150 Section 3/ Drugs Acting on ANSPROPRANOLOL
Propranolol is an optically active
compound. The β-adrenergic receptor
blocking activity resides entirely in the L-
isomer, although the D-isomer has equivalent
membrane stabilising activity. L-propranolol
is a competitive antagonist at both β 1 and β 2
receptor. It is not cardioselective although it
has slightly greater activity at the β 1 than at
β 2 receptor. It has no agonist activity but has
membrane stabilizing activity at
concentration exceeding 1 to 3 mg, though
such concentrations are rarely achieved
during oral therapy.
If adrenaline is administered to an
animal which has been pretreated with
propranolol the pressor action is potentiated
because the α-adrenergic vasoconstriction is
not affected but the β 2 vasodilator action is
blocked.
Pharmacokinetics
Propranolol is well absorbed after oral
administration. Peak concentration occurs
after 1-3 hrs after administration.
Propranolol undergoes extensive hepatic
first pass metabolism. The proportion of
drug, reaching the systemic circulation
increases as the dose is increased when the
hepatic circulation may become saturated.
It is rapidly distributed because it is lipid
soluble. It can readily cross blood brain
barrier (BBB).
It is highly bound to plasma protein
(90% to 95%). The major binding protein is
α 1 -acid glycoprotein. Plasma half life is 3 to
6 hrs, and excreted through urine (95%)
breast milk & 5% in faeces as glucuronide
metabolites.
Therapeutic Uses- Hypertension: Propranolol is antihy-
pertensive. Propranolol suppresses the
activation of heart by blocking the β 1
receptor. They reduce the work of heart
by decreasing the cardiac output and
causing a slight decrease in blood
pressure. - Glaucoma: Timolol and other ocular β-
blockers are used to treat glaucoma.
Propranolol is effective in diminishing
intraocular pressure in glaucoma. This
occurs by decreasing the secretion of
aqueous humor by ciliary epithelium.
It neither affects the ability of eye to
focus for near vision, nor changes pupil
size. Used in chronic cases only. - Migraine: Effective in reducing
migraine episodes due to blockade of
catecholamine induced vasodilatation
in the brain vasculature. Propranolol
decreases the incidence and severity of
the attack. - Hyperthyroidism: Propranolol blocks
the peripheral conversion of thyroxine
to triiodothyronine. It controls
palpitation, nervousness, tremor &
sweating etc. - Angina pectoris: Propranolol decreases
O 2 requirement and work of heart
muscle and therefore is effective in
reducing the chest pain on exertion
which occurs in angina. - Myocardial infarction: It blocks the
action of circulating catecholamines
which would increase the oxygen
demand in already ischemic heart
muscle thereby limiting the infarct size. - Anxiety: Exerts an antianxiety effect
during nervousness and panic attacks.