ADRENERGIC

RECEPTOR
ANTAGONISTS
B.Dian Novita, dr., MKed.
Faculty of Medicine WMCUS
ALPHA BLOCKERS
Classification of alpha blockers :
• Irreversible and Nonselective :
Phenoxybenzamine
• Reversible & Nonselective :
Ergot alkaloids – Ergotamine
Others -- Phentolamine, Tolazoline
• Reversible – Selective : Prazosin, Terazosin,
Doxazosin, Tamsulosin.
• Alpha 2 selective : Yohimbine
GENERAL EFFECTS OF ALPHA
BLOCKADE :
• Blockade of vasoconstriction -
hypotension
• Postural reflex is interfered – postural
hypotension
• Reflex tachycardia – due to fall of BP
• Failure of ejaculation
Phenoxybenzamine :
• Forming covalent bond with alpha receptors
• Effects lasts 3-4 days
• Also blocks H1, Ach & Serotonin receptors
• Penetrates BBB
• Oral absorption is erratic
• Used in Phaeochromocytoma
• AE : orthostatic hypotension, tachycardia, nasal
stuffiness, ejaculation failure, fatigue, sedation &
nausea
 PRAZOSIN :
• selective alpha -1 blocker
• It inhibits phosphodiesterase  ↑cAMP and
vasodilatation (both arterial & venous)
• No significant tachycardia
• Postural hypotension – first dose phenomenon
• P.O : 50% metabolisms in hepar
• Used in hypertension (emergency, chronic &
pheripheral vascular disease), benign prostrate
hypertrophy (BPH), urinary obstruction, migraine
(prophylaxis)
 TERAZOSIN (®HYTRIN):
• selective alpha -1 blocker
• Postural hypotension – first dose
phenomenon
• P.O : 50% metabolisms in hepar
• T1/2 : 9-12 hours
• Used in hypertension and benign prostrate
hypertrophy
DOXASOZIN (®CARDURA):
• selective alpha -1 blocker
• T1/2 : 22 hours & high bioavailability;
• Active metabolite

TAMSULOZIN (®FLOMAX):
• selective alpha -1 blocker
• High bioavailability
• T1/2 : 9-15 hours
• Affinity > in 1a & 1b  BPH
YOHIMBINE (®APHRODYNE):
• Selective alpha -2 blocker
• Serotonin antagonist
• ↑central sympathetic activation
• >> supplement nutrition
• Clinical use : orthostatic hypotension, male
erectile dysfunction (phosphodiesterase
inhib. ≈ sildenafil)
• AE : hypertension
BETA BLOCKERS
THE USE OF BETA BLOCKERS
• Cornerstone of Ischemic Heart Disease
therapy – except Prinzmetal’s angina
• Standard therapy for unstable and effort
angina
• One of the preferred therapies for
hypertension
• One of the anti-arrhythmic groups of drugs
• Standard therapy for chronic open-angle
glucoma
CLASSIFICATION OF BETA
BLOCKERS : (1)
• SELECTIVE
• NON – SELECTIVE

