PINDOLOL

Drugs in Pregnancy and Lactation.

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Name: PINDOLOL
Class: Sympatholytic (Antihypertensive)
Risk Factor:    BM*

Fetal Risk Summary

Pindolol, a nonselective b-adrenergic blocking agent, has been used for the treatment of hypertension occurring during pregnancy (1,2,3,4,5,6 and 7). Reproductive studies in rats and rabbits at doses exceeding 100 times the maximum recommended human dose (MRHD) found no evidence of embryotoxicity or teratogenicity (8). Impaired mating behavior and increased mortality of offspring were observed in female rats given doses 35 times the MRHD before and through 21 days of lactation (8). At 118 times the MRHD, increased fetal resorptions were noted (8).

A 1988 review compared the effects of b-blockers, including pindolol, in pregnancy and concluded that these agents are relatively safe (9) (see comment below).

Pindolol crosses the placenta to the fetus with maternal serum levels higher than cord concentrations (10). Cord:maternal serum ratios at 2 and 6 hours after the last dose were 0.37 and 0.67, respectively. Elimination half-lives in fetal and maternal serum were 1.6 hours and 2.2 hours, respectively.

The effect of pindolol on uteroplacental blood flow was studied in 10 women with pregnancy-induced hypertension given a 10-mg oral dose (11). A significant fall in the mean maternal blood pressure and mean arterial blood pressure occurred, but no significant changes were observed in maternal or fetal heart rates, uteroplacental blood flow index, or uteroplacental vascular resistance. In contrast, a 1992 study, comparing the effects of pindolol and propranolol in women with preeclampsia, found a significant reduction in uterine artery vascular resistance, prompting the authors to conclude that pindolol acted, at least in part, through a peripheral vascular mechanism (12).

No fetal malformations attributable to pindolol have been reported, but experience in the 1st trimester is lacking. In a study comparing three b-blockers for the treatment of hypertension during pregnancy, the mean birth weight of pindolol-exposed babies was slightly higher than that of the acebutolol group and much higher than that of the offspring of atenolol-treated mothers (3375 g vs. 3160 g vs 2745 g) (2). It is not known whether these differences were caused by the degree of maternal hypertension, the potency of the drugs used, or a combination of these and other factors.

The preliminary results of another study found that more than a third of the infants delivered from hypertensive women treated with pindolol were of low birth weight, but the authors thought this did not differ significantly from the expected rate for this population (3). In mothers treated with pindolol or atenolol, a decrease in the basal fetal heart rate was noted only in the atenolol-exposed fetuses (4). Additionally, in a prospective randomized study comparing 27 pindolol-treated women with 24 atenolol-treated women, no differences between the groups were found in gestational length, birth weight, Apgar scores, rates of cesarean section, or umbilical cord blood glucose levels (5). Treatment in both groups started at about 33 weeks' gestation.

A 1986 Reference described the comparison of pindolol plus hydralazine with hydralazine alone for the treatment of maternal hypertension (6). Treatment in both groups was started at about 25 weeks' gestation. The newborn outcomes of the two groups, including birth weights, were similar.

A 1992 report described the outcomes of 29 women with pregnancy-induced hypertension in the 3rd trimester (7). The women were randomized to receive either the cardioselective b-blocker atenolol (N=13), or the nonselective b-blocker pindolol (N=16). The mean maternal arterial blood pressure decrease in the two groups was 9 and 7.8 mm Hg, respectively (n.s.). In comparing before and after therapy, several significant changes were measured in fetal hemodynamics with atenolol but, except for fetal heart rate, no significant changes were measured with pindolol. The atenolol-induced changes included a decrease in fetal heart rate; increases in the pulsatility indexes (and thus, the peripheral vascular resistance) of the fetal thoracic descending aorta, the abdominal aorta, and the umbilical artery; and a decrease in the umbilical venous blood flow. Although no difference was observed in the birth weights in the two groups, the placental weight in atenolol-treated pregnancies was significantly less (529 g vs. 653 g, respectively).

