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5 Sympatholytics

Sympatholytics are adrenergic antagonists that bind to adrenoceptors but do not trigger the usual receptor-mediated effects. They prevent receptor activation by endogenous catecholamines. Alpha receptor antagonists can be reversible like phentolamine and prazosin or irreversible like phenoxybenzamine. Phenoxybenzamine nonselectively and irreversibly blocks both alpha1 and alpha2 receptors. Beta blockers competitively reduce receptor occupancy by catecholamines. Some are selective for beta1 receptors to avoid bronchoconstriction. Sympatholytics are used to treat hypertension, congestive heart failure, migraines, hyperthyroidism, pheochromocytoma,

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49 views

5 Sympatholytics

Sympatholytics are adrenergic antagonists that bind to adrenoceptors but do not trigger the usual receptor-mediated effects. They prevent receptor activation by endogenous catecholamines. Alpha receptor antagonists can be reversible like phentolamine and prazosin or irreversible like phenoxybenzamine. Phenoxybenzamine nonselectively and irreversibly blocks both alpha1 and alpha2 receptors. Beta blockers competitively reduce receptor occupancy by catecholamines. Some are selective for beta1 receptors to avoid bronchoconstriction. Sympatholytics are used to treat hypertension, congestive heart failure, migraines, hyperthyroidism, pheochromocytoma,

Uploaded by

Hussain Raza
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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SYMPATHOLYTICS

DR Hina Abrar
Assistant Professor
Dow College of Pharmacy, DUHS
Adrenergic antagonists/Sympatholytic agents
 Bind to adrenoceptors but do not trigger the
usual receptor-mediated intracellular effects.
These drugs act by either reversibly or irreversibly
attaching to the receptor, thus preventing its
activation by endogenous catecholamines.
Basic Pharmacology of the Alpha-
Receptor Antagonist Drugs
MECHANISM OF ACTION:
 Alpha-receptor antagonists may be
 Reversible,
 Phentolamine and prazosin.
 Irreversible,
 Phenoxybenzamine.
Phenoxybenzamine
 Nonselective block to both α1- and α2-receptors
 Actions: The block is irreversible and noncompetitive,
and the only mechanism the body has for overcoming
the block is to synthesize new adrenoceptors
 Cardiovascular effects:
 By blocking α receptors, phenoxybenzamine prevents
vasoconstriction of peripheral blood vessels by
endogenous catecholamines, reduce cardiac output.
Therapeutic uses:
 pheochromocytoma,
 Raynaud disease
 Frostbite
 Acrocyanosis
 Adverse eff ects:
 postural hypotension,
 nasal stuffi ness
 nausea, and vomiting
 reflex tachycardia, which is mediated by the baroreceptor
reflex.
Prazosin, terazosin, doxazosin,
tamsulosin, and alfuzosin
 selective competitive blockers of the α1 receptor
 Prazosin, terazosin, doxazosin are useful in the
treatment of hypertension.
 tamsulosin, and alfuzosin are indicated for the
treatment of benign prostatic hypertrophy (also
known as benign prostatic hyperplasia, or BPH).
 All of these agents decrease peripheral vascular
resistance and lower arterial blood pressure by
causing the relaxation of both arterial and venous
smooth muscle
 Prazosin and others are used to treat congestive heart
failure.
 By dilating both arteries and veins, these agents decrease
preload and afterload, leading to an increase in cardiac
output and a reduction in pulmonary congestion
 Alternative to surgery in patients with symptomatic BPH
 Tamsulosin is an inhibitor (with some selectivity) of the α
1A

receptors found on the smooth muscle of the prostate.


 This selectivity accounts for tamsulosin’s relatively
minimal effect on blood pressure and its use in BPH
PHARMACOLOGIC EFFECTS:
Cardiovascular Effects: Other Effects:
 Lowering of peripheral  Blockade of alpha
vascular resistance(Alpha receptors in other tissues
1). elicits miosis (small pupils)
 Non selective (alpha1 = and nasal stuffiness.
Alpha2) blockers usually  Alpha receptors are
1

cause significant expressed in the base of


tachycardia. the bladder and the
 Tachycardia may be more prostate, and their
marked with agents that blockade decreases
block alpha -presynaptic resistance to the flow of
urine.
2

receptors in the heart.


Phenoxybenzamine.
• Somewhat selective for Alpha 1 receptors.
• Causes irreversible blockade.
Phentolamine.
• Non Selective.
• Reversible.
Prazosin.
• Highly selective for Alpha 1 receptors.
• Extensively metabolized.
• Oral bioavailability: 50%, half-life is normally about 3 hours.
Terazosin.
• Selective for Alpha 1 receptors.
• Reversible.
Doxazosin.
• Longer half-life of about 22 hours.
Tamsulosin.
• Has higher affinity for Alpha1A and Alpha1D receptors.
Clinical Pharmacology of the Alpha-
Receptor–Blocking Drugs
 Pheochromocytoma  Peripheral Vascular Disease
 Use of phenoxybenzamine,  Alpha-receptor–blocking drugs
relatively (not absolutely) Alpha 1 do not seem to be effective.
selective.  Urinary Obstruction
 Hypertensive Emergencies  In case of BPH, choice of agent
 The -adrenoceptor antagonist depend on presence or absence
drugs have limited application in of underlying hypertension
the management of hypertensive  Alpha 1A is more specific
emergencies, labetalol instead
 Erectile Dysfunction
can be helpful.
 Chronic Hypertension
 Members of the prazosin family
of Alpha 1 -selective antagonists
Basic Pharmacology of the Beta-
Receptor Antagonist Drugs

