Propranolol

• Molecular and Vishnu Shinde

Cellular Toxicology (SMA0052) U1073020
 Chemical Structure:-

1) http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4946&loc=ec_rcs
 Physical properties:-
oMolecular/Linear formula :- C16H21NO2

oIUPAC name:- 1-(isopropylamino)-3-naphthalen-1-yloxy-

propan-2-ol

oSolubility:- Water and Ethanol

oMelting point:- 163˚ - 164˚ C

oMolecular weight:- 259.35

1) Essentials of Medical Pharmacology, 6th Edition ,page 142-143 (author : -K.D. Tripathi)
 Usage:-
Hypertension:-
Angina pectoris:-
Cardiac arrhythmias:-
Myocardial infarction:-
First choice of drug because of good patient
acceptability and cardio protective potential
All beta-blockers benefit angina of effort
Beta-blockers show suppressing activity for extra
systoles and tachycardia's especially for those which
mediated adrenergically
Act by preventing reinfaraction
Act by preventing sudden ventricular fibrillation at the
Second attack of MI

1) Essentials of Medical Pharmacology, 6th Edition ,page 142-143 (author : -K.D. Tripath
2) Determination of propranolol by HPLC-MS/Asian Journal of Pharmaceutical
Sciences 2009, 4 (3): 169-177
 Metabolism:-
It blocks adrenigically induced lipolysis and consequent increase it fatty acid level

 It specifically competes with beta-adrenergic receptor simulating agents for available

receptor sites

 Increase in LDL/HDL ratio observed in propranalol therapy is in heart

 inhibition of glycogenolysis in heart ,skeletal muscles and liver (inconstantly) due to

Adr release which occur during hypoglycmia

Metabolism of propranolol is done by three primary pathways (glucuronidation, side-chain

oxidation and ring oxidation).

no Effect on blood sugar level but prolong therapy of propranalol may reduce
carbohydrate tolerance

1) Essentials of Medical Pharmacology, 6th Edition ,page 138 (author : -K.D.

Tripathi)
2) http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d0a8c5d1-
bfc1-4829-bbf4-609e05e6d25c#nlm34089-3 (11/11/2010)
3) Partial metabolic clearances as determinants of the oral bioavailability of
propranolol, T. Walle, U. K. WALLE, L. S. OLANOFF & E. C. CONRADI,
 Metabolism:-
 Both ring oxidation and side-chain oxidation mediated by cytochrome P 450.

 Metabolism of CYP2C18, CYP2C9 catalysed by propranolol

In metabolism of propranolol UGT1A9, UGT2B7 enzymes are involved and they shows activity to
catalyse propranolol glucuronidation.

It has good absorption after oral administration but has low bioavailability due to high rate of first
pass metabolism

 a oral: parenteral ratio found is 40:1

 Metabolism of propranalol is hepatic blood flow dependent

Bioavialability of propranalol can be increased by administrating it with food.

 Food decreases its fist pass metabolism and increases its bioavailability in blood stream.
1) Essentials of Medical Pharmacology, 6th Edition ,page 138 (author : -K.D. Tripathi)
2) Partial metabolic clearances as determinants of the oral bioavailability of propranolol, T.
WALLE, U. K. WALLE, L. S. OLANOFF & E. C. CONRADI, (1986)
3) Stereoselective Metabolism of Propranolol Glucuronidation by Human UDP-
Glucuronosyltransferases 2B7 and 1A9, LUSHAN YU, MINRONG QIAN, YAO LIU,
TONGWEI YAO, AND SU ZENG, (2010)
Toxic Effects:-
Myocardial insufficiency and can precepitate CHF/edema by blocking sympathetic
support to the heart

Bradycardia

Chronic obstructive lung disease

Can particepate in life-threatening attack of bronchial asthma

 Carbohydrate tolerance may be impaired in prediabetics

 Alteration of plasma lipid profile alteration n prolong use

 Other side effects include lack of drive, nightmares, forgetfullness, rarely

hallucinations, sexual distress in male patient.

1) Essentials of Medical Pharmacology, 6th Edition ,page 139(author : -K.D.

Tripathi)
 Contraindications:-

 In asthmatics

 In partial or complete heart block

1) Essentials of Medical Pharmacology, 6th Edition ,page 139(author : -K.D.

Tripathi)
 Concentration in Blood:-
In 104 cases reported in literature the mean toxic (but non lethal) dose was 1.75 g
(Gross 1991) although survival has been reported after ingestion of 5 to 8 g

Toxic Dose Reported for Age

3 g. 28-year-old man
1.6 g 57-year-old man
70 mg 2-year-old child
100 mg 5-year-old child

An ingestion of 400 to 1,200 mg by a 3-year-old boy was uneventful after early induced
vomiting: the plasma level was 2.29 µg/L (Artman et al., 1982).

1) http://www.inchem.org/documents/pims/pharm/pim441.htm#SectionTitle:7.2
Toxicity (12/11/2010)
LD50 in mice:-

Route of Administration Dose (mg/kg)

Orally 565
Intravenous (iv) 22
Intraperitoneal (ip) 107

1) The Merck Index, fourteenth edition 2006, Merck Research Lbs., page no. 1348
 Analytical Determination Techniques:-

The mass spectra shown above is of the positive ion of propranolol (A)
and the IS (B) at a fragmentor voltage of 80 V. (IS=internal standard)

1) Determination of propranolol by HPLC-MS/Asian Journal of Pharmaceutical Sciences

2009, 4 (3): 169-177
 Analytical Determination Techniques:-

1) Determination of propranolol by HPLC-MS/Asian Journal of Pharmaceutical Sciences

2009, 4 (3): 169-177
 Analytical Determination Techniques:-
In the above slide ,

the LLOQ for propranolol in plasma (0.3 ng/ml) and the internal standard
(IS),(B),

plasma spiked with propranolol (30 ng/ml) and the internal standard(IS)
(C),

and

a sample of plasma of a healthy volunteer 5 h after (D)

a single oral administration 40 mg propranolol hydrochloride sustained-
release tablet: the plasma concentration of propranolol was estimated to
be 16.2 ng/ml

1) Determination of propranolol by HPLC-MS/Asian Journal of Pharmaceutical Sciences

2009, 4 (3): 169-177