Anti-Hypertensive Drugs: Ramipril and its Mechanism of Action

This article provides an in-depth understanding of Ramipril, an anti-hypertensive drug belonging to the category of Angiotensin Converting Enzyme (ACE) inhibitors. It discusses the mechanism of action of Ramipril, its effectiveness in lowering blood pressure, and its role in preventing cardiovascular events. The article also explores the normal physiology and pathophysiology of hypertension, important drug interactions, and side effects. Additionally, it provides insights into the dosage and administration of Ramipril for optimal patient care.

Running head: ANTI-HYPERTENSIVE DRUGS
ANTI-HYPERTENSIVE DRUGS
Name of the student:
Name of the university:
Author note:

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Introduction:
Ramipril is utilised for the treatment of hypertension and therefore it is often termed as an
anti-hypertensive drug. This drug helps to lower the blood pressure as well as this helps in the
reduction of the risk of the fatal and the non0fatal cardiovascular events which also include the
strokes and the myocardial infarctions. The benefits have been already proven in the stroke as
well as myocardial infarctions (Knoll et al. 2016). The benefits have been proved in the
controlled trials of the antihypertensive drugs from different pharmacologic classes that also
included this drug. This assignment would first discuss the category of the drug to which it
belongs. This would be followed by discussion of the normal physiology of the body, the
situations that take place in hypertension patients and how the drug helps in overcoming the
symptoms. The nursing professionals also need to know about the efficiency and limitation of
using the drug and thee aspects would be also discussed in details.
Drug category where Ramipril belongs:
Ramipril mainly is included the drug catrgory of Angiotensin converting enzyme (ACE)
inhibitors. These drugs are seen to inhibit the action of the enzyme called the ACE that helps in
controlling the blood pressure. Actually, angiotensin II is a very potent compound that is formed
with the help of ACE. This chemical compound mainly contributes in the muscles that surround
the blood vessels in contracting. Therefore, they become narrow and this causes increase of the
blood pressure (Nassiri et al. 2015). The medications called the Ace inhibitors mainly work by
inhibiting the function of the ACE and this causes reduction in the production of angiotensin II.
Thereby, this category of the drugs is seen to enlarge the blood vessels causing the reduction of
the blood pressure. This is seen to lower the blood pressure making it easier for the heart in

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pumping he blood and improving the function of failing heart. Moreover, studies also reveal that
this category of drugs slows down the progression of the kidney disease because of high blood
pressure as well as diabetes. Ramipril is one such drugs and its detailed working mechanism also
needs to be discussed.
Normal physiology and that pathophysiology that causes hypertension:
Hypertension or the high blood pressure mainly results from the derangement of a
multiple number of mechanisms that remain involved in the maintenance of the normal blood
pressure. These are the sympathetic nervous system, endothelial function plus sodium and water
retention, renin-angiotensin-aldosterone system. These had been extensively studied for
ascertaining mechanisms that involve in the development of the disease. The discussion would
be focused on one of the mechanism called the Renin-angiotensin-aldosterone system (RAAS).
This system is seen to play an important role in managing the maintenance of the normal blood
pressure and is found to be mainly activated by the dual mechanisms (Gandhi et al. 2018). This
dual mechanism comprises of that of the stimulation of the SNS as well as that of the glomerular
under perfusion. These are the stimuli which contribute in triggering the release of the rennin
from that of the juxtaglomerular apparatus when the blood volume or that of the sodium levels of
the body becomes low. Rennin is found to be responsible for the conversion of the
angiotensinogen to inactive angiotensin I. Again, the inactive angiotensin I is seen to undergo
further cleaving by that of the ACE or the endothelium bound angiotensin converting enzyme so
that it gets converted to that of the angiotensin II (Krupickova et al. 2018). It has been found that
angiotensin II makes the blood vessels undergo contriction making the blood pressure to rise
Studies have stated that when the concentration of salt intake gets decreased, RAAS is also seen
to trigger the releasing of the aldosterone from that of the adrenal glands. This in turn is seen to