An apparently significant drug interaction occurred when a woman, who was being treated with pindolol for preeclampsia, had indomethacin added for tocolysis to her therapy (13). Two weeks after starting pindolol, 15 mg/day, indomethacin was started with a 200-mg rectal loading dose followed by 25 mg daily for 5 days. A sudden rise in blood pressure (230/130 mm Hg) occurred on the 5th day with cardiotocographic changes in fetal vitality (13). A low-birth-weight newborn infant was delivered by cesarean section and the mother's blood pressure returned to normal (125/85 mm Hg) in the postpartum period. A similar interaction occurred in another patient who was being treated with propranolol (13).

b-Blockade in the newborn has not been reported in the offspring of pindolol-treated mothers. However, because this complication has been observed in infants exposed to other b-blockers (see Acebutolol, Atenolol, and Nadolol), close observation of the newborn is recommended during the first 24–48 hours after birth. Long-term effects of in utero exposure to b-blockers have not been studied but warrant evaluation.

Some b-blockers may cause intrauterine growth retardation and reduced placental weight (e.g., see Atenolol and Propranolol). Treatment beginning early in the 2nd trimester results in the greatest weight reductions. This toxicity has not been consistently demonstrated in other agents within this class, but the relatively few pharmacologic differences among the drugs suggests that the reduction in fetal and placental weights probably occurs with all at some point. The lack of toxicity documentation may reflect the number and type of patients studied, the duration of therapy, or the dosage used, rather than a true difference among b-blockers. Although growth retardation is a serious concern, the benefits of maternal therapy with b-blockers may, in some cases, outweigh the risks to the fetus and must be judged on a case-by-case basis.

[*Risk Factor D if used in 2nd or 3rd trimesters.]

Breast Feeding Summary

No reports have been located describing the use of pindolol during human lactation or measuring the amount, if any, excreted into breast milk. The manufacturer, however, states that pindolol is excreted in human milk (8). Because b-blockade has been observed in nursing infants exposed to other b-blockers (see Acebutolol and Atenolol), infants should be closely observed for bradycardia and other symptoms of b-blockade. Long-term effects of exposure to b-blockers from milk have not been studied but warrant evaluation.

References

  1. Dubois D, Petitcolas J, Temperville B, Klepper A. Beta blockers and high-risk pregnancies. Int J Biol Res Pregnancy 1980;1:141–5.
  2. Dubois D, Petitcolas J, Temperville B, Klepper A, Catherine PH. Treatment of hypertension in pregnancy with b-adrenoceptor antagonists. Br J Clin Pharmacol 1982;13(Suppl):375S–8S.
  3. Sukerman-Voldman E. Pindolol therapy in pregnant hypertensive patients. Br J Clin Pharmacol 1982;13(Suppl):379S.
  4. Ingemarsson I, Liedholm H, Montan S, Westgren M, Melander A. Fetal heart rate during treatment of maternal hypertension with beta-adrenergic antagonists. Acta Obstet Gynecol Scand 1984;118(Suppl):95–7.
  5. Tuimala R, Hartikainen-Sorri A-L. Randomized comparison of atenolol and pindolol for treatment of hypertension in pregnancy. Curr Ther Res 1988;44:579–84.
  6. Rosenfeld J, Bott-Kanner G, Boner G, Nissenkorn A, Friedman S, Ovadia J, Merlob P, Reisner S, Paran E, Zmora E, Biale Y, Insler V. Treatment of hypertension during pregnancy with hydralazine monotherapy or with combined therapy with hydralazine and pindolol. Eur J Obstet Gynecol Reprod Biol 1986;22:197–204.
  7. Montan S, Ingemarsson I, Marsal K, Sjoberg N-O. Randomized controlled trial of atenolol and pindolol in human pregnancy: effects on fetal haemodynamics. Br Med J 1992;304:946–9.
  8. Product information. Visken. Sandoz Pharmaceuticals, 1997.
  9. Frishman WH, Chesner M. Beta-adrenergic blockers in pregnancy. Am Heart J 1988;115:147–52.
  10. Grunstein S, Ellenbogen A, Anderman S, Davidson A, Jaschevatsky O. Transfer of pindolol across the placenta in hypertensive pregnant women. Curr Ther Res 1985;37:587–91.
  11. Lunell NO, Nylund L, Lewander R, Sarby B, Wager J. Uteroplacental blood flow in pregnancy hypertension after the administration of a beta-adrenoceptor blocker, pindolol. Gynecol Obstet Invest 1984;18:269–74.
  12. Meizner I, Paran E, Katz M, Holcberg G, Insler V. Flow velocity analysis of umbilical and uterine artery flow in pre-eclampsia treated with propranolol or pindolol. J Clin Ultrasound 1992;20:115–9.
  13. Schoenfeld A, Freedman S, Hod M, Ovadia Y. Antagonism of antihypertensive drug therapy in pregnancy by indomethacin? Am J Obstet Gynecol 1989;161:1204–5.

