Hydralazine

 Risk Factor: CM
 Class: CARDIOVASCULAR DRUGS / Vasodilators

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

No reports linking the use of hydralazine with congenital defects have been located. In England, hydralazine is the most commonly used antihypertensive agent in pregnant women (1). Neonatal thrombocytopenia and bleeding secondary to maternal ingestion of hydralazine have been reported in three infants (2). In each case, the mother had consumed the drug daily throughout the 3rd trimester. This complication has also been reported in series examining severe maternal hypertension and may be related to the disease rather than to the drug (3,4).

Hydralazine readily crosses the placenta to the fetus (5). Serum concentrations in the fetus are equal to or greater than those in the mother.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 8 of which had 1st trimester exposure to hydralazine (6, p. 372). For use anytime during pregnancy, 136 cases were recorded (6, p. 441). No defects were observed with 1st trimester use. There were 8 infants born with defects who were exposed in the 2nd or 3rd trimesters. This incidence (5.8%) is greater than the expected frequency of occurrence, but the severe maternal disease necessitating the use of hydralazine is probably responsible. Patients with preeclampsia are at risk for a marked increase in fetal mortality (7,8,9 and 10).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 40 newborns had been exposed to hydralazine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (2.5%) major birth defect was observed (two expected), a hypospadias (none expected).

A number of studies involving the use of hydralazine either alone or in combination with other antihypertensives have found the drug to be relatively safe for the fetus (4,7,8,9,10,11,12,13,14,15,16 and 17). Fatal maternal hypotension has been reported in one patient after combined therapy with hydralazine and diazoxide (18). Two reports published in 1989 associated adverse effects in the fetus and newborn with maternal hydralazine therapy (19,20).

In a woman with chronic hypertension maintained on methyldopa, an increase in blood pressure at about 35 weeks' gestation prompted the addition of hydralazine, 25 mg twice daily, to the treatment regimen (19). Fetal premature atrial contractions were diagnosed 1 week later, but tachyarrhythmias, which can be initiated by premature atrial contractions, were not observed (19). Hospitalization with bed rest allowed the patient's blood pressure to decline enough to discontinue hydralazine therapy. Within 24 hours of stopping hydralazine, the fetal arrhythmia resolved. The infant was delivered at 38 weeks and cardiac evaluation after discharge at 3 days indicated a regular heart rate. A syndrome resembling lupus erythematosus was diagnosed in a 29-year-old woman treated with IV hydralazine during the 28th week of pregnancy (20). The patient received 425 mg during a 6-day period for the treatment of hypertension. IV methyldopa was administered on the 6th day of therapy. Labor was induced for fetal distress and a 780-g growth-retarded male infant was delivered vaginally. The infant expired at 36 hours of age secondary to cardiac tamponade induced by 7 mL of clear sterile transudate in the pericardial space. Lupus-like symptoms consisting of macular rash, arthralgia, and bilateral pleural effusion developed in the mother on the 5th day of hydralazine therapy and gradually resolved after discontinuance of the drug and delivery. The findings of pericardial effusion and cardiac tamponade in the infant were also thought to represent clinical evidence of a lupus-like syndrome (20). The symptoms in both the mother and fetus were attributed to hydralazine sensitivity resulting in the induction of a lupus-like syndrome.

Breast Feeding Summary

Hydralazine is excreted into breast milk (5). In one patient treated with 50 mg 3 times daily, the milk:plasma ratio 2 hours after a dose was 1.4. This value is in close agreement with the predicted ratio calculated from the pKa (21). The available dose of hydralazine in 75 mL of milk was estimated to be 13 g (5). No adverse effects were noted in the nursing infant from this small concentration. The American Academy of Pediatrics considers hydralazine to be compatible with breast feeding (22).

