ADRENERGIC

ANTAGONISTS

What are adrenergic

antagonists?

They are drugs that bind to adrenergic

receptors but do not initiate the usual
intracellular response.

two major subdivisions of this drug

class.
1. blockers
2. blockers

another class of adrenergic

antagonists

the indirect adrenergic antagonists

 BLOCKERS

 blockers.

1.
2.
3.
4.

Prazosin 1 adrenergic selective, reversible

Doxazosin 1 adrenergic selective, reversible
Terazosin 1 adrenergic selective, reversible
Phenoxybenzamine nonselective, irreversible

Remember, phenoxybenzamine is the only adrenergic receptor mentioned that is nonreversible

5. Yobimbine 2 adrenergic selective, reversible

6. Phentolamine nonselective, reversible

PRAZOSIN, TERAZOSIN, AND

DOXAZOSIN

mechanism of action?

competitively and selectively block 1-adrenergic

receptors.

physiologic sequelae of 1 blockade.

Blockade of 1-adrenergic receptors on vascular
smooth muscle inhibits constriction of arterioles and
veins. This results in decreased peripheral vascular
resistance and a lower blood pressure.
Blockade of 1-adrenergic receptors in bladder smooth
muscle results in relaxation and decreased resistance
to urine flow.

PRAZOSIN, TERAZOSIN, AND

DOXAZOSIN

clinical uses
Treatment of hypertension
Prevention of urinary retention in patients who
have benign prostatic hypertrophy

adverse effects
Prazosin and structural analogues can cause:
Gastrointestinal hypermotility
Orthostatic hypertension, especially after the
initial dose
Sexual dysfunction, dry mouth, and dizziness

PHENOXYBENZAMINE

How does this drug work?

Phenoxybenzamine is unique in that it works by noncompetitively

blocking the 1-postsynaptic receptor and 2-presynaptic receptors.

physiologic actions

It blocks peripheral vasoconstriction.

It induces a reflex tachycardia.

How is phenoxybenzamine administered?

Orally

What is the duration of action?

Because it binds covalently to the receptor, this drug has a very long
duration of action (approximately 14-48 hours).

PHENOXYBENZAMINE

therapeutic use.

Treatment of patients with pheochromocytoma-induced hypertension.

Phenoxybenzamine is very effective because of its long duration of
action.
Treatment of patients with benign prostatic hypertrophy.
Phenoxybenzamine reduces the size of the prostate.
Treatment of patients with spinal cord injuries who may suffer from
hyperreflexia, which results in high blood pressure. Phenoxybenzamine
blunts this response.
Treatment of patients with Raynaud's disease

Toxicities

Orthostatic hypotension
Reflex tachycardiaIf severe, it may induce anginal pain; therefore
phenoxybenzamine is contraindicated in patients with coronary disease.
Inhibition of ejaculation due to lack of smooth muscle contraction in the
vas deferens

YOHIMBINE

What is it?

A selective 2-receptor antagonist

clinical use.

It is sometimes used to treat impotency via

direct penile injection.

PHENTOLAMINE

An imidazole derivative
mechanism of action : Reversibly blocks 2, and 2 receptors

How is this drug used clinically?

Because it has a half-life of only 4 hours, phentolamine is used for the

short-term control of pheochromocytoma-induced hypertension.

route of administration : IV or IMpoorly absorbed orally

adverse effects
Orthostatic hypotension
Gastrointestinal stimulation which may lead to peptic ulcers
Tachycardia, myocardial infarction, or arrhythmias due to reflex
sympathetic response

-BLOCKERS

subclassified

All of the -blockers are competitive

antagonists
1. Selectivity of receptor blockade
2. Possession of intrinsic
sympathomimetic activity
3. Capacity to block -adrenergic
receptors

1-SELECTIVE BLOCKERS

1.
2.
3.
4.

Atenolol
Esmolol
Acebutolol
Metoprolol

In general, -blockers starting with A or M

are cardioselective.

Is their 1-selectivity absolute?

No. At high doses these drugs will block

2-receptors.

What is the main advantage of 1

selectivity?

These drugs are sometimes called

cardioselective because they lack the
unwanted bronchoconstrictor and
hypoglycemic effects of nonselective
blockers.

