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ALPHA BLOCKERS

Alpha receptors have been further subdivided


into alpha1 and alpha2 receptors.
Alpha -1 receptors Upon stimulation, leads to
increased IP3 and DAG through Gq activated
PLC.
contraction of arterioles and venules.
contraction of radial fibers in the eye.
contraction of vas deferens (ejaculation).
contraction of bladder trigone.
ALPHA BLOCKERS
EFFECTS OF ALPHA-1 BLOCKER:
Blockade of vasoconstriction - hypotension
Postural reflex is interfered postural
hypotension
Reflex tachycardia due to fall in BP
Promote urinary outflow
Failure of ejaculation
ALPHA BLOCKERS
Irreversible Reversible Reversible Reversible Selective
ALPHA
Nonselective Nonselective Selective -1 selective -1A -2
BLOCKERS
blockers blockers blockers blockers blockers

Phenoxy -
Phentolamine Prazosin Tamsulosin
PROTYPE benzamine Yohimbine
Terazosin Silodosin
(PBZ)

Pheochromo Pheochromo Hypertension Erectile


INDICATIONS BPH
cytoma cytoma BPH dysfunction
ALPHA -1 BLOCKERS
PRAZOSIN (Minipress):
Orally active selective alpha-1 blocker.

Used in hypertension and treatment of urinary


retention due to benign prostrate hypertrophy.
Postural hypotension first dose phenomenon
start with low dose at bed time to reduce it.
Sexual dysfunction retrograde ejaculation.

Favorable effects on lipoproteins


BETA BLOCKERS
Cornerstone of Coronary Artery Disease
therapy except prinzmetals angina
Standard therapy for unstable and stable
angina.
One of the preferred therapies for
hypertension with myocardial infarction.
One of the major anti-arrhythmic group of
drugs.
BETA BLOCKERS

Non-selective Selective beta-1

NO INTRINSIC INTRINSIC AGONIST - RECEPTOR NO INTRINSIC INTRINSIC


AGONIST ACTIVITY ACTIVITY ACTIVITY ACTIVITY
BLOCKING ACTION
Atenolol
Metoprolol Acebutolol
Esmolol
Propranolol Pindolol Betaxolol
Labetolol
Nadolol Carvedilol
Timolol
BETA BLOCKERS
PROPRANOLOL :
It undergoes extensive first pass
metabolism and oral bioavailability is
low.
The proportion of drug reaching systemic
circulation increases as the dose is
increased suggesting that hepatic
extraction mechanism may be saturated.
BETA BLOCKERS
PROPRANOLOL :
Heart : Negative inotropic action

Negative chronotropic action


AV conduction is decreased
Long term use of beta blockers are

associated with unfavorable increase in


VLDL and decrease in HDL.
BETA BLOCKERS
PROPRANOLOL :
Eyes : decrease intraocular tension in
chronic simple glaucoma by reducing
aqueous humor production
CNS : sedation, lethargy, depression, sleep
disturbances
Skeletal muscle : antagonizes the
epinephrine induced tremors (-2)
Respiratory tract : bronchoconstriction and
can precipitate bronchial asthma
BETA BLOCKERS
PROPRANOLOL: Metabolic effects :
blocks the warning signals due to counter

regulatory effects of catecholamines during


hypoglycemia.
delays recovery from hypoglycemia in diabetes
mellitus.
CAUTION in DM : Beta-1 selective preferred

Benefits outweigh risks in diabetics and

myocardial infarction.
BETA BLOCKERS
PRECAUTIONS AND ADVERSE EFFECTS :
AV block and bradycardia

Bronchial asthma and COPD

Cold extremities

Depression

Hyperlipidemia

Sexual dysfunction
BETA BLOCKERS
USES OF BETA BLOCKERS:
Hypertension
Coronary artery disease and Arrhythmia
CCF low dose and in mild and moderate cases
Hypertrophic obstructive cardiomyopathy
Chronic Simple Glaucoma
Hyperthyroidism
Migraine prophylaxis
Prevention of esophageal varices bleeding in portal
hypertension / cirrhosis
Black Box Warning: SUDDEN DISCONTINUATION IN
PATIENTS WITH ISCHEMIC HEART DISEASE

