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Interactions Between Beta-Blockers and Ephedrine or Amphetamines
by Anon Doc
May 16, 2004
There is a concern that it could be dangerous to take beta-blockers such as Atenolol or Propranolol with adrenergic stimulants such as amphetamines or ephedrine because they act on (agonize/activate) both alpha- and beta-adrenergic receptors. There are reasons to be concerned about high doses of the combinations of these, but there is little evidence of real world harms caused by combining the two.

According to an unreferenced page on Yahoo Health, "Use of amphetamines with beta-blocking agents may increase the chance of high blood pressure and heart problems." The reasoning behind this type of warning is based on the action of the different adrenergic receptors. The alpha-adrenergic receptors control vasoconstriction while beta-adrenergic receptors control vasodilation. If a beta-selective chemical blocks the beta-adrenoceptors while leaving the alpha-receptors unaffected and a stimulant is taken that would normally act on both alpha- and beta-receptors, there is the potential to cause a dangerous imbalance.

Caution when combining strong stimulants and beta-blockers is warranted, but it's important to keep the risk in perspective. Many people use Propranolol after taking a variety of stimulants, including Ephedrine. The beta-blockers are often used to counter the jittery and agitating feelings that can accompany physical stimulation. Erowid has received a number of reports from people who have used these in combination without any reports of serious complications. The possible downsides, however, could be extremely serious including heart failure and death.

The following are some notes about the issue:

  1. Ephedrine is commonly used to treat asthma and Propranolol should almost never be used by asthma patients. If anything Propranolol represents a higher risk than Atenolol.
  2. There is no specific contraindication listed for the combo (of Ephedrine and a variety of beta blockers) in several prescribing texts I checked with. Nor did I find "drug interactions" reported in the two med interaction data base services I checked. Caution is sometimes recommended, but usually because of "decreased bronchodilation effects of Ephedrine. Sometimes there is the recommendation to inform a physician (if you add Inderal to Ephedrine) but no specific warnings.

    Somewhat typical of the kind of warnings noted is:
    "Ephedra (commonly known as ma huang) contains a compound called ephedrine. Taking nadolol completely blocks the increase in both heart rate and blood sugar usually observed in people taking ephedrine, but it does not completely affect its ability to increase calorie-burning. Consequently, nadolol may reduce the potential effectiveness of ephedra in and may eliminate other beneficial effects of ephedra, such as the reduction of [asthma] symptoms. More research is needed to explore the interactions (of Nadolol) between ephedra and amphetamines."
  3. I have seen sporadic reports of increases or the rare possibility of decreases of blood pressure with the combo.
  4. Propranolol may be a treatment for hyperthermia sometimes associated with Ephedra and similar agents, as noted below:

    Yamahara J, Kimata M, Sawada T, Fujimura H.
    Possible involvement of beta- 2-adrenoceptors in hyperthermic effect of l-ephedrine in rats.
    J Pharmacobiodyn. 1985 Aug;8(8):591-6.

    The experiments were conducted in order to examine the mechanism of hyperthermia induced by l-ephedrine in rats. beta-Adrenoceptor agonists have been known to enhance normal body temperature. Therefore, the effect of various beta-adrenoceptor agonists on body temperature in rats was examined to clarify the mechanism of action of l-ephedrine. The results showed that drugs with beta- 2-adrenoceptor agonist activity and l-ephedrine caused hyperthermia in rats and this effect was selectively inhibited by pretreatment of animals with propranolol (a mixed beta-adrenoceptor antagonist) or butoxamine (a selective beta- 2-adrenoceptor antagonist). These results suggest that hyperthermic action of l-ephedrine may largely be due to its effect on beta-adrenoceptors.
  5. Ephedrine by itself has resulted in some amount of cardiovascular toxicity. Some have recommended Propranolol as treatment for resulting tachycardia. Here's a somewhat contradictory recommendation:

    "... especially in patients without a history of hypertension. Vasodilators, such as phentolamine, nitroprusside, hydralazine and nifedipine, are the preferred agents for treating ephedra-associated hypertension.(2,5) B-blockers should not be used alone to treat hypertension because a hypertensive crisis may result from the unopposed effects of the a1-receptors on the vasculature. Tachyarrhythmias are usually responsive to treatment with lidocaine, low-dose propranolol or esmolol.(2,5,14)"

    And "Ma huang: All natural but not always innocuous by Charlotte Means, DVM, MLIS" to treat overdose or toxic reactions of ephedra:
    "Propranolol (0.02 to 0.06 mg/kg slowly intravenously) or other beta-blockers can be used to control tachycardia."
    On the other hand in a discussion of interactions the following is noted:
    "One of the ingredients in ma huang is ephedrine, an active alpha- and beta-adrenergic stimulant that produces increases in heart rate, blood pressure, and cardiac output. Ma huang has been reported to cause hypertension, hepatitis, nephrolithiasis, and sudden death in healthy, normotensive people."- Mil Med 2002 Jun;167(6):521-3 -- A mysterious blood pressure increase in a drilling Naval reservist. -- Wettach GE, Falvey SG.
  6. For what it's worth, even though Ephedrine OD is considered a possible etiology for pediatric tachycardia, propranolol is still listed as a recommended treatment.
  7. It should be kept in mind that beta-blockers are used in eye drops to treat glaucoma and may achieve some small systemic levels. Also "beta-blockers" vary in their selectivities and actions and may actually block alpha and beta receptors to varying degrees.