References

1. de Swiet M. Antihypertensive drugs in pregnancy. Br Med J 1985;291:3656.
2. Widerlov E, Karlman I. Storsater J. Hydralazine-induced neonatal thrombocytopenia. N Engl J Med 1980;303:1235.
3. Brazy JE, Grimm JK, Little VA. Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy. J Pediatr 1982;100:26571.
4. Sibai BM, Anderson GD. Pregnancy outcome of intensive therapy in severe hypertension in first trimester. Obstet Gynecol 1986;67:51722.
5. Liedholm H, Wahlin-Boll E, Ingemarsson I, Melander A. Transplacental passage and breast milk concentrations of hydralazine. Eur J Clin Pharmacol 1982;21:4179.
6. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
7. Bott-Kanner G, Schweitzer A, Schoenfeld A, Joel-Cohen J, Rosenfeld JB. Treatment with propranolol and hydralazine throughout pregnancy in a hypertensive patient. Isr J Med Sci 1978;14:4668.
8. Pritchard JA, Pritchard SA. Standardized treatment of 154 consecutive cases of eclampsia. Am J Obstet Gynecol 1975;123:54352.
9. Chapman ER, Strozier WE, Magee RA. The clinical use of Apresoline in the toxemias of pregnancy. Am J Obstet Gynecol 1954;68:110917.
10. Johnson GT, Thompson RB. A clinical trial of intravenous Apresoline in the management of toxemia of late pregnancy. J Obstet Gynecol 1958;65:3606.
11. Kuzniar J, Skret A, Piela A, Szmigiel Z, Zaczek T. Hemodynamic effects of intravenous hydralazine in pregnant women with severe hypertension. Obstet Gynecol 1985;66:4538.
12. Hogstedt S, Lindeberg S, Axelsson O, Lindmark G, Rane A, Sandstrom B, Lindberg BS. A prospective controlled trial of metoprolol-hydralazine treatment in hypertension during pregnancy. Acta Obstet Scand 1985;64:50510.
13. Gallery EDM, Ross MR, Gyory AZ. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. Br Med J 1985;291:5636.
14. Horvath JS, Korda A, Child A, Henderson-Smart D, Phippard A, Duggin GG, Hall BM, Tiller DJ. Hypertension in pregnancy: a study of 142 women presenting before 32 weeks' gestation. Med J Aust 1985;143:1921.
15. 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;22:197204.
16. Mabie WC, Gonzalez AR, Sibai BM, Amon E. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987;70:32833.
17. Owen J, Hauth JC. Polyarteritis nodosa in pregnancy: a case report and brief literature review. Am J Obstet Gynecol 1989;160:6067.
18. Henrich WL, Cronin R, Miller PD, Anderson RJ. Hypotensive sequelae of diazoxide and hydralazine therapy. JAMA 1977;237:2645.
19. Lodeiro JG, Feinstein SJ, Lodeiro SB. Fetal premature atrial contractions associated with hydralazine. Am J Obstet Gynecol 1989;160:1057.
20. Yemini M, Shoham(Schwartz) Z, Dgani R, Lancet M, Mogilner BM, Nissim F, Bar-Khayim Y. Lupus-like syndrome in a mother and newborn following administration of hydralazine: a case report. Eur J Obstet Gynecol Reprod Biol 1989;30:1937.
21. Daily JW. Anticoagulant and cardiovascular drugs. In Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia:ADIS Press, 1981:614.
22. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

Questions and Answers

Why is it that you shouldnt take hydralazine if you have peptic ulcer disease?, Does hydralazine make the condition worse? Or is it because of interactions of hydralazine with other drugs that patients may be on at the same time e.g. cimetidine, which effects metabolism of hydralazine?

Thanks

Hydralazine doesn't interact with cimetidine.

It is a smooth muscle relaxant though and with peptic ulcers is contraindicated as it relaxes the muscles which helps allow acid to wash into the peptic area, making ulcers worse.

What would happen if a perscription for hydroxyzine was misfilled with hydralazine and vice versa?, I'm writing a story about a misfilled perscription and I need a pharmacist or medical professionals take on what would happen if these two common names were mixed up. I was unable to find much on a basic search except injury law websites. I'd like the medical details please.

