Acetylator Phenotype in Patients with Hydralazine‐induced Lupoid Syndrome

I, Strandberg; Boman, Gunnar; Hassler, Leo; Sjöqvist, Folke

doi:10.1111/j.0954-6820.1976.tb08248.x

Cited by 96 publications

(8 citation statements)

References 23 publications

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“…The polymorphic acetylation of isoniazid (INH), some sulphonamides, hydralazine and procaine amide has been established in many investigations ( 4 , 6 , 7 , 11,16,17). It has also been shown that sideeffects of these drugs are more frequent in slow acetylators (1, 2,9,10,14,19,20). Phenotyping of patients before the beginning of therapy with these drugs would therefore be of clinical value.…”

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confidence: 99%

Evaluation of the Sulphapyridine Acetylator Phenotyping Test in Healthy Subjects and in Patients with Cardiac and Renal Diseases

Molin

Larsson

Karlsson

1977

Journal of Internal Medicine

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The acetylator phenotype of 35 healthy, drug‐free volunteers and 21 patients with cardiac and/or renal disease has been assessed using oral sulphapyridine. Comparative evaluation of a simplified and a more selective method of sulphapyridine analysis was performed. Thirteen of the patients were also phenotyped by determination of plasma isoniazid half‐life. 81% of the patients were slow acetylators, compared with only 51% of the volunteers. When phenotyping healthy, drug‐free subjects the analytical procedure, involving a direct estimation of sulphapyridine in urine with the Bratton‐Marshall procedure, was satisfactory. On the other hand, in patients receiving concomitant drug therapy the more selective analytical procedure was necessary in order to diminish the risk of methodological interference.

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confidence: 99%

Evaluation of the Sulphapyridine Acetylator Phenotyping Test in Healthy Subjects and in Patients with Cardiac and Renal Diseases

Molin

Larsson

Karlsson

1977

Journal of Internal Medicine

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“…It is well known that the acetylator phenotype of the patient has some influence on the occurrence of late toxicity of hydralazine. Thus hydralazine-induced systemic lupus erythematosus occurs primarily in slow acetylators (4, 33,35). and these patients have a higher concentration of hydralazine in plasma and a better BP control.…”

Section: Discussionmentioning

confidence: 99%

Hydralazine in Arterial Hypertension

Wulff

Lenz

Krogsgaard

et al. 1980

Journal of Internal Medicine

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Blood pressure (BP) control and tolerability of three two-week dosage regimens of hydralazine-conventional hydralazine q.i.d., conventional hydralazine b.i.d. and slow-release hydralazine b.i.d.-were compared in a double-blind, randomized, cross-over trial in 20 out-patients with arterial hypertension controlled with hydralazine in combination with other antihypertensive drugs. The efficacy of the treatments was assessed during the last two days of each treatment period by determination of BP and pulse rate every hour between 8 a.m. and 6 p.m. No statistically significant differences in BP and pulse rate were found between the three treatment regimens, either in the variation during the day or in the mean value for the day. There was a tendency to lowest BPs on conventional hydralazine q.i.d. and to highest on conventional hydralazine b.i.d. Mean differences in supine BP between conventional hydralazine b.i.d. and slow-release hydralazine b.i.d. were 3.2 systolic and 0.5 mmHg diastolic. In this short-term study, mean values with 95 % confidence limits indicate that conventional hydralazine in a q.i.d. dosage can be replaced by the same preparation or slow-release formulation in a b.i.d. dosage. Acetylator phenotype was determined and had no significant influence on the results, although there was a tendency to more widespread variability in systolic pressure and to a lower pulse rate in fast acetylators. Unwanted effects were few and did not differ obviously between the treatments. Whether the frequency of late toxicity of hydralazine is lower with slow-release formulation remains to be evaluated in long-term studies. K e y words: hydralazine, slow-release, day curve of BP, acetylator phenotype. Acta Med Scand 208: 49, 1980.Poor patient compliance with antihypertensive drug regimens is well documented ( I , 15, 40). The pa-tients, usually without symptoms, have to follow a long-term treatment schedule, which may involve polypharmacy and frequent dose regimens, both of which foster poor compliance. Gatley (11) and Malahy (25) found that the number of drug defaulters increased with the frequency of doses, and according to Ayd (3) over 80% of patients who were to take four or more drugs at least three times a day failed to take 2 5 4 0 % of the prescribed dose of each, whereas only 30% of those instructed to take one drug twice daily failed to take up to one fourth of the dose prescribed.Consequently, a one-or two-dose schedule has been introduced for P-blocking agents, such as propranolol(2), pindolol (10, 14, 18), metoprolol(34) and atenolol (26,42). Recently, slow-release formulations of propranolol (6, 27) and oxprenolol (8,19,30) have become available for administration once a day.Hydralazine was introduced as a hypotensive agent in the early 50s. Following the realisation that late toxicity with LED syndrome is dose-related, hydralazine in doses up to 200 mg daily has proved a valuable and efficient antihypertensive drug in combination with other preparations. Since the introduction of P-receptor blockers, gro...

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“…By comparison with the NAT2 genes, only a small number of NAT1 variants result in alteration of phenotypes. An increased incidence of drug toxicities in subjects carrying polymorphic NAT2 alleles has been reported when received hydralazine and sulfasalazine [32–34]. …”

Section: Drug-metabolizing Enzymesmentioning

confidence: 99%

Digging Up the Human Genome: Current Progress in Deciphering Adverse Drug Reactions

Chung

Hung³

2014

BioMed Research International

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Adverse drug reactions (ADRs) are a major clinical problem. In addition to their clinical impact on human health, there is an enormous cost associated with ADRs in health care and pharmaceutical industry. Increasing studies revealed that genetic variants can determine the susceptibility of individuals to ADRs. The development of modern genomic technologies has led to a tremendous advancement of improving the drug safety and efficacy and minimizing the ADRs. This review will discuss the pharmacogenomic techniques used to unveil the determinants of ADRs and summarize the current progresses concerning the identification of biomarkers for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing enzymes, drug-transporter proteins, and human leukocyte antigen (HLA). The knowledge gained from these cutting-edge findings will form the basis for better prediction and management for ADRs, ultimately making the medicine personalized.

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Acetylator Phenotype in Patients with Hydralazine‐induced Lupoid Syndrome

Cited by 96 publications

References 23 publications

Evaluation of the Sulphapyridine Acetylator Phenotyping Test in Healthy Subjects and in Patients with Cardiac and Renal Diseases

Evaluation of the Sulphapyridine Acetylator Phenotyping Test in Healthy Subjects and in Patients with Cardiac and Renal Diseases

Hydralazine in Arterial Hypertension

Digging Up the Human Genome: Current Progress in Deciphering Adverse Drug Reactions

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