Index

Q&A about Pindolol

samantha k
Does anyone take pindolol and it causes you to be unable to sleep?
taken for heart condition
L_H Qutub(Retired)
Possible as side effect, have yourself reviewed by your doctor.
MRCarroll B
Other conditions for use of Pindolol?
Can this product be used as a dieretic? I'm on 1/2 of 5MG two times daily. I did have Heart Surgery July 1983. I do take vitimans and try for the most part to eat healthy. I am 66" tall weight is between 155 to 158 daily after arising inthe AM. My waist measurement was 36" but I wear 33 waist trousers.
nicedoc
Pindolol is a beta-blocker and not a diuretic.
koifox_1...
is anyone taking pindolol?
have you had or noticed any problems with this beta blocker? thanks!
Tony
pindolol (Visken), is a beta-blocker like you said, but it's rarely used. Sorry I couldn't help you. This drug, however, is a little more expensive than the others.
Question...
What diet aids can I take while taking beta blockers for my heart condition?
I am on Pindolol- weight gainor
Just the Facts, Ma'am
icv76 - You should speak to your doctor about this, but I am glad you are asking the question at least. I do agree with ChornayaKiska and mdel that improving your diet and exercise regimen should be the FIRST steps towards achieving a healthy weight. However, some people do require additional help, and this is best done under the supervision of a physician. There are some diet aids that you can take, but they are largely going to be the ones available by prescription only. The over-the-counter diet aids that you see advertised are virtually all stimulants that help you to "burn calories". Many advertise that they are ephedra-free, but use herbal supplements that are known to be stimulants. They can cause your heart rate and blood pressure to increase to varying degrees. Unfortunately, this goes directly against what beta-blockers are meant to accomplish. They block some of the effects of adrenaline to keep your blood pressure and heart rate under control. Taking these supplements while you are on beta-blockers is like stepping on the gas and the brakes at the same time. There are a few prescription diet aids that you can ask your doctor about. They are not stimulants and will not work against the beta blocker, but can either help to reduce your appetite (Meridia) or reduce your GI absorption of dietary fat (Xenical). Another promising drug that should be available in the US soon is rimonabant. I can't say if any of these may be appropriate for you, but your doctor should be able to make some recommendations.
MRCarroll B
Other conditions for use of Pindolol?
Can this product be used as a dieretic? I'm on 1/2 of 5MG two times daily. I did have Heart Surgery July 1983. I do take vitimans and try for the most part to eat healthy. I am 66" tall weight is between 155 to 158 daily after arising inthe AM. My waist measurement was 36" but I wear 33 waist trousers. Age is 75 yrs. I am active do my own yard work, takes about 1 hr. week. I do about any thing I want to I do not use tobaco and very little alchol. My meds include 90 MG thyroid daily, 150 MG Rantidine twice daily, Flownaze once daily and Combvent twice daily.
ilse72
Pindolol has no diuretic effects. It is used to lower the blood pressure but has no effect on removing or preventing water retention.

It is a beta blocker ordered to block the effects of epinephrine and adrenalin on the heart and blood vessels. This in turn lowers the blood pressure, reduces the strain on the heart and lowers the heart rate.

The primary reasons it is prescribed it to lower blood pressure or to treat angina.