Adrenergic Receptor Antagonists
Adrenergic Receptor Antagonists
Adrenergic Receptor Antagonists
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)
®