ADRENOCEPTOR BLOCKING
DRUGS
• Can be alpha blockers or beta blockers.
• Blockade of peripheral dopamine receptors have
no therapeutic application at the moment.
Alpha antagonists
• Alpha antagonists are either reversible or
irreversible.
• Reversible antagonists dissociate from the
receptors and the blocksde can be overcome
with high concentrations of agonists.
• Examples of reversible antagonists are phentolamine,
labetalol and prazosin.
• Phenoxybenzamine is an example of an irreversible blocker.
Pharmacologic actions:
• Decreased peripheral vascular resistance and bp.
• Reflex tachycardia.
• Postural hypotension.
• Meiosis.
• Nasal stuffiness.
• Decreased resistance to urinary flow.
Phentolamine
• Competitive antagonist at both alpha 1 and 2
receptors.
• Produces decreased peripheral vascular resistance.
• Also causes cardiac stimulation through baroreceptor
mechanisms and also through inhibition of alpha2
presynaptic receptors leading to enhanced release of
noradrenaline.
• Minor inhibitory effects at serotonin receptors.
• Agonist at muscarinic, H1 and H2 receptors.
• Limited absorption following oral
administration.
• T1/2 of 5-7 hrs.
• Adverse effects include severe tachycardia,
arrythmias, nasal congestion, headache,
myocardial ischaemia.
• Uses: Pheochromocytoma, erectile
dysfunction.
Phenoxybenzamine
• Irreversible blocker of alpha receptors.
• Inhibits NA reuptake.
• Blocks serotonin, H1 and Ach receptors.
• It causes a reduction in blood pressure when sympathetic
tone is high.
• Oral administration with low bioavailability.
• Use: pheochromocytoma.
• Side effects: postural hypotension, tachycardia, nasal
stuffiness, inhibition of ejaculation, fatigue, sedation,
nausea.
Prazosin.
• Highly selective for alpha1 receptors.
• Causes relaxation of arterial and venous
vascular smooth muscle and prostatic smooth
muscle.
• Subject to extensive first pass metabolism with
only about 50% bioavailability.
• T1/2 of 3 hrs.
• Used in mgt of hypertension.
Tamsulosin
• Competitive alpha1 antagonist.
• High bioavailability.
• T1/2 of 9-15 hours.
• Hepatic metabolism.
• It is used in the management of BPH.
Clinical pharmacology of alpha receptor blocking
agents:
• Pheochromocytoma.
• Hypentensive emergencies.
• Chronic hypertension.
• Peripheral vascular diseases.
• Local vasoconstrictor excess.
• Urinary obstruction.
• Erectile dysfunction.
Beta receptor antagonists
• Act by occupying beta receptors and
competitively reducing receptor occupancy by
catecholamines and other beta agonists.
• Some are full agonists while others may be
partial agonists or inverse agonists.
• Some are non specific while others show
specificity for either beta1 or beta 2 receptors.
• Good oral absorption.
• Peak plasma concentration in 1-3 hours.
• Most are subject to extensive first pass hepatic
metabolism. Exeptions to this are betaxolol,
penbutolol, pindolol, sotalol.
• Most have t1/2 of 3-10 hrs. nadolol has a t1/2 of
about 24 hours.
• Metabolism is in the liver except for nadolol which is
excreted in the urine unchanged.
Actions
CVS: decreased bp in hypertensives.
• Negative inotropic and chronotropic effects.
• Reduced AV conduction, increased PR interval.
Eye:
• Reduced intraocular pressure due to reduced
aqueous humor production.
Respiratory system
• Increased airway resistance especially in
asthmatics due to beta2 blockade.
Metabolic/endocrine effects
• Inhibition of SNS stimulation of lipolysis.
• Chronic use is associated with increased
plasma concentrations of VLDL and decresed
conc of HDL cholesterol
Others:
• local anesthetic effects due to blockade of
sodium channels.
• Antiarrythmic effect – sotalol. (potassium
channel blockade).
Propranolol
• Prototype beta blocker.
• Low and dose dependent bioavailability.
• Non-selective beta blocker.
Metoprolol, atenolol
• examples of beta1 selective agents.
• They are safer in asthmatics but should still be used with
caution in them.
• They are preferrable in patients with peripheral vascular dx
or diabetes who require beta blo ckers for other indications.
Timolol
• Non-selective.
• No local anesthetic effect.
Clinical uses
• Systemic hypertension.
• Ischaemic hrt dx
• Cardiac arrythmias.
• Heart failure
• Obstructive cardiomyopathy
• glaucoma
• Hyperthyroidism.
• Neurologic disorders: migraine, tremors, anxiety,
symptomatic treatment of alcohol withdrawal.
ADR
• allergy: rare
• Sedation, sleep disturbances, depression.
• Psychotic reactions, rarely.
• Worsening of preexisting asthma and other forms
of airway obstruction.
• Depressed myocardial contractility and
excitability.
• Hypoglycemia.