 Beta-blocking drugs occupy receptors and


competitively reduce receptor occupancy by
catecholamines and other agonists.
 A few which have irreversible action are in research
phase.
 Some have a higher affinity for Beta1 than for Beta2
receptors.
Propranolol (A nonselective β antagonist)
 prototype β-adrenergic antagonist and blocks both β1 and
β2 receptors with equal affinity
 Cardiovascular
 diminishes cardiac output, having both negative inotropic and
chronotropic effects
 Cardiac output, work, and oxygen consumption are decreased
by a blockade of β1 receptors, and these eff ects are useful in
the treatment of angina
 Peripheral vasoconstriction
 Blockade of β receptors prevents β2-mediated vasodilation
 The reduction in cardiac output leads to decreased blood
pressure
 No postural hypotension occurs, because the α1-adrenergic
receptors are unaffected.
 Bronchoconstriction
 This can precipitate a respiratory crisis in patients with
chronic obstructive pulmonary disease (COPD) or asthma.
 Increased Na+ retention:
 Reduced blood pressure causes a decrease in renal
perfusion, resulting in an increase in Na+ retention and
plasma volume
 β blockers are often combined with a diuretic to prevent
Na+ retention
 Disturbances in glucose metabolism:
 β Blockade leads to decreased glycogenolysis and
decreased glucagon secretion
Therapeutic effects
 Hypertension
 Decreased cardiac output is the primary mechanism
 inhibition of renin release from the kidney
 Migraine
 Hyperthyroidism
 Angina pectoris
 decreases the oxygen requirement of heart muscle
 Myocardial infarction
Adverse effects
 Bronchoconstriction
 Arrhythmias
 Sexual impairment
 Metabolic disturbances
 CNS eff ects
 depression
 dizziness
 lethargy
Fatigue
Weakness
Visual disturbances
Hallucinations
short-term memory loss
 emotional
lability, vivid dreams
Nonselective β antagonists; Glaucoma
 timolol,betaxolol, or carteolol are
 Timolol reduces the production of aqueous
humor in the eye. It is used topically in the
treatment of chronic open-angle glaucoma
 This occurs by decreasing the secretion of
aqueous humor by the ciliary body
 These drugs neither affect the ability of the eye to
focus for near vision nor change pupil size, as do
the cholinergic drugs
Acebutolol, atenolol, metoprolol, bisoprolol, betaxolol, nebivolol,
and esmolol: Selective β1 antagonists

 Cardioselective β blockers
 eliminate the unwanted bronchoconstrictor effect
(β2 effect)
 lower blood pressure in hypertension and
increase exercise tolerance in angina
 hypertensive patients with impaired pulmonary
function.
 Pindolol and acebutolol:
Antagonists with partial agonist
activity
 have the ability to weakly stimulate
both β1 and β2 receptors
 minimize the disturbances of lipid
and carbohydrate metabolism
 hypertensive patients with moderate
bradycardia
Labetalol and carvedilol: Antagonists of both α and adrenoceptors
 β blockers with concurrent α1-blocking actions that produce
peripheral vasodilation, thereby reducing blood pressure
 Carvedilol also decreases lipid peroxidation and vascular wall
thickening
 Carvedilol also used to prevent cardiovascular mortalities in
patients with heart failure
 Labetalol is useful for treating the elderly or black
hypertensive patients
 IV labetalol is also used to treat hypertensive emergencies
 Adverse eff ects:
 Orthostatic hypotension and dizziness are associated with α1
blockade
Pharmacodynamics of the Beta-
Receptor Antagonist Drugs

 Cardiovascular System.
 Respiratory Tract.
 Eye.
 Metabolic and Endocrine Effects.
 Local anesthetic action.
Propranolol.
• Non selective.

Metoprolol, atenolol.
• Beta1 selective.

Nebivolol.
• most highly Beta1 selective.

Pindolol, acebutolol, carteolol, bopindolol, oxprenolol, celiprolol,


and penbutolol.
• Partial -agonist activity.

And no. of other compounds….


Clinical Pharmacology of the Beta-
Receptor–Blocking Drugs
 Hypertension.
 Ischemic Heart Disease.
 Cardiac Arrhythmias.
 Heart Failure.
 Metoprolol, bisoprolol, and carvedilol—are effective in
reducing mortality in selected patients with chronic heart
failure.
 Glaucoma.
 Hyperthyroidism.
 Excessive catecholamine action is related to the
pathophysiology of hyperthyroidism
 Neurologic Diseases.
 migraine headache, The mechanism is not known.
 That’s it
 Good Luck!

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