1) The document discusses sympatholytics, which are drugs that block alpha and/or beta adrenergic receptors to antagonize the actions of endogenous and exogenous sympathomimetic agents. 2) It describes the classification, mechanisms, and effects of alpha-adrenergic receptor antagonists and beta-adrenergic receptor blockers. 3) The therapeutic uses of these drugs include hypertension, benign prostatic hyperplasia, pheochromocytoma, and others.

1. DEPARTMENT OF PHARMACEUTICAL SCIENCES
AND TECHNOLOGY
MAHARAJA RANJIT SINGH PUNJAB TECHNICAL
UNIVERSITY
SYMPATHOLYTICS
Presented by: Riya Garg
(Pharmacology 1st year)

2. INTRODUCTION
Adrenergic receptors are membrane bound G- protein
coupled receptors which function primarily by increasing or
decreasing the intracellular production of second messengers
cyclic AMP or IP3/DAG .
Adrenergic
receptors
Alpha(α)
α1receptor
α2receptor
Beta (β)
β1receptor
β2receptor
β3receptor

3. α1 α2 β1 β2 β3
Location Post
junctional
on effector
organs
Autoreceptor
s, pancreas
βcells and
platelets
Heart ,
Kidney
JG cells
Bronchi,
blood
vessels,
uterus,
liver, git,
urinary
tract
Adipose
tissue
Function
subserve
d
Smooth
muscle
contraction
,
vasoconstr
iction,
glycogenol
ysis
↓ NA release
and insulin
release,
vasoconstricti
on
Tachycar
dia,
rennin
release
Smooth
muscle
relaxation(
bronchi,
git, UT)
Lipolysis
Selective
agonist
Phenyleph
erine
Clonidine Dobutami
ne
Salbutamo
l
Mirabegro
n

4. ANTIADRENERGIC DRUGS
The drugs which block the alpha and/or beta receptors
therefore antagonize the action of endogenous as well as
exogenously administered sympathomimetic agents on these
receptors are called antiadrenergic receptor antagonist or
sympatholytic agent.
Classification
A. Adrenergic receptor antagonists
1. α-receptor blockers
2. β-receptor blockers
B. Adrenergic neuron blockers
1. Drugs affecting NA synthesis
2. Drugs affecting NA release

6. α-Adrenergic Receptor Antagonists
 The α adrenergic receptors mediate many of the important actions of
endogenous catecholamine which are antagonized by alpha adrenergic
antagonists.
 The clinically important α-blockers fall primarily into three chemical
groups: the haloalkylamines (e.g. phenoxybenzamine),the imidazolines
(e.g.,phentolamine), and the quinazoline derivatives (e.g.,prazosin).

7. HALOALKYLAMINES IMIDAZOLINES QUINAZOLINES
Prototype phenoxybenzamine phentolamine prazosin
Others ------ Tolazoline Terazosin
Doxazosin
trimazosin
Antagonism Irreversible competitive competitive
Selectivity α1 with some α2 Nonselective
between α1 and α2
Selective for α1
Hemodyna
mic
Decreased PVR and
blood pressure
Venodilation is
prominent
Similar to
phenoxybenzamin
e
Decreased PVR
and blood
pressure.
Veins less
susceptible than
arteries thus
postural hypotnsn
less of a problem

8. HALOALKYLAMINES IMIDAZOLINES QUINAZOLINES
Actions other
than α blockade
Some antagonism of
Ach,5-HT, and histamine,
blockade of neuronal and
extraneuronal uptake
Cholinomimetic;
adrenomimetic;
histamine-like
actions, antagonism
of 5-HT
At high doses some
direct vasodilator
action, probably due
to PDE inhibition
Routes of
administration
Intravenous and oral; oral
absorption incomplete and
erratic
Similar to
phenoxybenzamine
oral
Adverse
reactions
Postural hypotension,
tachycardia, nasal
stuffiness, failure of
ejaculation
Same as PBZ, plus
GI disturbances due
to Cholinomimetic
and histamine-like
actions
Some postural
hypotension,
especially with the
first dose; less of a
problem overall than
with PBZ or
phentolamine
Therapeutic uses Conditions of
catecholamine excess
(e.g., pheochromocytoma)
Peripheral vascular
disease
Same as PBZ Primary hypertension
Benign prostatic
hypertrophy

