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

ALPHA BLOCKERS

Irreversible Nonselective blockers

Reversible Nonselective blockers

Reversible Selective α-1 blockers

Reversible selective α-1A blockers

Selective α-2blockers

PROTYPEPhenoxy -benzamine (PBZ)

Phentolamine Prazosin Terazosin

Tamsulosin Silodosin

Yohimbine

INDICATIONSPheochromo cytoma

Pheochromocytoma

Hypertension BPH

BPH Erectile 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 prinzmetal’s 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

α- RECEPTOR BLOCKING ACTION

Non-selective Selective beta-1

NO INTRINSIC AGONIST ACTIVITY

INTRINSIC AGONIST ACTIVITY

Propranolol Nadolol Timolol

Pindolol LabetololCarvedilol

NO INTRINSIC ACTIVITY

Atenolol MetoprololEsmololBetaxolol

INTRINSIC ACTIVITY

Acebutolol

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 (β-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

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.

Black Box Warning: SUDDEN DISCONTINUATION IN PATIENTS WITH ISCHEMIC HEART DISEASE

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 blockersEFFECTOR ORGANS

DOMINANT SYSTEM

EFFECTS OF GANGLIONIC 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.

0

100

-100

Heart rateControl Trimetho

phanAtropine

Ganglion blocking agents

Drug Z is probably a drug similar to A. Acetylcholine B. Dopamine C. Epinephrine D. Phenylephrine D. Norepinephrine

GlaucomaGlaucoma 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

Beta blockers Alpha-2 agonist CA inhibitor

Pilocarpine PG analog

TREATMENT OF CHRONIC SIMPLE GLAUCOMA

DRUG GROUP FOR CHRONIC SIMPLE GLAUCOMA

MECHANISM OF ACTION ADDITIONAL COMMENTS

PROSTAGLANDINS LatanoprostBimatoprost, Travoprost

Increase uveoscleral outflow and may decrease production of aqueous humor

Drugs of 1st Choice

BETA BLOCKERSTimolol (β1and β2 )Betaxolol (β1 selective)

Reduce formation of aqueous humor and may increase outflow

Can cause severe bronchospasm in asthmatics; probably 2nd choice

ALPHA2 AGONISTSBrimonidineApraclonidine

Reduce formation of aqueous humor and may enhance outflow

Usually “add on” choice

CARBONIC ANHYDRASE INHIBITORSDorzolamide, Acetazolamide

Reduce formation of aqueous humor

Usually “add on” choice

CHOLINOMIMETICSPilocarpineCarbachol

Increase outflow by its effects on ciliary and sphincter pupillae muscles

Much less popular now due to unwanted effects