Following abrupt cessation of therapy with certain beta-blocking agents,


an increased incidence of angina pectoris and, in some cases,
myocardial infarction have occurred. When discontinuing chronically
administered metoprolol-XL (Toprol-XL ), particularly in patients with
ischemic heart disease, the dosage should be gradually reduced over a
period of 1 - 2 weeks and the patient should be carefully monitored. If
angina markedly worsens or acute coronary insufficiency develops,
metoprolol-XL administration should be reinstated promptly, at least
temporarily, and other measures appropriate for the management of
unstable angina should be taken. Warn patients against interruption or
discontinuation of therapy without the physician's advice. Because
coronary artery disease is common and may be unrecognized, it may be
prudent not to discontinue metoprolol-XL therapy abruptly even in
patients treated only for hypertension.
Ganglion blockers
Ganglion blockers are competitive
antagonist at nicotinic N-type receptors in
autonomic ganglia.
Net effect of the blocker is to reduce the
predominant tone.
Effects are predictable and depend on the
relative dominance in terms of PANS and
SANS.
Ganglion blockers
EFFECTOR DOMINANT EFFECTS OF GANGLIONIC
ORGANS SYSTEM BLOCKADE
Arterioles/ veins SANS Vasodilatation, hypotension
Sweat glands SANS (cholinergic) Anhydrosis
Genitals PANS/SANS Impotence
Heart PANS Tachycardia
Iris PANS Mydriasis
Ciliary muscle PANS Cycloplegia
Bladder PANS Urinary retention
Salivary PANS Xerostomia
GIT PANS Constipation.
Ganglion blockers
Ganglionic blocking agents :
Mecamylamine, Trimethaphan.

It is occasionally used in treatment of


hypertensive crisis and dissecting aortic
aneurysm.
Ganglion blocking agents
Ganglion blocking agents block the reflex
changes in heart rate elicited by increase /
decrease in blood pressure.
Trimethaphan will block the reflex bradycardia
that occurs when phenylephrine causes
vasoconstriction, but it will not block a
bradycardia that results from direct activation of
muscarinic receptors in heart.
Role of ganglionic blockers
Ganglion blocking agents
The result of the test drug Z are shown in
the graph.
100
Control Trimetho Atropine
Heart rate phan

-100
Ganglion blocking agents
Drug Z is probably a drug similar to
A. Acetylcholine

B. Dopamine

C. Epinephrine

D. Phenylephrine

D. Norepinephrine
Glaucoma
Glaucoma is divided into
Chronic Simple Glaucoma - Common

Acute Congestive Glaucoma - Surgery

The routes of aqueous humor drainage --

~ 90% through trabecular route


~ 10% passes through within the ciliary muscle into
episceral vessels (uveosceral flow)
Objective of glaucoma therapy : ---
1. increase outflow of aqueous humor
2. decrease production of aqueous humor
TREATMENT OF CHRONIC SIMPLE
GLAUCOMA

Beta blockers
Alpha-2 agonist Pilocarpine PG analog
CA inhibitor
DRUG GROUP FOR CHRONIC MECHANISM OF ADDITIONAL
SIMPLE GLAUCOMA
ACTION COMMENTS
PROSTAGLANDINS Increase uveoscleral Drugs of 1st Choice
Latanoprost outflow and may decrease
Bimatoprost, Travoprost production of aqueous humor
BETA BLOCKERS Reduce formation of Can cause severe
Timolol (1and 2 ) aqueous humor and may bronchospasm in asthmatics;
Betaxolol (1 selective) increase outflow probably 2nd choice

ALPHA2 AGONISTS Reduce formation of Usually add on choice


Brimonidine aqueous humor and may
Apraclonidine enhance outflow

CARBONIC ANHYDRASE Reduce formation of Usually add on choice


INHIBITORS aqueous humor
Dorzolamide, Acetazolamide

CHOLINOMIMETICS Increase outflow by its Much less popular now due to


Pilocarpine effects on ciliary and unwanted effects
Carbachol sphincter pupillae muscles