Captopril

Brand Names: Capoten

Clinical Names: Captopril

Summary

generic name: Captopril

trade name: Capoten®

type of drug: Angiotensin-converting enzyme (ACE) inhibitor.

used to treat: Hypertension or congestive heart failure; also used to prevent the progression of renal dysfunction induced by hypertension and diabetes mellitus; often combined with a diuretic and/or digoxin (Lanoxin).

mechanism: ACE inhibitors such as captopril lower blood pressure by inhibiting angiotensin-converting enzyme (ACE), which is important for the formation of angiotensin II. Angiotensin II normally would cause constriction of arteries and elevation of blood pressure so its inhibition will relax the arteries and lower blood pressure, and improve the cardiac pumping efficiency and output in patients with heart failure.

overview of interactions:
• nutrient affecting drug performance: Iron

• nutrient affected by drug: Magnesium

• nutrient affected by drug: Potassium

• nutrient affected by drug: Sodium

• nutrient affected by drug: Zinc




Interactions

nutrient affecting drug performance: Iron

• mechanism: Concurrent ingestion of iron and captopril decreases the drug's bioavailability by forming a stable complex with it.
(Campbell NR, Hasinoff BB. Brit J Clin Pharmacol 1991 Mar;31(3):251-255.)

nutrient affected by drug: Magnesium

• mechanism: Captopril increases lymphocyte magnesium levels, though possibly only in patients with pre-existing low levels.
(Lavin F, et al. Cardiology 1993;82(6):405-408; O'Keeffe S, et al. Cardiology 1992;80(2):100-105.)

nutrient affected by drug: Potassium

• mechanism: Captopril increases lymphocyte potassium levels, though possibly only in patients with pre-existing low levels. In general, ACE inhibitors enhance potassium levels in the blood.
(Lavin F, et al. Cardiology 1993;82(6):405-408; O'Keeffe S, et al. Cardiology 1992;80(2):100-105; Good CB, et al. JAMA 1995 Aug 16;274(7):538.)

• nutritional concerns: Potassium supplements and even high-potassium foods, such as fruit, can lead to problematic interactions and should be avoided. A patient using an ACE inhibitor, such as captopril, is advised to discuss these issues with their prescribing doctor, a pharmacist, or both.

nutrient affected by drug: Sodium

• mechanism: Captopril may cause hyponatremia and may also exert an anti-aldosterone effect.
(Nicholls MG, et al. Br Med J 1980 Oct 4;281(6245):909; Vitola D, et al. Arq Bras Cardiol. 1988 Dec;51(6):463-465.)

nutrient affected by drug: Zinc

• mechanism: All ACE inhibitors bind to zinc ions located in the active site of the ACE molecule. ACE inhibitors can be classified according to the ligand of the zinc ion of ACE, captopril has a sulfhydryl moiety as the ligand ACE, and according to the excretion route of their active moiety, captopril is excreted mainly through the kidneys.

• research: Several studies have shown that taking captopril is likely to cause significant loss of zinc through the urine. In these studies, depletion of zinc has been associated with reduced red blood cell levels of zinc and reduced taste acuity.
(Abu-Hamdan DK, et al. Am J Hypertens 1988 Jul;1(3 Pt 3):303S-308S; Golik A, et al. Biol Trace Elem Res 1993 Nov;39(2-3):171-175; Golik A, et al. J Am Coll Nutr 1998 Feb;17(1):75-78.)

• nutritional support: A test for assessing zinc levels can be performed or ordered by a physician. There seems to be adequate grounds for recommending that individuals taking captopril on a long-term basis take a zinc supplement or a multimineral tablet containing zinc as a precaution. However, any multimineral or multivitamin supplement source should not contain more than 99 mg of potassium, to avoid triggering an interaction with the Captopril, but should include enough copper to protect against a zinc-induced copper deficiency.

• related herbal research: Research into herbs with actions similar to pharmaceutical ACE inhibitors has found that several traditional medicines yielded promising results.
(Adsersen A, Adsersen H.J Ethnopharmacol 1997 Nov;58(3):189-206 ; Nyman U, et al. J Ethnopharmacol 1998 Apr;60(3):247-263.)

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.