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increase the re-absorption of that of salt and this is seen to get coupled with that of water
retention. This is ultimately seen to increase the blood pressure. Actually, angiotensin II as well
as aldosterone causes the renal tubules in retaining sodium and water and thereby it causes the
excretion of the potassium. Both the compounds are seen to work together in retaining the blood
volume as well as the blood pressure and the levels of sodium in the blood. This helps in
restoring the normal balance of sodium, fluids and potassium (Lawler et al. 2015). In cases of
many disorders, the rennin-angiotensin systems are seen to become overactive and this causes a
consistent high blood pressure which brings out occurrence of different disorders resulting from
hypertension. Hence, in such situations, ramipril is used as the ACE-inhibitors that help in
restoring the normal RAAS system thereby lowering the blood pressure levels (Kretzschmar et
al. 2017).
Mechanism of action of ramipril:
Ramipril is mainly seen to work by the inhibition of the above mentioned RAAs system.
This medication compound is mainly seen to bind to and then inhibit the ACE. It thus results in
the prevention of the conversion of angiotensin to that of the angiotensin II. Therefore, it can be
seen that as the plasma levels of angiotensin II is seen to fall, there is found to be less activation
occurring of the G-protein coupled receptors angiotensin receptor I (AT1R) and angiotensin
receptor II (AT2R). AT1R is mainly responsible for the mediation of the vasoconstriction,
inflammation, fibrosis, and oxidative stress (Krupickova et al. 2016). This is mainly seen to take
place through a number of different types of signaling pathways. These signaling pathways are
seen to be including Gq coupling to the inositol triphosphate pathway, activation of
phospholipases C, A2, and D. studies are of the opinion that this is seen to contribute to the
eicosanoid production, activation of Ca2+-dependent and MAP kinases, Gi and G12/13, and

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eventual activation of the Jak/STAT pathway. Bull et al. (2015) has found that these pathways
mainly help in the cell growth as well as the production of the extracellular matrix components.
Many of the researchers are of the opinion that activation of the AT1R also cause increase in the
activities of the membrane-bound NADH/NADPH oxidase. It has been found that they
contribute in the production of the reactive oxygen species also called the Ros. Reduction in the
activation of the receptor helps mainly by mediating the renoprotective, antihypertensive, and
cardio-protective effects of the medication mainly by the reduction of the inflammation as well
as vasoconstriction (Mietus et al. 2017). Another receptor called the AT2R are seen to be acting
in the opposition to that of the impacts of the AT1R and this is mainly seen to work with the
activation of that of the phosphotyrosine phosphatases. This is mainly seen to work by inhibition
of the MAP kinases by inhibiting the opening of the calcium channels and causing stimulation to
that of the production of the cGMP and nitric oxide. This is seen to help in the vasodilation. The
MAS receptor mainly shares the counteracting effects. The Mas receptor is mainly seen to get
activated by that of the Ang(1-7) which is actually a subtype of the angiotensin produced by the
plasma enterases from AngI or by ACE2 from AngII produced through a secondary pathway by
tonin and cathepsin G. Studies are of the opinion that Ang(1-7) causes activation of the AT2R
although it has been stated that the bulk o the effect is mediated by MAS R (Cianfrone et al.
2017).
Ramipril is also seen to be the Ace inhibitor that causes inhibition of the actions of that of
the ACE or angiotensin converting enzyme which then lowers the production of the angiotensin
II and at the same time they prevent or decrease the breakdown of bradykinin. It has been found
that reduction of angiotensin II actually contributes the relaxation of the smooth muscles of the
arteriole and this leads to the decrease in the peripheral resistance (Uduman et al. 2016). This

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actually contributes in the reduction of the blood pressure because the blood is now seen to get
pumped through the widened vessels. Moreover, the effect on the bradykinin is also found to be
responsible for the dry cough side effect (Sigaroudi et al. 2018).
Drug interactions that need to be considered by the nurse before administering in the patients:
Firstly, the nurse needs to be extra careful with patients who are undertaking diuretic
therapy. Patients who are on diuretics might be found to be experiencing an excessive reduction
in the blood pressure after ramipril is initiated. The nursing professionals can reduce the
hypotension by either causing reduction as well as the discontinuing of the diuretics or by
increasing the salt intake prior to that of the initiation of the ramipril medication (Jekell et al.
2019). Secondly, the nursing professionals should know that co-administration of ramipril with
that of the other drugs which raises the potassium levels in the serum might cause the occurrence
of hyperkalemia and should therefore monitor the serum potassium levels in such patients.
Third, the professionals should avoid the combination use of other RAs inhibitors with that of
the ramiprils in patients with diabetes. Fourth, the nurses should be careful of not combining
ramipril doses with who are also undergoing therapy with lithium as this might result in high
level of lithium toxicity. Fifth, the patients who are undertaking concomitant mTOR inhibitor
(e.g. temsirolimus) therapy might be also found to be at an increased risk for the angioedema
(Bosone et al. 2017).
Important information the medication that needs to be kept in mind by the professionals:
Ramipril is mainly found to be well-tolerated by most of the patients and the side effects
are usually mild and is transient. The different common side effects that the nurses need to be
careful are dry, persistent cough and also increment in the potassium in the blood. The other

