Adrenoceptor Antagonists

Sympatholytics

Dr.Gaye HAFEZ
Altınbaş University
Faculty of Pharmacy
Department of Pharmacology
2023
Alpha- Beta-
blocker blocker
 α-blockers
• affect blood pressure
• reduce the sympathetic tone of the blood vessels
• decrease peripheral vascular resistance

❑ reflex tachycardia
Phenoxybenzamine
Phentolamine
Prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin
Yohimbine
• Adrenergic blockers on the
changes in blood pressure
induced by isoproterenol,
epinephrine, and
norepinephrine
 Phenoxybenzamine

• Non-selective to both α1-postsynaptic • Epinephrine reversal

and α2-presynaptic receptors
• Prevents vasoconstriction of
peripheral blood vessels by
endogenous catecholamines
• The decreased peripheral resistance
provokes reflex tachycardia.
• Blocking presynaptic inhibitory α2
receptors in the heart can contribute
to an increased cardiac output.
• Not used clinically
Therapeutic uses

• Pheochromocytoma ADEs:
• Chronic management of these • postural hypotension, nasal
tumors, particularly when the stuffiness, nausea, and vomiting
catecholamine secreting cells • reflex tachycardia, mediated by
are diffuse and, therefore, the baroreceptor reflex
inoperable

in decreased coronary perfusion

contraindicated
 Phentolamine (Regitin Ampoule®)

• Competitive block of α1 and α2 • Used in short-term

receptors management of
• It produces postural pheochromocytoma
hypotension and causes
epinephrine reversal
• Reflex cardiac stimulation and
tachycardia

In patients with decreased

coronary perfusion
ADEs of nonselective α-adrenergic
blocking agents
 Prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin

Used in
Longest action Used in BPH
hypertension

• selective competitive blockers of the α1 receptor

All of these agents decrease peripheral
vascular resistance and lower arterial
blood pressure by causing the
• Tamsulosin is a more potent
relaxation of both arterial and venous
smooth muscle. inhibitor of the α1a receptors
found on the smooth muscle of
First-dose effect: the prostate. This selectivity
• An exaggerated orthostatic accounts for tamsulosin's
hypotensive response that can minimal effect on blood
result in syncope pressure.
• Dose adjustment is required

• ADEs: dizziness, a lack of energy, nasal congestion,

headache, drowsiness, orthostatic hypotension
 Yohimbine

• selective competitive α2
blocker • in CNS and cardiovascular
• a sexual stimulant (erectile conditions because it is a CNS
dysfunction) and cardiovascular stimulant
• Yohimbine works at the level of
the CNS to increase
sympathetic outflow to the
periphery.
• Not used in clinic
 β-blockers
şğ
• Competitive antagonists
• Lower blood pressure in
hypertension
• They do not induce postural
hypotension, because the α-
adrenoceptors remain
functional.
Effective in treating:
• Angina
• Cardiac arrhythmias
• Myocardial infarction
• Congestive heart failure
• Hyperthyroidism
• Glaucoma
• Prophylaxis of migraine
headaches
• β-Blockers exert
an “anxiolytic”
action that may
be due to the
suppression of
somatic
responses
(palpitations;
trembling) to
epinephrine
release that is
induced by
emotional stress
 Propranolol: A nonselective β antagonist (Dideral®)
Diminishes cardiac output
• Prototype
Negative inotropic and chronotropic effects
It directly depresses sinoatrial and
atrioventricular activity.
in patients with COPD
or asthma Peripheral vasoconstriction

Bronchoconstriction

Increased Na+ retention

Disturbances in glucose metabolism

• In the presence of a β-blocker, epinephrine no
longer lowers diastolic blood pressure or
stimulates the heart, but its vasoconstrictive action
(mediated by α-receptors) remains unimpaired
• The actions of NE on the cardiovascular system are
mediated primarily by α-receptors and are,
therefore, unaffected.
Therapeutic uses:

• Hypertension
Topically applied timolol, are effective in
• Glaucoma diminishing intraocular pressure in glaucoma.
• Migraine This occurs by decreasing the secretion of
aqueous humor by the ciliary body.
• Hyperthyroidism
• Angina pectoris
Propranolol is also effective in reducing
• Myocardial infarction migraine episodes when used prophylactically
• ADEs of propranolol: Bronchoconstriction,
arrhythmias, sexual impairment, disturbances in
metabolism, drug interactions
 Timolol and nadolol: Nonselective β antagonists

• reduces the
production of
aqueous humour in
the eye.
• It is used topically in
the treatment of
chronic open-angle
glaucoma.
Acebutolol, atenolol, metoprolol, and esmolol:
Selective β1-antagonists

• lower blood pressure in hypertension and increase

exercise tolerance in angina
Pindolol and acebutolol:
Antagonists with partial agonist activity

• They have the ability to weakly stimulate both β1 and β2

receptors and are said to have intrinsic sympathomimetic
activity (ISA).
Labetalol and carvedilol (Dilatrend®):
Antagonists of both α and β adrenoceptors

• reversible β-blockers with concurrent α1-blocking actions that

produce peripheral vasodilation, thereby reducing blood pressure.
• Detailed information about indications will be
discussed in next lessons.
 Drugs Affecting Neurotransmitter Release or Uptake

• Reserpine (Regroton®) : blocks NE, dopamine, and serotonin from the

cytoplasm into storage vesicles in the adrenergic nerves of all body
tissues

Guanethidine: blocks the release of

stored norepinephrine as well as
displaces NE from storage vesicles

Cocaine: Although cocaine inhibits

norepinephrine uptake, it is an
adrenergic agonist.
Question:

• A 60-year-old asthmatic man comes in for a checkup and complains that he is

having some difficulty in starting to urinate. Physical examination indicates
that the man has a blood pressure of 160/100 mm Hg and a slightly enlarged
prostate. Which of the following medications would be useful in treating both
of these conditions?
A. Doxazosin
B. Labetalol
C. Phentolamine
D. Propranolol
E. Isoproterenol
Pierre-Auguste Renoir