References

Abu-Hamdan DK, Desai H, Sondheimer J, Felicetta J, Mahajan S, McDonald F. Taste acuity and zinc metabolism in captopril-treated hypertensive male patients. Am J Hypertens 1988 Jul;1(3 Pt 3):303S-308S.
Abstract: Reduced taste acuity is a commonly reported side effect of captopril associated with zinc deficiency. This study assessed taste acuity using Henkin's three-drop stimulus technique and measured plasma zinc (PZn) level and urinary zinc excretion in 31 hypertensive patients. Of these,11 were long-term, high-dose captopril recipients, six were short-term captopril recipients, and the remaining 14 served as noncaptopril controls. Compared to controls, the long-term captopril group had significantly higher taste detection and recognition thresholds, lower PZn and higher urinary zinc excretion. The short-term captopril group did not differ significantly from the noncaptopril group except for higher taste-recognition thresholds for NaCl and sucrose. Discontinuing captopril improved and almost normalized zinc parameters in two patients on long-term captopril. These results suggest that abnormalities of taste are commonly associated with captopril therapy and may be related to changes in zinc metabolism. This is especially true in patients on long-term, high-dose captopril therapy.

Adsersen A, Adsersen H. Plants from Reunion Island with alleged antihypertensive and diuretic effects--an experimental and ethnobotanical evaluation. J Ethnopharmacol 1997 Nov;58(3):189-206.
Abstract: Eighty species of vascular plants were collected on Reunion Island and tested for their ability to inhibit the angiotensin converting enzyme (ACE), which plays an important role in the regulation of blood pressure and diuresis. Of these species, 26 serve as antihypertensive remedies in traditional medicine, and 38 as diuretics-10 of the 64 species have both alleged antihypertensive and diuretic effects. Of the species with alleged antihypertensive or diuretic effect, 44% proved active. Of the species with no report of such effects, 31% proved active. 

Campbell NR, Hasinoff BB. Iron supplements: A common cause of drug interactions. Brit J Clin Pharmacol 1991 Mar;31(3):251-255. (Review)
Abstract: Iron-drug interactions of clinical significance may occur in many patients and involve a large number of therapies. Concurrent ingestion of iron causes marked decreases in the bioavailability of a number of drugs. The affected drugs, tetracycline, tetracycline derivatives (doxycycline, methacycline and oxytetracycline), penicillamine, methyldopa, levodopa, carbidopa and ciprofloxacin have diverse chemical structures and clinical effects. The major mechanism of these drug interactions is the formation of iron-drug complexes (chelation or binding of iron by the involved drug). A large number of other important and commonly used drugs such as thyroxine, captopril and folic acid have been demonstrated to form stable complexes with iron. There is little known about the effects of concurrent therapy with iron supplements for most of the drugs.

Golik A, Cohen N, Ramot Y, Maor J, Moses R, Weissgarten J, Leonov Y, Modai D. Type II diabetes mellitus, congestive heart failure, and zinc metabolism. Biol Trace Elem Res 1993 Nov;39(2-3):171-175.

Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, Berman S, Weissgarten J. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr 1998 Feb;17(1):75-78.

Good CB, McDermott L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995 Aug 16;274(7):538. (Letter)

Kotsaki-Kovatsi VP, Koehler-Samouilidis G, Kovatsis A, Rozos G. Fluctuation of zinc, copper, magnesium and calcium concentrations in guinea pig tissues after administration of captopril (SQ 14225). J Trace Elem Med Biol 1997 Apr;11(1):32-36.
Abstract: The effect of the administration of captopril on Zn (zinc), Cu (copper), Ca (calcium) and Mg (magnesium) concentrations in guinea pig tissues was studied. For nine weeks 2 mg captopril per kg b.w. were administered daily to adult male guinea pigs intraperitoneally. The concentrations of the studied metals were determined in several tissues. Captopril significantly decreased Zn concentration in liver, Cu concentration in liver, adrenals, jejunum, urine and hair and Mg concentrations in blood and urine. A significant increase was observed in testicular and epididymal Zn, in heart, epididymal and fecal Cu, in Mg concentration of lung, kidney, adrenals, jejunum, epididymis and hair and in Ca concentrations in brain, heart, lung, kidney, spleen and stomach. No significant changes were observed in the colon and the thigh bone concentrations of the various elements tested. In conclusion Captopril treatment can produce translocation and/or elimination of Zn, Cu, Mg and Ca ions in various tissues of guinea pigs.

