Propranolol

Brand Names: Inderal

Clinical Names: Propranolol

Summary

generic name: Propranolol

trade name: Inderal®

type of drug: Controlled release beta-adrenergic receptor blocking agent (beta blocker).

used to treat: Hypertension; angina pectoris, preventively; cardiac arrhythmias, especially supraventricular arrhythmias; tachyarrhythmias of digitalis intoxication; resistant tachyarrhythmias due to excessive catecholamine action during anesthesia; post-myocardial Infarction, for the reduction of cardiovascular mortality in patients who have survived the acute phase; migraine headache prevention; essential tremor; hypertrophic subaortic stenosis; adjunctive therapy for pheochromocytoma

overview of interactions:
• nutrient affecting drug performance: Vitamin C (Ascorbic Acid)

• nutrient affecting drug toxicity: Coenzyme CoQ10 (Ubiquinone)

• diet affecting drug performance: Alcohol

• diet affecting drug performance: Food

• herb affecting drug performance: Commiphora mukul (Guggul)

• herb affecting drug performance: Piperine, as in Pepper (Piper nigrum, Piper longum)



Interactions

nutrient affecting drug performance: Vitamin C (Ascorbic Acid)

• research: Ascorbic acid has been found to slow absorption and first pass metabolism of inderal, reduce plasma concentrations and lower urinary excretion of propranolol and its metabolites.
(Gonzalez JP, et al. Eur J Clin Pharmacol 1995;48(3-4):295-297.)

• nutritional concerns: Individuals using propranolol should not supplement with high doses of Vitamin C (greater than 2000 mg per day) without first consulting the prescribing physician and/or a nutritionally-trained healthcare provider. Caution is advised as no definitive research has demonstrated the safety of combining these two substances.

nutrient affecting drug toxicity: Coenzyme CoQ10 (Ubiquinone)

• mechanism: Propranolol inhibits enzymes dependent on Coenzyme Q1O (CoQ10).

• nutritional support: One study found that 60 mg of CoQ1O per day significantly reduced symptoms induced by propranolol.
(Hamada, M, et al. 1984,263-270.)

diet affecting drug performance: Alcohol

• research: Researchers have found alterations in propranolol absorption secondary to concomitant ethanol administration. With alcohol administration, there was an increase in the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (CPmax). Ethanol caused a decrease in the rate of absorption and an increase in the rate of elimination of propranolol. Furthermore, reducing liver blood flow propranolol may reduce the systemic clearance of other high extraction drugs may reduce systemic clearance of alcohol and increase other effects of alcohol by reducing liver blood flow.
(Grabowski BS, et al. Int J Clin Pharmacol Ther Toxicol 1980 Jul;18(7):317-319.)

• nutritional concerns: Propranolol is known to cause drowsiness or dizziness. Individuals who use alcohol while they are taking propranolol use of alcohol may experience increased dizziness. Combining propranolol and alcohol should be avoided due to the increased risk associated with these enhanced side effects.

diet affecting drug performance: Food

• research: The simultaneous ingestion of food and propranolol can result in enhanced absorption and bioavailability of propranolol.  High-protein foods may interfere with propranolol metabolism, increasing propranolol blood levels and activity.
(Liedholm H, Melander A. Clin Pharmacol Ther 1986 Jul;40(1):29-36; Threlkeld DS, ed. Feb 1993; Holt GA. 1998, 225; Dongowski G, et al. Pharmazie 1998 Dec;53(12):871-875.)

• nutritional concerns: Propranolol should be taken consistently, at the same time each day, always with or always apart from food. Individuals taking propranolol who are concerned with potential dietary effects on their medication should consult with their prescribing physician and/or pharmacist.

herb affecting drug performance: Commiphora mukul (Guggul)

• research: Dalvi et al found that a single oral dose of 1 gm gugulipid significantly reduced bioavailability of single oral dose of propranolol (40 mg) in 10 normal healthy male volunteers. Such interaction due to gugulipid consumption, as extract or potentially as whole herb, may lead to diminished efficacy or nonresponsiveness in individuals receiving propanolol.
(Dalvi SS, et al. J Assoc Physicians India 1994 Jun;42(6):454-455.)

herb affecting drug performance: Piperine, as in Pepper (Piper nigrum, Piper longum)

• research: Black peppers contain a substance called piperine. In a human study Bano et al observed increased blood levels of propranolol in subjects given 20 mg of piperine daily for 7 days.
(Bano G, et al. Eur J Clin Pharmacol 1991;41:615-617.)

• herbal synergy: Though this interaction in a research setting may lack strong relevance to the typical dietary consumption of pepper, it could have therapeutic value. In clinical practice, the enhanced systemic availability of propranolol could conceivably be used to reduce doses and side effects, achieve better therapeutic control, and improve patient compliance. Further research will determine whether these potential benefits will bear out. In the meantime, individuals using propranolol should not change their dose of the medication without consulting their prescribing physican.

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References

Bano G, Raina RK, Zutshi U, Bedi KL, Johri RK, Sharma SC. Effect of piperine on bioavailability and pharmocokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41(6):615-617.
Abstract: The effect of piperine on the bioavailability and pharmacokinetics of propranolol and theophylline has been examined in a crossover study. Six subjects in each group received a single oral dose of propranolol 40 mg or theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7 days. An earlier tmax and a higher Cmax and AUC were observed in the subjects who received piperine and propranolol. It produced a higher Cmax, longer elimination half-life and a higher AUC with theophylline. In clinical practice, the enhanced systemic availability of oral propranolol and theophylline could be exploited to achieve better therapeutic control and improved patient compliance.