The stock bottles try and make the difference clear. Hydroxyzine is an anti-histamine, and hydralazine is a blood pressure medication. Most of the time the pharmacy will refund the money and give the correct prescription for free. Most people are happy with that. Sometimes you throw in a gift card. Go to some of the pharmacy organizations websites, and they'll have stories about this. APhA's website is http://www.pharmacist.com

Why does isosorbide dinitrate and hydralazine work in treating congestive heart failure in african americans?, Results from the African-American Heart Failure Trial suggested a strong improvement. I just want to know whether there are any biological justifications found.

Seems all very muddy at this stage but there are some findings....

Firstly in 2001, the prevalence of HF was 40% more common in black males than white males (3.5% vs 2.3%) and twice as common in black females as white females (3.1% vs 1.5%).

In this debate, one issue that is commonly confused is the difference between race and ancestry. Ancestry refers to objective genetic relationships between individuals and among populations, whereas race has always been a somewhat arbitrary definition of population boundaries. For example, while an individual might have ancestors from Europe, Africa, and North America, he or she still might be categorized as an African American. Therefore, race captures some biological information about ancestry, but it is not equivalent to ancestry.

Yet clinicians often want to know whether it is valid and reliable to use race as a proxy to infer an individual's genetic risk for disease and treatment response. Whether race matters is, however, complicated because it depends on the relationship between the genetic risk factor, ancestry, and race. For example, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors for hypertension treatment may not work as well, on average, in African Americans compared with European Americans, but both types of drugs appear to work perfectly well in a large fraction of African Americans and poorly in some European Americans.

The observation might be explained by a hypothetical genetic predictor of positive response to ACE inhibitors that is common in European Americans but that is also present in some African Americans because of admixture and absent in some European Americans. In such a case, the best predictor of treatment response might be the presence of the variant (ie, direct testing); the next best might be an accurate estimator of genetic ancestry, and race might be only a poor predictor of genetic risk and therefore treatment response.

Does hydralazine block the vagus nerve?,

You better believe it does.....

what is the drug hydralazine used for?, take one every six hours, 25mg tablets

Hydralazine is used to treat severe hypertension of unknown cause when there is an urgent need to lower blood pressure.

frequency of hydralazine HCl?,

you should add more details to this query.

what do you mean?

takes hydralazine.

I have severe refractory edema from CHF - I value hearing your insights?, I got CHF after MASSIVE MI post car crash. Today, my Ejection fraction is 50% & holding steady. My kidney functions, creatinine clearance, albumin, liver panel & lipids are fine. 9 months after car crash, I thought myself stable. slowly, urination dwindled & fluids swelled up throughout lower trunk & liver area. I am nauseous, can barely drink a bit of liquid. I can't sleep lying down, breathing worsens, I sleep standing up,(U figure) I gasp upon exertion, mild activity, I have legs rigid and swollen like pressurized balloon. AM in agony from pain. Drs gave me torsemide diuretic. Totally failed to expel fluids. (btw I take lisinopril & hydralazine for HTN) Tell me, someone, anyone, when diuretics fail, & fluid swells the body, what are possible treatments? I won't enter hospital;- I'm terrified,uninsured & I've been told that diuretics are their only reliance also. Any uncommon meds U know of for outpatients? If I am hopeless, how will my death come about?? PRAY FOR ME, PLEASE!

To be honest, ir oral torsemide isn't cutting it any more then you're probably stuck needing an IV diuretic. If you can still afford to see your doctor (even if you can't afford to be hospitalized), you might want to ask to add zaroxylyn (a different type of oral diuretic) to take before the torsemide--it can help to potentiate it. Strict blood pressure control with the hydralazine and lisinopril will also in the long run help you to mobilize fluids. It doesn't sound like salt or fluid restriction will help much at this point.

Just saw your update--if you're not getting any urine output from torsemide, you're absolutely right, you're not perfusing your kidneys well enough right now. Yes, if I were admitting you to the hospital, I'd use IV toresemide, but it gets absorbed about 2-3x as well as oral torsemide, as when you're in florid CHF your gut become swollen and can't absorb meds. At this point aldactone, while an excellent med, won't give you the diuresis you need. I've seen a lot of patients turn around with a few days of IV torsemide. That being said, if your kidneys aren't working very well, you could get IV meds that aren't available to outpatients, namely natrecor and dobutamine, which would help take the fluid off and improve the pumping power of your heart. This isn't a hopeless situation, the meds can make you feel a heckuva lot better--it's not just diuretics. You should take a trip to the local ER ASAP.