NON-SELECTIVE
• No intrinsic sympathetic activity : Propranolol,
Timolol, Sotalol, Nadolol
• Membrane stabilizing activity : Propanolol,
Pindolol
• Intrinsic sympathetic activity : Pindolol
CLASSIFICATION OF BETA
BLOCKERS : (2)
• SELECTIVE Beta 1 Blocker :
Atenolol, Metoprolol, Esmolol
• Alpha 1 and Beta blocker :
Labetalol, Carvedilol
PROPRANOLOL :
• Non selective beta blocker
• Orally absorbed (25 %), prolonged absorption >
24 hours
• Extensively metabolized in the liver (1st pass
effect)
• Lipophilic and enters the brain  dose ↑ has
local anesthetic activity ≈ lidocain
• Excreted in urine as glucuronide metabolites
ACTIONS OF PROPRANOLOL :
• Heart : negative inotropic action
negative chronotropic action
negative dromotropic action
• AV conduction is decreased
• Respiratory tract : bronchoconstriction and can
precipitate bronchial asthma.
• Eyes : ↓ IOT by ↓ aqueous humor production
• CNS : sedation, lethargy, depression, sleep
disturbances
• Skeletal muscle : antagonizes the adrenaline
induced tremors
METABOLIC EFFECTS OF
PROPANOLOL :
• blocks the hypoglycemia induced
tachycardia
• blocks epinephrine induced glycogenolysis
(in hypoglycemia)
• blocks T3 & T4 conversion  tx for
hyperthyroid
• Tx for Pheochromocytoma & migraine
(prophylaxis), anxiety – panic attack
PRECAUTIONS AND ADVERSE
EFFECTS OF PROPANOLOL :
• AV block
• Bradycardia
• COPD and asthma
• Diabetes mellitus
• Up regulation : chronic beta blocker
therapy results in proliferation of the
receptors -- sudden stoppage of blockers
result in rebound hypertension and angina
NADOLOL ( CORGARD)
®

• Non selective beta blocker

• Water soluble & incomplete absorps
• t1/2 of the drug in plasma is ~20 hours 
administered once daily
• may accumulate in patients with renal
failure, and dosage should be adjusted
• Clinical use : tx HT & angina pectoris
TIMOLOL (®BLOCADREN)
• Non selective beta blocker
• 1st pass metabolism
• Clinical use : hypertension, congestive
heart failure, acute MI, migraine
prophylaxis, treatment of open-angle
glaucoma and intraocular hypertension
 PINDOLOL
• non-selective receptor antagonist with intrinsic
sympathomimetic activity (ISA), has low
membrane-stabilizing activity & low lipid solubility
• used to treat angina pectoris and hypertension
• 50% of pindolol ultimately is metabolized in the
liver (hydroxylated derivatives that subsequently
are conjugated with either glucuronide or sulfate
before renal excretion), excreted unchanged in the
urine, clearance is reduced in patients with renal
failure  dosage adjustment
METOPROLOL ( LOPRESSOR) ®

• Beta-1 selective blocker

• Metabolism unchanged in urine
• Clinical use : tx hypertension, angina
pectoris, tachycardia, heart failure,
vasovagal syncope, 2nd prevention after
myocardial infarction, an adjunct in
treatment of hyperthyroidism, and for
migraine prophylaxis
ATENOLOL (®TENORMIN)
• Beta-1 selective blocker
• hydrophilic & appears to penetrate the CNS
only to a limited extent
• excreted largely unchanged in the urine,
and can be accumulated in patients with
renal failure  dosage adjustment
 ESMOLOL …1
• Beta-1 selective blocker with a rapid onset and a
very short duration of action, urine excreted
• Slow i.v
• The onset and cessation of receptor blockade with
esmolol are rapid; peak hemodynamic effects occur
within 6-10 minutes of administration of a loading
dose, and there is substantial attenuation of
blockade within 20 minutes of stopping an infusion
ESMOLOL …2
• need loading dose typically is administered &
followed by a continuous infusion of the drug
• If an adequate therapeutic effect is not observed
within 5 minutes, the same loading dose is
repeated, followed by a maintenance infusion at a
higher rate
• used in patients during surgery to prevent or treat
tachycardia and in the treatment of
supraventricular tachycardia & severe post op HT
 LABETOLOL (®NORMODYNE)
• selective blockade of 1 receptors, blockade
of 1 and 2 receptors, partial agonist activity
at 2 receptors, and inhibition of neuronal
uptake of NE (cocaine-like effect)
• p.o tx of chronic hypertension & i.v use in
hypertensive emergencies
• should be given ante coenam
• rate of metabolism is sensitive to changes in
hepatic blood flow
 CARVEDILOL ( COREG) ®

• 1, 1, 2 blocker

• has antioxidant effects  bind to & scavenge
with ROS
• has anti-inflammatory effects
• has MSA but little ISA
• lipophilic & extensively distributed into
extravascular tissues
SUMMARY
QUESTIONS ?