Dalvi SS, Nayak VK, Pohujani SM, Desai NK, Kshirsagar NA, Gupta KC. Effect of gugulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India 1994 Jun;42(6):454-455.
Abstract: The effect of single oral dose of 1 gm gugulipid was studied on bioavailability of single oral dose of propranolol (40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male volunteers respectively. It was a randomised within group crossover study. Blood samples were collected at hourly intervals upto 8 hrs. Gugulipid significantly reduced (P < .01) peak
plasma concentration (Cmax) and area under curve (AUC 0-8 hrs) of both the drugs in normal volunteers. Such interaction in patients receiving propanolol or diltiazem with gugulipid may lead to diminished efficacy or nonresponsiveness due to significant reduction in bioavailability.

Dongowski G, Neubert RH, Platzer M, Schwarz MA, Schnorrenberger B, Anger H. Interaction between food components and drugs. Part 6: Influence of starch degradation products on propranolol transport. Pharmazie 1998 Dec;53(12):871-875.
Abstract: Interactions between different starch degradation products and propranolol (P) were studies using permeation experiments and affinity capillary electrophoresis (ACE). In the presence of maltooligosaccharides (MO), the transport of P across artificial lipid membranes was retarded. The most intensive interaction with the drug was found in the presence of the not-debranched MO from maize starch. The electrophoretic mobility mu of the drug was decreased in dependence of the MO concentration. However calculation of equilibrium binding constants from the ACE experiments was not possible because of the relatively weak influence of starch degradation products on the electrophoretic behaviour of the drug. With both methods the same tendency in strength of interactions between the different MO and P was found. Molecular parameters of the MO and their viscosity play a role in the interactions and in the decreased permeation of the drug.

Gonzalez JP, Valdivieso A, Calvo R, Rodriguez-Sasiain JM, Jimenez R, Aguirre C, du Souich P. Influence of vitamin C on the absorption and first pass metabolism of propranolol. Eur J Clin Pharmacol 1995;48(3-4):295-297.
Abstract: The effect of ascorbic acid on the availability of propranolol has been examined. After oral administration of propranolol 80 mg with or without ascorbic acid pretreatment (2 g), the plasma concentrations and urinary excretion of propranolol and its metabolites, 4-hydroxy-propranolol and propranolol-conjugated, were determined by HPLC. Compared to controls, vitamin C decreased the maximum concentration of propranolol from 463 to 334 nmol.l-1, and the area under the propranolol concentration-time curve (from 0 to 24 hours) from 3.13 to 1.96 mumol.l-1.h. The time to reach maximum propranolol concentration was increased from 1.9 to 2.7. The total amount of drug recovered in urine has also significantly diminished (from 12.6 to 4.29 mg). No change in elimination rate was observed, indicating that ascorbic acid had affected both the absorption process and the first pass metabolism. The heart-rate decreased less when propranolol was administered with ascorbic acid in comparison to control subjects, although this interaction has little biological importance.

Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol 1980 Jul;18(7):317-319.
Alterations in propranolol absorption secondary to concomitant ethanol administration was investigated in five normal adults. With alcohol administration, there was an increase in the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (CPmax). Ethanol caused a decrease in the rate of absorption and an increase in the rate of elimination of propranolol. It appears that the acute, concomitant administration of alcohol with propranolol will alter the bioavailability of propranolol.

Hamada, M, Kazatain, Y, Ochi, T, et al. Correlation between serum CoQ1O level and myocardial contractility in hypertensive patients. In Biomedical and Clinical Aspects of Coenzyme Q, vol 4, Ed. Folkers, K, Yaniamnra, Y. Amsterdam: Elsevier, 1984,263-270.

Holt GA. Food and Drug Interactions. Chicago: Precept Press, 1998, 225.

Liedholm H, Melander A. Concomitant food intake can increase the bioavailability of propranolol by transient inhibition of its presystemic primary conjugation. Clin Pharmacol Ther 1986 Jul;40(1):29-36.
Abstract: The influence of concomitant food intake on the bioavailability and presystemic primary conjugation of propranolol (80 mg) was studied in 11 healthy women. Food increased the maximum serum concentration and serum AUC of propranolol (P less than 0.05) and reduced those of conjugated propranolol (P less than 0.05). The mean AUC ratio of conjugated/unchanged propranolol was 13:1 in the fasting state but only about 6:1 in the nonfasting state (P less than 0.001). The time to maximum serum concentration and the t1/2 were not affected by food. There was no influence of food on any kinetic parameter of propranolol or conjugated propranolol when a slow-release formulation was used. We conclude that concomitant food intake can evoke a short-lasting, delivery rate-dependent inhibition of the presystemic primary conjugation of propranolol. This is one, but not the sole, mechanism by which food can enhance propranolol bioavailability.

Neubert R, Fritsch B, Dongowski G. Interactions between food components and drugs. Part 3. Interactions between pectin and propranolol. Pharmazie 1995 Jun;50(6):414-416.

Threlkeld DS, ed. Diuretics and Cardiovasculars, Beta-Adrenergic Blocking Agents. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1993.