If you are MD or if you yourself suffer from CHF & severe edema-please REPLY?, I recently developed CHF with painful edema after MASSIVE MI. Diuretics fail in my body, no diuresis happens. only toxic reactions happen. I will not enter hospital, I'm uninsured, terrified, & unwilling to play guessing game with IV drugs same as I now take to no avail .I could be in hospitals for months with no improvements.
Tell me - is there any device or technique whereby th MDs can drain out from tissues of thighs calves, ankles, abdomen - all the stored water? does a drain exist ? I am suffering greatly, cannot sleep or lie down, nauseous, legs rigid, cannot flex or bend to step down stairs or into car. My Ejection Fraction is 50%-I have Severe global hypokinesis,severe reduced left ventricular systolic function, & right ventricular failure as well. I take lisinopril, hydralazine, for
BP. My abdomen is distended, cannot close pants on it. I am also seeking treatment by ultrafiltration periodically. My albumin & all liver/kidney/lipids/TSh are fine. Please reply.

Go to an emergency room and let them help you. They should take you, regardless of your ability to pay. Then try to get on Medicaid. With your serious medical problems, you need to be under a doctor's care.

I am not aware of any kind of a mechanical drain that can drain the fluid out of your legs.

I hope it all works out and that you feel better soon.

Heart disease?, One year ago I had mild to moderate aortic insufficency, this years echo showed that the aortic regurgatation is now moderate; also all of the other valves are regurgating mildly. Basically all of the valves in my heart are leaking, I am 39 years old and taking 5 pills a day for my heart; 3 hydralazine and 2 clonidine. Just how serious is this condition? I stay tired all the time. I do have a history of heart disease in my family. Anyone familar with this condition or medications to treat it?

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ICU nurses or docs or RRTs to answer please ... vent. settings?, One of my intubated patients (dominant-hemisphere meningioma that beld) had been "chugging" really bad on the vent. I'd been suctioning for scant sputum. The nurse giving me shift change repor said the intensivist said his PSV was set at too low a rate. He was in a hurry to go, so I didn't have chance to ask why this helped. Before *his* shift, the previous RN had given him 800 mcg fentanyl, 15 mg Versed, 200 mg of hydralazine, and 60 mg labetalol for high SBP (>180) and high ICP (in the high 20s to low 30s (mmHg)). After the PSV was raised from +6 to +10 (cm H20), the patient's BP was under control and he was settled, needing only 200 mcg fentanyl and 20 mg hydralazine on the shift befor mine, and absolutely nothing on my shift. What is the rationale for increasing the pressure support? Also, what is "autopeeping?" -- his PEEP was raised to +15 to prevent autopeep.

Actually, increasing the pressure support would not fix autopeeping -- as you know, PSV allows the patient to initiate breaths and augments each breath with an additional volume until a defined pressure (e.g 6 cm H2O) above atmospheric pressure is reached. Increasing the pressure support, in itself, cannot prevent autopeep! Only increasing the value of the vent PEEP can do that -- it's an usually an empiric change (i.e. you first suspect autopeeping then raise the PEEP until evidence of continued autopeep disappears).

Based on what we know from what you wrote, I suspect the reason for your patients requirement of fewer sedatives and antihypertensive drugs was simple -- his WOB was decreases by increasing the PS from +6 to +10, making it such that he didn't have to "fight the circuit" to breathe. Even though PS is a "pressure mode," his tidal volumes will be greater on a higher PS, so watch that they don't get too high. Also, he may begin to 'air trap' again if the PEEP is decreased, e.g. in an effort to decrease ICP, one dangerous option would be to turn the peep down too quickly. Of course, during his stay, both his PEEP and PS will have to be weaned before he's extubated.

Being a neurosurgical ICU nurse, I'd be interested to see what his CPPs are now that his BP is under control. Hopefully his ICP readings are consistently below 20 and he hasn't developed any sort of global ischemia; make sure there's a low SBP/MAP/CPP parameter order.