

Delays recovery from hypoglycemia
* β2-mediated effects of catecholamine on gluconeogenesis and glycogenolysis
* β1-selective antagonists are less likely to delay recovery from hypoglycemia

Blunts the perception of symptoms of hypoglycemia
* Tremor, tachycardia, nervousness

Propranolol (first gen. non-selective prototype) mechanism of action.

receptors / onset / bioavailability

Study These Flashcards

Competitive, reversible antagonist of β1 and β2 receptors
Rapid and completely absorbed
Substantial first pass metabolism causes variable bioavailability

PROPRANOLOL clinical uses

BP / heart /

Study These Flashcards

Hypertension

Angina pectoris

Cardiac arrhythmias

Myocardial infarction

Pheochromocytoma
-As an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine- secreting tumors

Migraine prophylaxis

Essential tremor

PROPRANOLOL Adverse effects

Study These Flashcards

Cardiovascular:
* Bradycardia
* Hypotension
* Acute heart failure

Other:
* Bronchospasm
* Blunt recognition of hypoglycemia
* Fatigue

Abrupt withdrawal symptoms

TIMOLOL (non-selective 1st Gen) mechanism of action / therapeutic use

Study These Flashcards

Competitive, reversible antagonist of β1 and β2 receptors

Major therapeutic use
* Glaucoma
- Decreases aqueous humor formation

Also available orally and used similarly as propranolol

METOPROLOL (B1 2nd gen) mechanism of action

Study These Flashcards

Competitive, reversible antagonist of β1 receptors
* Cardioselective

At low doses, is more selective for β1 receptor (10 fold)

METOPROLOL Clinical Uses

Study These Flashcards

Hypertension
Angina
Acute myocardial infarction
Congestive heart failure

METOPROLOL: Adverse Effects

Study These Flashcards

Some overlap with propranolol, especially with cardiovascular effects:
* Bradycardia
* Hypotension
* Acute heart failure
* Fatigue

Less risk of bronchoconstriction or metabolic effects
* Mediated by β2 receptors

ESMOLOL: Mechanism of action / half-life / metabolism / route / and clinical uses

Moderately selective β1 receptor antagonist Ultra-short acting * t1/2 = ~8 min Cleaved by esterases in the plasma Administered intravenously and is used when β blockade of short duration is desired * Intraoperative and postoperative tachycardia and/or hypertension * Sinus tachycardia * Supraventricular tachycardia and atrial fibrillation/flutter

Labetalol: Mechanism of action / clinical uses

Competitive, reversible antagonist of α1 and both β receptors Used to treat: * Hypertension * Hypertensive emergencies (IV administration)

Nebivolol: Mechanism of action / vascular effects / clinical uses

Highly selective β1 receptor antagonist Also stimulates NO-mediated vasodilation Used to treat: * Hypertension

Carvedilol: Mechanism of action / inflammation / clinical uses

Competitive, reversible antagonist of α1 and both β receptors Also has antioxidant and anti- inflammatory properties Blocks L-type calcium channels at higher doses Used to treat: * Heart failure with reduced ejection fraction * Hypertension * Reduces mortality in patients after myocardial infarction

Efficacy of BETA ADRENERGIC RECEPTOR ANTAGONISTS treating hypertension | first line therapy? /

Effective and well-tolerated No longer a first-line therapy, particularly in patients over age 60 years * May be associated with inferior protection against stroke risk (particularly among smokers) Beta blockers without ISA are preferred in patients with angina or a history of myocardial infarction

How do BETA ADRENERGIC RECEPTOR ANTAGONISTS help treat Ischemic Heart Disease? | cardiac work / O2 / angina / exercise / MI / indicated during...

Blockade of cardiac β receptors results in: * Decreased cardiac work * Reduction in oxygen demand Reduces the frequency of angina episodes Improves exercise tolerance in many patients with angina Prolongs survival of patients who have had a myocardial infarction * Timolol, propranolol, metoprolol Strongly indicated in the acute phase of myocardial infarction * To reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable * Should use a β antagonist without ISA (Intrinsic sympathomimetic activity)

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS for Cardiac arrhythmias | AFIB / AV-node / ectopic beats / esmolol / sotalol

Effective in the treatment of both supraventricular and ventricular arrhythmias Slows ventricular response rates to atrial flutter and fibrillation * Increases atrioventricular nodal refractory period Can also reduce ventricular ectopic beats, especially if precipitated by catecholamines Esmolol is useful against acute perioperative arrhythmias * Short duration of action Sotalol has antiarrhythmic effects involving ion channel blockade

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS in Heart failure

Effective in reducing mortality in patients with chronic heart failure * Metoprolol, bisoprolol, carvedilol Mechanisms are uncertain * Beneficial effects on myocardial remodeling * Decreases the risk of sudden death

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS in Glaucoma | pressure / topical administration / adverse effects

Reduces intraocular pressure * Reduced production of aqueous humor by the ciliary body Open-angle glaucoma * Comparable efficacy to epinephrine or pilocarpine * Better tolerated Beta blockers that lack local anesthetic properties are suitable for local use in the eye Topical administration: * Timolol * Local daily dose applied is small compared to common systemic doses * Still, may be absorbed from the eye and cause serious adverse effects in the heart and airways

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS in Hyperthyroidism

Beta blockers ameliorate the symptoms of hyperthyroidism that are caused by increased beta-adrenergic tone * These include palpitations, tachycardia, tremulousness, anxiety, and heat intolerance Should be given to most hyperthyroid patients who do not have a contraindication to their use

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS for Migraines | preventative / effective / maybe effective

Preventative treatment * Reduces the frequency and intensity * Established as effective * Propranolol, metoprolol, timolol Probably effective * Atenolol, nadolol

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS for Essential Tremors

Sympathetic activity may enhance skeletal muscle tremor * Propranolol

CLINICAL USE OF BETA ADRENERGIC RECEPTOR ANTAGONISTS for performance anxiety

* Reduction of the somatic manifestations of anxiety * Propranolol

B1-selective antagonists are preferable in patients with:

* Bronchospasm * Diabetes * Peripheral vascular disease * Raynaud’s phenomenon * Third generation β antagonists may offer therapeutic advantages

BETA ADRENERGIC RECEPTOR ANTAGONISTS Flashcards

(38 cards)