Clinical use of cardioselective

blockers

Atenolol

Esmolol

Because of its very short duration of action (10

minutes), it is used when immediate blockade
is needed, such as for thyroid storm. It is only
administered IV.

Acebutolol

Hypertension, myocardial infarction

Hypertension

Metoprolol

Hypertension, anginal pain, myocardial infarction

NONSELECTIVE -ADRENERGIC
ANTAGONISTS

prototype Propranolol

pharmacologic actions

Decreased cardiac output and blood pressure

Reduction of sinus rate and conduction
through the atria
Peripheral vasoconstriction
BronchoconstrictionRemember, the
cardioselective 1 blockers lack the
bronchoconstrictive and hypoglycemic effects
of nonselective blockers.
Decreased glycogenolysis and glucagons
secretion
Increased VLDL and decreased HDL

How is propranolol absorbed?

This drug is almost completely absorbed after

oral administration, but only approximately
25% reaches the systemic circulation because
of first-pass metabolism.

What is the site of propranolols

metabolism?

The liver

clinical situations indicated

Hypertension
Angina, tachycardia
Arrhythmia
Thyroid storm
Acute panic syndrome.
Migraine headaches

Name two other nonselective adrenergic antagonists.

Timolol and nadololThey have extremely

long half-lives (20 hours).

What is the clinical use of these two

drugs?

Treatment of glaucomaThey decrease the

production of aqueous humor by the ciliary
body.

adverse effects

Bradycardia
Bronchoconstrictioncan result in an
asthmatic attack
May hide warning signs of hypoglycemia
such as tachycardia; therefore, it is
critical to monitor diabetics who are
receiving -blockers.
Fatigue
Depression
Sexual dysfunction

 BLOCKERS WITH INTRINSIC

SYMPATHOMIMETIC ACTIVITY

Acebutolol and pindolol

Why are these drugs considered to be partial agonists?

They very mildly stimulate both 1 and 2-adrenergic receptors.

However, their intrinsic effects are not as strong as that of a full
agonist, such as isoproterenol.

For treatment of hypertension in patients prone to

bradycardia

advantages

Acebutolol and pindolol produce bronchoconstriction only at

extremely high doses. They do not induce bradycardia to the degree
that full antagonists do, and they cause very minimal disruption of
lipid and carbohydrate metabolism.

 BLOCKERS WITH BLOCKING

CAPACITY

Labetalol

Nonselective -blockade along with 1-adrenergic selective blockade, which results in

peripheral vasodilation rather than the vasoconstriction that occurs with the other
blockers
For treatment of hypertension and atrial fibrillation
adverse effects : Orthostatic hypotension and dizziness

Carvedilol

A blocker that also has 1-blocking properties

clinical uses :
Treatment of hypertension
Treatment of chronic CHF
Although it may seem paradoxical to use blockers in the treatment of CHF, since they can

also worsen symptoms, they appear to benefit the patient by reducing sympathetic activity.
They may also improve diastolic dysfunction by prolonging diastolic filling time.

mechanisms of action :
Reduction of sympathetic activity
Improvement of diastolic dysfunction by prolonging diastolic filling time

contraindications to use : blockers are contraindicated in the treatment of acute CHF.

They are only used when the patient is hemodynamically stable

2 SELECTIVE BLOCKERS

Butoxamine

A selective 2-adrenergic antagonist

Does this drug have any clinical use?

No, not currently

INDIRECT ADRENERGIC
ANTAGONISTS

Why are guanethidine and reserpine

considered indirect adrenergic
antagonists?

They do not directly block or adrenergic

receptors. They do, however, block the release
of norepinephrine from nerve endingsin
effect, they antagonize the effects of the
sympathetic system.

GUANETHIDINE

mechanism of action

It enters the peripheral adrenergic nerve by a

reuptake mechanism for norepinephrine and binds
to storage vesicles, the action of which subsequently
blocks the release of stored norepinephrine.

clinical use : treatment of hypertension

adverse effects :
Orthostatic hypotension
Sexual dysfunction

RESERPINE

A Rauwolfia alkaloid

mechanism of action

It blocks norepinephrine transport from cytoplasm into

intracellular storage vesicles. Subsequently, the neuron
is not able to release any catecholamines.

Clinically use : For treating hypertension (very

rarely used)

adverse effects : CNS depression and bradycardia