propranolol presentation final

PropranolPropranololol

• Molecular and Vishnu Shinde

Cellular Toxicology (SMA0052) U1073020

1) http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4946&loc=ec_rcs

Chemical Structure:-

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)

Physical properties:-

1) Essentials of Medical Pharmacology, 6th Edition ,page 142-143 (author : -K.D. Tripathi)2) Determination of propranolol by HPLC-MS/Asian Journal of Pharmaceutical Sciences 2009, 4 (3): 169-177

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 reinfaractionAct by preventing sudden ventricular fibrillation at the Second attack of MI

Usage:-

Hypertension:-

Angina pectoris:-

Cardiac arrhythmias:-

Myocardial infarction:-

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, (1986)

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)

Metabolism:-

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)

Toxic Effects:-

In asthmatics In asthmatics

In partial or complete heart block In partial or complete heart block

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

Contraindications:-

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

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)

Toxic Dose Reported for Age 3 g. 28-year-old man1.6 g 57-year-old man70 mg 2-year-old child

100 mg 5-year-old child

Concentration in Blood:-

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

LD50 in mice:-

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:-

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



propranolol presentation final

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