ADRENOCEPTOR BLOCKERS

ADRENOCEPTOR
BLOCKERS
ADRENOCEPTOR ANTAGONISTS

Alpha-blockers Beta-blockers

Alpha2-selective Beta 2-
selective
Alpha1-selective Beta 1-selective
Nonselective Nonselective

Reversible(phentolamine)
Irreversible(phenoxebenzamine)
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Pharmacologic antagonists
Divided into primary subgroups based
on receptor selectivity
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Alpha and beta blockers

Differ in their effects and clinical
application
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ALPHA BLOCKING DRUGS

All active by:
Oral route

Parenteral route
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ALPHA BLOCKING DRUGS
CLASSIFICATION/PHARMACOKINETICS/MOA
IRREVERSIBLE LONG-ACTING
PHENOXYBENZAMINE
Prototype nonselective,binds covalently to

- receptors
Has only slight alpha
1 blocking effects.
Causes tachycardia due to presynaptic
alpha-2 blockade & postural hypotension
due to alpha1 blockade.
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ALPHA BLOCKING DRUGS

CLASSIFICATION/PHARMACOKINETICS/MOA
IRREVERSIBLE LONG-ACTING
PHENOXYBENZAMINE
Oral Long duration of action (48 hours).

Binds covalently to it - receptors.

Used in phaeochromocytoma(tumor of

adrenal medulla) to control BP

preoperatively
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ALPHA BLOCKING DRUGS
CLASSIFICATION/PHARMACOKINETICS/MOA
REVERSIBLE SHORT-ACTING
PHENTOLAMINE
Prototype

Nonselective (alpha =alpha )

1 2
Competative antagonist
It reduces PVR causing hypotension, and
causes tachycardia due to 2- adrenoceptor
blockade
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ALPHA BLOCKING DRUGS
CLASSIFICATION/PHARMACOKINETICS/MOA
REVERSIBLE SHORT-ACTING
PHENTOLAMINE
Causes postural hypotension due to reduction of
PVR (1 effect) and tachycardia (2 effect).
Duration of action

Oral (2-4 hours)

IV (20-40 minutes)
 Pheochromocytoma ia a tumor of adrenal
medulla in which there is excessive
release of epinephrine and norepinephrine
with their metabolites metanephrine and
normetanephrine which are used for
diagnosis of the disease
Pts with pheochromocytoma show
symptoms of hypertension,palpitations,
headache and increased sweating
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ALPHA BLOCKING DRUGS
CLASSIFICATION/PHARMACOKINETICS/MOA
ALPHA1 -SELECTIVE
PRAZOSIN,terazocin,Doxazocin and Tamsulosin
Prototype

Selective reversible alpha blocker

1
Causes postural hypotension but less
tachycardia than phentalamine &
phenoxybenzamine due to less 2 blockade.
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ALPHA BLOCKING DRUGS
CLASSIFICATION/PHARMACOKINETICS/MOA
ALPHA1 -SELECTIVE
PRAZOSIN
Is extensively metabolized in liver with 50%

bioavailability of oral dose

Duration of action 8-24 hours(orally)

Doxasozin, terazosin and tamsulosin are

congeners of prazocin used in hypertension

and benign prostatic hyperplasia(BPH).
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ALPHA BLOCKING DRUGS

CLASSIFICATION/PHARMACOKINETICS/MOA
ALPHA2 -SELECTIVE
YOHIMBINE, RAUWOLSCINE
Prototype

Selective alpha competitive blockers

2
Used primarily in research application
 Other alpha-adrenoceptor
antagonists
Alfuzocin is a selective 1 antagonist used in
BPH with 60% bioavailability
Indoramin,urapidil are selective 1 blockers
used in hypertension
Chlorpromazine and haloperidol are potent
dopamine receptor antagonists with -receptor
antagonism
Trazodone(antidepressant) is an 1 antagonist
Ergot alkaloids(ergotamine,dihydroergotamine)
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ALPHA BLOCKING DRUGS

EFFECTS
NONSELECTIVE BLOCKERS
Most important effects are on the

CVS system
Reduction in cardiovascular tone

Reduction of both arterial and venous

pressure (decrease in BP)

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ALPHA BLOCKING DRUGS

EFFECTS
NONSELECTIVE BLOCKERS
Cause baroreceptor reflex-mediated

tachycardia as a result of the drop

in mean arterial pressure (MAP) which
causes reflex stimulation of
adrenoceptors in vasomotor center
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ALPHA BLOCKING DRUGS

EFFECTS
NONSELECTIVE BLOCKERS
Tachycardia may be exaggerated due to

alpha2 receptor blockade of presynaptic 2-receptors on

adrenergic nerve terminals
in the heart which normally reduce the
release of NE are also blocked
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ALPHA BLOCKING DRUGS

EFFECTS
NONSELECTIVE BLOCKERS
EPINEPHRINE REVERSAL
Predictable result of the use of an

agonist in a patient who has received

an alpha-blocker
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ALPHA BLOCKING DRUGS

EFFECTS
NONSELECTIVE BLOCKERS
EPINEPHRINE REVERSAL
Reversal in the BP effect of large doses of

epinephrine
From pressor response (alpha receptors)

to a depressor response (beta receptors)

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ALPHA BLOCKING DRUGS

EFFECTS
NONSELECTIVE BLOCKERS
EPINEPHRINE REVERSAL
Not observed with phenylephrine

or NE because they lack sufficient

beta2 effects
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ALPHA BLOCKING DRUGS

