Captopril is a potent drug which is a competitive inhibitor on the angiotensin converting enzyme which functions to convert the renal angiotensin I to angiotensin II. The angiotensin II is involved in the regulation of blood pressure as well as in the renin-angiotensin-aldosterone system (Sonsalla et al., 2013). In most cases therefore, captopril is applied in the treatment of high blood pressure among many other uses. With the increase in high blood pressure among the populations today, captopril therefore finds widespread applications in the medical sector. This drug contains sulphydryl groups and thus can bind to the albumin among many other proteins. Captopril also forms mixed disulphides with other compounds that contain endogenous thiol groups like cysteine and glutathione. Once these components are present in blood and urine, they can be collectively measured and get the total captopril. The aim of this essay is thus to explore the pharmacodynamics and pharmacokinetics of captopril.
Captopril is used to treat congestive heart failure and high blood pressure since it is an oral drug which fall in the class of angiotensin converting enzyme inhibitors. Therefore, the administration of captopril leads to a reduction in the peripheral artery resistance especially in the hypertensive patients who have a high or no change in cardiac output (Miguel-Carrasco et al., 2010). When there is a low blood pressure, there are low risks of stroke and heart attacks to the patients. On the other hand, captopril plays crucial role in increasing the survival of patients after kidney illnesses and heart attack. This drug also increases the levels of plasma renin activities as well as the levels of bradykinin. When the levels of angiotensin II are reduced, this results in low abilities of retaining water and sodium ions in the body.
In essence, captocapril antagonizes the effects of the RAAS system. The RAAS system is a hemostatic system which regulates the water and electrolyte balance in the living body. Thus during sympathetic stimulation or in cases when the blood pressure in the kidneys is low, renin is released in the kidneys and this renin function convert angiotensinogen to angiotensin I, which is then converted to angiotensin II, through a cleavage biochemical reaction. This stimulates the production of the hormone aldosterone from the kidney cortex which increases the sodium channels, as well as the release of vasopressin which increases the reabsorption of water from kidneys. Being an analog of the amino acid proline, captopril thus performs the roles of antihypertensive by competitively inhibiting the roles of the angiotensin converting enzyme (Ni et al., 2012). This in turn lowers the concentrations of angiotensin II, raising the plasma renin levels and lowering the rates of aldosterone secretion. The blood vessels dilate leading to low blood pressure, which makes it easy for the heart to pump blood and thus improve a failing heart. This also slows down the progression of a disease in the blood vessels inside the kidneys which could have resulted from either diabetes or high blood pressure (Roozbeh et al., 2010).
In cancer treatment, captopril has also been found to have antineoplastic roles whereby it inhibits tumor angiogenesis. The reduction of blood pressure is maximal between one to one and a half hours after the oral captopril administration. The duration of this dose is tolerated and the reduction in pressure could be progressive in order to reach the therapeutic levels. It has been found that the ability of captopril to lower the blood pressure is additive, although captopril and other beta blockers have been found to have a low additive effects.
The dosage of captopril is about 25 to 150 mg either two or three times per day. This drug should be taken on an empty stomach because the absorption of captopril is lowered in case it is taken with food. The absorption of captopril in the gastrointestinal tract occurs with detectable plasma concentrations as early as fifteen minutes. The extent of captopril absorption is about 75% in oral doses. The increased oral bioavailability of captopril is high in chronic patients receiving this drug in their therapy as compared to those in the acute stages of a disease. As a result, in the chronic phase, it is possible that the dosage can be reduced and at the same time make it possible to reach the dosage levels in controlling the blood pressure.
The captopril has a half-life and in most cases half of the drug remains unchanged and thus the high level of effectiveness. The remaining part is in the form of disulfide dimer of captopril and captopril;-cysteine disulfides (Bojarska et al., 2015). Distribution is also affected by protein binding and some portion of captopril can cross the placenta and enters into the breast milk, raising its levels in the maternal blood. In most cases, the distribution of captopril occurs in three compartments in human beings, more so the deep tissues.
This drug is metabolized in an extensive way whereby the major metabolite is captopril dimer known as SQ 14,551. This metabolite is less active than the actual captopril drug as an inhibitor of the angiotensin converting enzyme.
