Captopril: a potent drug which is a competitive inhibitor on the angiotensin converting enzyme

The angiotensin II is involved in the regulation of blood pressure as well as in the renin-angiotensin-aldosterone system (Sonsalla et al., 2013). 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

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Pharmacology
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Introduction
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.
Pharmacodynamics
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.

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Pharmacokinetics
Absorption
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.
Distribution
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.
Metabolism
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.
Excretion
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.
Toxicity
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).

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Figure 1: the structure of captopril.
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).
Conclusion
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.

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