9. PHARMACOLOGICAL ACTIONS
1. CVS: The important effects are on CVS both through CNS and at
periphery. The effect depends on patient cardiovascular status and
selectivity of a drug for a particular receptor.
 Hypotension: α1 antagonists block vasoconstriction due to
endogenous catecholamines leading to vasodilation in both arterioles
and veins. This causes reduced peripheral vascular resistance and
fall in BP. The hypotensive effect is less in supine than in standing
position due to different sympathetic activity.
 Reflex tachycardia: this is due to blockade of α2 autoreceptor by
nonselective agents and α2 selective blockers.
 Nasal stuffiness: this is due to the vasodilation in both arterioles (α2
blockade) and veins (α1 blockade) in nasal mucous membrane.

10. 2. Other effects
 Miosis : Miosis occurs due to blockade of α-receptors
present in radial muscles of iris.
 Inhibition of ejaculation and impotence: stimulation of α-
receptors present in vas deferens causes ejaculation and so
blockade of these receptors causes inhibition of ejaculation that
lead to impotence.
 Contraction of trigone and sphincter muscles in urinary
bladder and in prostate may be inhibited by α1 blockers so that
urine outflow is facilitated. This is the basis of using α blocker
in benign hyperplasia of prostate.

11.  Diarrhoea : In git both α and β receptors stimulation leads to
reduced GI motility. By blocking α-receptors GI motility is
increased partly and diarrhoea may occur.
 Insulin released is enhanced in β cells of islets of langerhans
due to blockade of α2 receptors.
 Platelet aggregation: α2A receptors cause platelet
aggregation.
 Dale vasomotor reversal: Adrenaline cause rise in MAP
(vasopressor response) due vasoconstriction by α 1. When α1
are blockade then β2 receptor mediated vasodilation is
manifested causing fall in BP(depressor response) .Thus,
vasopressor response of adrenaline is converted into depressor
response after α blockade and is known as Dales reversal
phenomenon.

12. CLINICAL USES OF α-BLOCKERS
 Hypertension
 Benign Hyperplasia of prostate
 Pheochromocytoma
 To overcome action of α agonist
 Shock
 CHF
 Peripheral vascular disease
 Male erectile dysfunctional and aphrodisiac

13. β-ADRENOCEPTOR BLOCKING AGENTS
 All of the β -blockers exert equilibrium-competitive
antagonism of the actions of catecholamines and other
adrenomimetic at β receptors.
 Competitive antagonists of β-adrenergic receptors, or β
blockers, have received enormous clinical attention because of
their efficacy in the treatment of hypertension, ischemic heart
disease, congestive heart failure, and certain arrhythmias
 Propranolol, a nonselective β-antagonist, was the first to be
introduced and is the prototypical drug with which the others
are compared.
 β-blocking agents have greater structural similarity to their
corresponding agonists than do the α-blockers.

14. Pharmacological Properties
 Cardiovascular System:
Heart: Since catecholamines have positive chronotropic and
inotropic actions, β receptor antagonists slow the heart rate and
decrease myocardial contractility.
 Respiratory tract: Propranolol increases bronchial resistance by
blocking β2 receptors. The effect is hardly discernible in normal
individuals because sympathetic bronchodilator tone is minimal. In
asthmatics, however, the condition is consistently worsened and a
severe attack may be precipitated .
 Local anesthetic Propranolol is as potent a local anesthetic as
lidocaine, but is not clinically used for this purpose because of its
irritant property.