The elimination of captopril takes place in the renal system via tubular secretions. The renal excretion is rapid occurring within four hours with ninety percent efficiency. This drug is excreted via urine with more than half of its concentrations being unchanged. The elimination half-life is about one to two hours although this can increase in the event of renal damage (Siska et al., 2018). It has been found that the pharmacokinetic properties of captopril in patients with uncomplicated hypertension is similar in healthy patients. The metabolites of captopril are labile and thus the interconversions can also occur in vivo. About forty percent of the captopril dose which is administered remains unchanged inside the urine for a whole day as metabolites. The excretion half-life is about two hours and the radioactivity is about four hours. Additionally, the elimination half-life of captopril can increase as the renal function decreases, an indication that elimination correlates with creatinine clearance. As a result, the dose adjustment needs to be carried out especially in the patients who have renal infections.
Just like other angiotensin converting enzyme inhibitors, captopril is associated with a low rates of elevations in serum aminotransferases. It causes liver and kidney toxicities which can begin between two to twelve weeks after the therapy has been initiated (Kelleni et al., 2016).
While this drug is generally tolerated well, the side effects associated with captopril are transient and mild. The use of captopril is associated with persistent coughs, although this is common even in the use of other angiotensin converting enzyme inhibitors. Other common side effects include anemia, skin rashes, fever, eosinophilia, chest pain, congestive heart failure, dysgeusia, hepatitis, cholestasis, jaundice and dehydration among many more (Islam et al., 2015).
It is therefore evident that captopril is an oral drug which plays critical roles in maintaining a controlled blood pressure. It has desirable pharmacodynamics and pharmacokinetic properties which makes its use widespread. Recently, captopril has been found to play other immunomodulatory functions like the treatment of rheumatoid arthritis and preventing complications that are associated with insulin dependent diabetes mellitus. In schistomiasis infections, this drug reduces the inflammation reactions. The most probable ways via which captopril enhances patient survival includes attenuating progressive left ventricle dilations and the deterioration in the left ventricle functions. Thus, patients to whom captopril have been administered can have increased cardiac output, cardiac index as well as stroke volume index.
Bojarska, J., Maniukiewicz, W., Fruzi?ski, A., Siero?, L. and Remko, M., 2015. Captopril and its dimer captopril disulfide: comparative structural and conformational studies. Acta Crystallographica Section C: Structural Chemistry, 71(3), pp.199-203.
Kelleni, M.T., Ibrahim, S.A. and Abdelrahman, A.M., 2016. Effect of captopril and telmisartan on methotrexate-induced hepatotoxicity in rats: impact of oxidative stress, inflammation and apoptosis. Toxicology mechanisms and methods, 26(5), pp.371-377.
Roozbeh, J., Banihashemi, M.A., Ghezlou, M., Afshariani, R., Salari, S., Moini, M. and Sagheb, M.M., 2010. Captopril and combination therapy of captopril and pentoxifylline in reducing proteinuria in diabetic nephropathy. Renal failure, 32(2), pp.172-178.
Miguel-Carrasco, J.L., Zambrano, S., Blanca, A.J., Mate, A. and V?zquez, C.M., 2010. Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB. Journal of inflammation, 7(1), p.21.
Sonsalla, P.K., Coleman, C., Wong, L.Y., Harris, S.L., Richardson, J.R., Gadad, B.S., Li, W. and German, D.C., 2013. The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism. Experimental neurology, 250, pp.376-383.
Ni, H., Li, L., Liu, G. and Hu, S.Q., 2012. Inhibition mechanism and model of an angiotensin I-converting enzyme (ACE)-inhibitory hexapeptide from yeast (Saccharomyces cerevisiae). PloS one, 7(5), p.e37077.
Islam, S.B., Mazumder, R.N. and Chisti, M.J., 2015. Captopril in Congenital Chloride Diarrhoea: A Case Study. Journal of health, population, and nutrition, 33(1), p.214.
Siska, S., Munim, A., Bahtiar, A. and Suyatna, F.D., 2018. Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats. Scientia pharmaceutica, 86(1), p.6.