EFFECTS
SELECTIVE ALPHA1 BLOCKERS
Block alpha1 receptors much more
effectively
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ALPHA BLOCKING DRUGS

EFFECTS
SELECTIVE ALPHA1 BLOCKERS
Cause much less tachycardia than
the nonselective blockers when
reducing BP
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ALPHA BLOCKING DRUGS

CLINICAL USES
NONSELECTIVE ALPHA BLOCKERS
Limited clinical application

Presurgical treatment of

pheochromocytoma
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ALPHA BLOCKING DRUGS

CLINICAL USES
NONSELECTIVE ALPHA BLOCKERS
Phenoxybenzamine is used during

the preparatory phase in treatment of

pheochromocytoma.
Phentolamine during surgery
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ALPHA BLOCKING DRUGS

CLINICAL USES
NONSELECTIVE ALPHA BLOCKERS
Severe hypertension caused by

overdose with drugs of abuse such

as amphetamine, cocaine, or
phenylpropanolamine
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ALPHA BLOCKING DRUGS

CLINICAL USES
SELECTIVE ALPHA BLOCKERS
Prazosin, doxazosin, and terazosin are

used in hypertension
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ALPHA BLOCKING DRUGS

CLINICAL USES
SELECTIVE ALPHA BLOCKERS
Used together with tamsulosin for

urinary hesitancy and prevention

of urinary retention in patients with
benign
prostatic hyperplasia.
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ALPHA BLOCKING DRUGS

TOXICITY
Main manifestation is orthostatic

hypotension
For nonselective agents, marked

reflex tachycardia
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ALPHA BLOCKING DRUGS

TOXICITY
Nausea and vomiting when taken orally

Exaggerated orthostatic hypotensive

response to the first dose of alpha1-

selective agents(called first dose
effect).
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BETA BLOCKING DRUGS

Competitive pharmacologic antagonists
of -receptors
Propranolol is the prototype
Developed for chronic oral use
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BETA BLOCKING DRUGS

Bioavailability and duration of
action vary widely
Usually classified into subgroups
(Table in Katzung)
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
RECEPTOR SELECTIVITY
Beta receptor selectivity
1
Beta block>beta block
1 2
Advantage when treating patients

with asthma
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
RECEPTOR SELECTIVITY
Beta1 receptor selectivity
Acebutolol
Atenolol
Esmolol
Metoprolol
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
RECEPTOR SELECTIVITY
Nonselective beta-blockers
Nadolol

Propranolol

Timolol
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
RECEPTOR SELECTIVITY
Combined alpha and beta-blockers
Labetalol

Carvedilol

Optically active
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
PARTIAL AGONIST ACTIVITY
Intrinsic sympathomimetic activity

Pindolol

Acebutolol
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
PARTIAL AGONIST ACTIVITY
May be an advantage in treating

patients with asthma

At maximum dose, can cause some

bronchodilatation
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BETA BLOCKING DRUGS
CLASSIFICATION/SUBGROUPS/MECHANISMS
LOCAL ANESTHETIC ACTIVITY
Membrane stabilizing abilitydue to Na+

channel blockade
Disadvantage when a beta-blocker is

used topically in the eye because it

decreases protective reflexes and
increases the risk of corneal ulceration
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BETA BLOCKING DRUGS

CLASSIFICATION/SUBGROUPS/MECHANISMS
LOCAL ANESTHETIC ACTIVITY
Acebutolol

Labetalol

Metoprolol

Propranolol

Are not used in treatment of glaucoma

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BETA BLOCKING DRUGS

ESMOLOL
Short-acting ester (t1/2 10 min)

Used only parenterally

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BETA BLOCKING DRUGS

NADOLOL
Longest acting beta-blocker
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BETA BLOCKING DRUGS

ACEBUTOLOL, ATENOLOL and NADOLOL
Less lipid soluble

Enter the CNS to a lesser extent

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BETA BLOCKING DRUGS

EFFECTS
1. CVS
Decrease BP by:
(-) inotropic effect
(-) chronotropic effect
Antagonize rennin secretion by kidney
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BETA BLOCKING DRUGS
EFFECTS
2. RESPIRATORY
Bronchoconstriction
Increase airway resistance
Thus not suitable for hypertensives with
asthma except for1-selective agents
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BETA BLOCKING DRUGS

EFFECTS
3. EYE
Decrease intraocular pressure
Decrease production of aqueous
humor
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BETA BLOCKING DRUGS

EFFECTS
4. METABOLIC AND ENDOCRINE
Reduce insulin secretion
Caution for insulin dependent DM
Inhibit glycolysis &
gluconeogenesis
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BETA BLOCKING DRUGS

CLINICAL USES
Open-angle glaucoma(agents with no

local anesthetic effect e.g timolol).

Hypertension

Angina
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BETA BLOCKING DRUGS

CLINICAL USES
Arrhythmias

Pheochromocytoma

Hyperthyroidism(propranolol)

Migraine headache(propranolol)
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BETA BLOCKING DRUGS

TOXICITY
1. CVS
Bradycardia
AV blockade
Heart failure
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BETA BLOCKING DRUGS

TOXICITY
2. RESPIRATORY
Worsen the asthma
Are contraindicated in asthmatics
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BETA BLOCKING DRUGS
TOXICITY
3. CNS
Sedation
Fatigue
Sleep alteration
Depression
Psychosis
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Review the Tables in Katzung

Properties of several beta-blocking
drugs
Clinical application of beta-blockers
Drugs used in glaucoma