The data base for rational guidelines to safe, efficacious drug prescribing in adults with renal insufficiency are presented in tabular form. Current medical literature was extensively surveyed to provide as much specific information as possible. When information is lacking, however, recommendations are based on pharmacokinetic variables in normal subjects. Nephrotoxicity, important adverse effects, and special considerations in renal patients are noted. Adjustments are suggested for hemodialysis and peritoneal dialysis when appropriate.

https://www.ajkd.org/article/S0272-6386(83)80060-2/pdf

Drug Prescribing in Renal Failure: Dosing Guidelines for Adults

Captopril is the first orally active inhibitor of angiotensin-converting enzyme to become available. It has been studied primarily in hypertension. In mild to moderate essential hypertension captopril is about as effective as usual doses of hydrochlorothiazide or propranolol, about one-half of such patients needing the addition of a diuretic to achieve satisfactory control of blood pressure. In severe hypertension captopril plus a diuretic (and in some patients a beta-blocker) usually reduced blood pressure significantly more than could be achieved with 'standard triple therapy' in patients not responding adequately to such a regimen, and often resulted in an improved feeling of well-being in severely hypertensive patients previously receiving intensive multiple drug therapy. Indeed, at the present stage of the drug's development, patients not responding to or not tolerating 'traditional' antihypertensive therapy represent the most suitable candidates for captopril treatment. While captopril has been well tolerated in most patients, some troublesome or potentially serious side effects have been reported, including agranulocytosis, dysgeusia and reduced renal function; although a clear causal relationship with captopril was not always established, it would appear that the final place of captopril in the treatment of hypertension may ultimately depend on further clarification of its adverse effects profile. In addition to studies in hypertension, captopril has produced encouraging improvement in a small number of patients with severe congestive heart failure resistant to conventional therapy. Captopril must be considered an exciting addition to the therapeutic armamentarium; it, and pharmacologically related compounds of the future, will continue to generate much interest as their final place in therapy becomes better defined through additional well designed studies and wider clinical experience.

Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy.

BACKGROUND

Therapy with alkylating agents, such as cyclophosphamide, can be associated with irreversible gonadal toxicity in male survivors of adult cancer. To the authors's knowledge the effect of high dose therapy with cyclophosphamide during childhood on adult testicular reproductive and endocrine function has not been established.



METHODS

Gonadal function was studied in 17 adult male survivors of childhood sarcomas treated with high dose pulse cyclophosphamide therapy as part of a VAC (vincristine, actinomycin, and cyclophosphamide) or Adria-VAC (doxorubicin, vincristine, actinomycin, and cyclophosphamide) chemotherapy regimen. Patients answered a questionnaire concerning sexual functioning and underwent a comprehensive physical examination, semen analysis, and hormonal evaluation.



RESULTS

Of the 17 males who underwent semen analysis, 10 (58.8%) had azoospermia, 5 (29.4%) had oligospermia, and only 2 (11.8%) were found to have a normal sperm count. All patients treated prior to the onset of puberty had an abnormal semen analysis. The 2 patients with normal sperm counts received the lowest doses of cyclophosphamide ( 3 times that of baseline in 13 of /14 patients (92.9%), suggesting some degree of Leydig cell insufficiency.



CONCLUSIONS

The results of the current study show a high risk of gonadal dysfunction in men exposed to cyclophosphamide during childhood as part of a VAC/Adria-VAC chemotherapy regimen. Exposure prior to puberty was not found to be protective, and the risk of infertility appeared to increase with higher doses of therapy. To the authors' knowledge the clinical significance of impaired Leydig cell function beginning at a young age is unknown and merits further study. Cancer 2001;91:613–21. © 2001 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2820010201%2991%3A3%3C613%3A%3AAID-CNCR1042%3E3.0.CO%3B2-R

High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood

Objective

To determine the incidence of ovarian failure after cyclophosphamide (CYC) treatment for systemic lupus erythematosus (SLE) and to identify the risk factors for this complication.



Methods

The records of 70 premenopausal female SLE patients treated with CYC were reviewed retrospectively. Information on demographic features, autoantibody profiles, and CYC treatment was obtained, and comparisons were made between those who developed ovarian failure and those who did not. Data on the CYC-treated patients were also compared with data on 2 control groups of non-CYC-treated SLE patients.



Results

Eighteen patients developed ovarian failure after CYC treatment, for an overall incidence of 26%. The incidence of ovarian failure showed a linear trend of increase with increasing age at the start of CYC (P = 0.007). The cumulative CYC dose was significantly higher in the patients with ovarian failure than in those without (28.3 gm versus 15.4 gm; P = 0.004). The risk of ovarian failure also showed a linear trend of increase with increasing cumulative CYC dose (P < 0.001). Using multiple logistic regression, the age at the time of CYC treatment initiation (β = 0.37, SE = 0.11, P = 0.001) and the cumulative dose of CYC received (β = 0.69, SE = 0.29, P = 0.02) were found to be independent risk factors for CYC-induced ovarian failure.



Conclusion

In our population of female SLE patients, CYC-induced ovarian toxicity is a significant problem, particularly in patients above the age of 40. The age at the start of CYC therapy and the cumulative dose are the major determinants for the development of this complication. For older patients with SLE in whom the use of CYC is warranted, a shorter course and lower dosage should be considered.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28199805%2941%3A5%3C831%3A%3AAID-ART9%3E3.0.CO%3B2-1

PhillipJ. Hoedemaeker

Papers

Immune-complex glomerulopathy in patients treated with captopril