15.  Metabolism
 Effecton lipidmetabolism:
↓ Lipolysis (β3 blockade)
 Effect on carbohydratemetabolism:
• ↓ glycogenolysis in liver (β2 blockade)
• Delay in recovery from hypoglycemia in Insulin dependent
Diabetics; specially in patients withlow Glucagon reserve.
 Effecton lipoproteins:
• ↑ VLDL & ↓ HDL cholesterol ----- ↑ risk of coronary
artery disease(CAD).
• Less likelyto occur with β blockers possessingISA.

16.  Effects on Eye:
o ↓ IOP---- ↓synthesis of aqueous humour due to blockade
of β1 in ciliary epithelium.
o beta blockers are used in glaucoma e.g.Timolol, Betaxolol
– topically as eye drops.
• Blood vessels
o Initially there is ↑ PVR due to inhibition of β2
receptor mediated vasodilatation.
o On long term ---- ↓ peripheral resistance & ↓ blood
pressure due to β1-blockade

17. THERAPEUTIC USE OF β-BLOCKERS
1) Treatment ofhypertension:
 Selective β1-blockers are preferable in asthmatic and
diabetic patients and in patients with Raynaud’s
disease.
 Postural hypotension is not prominent.
 Very useful as mono therapy in mild to moderate hypertnsn.
2) MyocardialInfarction(MI): given immediately(fewhours)
afterMIreducesthe infarct sizeandenhancecardiacreperfusion and
recovery; esmolol ,atenolol, Propranolol, andmetoprolol areused.

18. 3) Pheochromocytoma :
o β- blockers may be given after Alpha blockers to reverse the
cardiac effects of catecholamines.
o If given before Alpha blockers, there will be enhanced
effects of catecholamines on alpha receptors--- further rise
in blood pressure.
4) Glaucoma: The mechanism by which ocular pressure is
reduced appears to depend on decreased production of
aqueous humor. Timolol has a somewhat greater ocular
hypotensive effect than do the available Cholinomimetic or
adrenomimetic drugs.
5) Migraine: The β-blockers may offer some value in the
prophylaxis of migraine headache, possibly because a
blockade of cardiovascular β-receptors results in reduced
vasodilation. The painful phase of a migraine attack is
believed to be produced by vasodilation.

19. ADVERSE EFFECT OF β-BLOCKERS
1.On CVS: Generally the extensions of pharmacologic
effects.
o Bradycardia
o AVblock
o Hypotension
o Heart failure- in patients where CO is
dependent uponsympathetic drive.
Antidote: Isoproterenol & glucagon.
 Coldness of extremities, fatigue with non -selective β-
Blockers , specially in patients of peripheral vascular
disease or vasospastic disorders.

20. 2) Drug withdrawal in patients of IHD:
on abrupt discontinuation of β-antagonists therapy in IHD
after chronic use--Angina or acute myocardial infarction may
occur:-this may be due to adrenergicreceptor super-sensitivity
mediated by receptor up-regulation or re-enhancement of
sympathetic cardiac drive.
3)Respiratory:
worsening of pre-existing asthma or COPD (with non
selective beta blockers).
4) CNS:
Sedation, sleep disturbance and depression
5) Metabolic:
Hypoglycemic episodes in insulin dependent diabetics
(typeI) with non selective β-Blockers.

21. Combined alpha and beta blockers
Ex:- Labetalol , Carvedilol , Medroxalol
Non selective β & α1 selectiveblocker.
Used as antihypertensive ----less tachycardia than α
blockers
Labetalol
• Labetalol possesses both αblocking and β-blocking
activity and is approximately one-third as potent as
Propranolol as a β-blocker and one-tenth as potent as
phentolamine as an α-blocker.
• The ratio of β- to α-activity is about 3:1 when Labetalol is
administered orally and about 7:1 when it is administered
intravenously.

22. USES:
• Labetalol is useful for the chronic treatment of
primary hypertension.
• Labetalol, because it possesses both α- and β-
blocking activity, is useful for the preoperative
management of patients with a
pheochromocytoma.
SIDE EFFECT:
• These include postural hypotension,
gastrointestinal distress, tiredness, sexual
dysfunction, and tingling of the scalp.