Pro. Dr.

Muhammad Ashraf
Chairman Department of Pharmacology and
Toxicology, UVAS, Lahore
 ADRENERGIC BLOCKING AGENTS

Prof. Dr. M. Ashraf

D.V.M , M.Sc(Hons) , PhD (USA)

DEPARTMENT:
Pharmacology And Toxicology
 ADRENERGIC BLOCKING AGENTS

 Sympatholytics
Block or decrease the effects of
Sympathetic nerve stimulation,
Endogenous catecholamines and
Adrenergic drugs
Alpha Blockers
 Non Selective Alpha Blockers
 Phenoxybenzamine (Dibenzyline): Non competative
 Phentolamine: Competative
 Tolazoline

 Selective Alpha-1 Blocker

 Prazosin
 Doxazosin
 Terazosin
 Tamsulosin

 Selective Alpha-2 Blocker

 Yohimbine
 Atipamizole
Beta Blockers
 Non Selective Beta Blockers
 Propranolol: Prototype drug
 Nadolol,
 Pindolol,
 Timolol

 Selective Beta-1 Blockers

 Atenolol, Metoprolol, Esmolol, Acebutolol

 Selective Beta-2 Blockers

 Butoxamine

 Alpha, Beta blockers

 Labetalol,
 Carvedilol
 THERAPEUTIC USES

 Treatment and diagnosis of Pheochromocytoma

(Alpha-1 blockers)
 Hypertension
 BPH (Benign Prostatic Hyperplasia) ) ( Doxazosin)
 Glaucoma (Timolol)
 Cardiac Arrhythmia ( Beta blockers)

ADVERSE EFFECTS

 Hypotension
 Orthostatic Hypotension ( Alpha-1 blockrs)
Mechanism of Action
 Antiadrenergic effects
 Can occur by blocking Beta or alpha-1 receptors
postsynaptically
 OR
 By stimulation of presynaptic alpha-2 receptors.
 OR
 By decreasing NT release
 Presynaptic alpha-2 receptor agonists.
Clonidine ,
Xylazine,
Detomidine,
Medetomidine,
Alpha methly dopa
 Drugs affecting release of Norepinephrine
Guanethedine,
Reserpine,
Alpha methly dopa
 Alpha-1 blockers

Act on skin, mucosa, intestines, lungs and

kidneys to prevent vasoconstriction
Effects:
Dilation of arterioles and veins
Decreased blood pressure
Pupillary constriction
 Increased motility of GI tract
Minipress (prazosin)—prototype.
Hytrin (Terazosin) and Cardura (Doxazosin) both are longer acting
than Minipress

Flomax (Tamsulosin)
Used in BPH.
Produces smooth muscle relaxation of prostate gland and bladder
neck.
Minimal orthostatic hypotension.
 Cardiovascular effects – peripheral and central
effects
 Blocks other receptors also – serotonin, dopamine
 Increases ADH release
 Enhances sexual activity – aphrodisiac
 Potential uses: depression, obesity
 Phenoxybenzamine

Prazosin Yohimbine
 PHENOXYBENZAMINE
Irreversible Binding

PHENTOLAMINE
Reversible binding
Diagnose Pheochromocytoma

NOTE

Alpha 1 Blockers cause ORTHOSTATIC HYPOTENSION

 Beta blockers

Prevent receptors from responding to

 Sympathetic nerve impulses,

Catecholamines and
Beta adrenergic drugs
 OH OH OH
OH H H
H O H N
O N O N
N

O N O
H

Propranolol Carteolol O Levobunolol Metipranolol

(OptiPranolol, Glaucoma)

OH OH OH
H H H
O N O N N
O
OH
H
HO N MeSO2
N
H
N
HO H Sotalol
(also inhibits inward potassium channels
Nadolol Oxprenolol Pindolol in the heart)
(Corgard, blood pressure, chest pain)

OH
H
O N
O Timolol
N
N
(oral form is Blocadren)
(Opthalmic form Timoptol or Timoptic)
N S
 OH OH OH OH
OH H H H H
O O N O N O N
H N
O N
O

NH2 O O
HN

O
O Metoprolol
Betaxolol Esmolol (Lopressor, Novartis)
Acebutolol Atenolol (Betoptic, Lokren) (Brevibloc) (also Toprol-XL,
Betaloc (AstraZeneca)
 Effects of Beta blockers

Decreased heart rate

Decreased force of contraction
Decreased CO
Slow cardiac conduction
Decreased automaticity of ectopic pacemakers
Decreased renin secretion from kidneys
Decreased BP
Bronchoconstriction
Less effective metabolism of glucose.
May result in more pronounced hypoglycemia
Decreased production of aqueous humor in eye
Blockage of Beta 2 Receptor
Therapeutic Uses of Adrenergic Blocking Agents

Treatment and diagnosis of

Pheochromocytoma (Alpha-1
blockers)
Hypertension
BPH (Benine Prostatic Hyperplasia)
Glaucoma
Cardiac Arrhythmia
Alpha 1 blocking agents
Alpha 1 blocking agents are used for
Treatment of hypertension,
BPH, in vasospastic disorders, and
 Persistent pulmonary hypertension in the
newborn
May be useful in treating
pheochromocytoma
May be used in Raynaud’s or frostbite to
enhance blood flow
Beta blocking agents
Mainly for cardiovascular disorders (angina,
dysrhythmias, hypertension, MI and glaucoma)
In angina, beta blockers decrease myocardial
oxygen consumption by decreasing rate, BP and
contractility. Slow conduction both in SA node
and AV node

In glaucoma, reduce intraocular pressur by

binding to beta-adrenergic receptors in ciliary
body, thus decrease formation of aqueous
humor
 ß-adrenergic blockers
 Alpha-2 selective agonists
 Carbonic Anhydrase Inhibitors
Inderal (propranolol) is prototype

Useful in treatment of
Hypertension
Dysrhythmias
Angina pectoris
Useful in pheochromocytoma in
conjunction with alpha blockers
Adverse Effects of Adrenergic Blocking Agents

Alpha Blockers
Body System Side/Adverse Effects
Cardiovascular Palpitations, orthostatic
hypotension, tachycardia,
edema, dysrhythmias, chest pain

CNS Dizziness, headache, drowsiness,

anxiety, depression, vertigo,
weakness, numbness, fatigue
Alpha Blockers
Body System Side/Adverse Effects
Gastrointestinal Nausea, vomiting, diarrhea,
constipation, abdominal pain

Other Incontinence, nose bleeding,

tinnitus, dry mouth, pharyngitis,
rhinitis
Beta Blockers
Body System Side/Adverse Effects
Gastrointestinal Nausea, dry mouth, vomiting,
diarrhea, cramps, ischemic colitis

Other Impotence, rash, alopecia,

bronchospasms