Drug interactions of Beta blockers and Alpha blockers

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V. Alpha blockers and beta blockers:

Alpha blockers were found to exhibit differential interactions with beta blockers; the critical factor being the drug which was administered first. Intensity and likeliness of interaction were found to differ among the drugs of the same class. Tamsulosin has no clinically significant effect on interaction with the beta blockers and so was the case with Doxazosin, except postural hypotension occurred with the latter, which is an established effect. [1]

Clinical significance:

  • Marked hypotensive reaction was observed in 3 out of 6 patients who were under alprenolol medication, when they were given a combination therapy of prazosin and alprenolol. But the interaction was observed only when the order of administration was prazosin first and alprenolol next.[2]
  • No fall in blood pressure was observed when patients taking prazosin were administered a combination therapy of prazosin and alprenolol with alprenolol being administered first. [2]
  • In the case of normotensive subjects taking prazosin, the severity of first dose effect normally observed with the drug was much more pronounced when a single dose of propanolol was given simultaneously. [3]
  • Administration of tamsulosin in patients receiving atenolol had no clinically significant effects on blood pressure. Also, there wasn't any appreciable lowering of blood pressure when the dose was increased. [4]
  • In an interesting study involving patients using terazosin for the treatment of hypertension, it was found that:

When a betablocker was added to the treatment, there was lowering of blood pressure only if the blood pressure remained uncontrolled by terazosin. No change in blood pressure was observed in normotensive patients. [5]

  • A similar situation was observed in patients using betablockers, to whose treatment, terazosin was added.
  • For drugs such as Alfuzosin, Indoramin; simultaneous administration with betablockers necessitates the need of dose titration of the latter. [6]
  • Absence of enhanced blood pressure lowering in the case of Doxazosin was observed. [7]

Mechanism:

Compensatory effect of blood pressure regulation which follows after the first dose effect is diminished by the concurrent administration of beta blocker leading to enhanced hypotensive effect. Absence of any significant effect in the case of tamsulosin can be attributed to its selectivity towards alpha receptors in the prostate gland.

Conclusions:

  • It is an established interaction.
  • When alpha blockers are to be included in the dosage regimen containing beta blockers; the dose of beta blockers is to be reduced to a maintenance dose level. This point holds true when beta blockers are to be included in the dosage regimen containing alpha blockers.
  • Administration of the first dose of alpha blockers before going to bed is recommended.
  • Management of postural hypotension by adopting simple measures (i.e. to lie down, raise the legs and get up slowly) is essential.

References:

    1. Stockley's drug interactions, 7th edition; Pharmaceutical press.68-69 [access date: 9th October, 2010]
    2. Seideman P, Grahnen A, Haglund K, Linstrom B, von Bahr C. Prazosin first dose phenomenon during combined treatment with a beta adrenoceptor in hypertensive patients. Br J Clin Pharmacol (1982) 13, 865-70 [access date: 9th October, 2010]
    3. Elliott HL, McLean K, Sumner DJ, Meredith PA, Reid JL. Immediate cardiovascular esponses to oral Prazosi-effects of beta blockers. Clin Pharmacol Ther (1981) 82, 373-9 [access date: 9th October, 2010]
    4. Lowe FC. Coadminstration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect. Clin Ther (1997) 19, 730-42 [access date: 9th October, 2010]
    5. Kirby Rs. Terazosin in benign prostatic hyperplasia: effects on blood pressure in normotensive and hypertensive men. Br J Urol (1998) 82, 373-9 [access date: 9th October, 2010]
    6. Xatral(Alfuzosin). Sanofi-Aventis. UK Summary of product characteristics, March 2003. Uroxatral(Alfuzosin). Sanofi-Synthelabo Inc. US Prescribing information. June 2003. Doralese(Indoramin). GlaxoSmithKline UK. UK Summary of product characteristics, December 2003 [access date: 9th October, 2010]
    7. Cardura(Doxazosin). Pfizer Ltd. UK Summary of product characteristics, May 2003. Cardura(Doxazosin). Pfizer Inc. US prescribing information, April 2002 [access date: 9th October, 2010]

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    About the Author

    Niklesh Rao V's picture
    Author: Niklesh Rao V

    Comments

    Prof. J. Vijaya Ratna's picture

    Dear Niklesh I have seen many B.P patients and the drugs mostly used by doctors in A.P are amlodipine, frusemide, atenelol and nifedipine. Why don't you search and come out with some interactions involving some commonly used antihypertensives? Please explain the interaction between grapefruit juice and antihypertensives. Please give a picture of grapefruit if you can, If you talk about some great patented, obscure drugs, well, we can't relate with them. Vijaya Ratna
    Uma Pratyusha's picture

    Dear Niklesh, Please tell me the mechanism of how beta blockers lower the blood pressure?

    Regards

    Uma Prathyusha

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