Jackson (Tier 2): Adrenergic Agonists and Antagonists

What adrenergic receptors regulate vascular constriction and dilation?

α1 causes constriction; β2 causes dilation

What receptor increases cardiac muscle contractility?

β1

What receptor increases heart rate through the SA and AV nodes?

β1

What receptor decreases GI smooth muscle motility?

β2

What receptor causes GI sphincter constriction?

α1

What receptor causes bladder sphincter constriction?

α1

What receptor causes bladder detrusor relaxation?

β2

What receptor is associated with ejaculation?

α1

What adrenergic receptors affect the uterus?

α1 causes contraction; β2 causes relaxation

What receptor causes bronchodilation?

β2

What does stimulation of CNS α2 receptors do to blood pressure?

↓ BP

Why can adrenergic drugs produce different effects in different tissues?

Most tissues contain both α and β receptors, so the response depends on the receptor activated and receptor population

What blood vessels are dilated by dopamine receptor stimulation?

Renal, mesenteric, coronary, and cerebral vessels

What is the result of dopaminergic vasodilation?

↑ blood flow

Which adrenergic agonist is a selective α1 agonist?

Phenylephrine

Which adrenergic agonist is a selective α2 agonist?

Clonidine

Which adrenergic agonist is a selective β1 agonist?

Dobutamine

Which adrenergic agonist is a selective β2 agonist?

Terbutaline

Which receptors does oxymetazoline stimulate?

α1 and α2

Which receptors does isoproterenol stimulate?

β1 and β2

Which receptors does epinephrine stimulate?

α1, α2, β1, and β2

Which receptors does norepinephrine stimulate?

α1, α2, and β1

What type of adrenergic agonist is ephedrine?

Mixed-acting agonist

Which indirect adrenergic agonists act as releasing agents?

Amphetamine and tyramine

Which indirect adrenergic agonist inhibits catecholamine uptake?

Cocaine

Which drug listed in the lecture indirectly increases adrenergic activity by inhibiting MAO?

Selegiline

Which drug listed in the lecture indirectly increases adrenergic activity by inhibiting COMT?

Entacapone

What major cardiovascular and respiratory effects does epinephrine produce?

↑ BP, ↑ HR, bronchodilation, and peripheral vasoconstriction

What metabolic changes are produced by epinephrine?

↑ blood glucose, lactate, and fatty acids and ↓ insulin secretion

Which receptors does epinephrine affect?

Both α and β receptors

Which adrenergic effects predominate at usual epinephrine doses?

β effects

Which adrenergic effects predominate at high epinephrine doses?

α effects

Why does epinephrine help treat anaphylaxis?

It treats bronchospasm and laryngeal edema through its adrenergic effects

What important cardiac emergency use of epinephrine is listed in the lecture?

Cardiac arrest

Why may epinephrine be added to a local anesthetic?

For its vasoconstrictive effect

What routes of epinephrine administration are listed in the lecture?

IV, inhalation, and topical

Is epinephrine given orally according to the lecture?

No

How does epinephrine relate physiologically to histamine?

Epinephrine is a physiologic antagonist to histamine

What may happen to the epinephrine dose requirement in a patient taking a β-blocker?

A larger dose may be needed

What is ephedrine's adrenergic mechanism?

Mixed acting; stimulates α and β receptors

How does ephedrine's duration compare with epinephrine?

Ephedrine is longer acting

Which receptors does isoproterenol stimulate?

β1 and β2

Does isoproterenol stimulate α receptors?

No

What major effects does isoproterenol produce?

Cardiac stimulation, skeletal muscle vasodilation, and bronchodilation

What uses of isoproterenol are listed in the lecture?

Heart block when a pacemaker is unavailable and bronchodilation

Why are β2 agonists used as bronchodilators?

β2 stimulation relaxes bronchial smooth muscle

Which β2 bronchodilators are emphasized in the lecture list?

Albuterol, levalbuterol, terbutaline, salmeterol, metaproterenol, isoetharine, isoproterenol, ephedrine, and epinephrine

How do α agonists relieve nasal congestion?

Constrict dilated nasal arterioles → ↓ nasal blood flow and congestion

Which α agonist is specifically noted for sinus congestion?

Phenylephrine

What important adverse effect can occur with phenylephrine used for nasal congestion?

Rebound congestion

How do ophthalmic α agonists relieve conjunctival congestion?

Stimulate α receptors on small arterioles → vasoconstriction

How can α agonists help treat vascular headaches?

Constrict dilated arteries supplying the brain

How can α agonists help control postpartum bleeding?

Promote uterine contraction through vasoconstrictive effects

Why are vasoactive sympathomimetics used in cardiac failure or shock?

To support cardiac function

Which sympathomimetics are listed for cardiac failure/shock support?

Norepinephrine, phenylephrine, epinephrine, dobutamine, dopamine, and milrinone

What are the major CNS adverse effects of α agonists?