Lavin F, O'Keeffe S, Grimes H, Finn J, Mannion A, Daly K. Effect of prolonged nifedipine or captopril therapy on lymphocyte magnesium and potassium levels in hypertension. Cardiology 1993;82(6):405-408.
Abstract: The effect of prolonged treatment with calcium channel blockers on potassium and magnesium stores is uncertain. We measured lymphocyte and serum magnesium and potassium in 28 patients treated for hypertension for 6 months with nifedipine or captopril. There was no difference in serum or lymphocyte concentrations in the two groups compared to 45 healthy, normotensive controls. These results suggest that intracellular cation levels are maintained with prolonged therapy with calcium channel blockers.

Nicholls MG, Espiner EA, Ikram H, Maslowski AH. Hyponatraemia in congestive heart failure during treatment with captopril. Br Med J 1980 Oct 4;281(6245):909.

Nyman U, Joshi P, Madsen LB, Pedersen TB, Pinstrup M, Rajasekharan S, George V, Pushpangadan P. Ethnomedical information and in vitro screening for angiotensin-converting enzyme inhibition of plants utilized as traditional medicines in Gujarat, Rajasthan and Kerala. J Ethnopharmacol 1998 Apr;60(3):247-263.
Abstract: Plants utilized as traditional medicines in India have been investigated for their ability to inhibit the angiotensin converting enzyme (ACE). In total, 75 species belonging to 42 families have been investigated and new ethnomedical information has been obtained for 41 species. Four species were found to possess a high ACE inhibiting ability and were low in their tannin content.

O'Keeffe S, Grimes H, Finn J, McMurrough P, Daly K. Effect of captopril therapy on lymphocyte potassium and magnesium concentrations in patients with congestive heart failure. Cardiology 1992;80(2):100-105.
Abstract: Lymphocyte potassium and magnesium were measured before and 3 months after the introduction of captopril in 18 patients taking diuretics for congestive heart failure. Compared to 32 healthy controls, 9 patients who had been on potassium supplements plus frusemide had decreased baseline lymphocyte magnesium and potassium concentrations (p less than 0.01), in spite of similar plasma electrolyte levels. There was a significant (p less than 0.01) increase in both lymphocyte potassium and magnesium levels after 3 months' treatment with captopril and frusemide in these patients. Nine patients who had been taking a potassium-sparing combination diuretic also had an increase in lymphocyte magnesium (p less than 0.05) following the introduction of captopril. Increased intracellular potassium and magnesium may be one mechanism whereby angiotensin-converting enzyme inhibitors reduced arrhythmias and improve survival in patients with congestive heart failure.

Peczkowska M. [Influence of angiotensin I converting enzyme inhibitors on selected parameters of zinc metabolism]. Pol Arch Med Wewn 1996 Jul;96(1):32-38. [Article in Polish]
Abstract: In a randomized, double-blind trial, thirty one patients with essential hypertension (EH) were divided into two groups: the first group were treated with benazepril (nonsulphydryl ACEI), and the second group received captopril (sulphdryl ACEI). Erythrocyte (ZnE) and serum (ZnS) zinc as well as 24 hour urinary zinc excretion (ZnU) and glomerular filtration rate were assessed before starting treatment and after 4 and 8 weeks of ACEI therapy. The study found that ZnS significantly lowered and ZnU increased during ACEI therapy whereas ZnE did not change. Up to 4 weeks there were no statistical differences between captopril and benazepril regarding their influence on zinc metabolism. After 8 weeks of therapy ZnS decreased more significantly in captopril group (p < 0.01). Glomerular filtration rate did not significantly change during ACEI therapy.

Shionoiri H, Shigemasa T, Takasaki I. [Angiotensin-converting enzyme inhibitors: recent therapeutic aspect]. Nippon Rinsho 1997 Aug;55(8):2067-2074. [Article in Japanese]

Vitola D, Bittar AE, Junges F, dos Santos AA, Rodrigues R. [Hyponatremia induced by captopril in patients with congestive cardiac insufficiency. A report of 2 cases]. Arq Bras Cardiol. 1988 Dec;51(6):463-465. [Article in Portugese]