Adrenoceptor Blockers
Dumrongsak Pekthong
M.Sc.(Pharmacology)
Wording
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Adrenoceptor Blocker
Adrenergic Antagonist
Subgroups in Sympathoplegic drugs
Alpha Blocker, Alpha Antagonist
Beta Blocker, Beta Antagonist
Objectives
1. Describe the effects of E and NE in the
presence and in the absence of Alpha Blocker.
2. Compare the effects among Beta Blockers
3. Compare the pharmacokinetics among Beta
Blockers
4. Describe the clinical applications and toxicity of
typical Alpha- and Beta Blockers.
Outline
I. Concepts
II. Alpha-Blocking Drugs
A. Classification
B. Pharmacokinetics
C. Mechanism of Action
D. Effects
Outline
II. Alpha-Blocking Drugs (cont’d)
E. Clinical Uses
F. Adverse Effects
III. Beta-Blocking Drugs
A. Classification and Mechanisms
B. Effects and Clinical Uses
C. Adverse Effects
I. Concepts
• Classification is based on receptor
selectivity.
• These drugs differ markedly in
their effects and clinical
applications.
II. Alpha-Blocking Drugs
A. Classification
– based on: selective affinity for alpha
receptors, reversibility
1. Irreversible, long-acting alpha blockers
2. Reversible, short-acting alpha blockers
3. Alpha1-selective blockers
4. Alpha2-selective blockers
A. Classification
1. Irreversible alpha blockers :
Phenoxybenzamine
– slightly a 1 -selective, long-acting
2. Reversible alpha blockers: Phentolamine
(nonselective), tolazoline (slightly a 2 -selective)
3. a 1 blockers: Prazosin, Doxazosin, Terazosin
4. a 2 blockers: Yohimbine, rauwolscine
• used primarily in researches
B. Pharmacokinetics
• All active orally as well as parenterally
• Phenoxybenzamine: short t1/2 but long
duration-48 hr (covalent bond)
• Phentolamine, tolazoline: parenteral, duration
20-40 min by parenteral route
• Prazosin: oral, duration 8-10 hr
C. Mechanism of Action
• Phenoxybenzamine: binds covalently--irreversible
(insurmountable) blockade (slightly a 1 -selective)
• Other agents: competitive antagonists--the effects
n
can be overcome by increased conc of agonist
D. Effects of Alpha Blockers
1. Nonselective alpha blockers
– block alpha-mediated sympathetic responses
and exogenous sympathomimetics
– Most important effects: CVS effects
• vasodilation --reduce arterial and venous
pressure (a 1 )
• no significant direct cardiac effects
D. Effects of Alpha Blockers
1. Nonselective alpha blockers (cont)
• Cause reflex tachycardia (due to decreased MAP)
• Tachycardia may be exaggerated because a 2
receptors are also blocked.
• e.g. phenoxybenzamine, phentolamine, tolazoline
D. Effects of Alpha Blockers
2. Selective a 1 blockers
• The same effects as nonselective alpha blockers
• But cause much less tachycardia than
nonselective blocker
• e.g. Prazosin, Doxazosin, Terazosin
Epinephrine Reversal
 occur when alpha blockers are given before Epi
---> Epi produce the opposite effects : decreased
BP resulting from b 2 effect
(a 1
,a 2, b 1 ,b 2 )
Antagonistic effect of alpha blocker on
pretreatment with alpha agonist
E. Clinical Uses
1. Nonselective alpha-blockers
 Presurgery of pheochromocytoma: phenoxybenzamine
 During surgery: phentolamine (sometimes)
 Carcinoid tumor: phenoxybenzamine (5-HT blocking)
 Mastocytosis: phenoxybenzamine (H1 antihistamine)
 Accidental local infiltration of alpha agonist:
phentolamine
 Overdose of sympathomimetics (amphetamine,
cocaine, phenylpropranolamine)
 Raynaud’ s phenomenon, erectile dysfunction
(phentolamine)
E. Clinical Uses
2. Selective a 1 -blockers
 Prazosin and others
 Essential Hypertension
 Urinary hesitancy
 Prevention of urinary retention in
benign prostatic hyperplasia (BPH)
F. Adverse effects of Alpha blockers
 Orthostatic hypotension (venodilatation)
 Reflex tachycardia (nonselective >
selective)
 First dose hypotension (take before going
to bed)
 Nausea/vomiting
 Caution in patients with coronary artery
disease (CAD or CHD): angina
III. Beta-Blocking Drugs
A. Classification and Mechanisms
All are competitive antagonists
Propranolol is prototype
Classification is based on
 Beta subtypes selectivity
 Partial agonist activity
 Lipid solubility
 Local anesthetic action
A. Classification and Mechanisms
1. Receptor selectivity
– b 1 -selective: metoprolol, atenolol
– b 2 -selective: butoxamine (research only)
– Nonselective: propranolol
– Combined beta- and alpha-blocking:
labetalol
A. Classification and Mechanisms
2. Partial agonist activity
– Intrinsic sympathomimetic activity, ISA
– eg, pindolol, acebutolol
– may be useful in patients with asthma
A. Classification and Mechanisms
3. Local anesthetic activity (membranestabilizing activity):
– disadvantage when used topically in the eye
– timolol: no this activity
4. Lipid solubility
– responsible for CNS adverse effects:
propranolol
Pharmacokinetics of Beta blockers
• For systemic effects, developed for chronic
oral use
• Esmolol: short-acting--only used
parenterally
• Nadolol: longest-acting
• Atenolol, acebutolol are less lipid-soluble
B. Effects and Clinical Uses
• Predict from beta blockade
– decreased HR, force of contraction
– decreased A-V conduction
– slow firing rate of SA node
• Cardiovascular and ophthalmic
applications are extremly important
B. Clinical Uses
• CVS: hypertension, angina pectoris,
arrhythmia prophylaxis after MI,
supraventricular tachycardias, hypertrophic
cardiomyopathy, congestive heart failure*
• Glaucoma: reduce aqueous humor secretion
(timolol)
B. Clinical Uses
• Migraine: propranolol
• Thyroid storm, thyrotoxicosis: propranolol
• Famillial tremor, other types of tremor,
“stage fright” : propranolol
C. Adverse effects
• CVS: bradycardia, A-V blockade,
congestive heart failure
• Patients with airway disease: asthmatic
attack
• Mask sign of hypoglycemia in diabetic
patients: tachycardia, tremor, anxiety
• CNS effects: sedation, fatigue, sleep
alterations
Drug List
Alpha-blockers
– Nonselective: phenoxybenzamine*,
phentolamine*
– a 1 -selective: prazosin*, terazosin,
doxazosin
– a 2 -selective: yohimbine
Drug List
Beta-blockers
– Nonselective: propranolol*, timolol,
nadolol
– Combined a - and b - blocking:
carvedilol, labetalol
–
b 1 -selective:
metoprolol, atenolol
–
b 2 -selective:
butoxamine
The End