Headache, restlessness, excitement, insomnia, and euphoria

What are the major cardiovascular adverse effects of α agonists?

Palpitations/dysrhythmias, tachycardia, vasoconstriction, and hypertension

What are the major CNS adverse effects of β agonists?

Tremor, headache, nervousness, and dizziness

What are the major cardiovascular adverse effects of β agonists?

↑ HR, palpitations/dysrhythmias, and BP fluctuations

What conditions are listed as contraindications/major cautions for adrenergic agonists?

Cardiac dysrhythmias, angina, hypertension, hyperthyroidism, cerebrovascular disease, distal areas with a single blood supply, and renal impairment

Why should adrenergic vasoconstrictors be avoided in distal areas with a single blood supply?

Excessive vasoconstriction can compromise blood flow

How are adrenergic-blocking drugs classified?

By the adrenergic receptors they block: α1, α2, β1, and/or β2

What is the mechanism of α1 antagonists?

Postsynaptic blockade of α1 receptors

What α1 antagonist is the prototype in this lecture?

Prazosin

Which α1 antagonists are longer acting than prazosin?

Terazosin and doxazosin

How do α blockers lower blood pressure?

Cause arterial and venous dilation → ↓ peripheral vascular resistance and BP

How do α blockers improve BPH symptoms?

↓ resistance to urinary outflow by relaxing smooth muscle in the prostate/bladder region

What is tamsulosin primarily used for?

BPH

How does tamsulosin relieve BPH symptoms?

Relaxes smooth muscle of the prostate and bladder neck

What advantage of tamsulosin is emphasized in the lecture?

Minimal orthostatic hypotension

What is phentolamine used for in vasopressor-associated tissue injury?

Rapidly reverses NE/Epi vasoconstriction to restore blood flow and prevent tissue necrosis

What is the hallmark cardiovascular adverse effect to remember with α blockers?

Orthostatic hypotension

What other cardiovascular adverse effects can occur with α blockers?

Palpitations, tachycardia, edema, dysrhythmias, and chest pain

What is the basic mechanism of β blockers?

Compete with norepinephrine and epinephrine and block β-receptor stimulation

Where are β1 receptors located primarily?

Heart

What are β1-selective antagonists also called?

Cardioselective β blockers

Where are β2 receptors located primarily?

Smooth muscle of bronchioles and blood vessels

What effects do cardioselective β1 blockers have on the heart?

↓ HR, prolonged SA node recovery, slowed AV conduction, and ↓ myocardial contractility

Why do β1 blockers decrease myocardial oxygen demand?

They decrease myocardial contractility and heart rate

Which β blockers are listed as β1-selective/cardioselective?

Atenolol, acebutolol, betaxolol, esmolol, and metoprolol

What receptors are blocked by nonselective β blockers?

β1 and β2

How do nonselective β blockers affect the heart?

Same cardiac effects as cardioselective β1 blockers

What happens in the bronchioles when β2 receptors are blocked?

Bronchoconstriction → narrowed airways and shortness of breath

What happens to blood vessels with β2 blockade?

Vasoconstriction

Which nonselective β blockers are listed in the lecture?

Propranolol, carteolol, levobunolol, metipranolol, nadolol, sotalol, and timolol

Why are nonselective β blockers concerning in patients with COPD?

β2 blockade can cause bronchoconstriction

What are the major therapeutic uses of β blockers?

Angina, cardioprotection, dysrhythmias, hypertension, migraine, and glaucoma

What antiarrhythmic class are β blockers?

Class II

Why are β blockers useful for angina?

They decrease myocardial oxygen demand

What major cardiovascular adverse effects can β blockers cause?

AV block, bradycardia, CHF, and peripheral vascular insufficiency

What important respiratory adverse effect can β blockers cause?

Bronchospasm

How do lipophilic β blockers generally behave pharmacokinetically?

Readily GI absorbed, hepatically metabolized, large Vd, and good BBB penetration

Which β blockers are listed as lipophilic?

Propranolol, metoprolol, oxprenolol, bisoprolol, and carvedilol

How do hydrophilic β blockers generally behave pharmacokinetically?

Less readily absorbed, not extensively metabolized, and have long plasma half-lives

Which β blockers are listed as hydrophilic?

Acebutolol, atenolol, betaxolol, carteolol, nadolol, and sotalol

Which organ failure prolongs the half-life of lipophilic β blockers?

Hepatic failure

Which organ failure prolongs the half-life of hydrophilic β blockers?

Renal failure

What is intrinsic sympathomimetic activity (ISA) in a β blocker?

β-agonist activity while still blocking increased sympathetic β activity

Which β blockers are listed as having ISA?

Pindolol, acebutolol, carteolol, and oxprenolol

How do β blockers with ISA affect resting vs exercise heart rate?

Little/no resting HR depression but block the exercise-induced HR increase