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common side effects are the abdominal pain, diarrhoea, constipation, dizziness, rash, fatigue,
headache and others. Patients may also suffer from loss of taste and appetite, vomiting and
nausea and even numbness and tingling of the hands. The ACE inhibitors like that of ramipril are
also harmful to the fetus and therefore should not be administered by nurses during the time of
pregnancy (Ganeson et al. 2018). The medication should not be used for women who are
breastfeeding. In order to administer the perfect dose for the patient, the nurse can provide the
usual dose of the ramipril for which would be comprising of 2.5-20 mg a day as a single dose or
two divided doses. Those individuals who take diuretics or those who have reduction of the
kidney function might require lower doses. Studies are of the opinion that heart failure is seen to
be initially treated with that of the 1.25-2.5 mg two times a day which should then be titrated
upto 10 mg once daily or 5 mf two times daily. The correct dose for that of the prevention of the
heart attacks and stroke is 2.5 mg to 10 mg every day. The nurse should be instructing the patient
about the ways by which they can increase the efficiency of the medication. This would be
including lifestyle changes. This would include stress reduction programs as well as exercises
and different dietary changes that can increase the effectiveness of the medication (Abdelghany
et al. 2016).
Conclusion:
From the above discussion, it can be seen that ramipril is one of the anti-hypertensive
which participate in controlling the blood pressure of patients and help them to bring under
control. This medication mainly belongs to the category of the angiotensin converting enzyme
inhibitors. This medication mainly works by preventing the action of the ACE which in turn
prevents the formation of angiotensin II. This medication mainly acts by blocking the substance
in the body which causes the blood vessels to become tightened. This medication helps in the

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relaxation of the blood vessels thereby lowering the blood pressure. This is seen to increase the
supply of the blood and the oxygen to that of the heart preventing the heart from suffering from
acute myocardial infarctions and other heart disorders. The nursing professionals who would be
administering this medication to the patient must be very well aware of the side effects and the
drug interactions that it might cause in the patient. The nurse should be administering the correct
dose of the medication and should also try their best to teach the patients in ways by which they
can adhere to the treatment and increase the efficiency of the medication.

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References:
Abdelghany, T.M.M., Abdelsalam, R.M., Attia, A.S. and Elsayed, M.E., 2016. Ramipril could
attenuate thioacetamide-induced liver fibrosis in rats.
Bosone, D., Costa, A., Ghiotto, N., Ramusino, M.C., Zoppi, A., D’Angelo, A. and Fogari, R.,
2017. Effect of ramipril/hydrochlorothiazide and ramipril/canrenone combination on atrial
fibrillation recurrence in hypertensive type 2 diabetic patients with and without cardiac
autonomic neuropathy. Archives of medical science: AMS, 13(3), p.550.
Bull, S., Loudon, M., Francis, J.M., Joseph, J., Gerry, S., Karamitsos, T.D., Prendergast, B.D.,
Banning, A.P., Neubauer, S. and Myerson, S.G., 2015. A prospective, double-blind, randomized
controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis
(RIAS trial). European Heart Journal–Cardiovascular Imaging, 16(8), pp.834-841.
Cianfrone, P., Simeoni, M., Comi, N., Piraina, V., Talarico, R., Cerantonio, A., Gentile, I.,
Fabiano, F.F., Lucisano, G., Foti, D. and Gulletta, E., 2017. How to improve duration and
efficiency of the antiproteinuric response to Ramipril: RamiPROT—a prospective cohort
study. Journal of nephrology, 30(1), pp.95-102.
Gandhi, S.M., Patel, B., Karki, R., Pandey, A., Goli, D. and Singh, K., 2018. Formulation and
Evaluation of Microballoons of Ramipril. Research & Reviews: A Journal of Drug Formulation,
Development and Production, 5(2), pp.13-30.

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Ganesan, D., Holkar, A., Albert, A., Paul, E., Mariakuttikan, J. and Selvam, G.S., 2018.
Combination of ramipril and rutin alleviate alloxan induced diabetic nephropathy targeting
multiple stress pathways in vivo. Biomedicine & Pharmacotherapy, 108, pp.1338-1346.
Jekell, A., Kalani, M. and Kahan, T., 2019. The interrelation of endothelial function and
microvascular reactivity in different vascular beds, and risk assessment in hypertension: results
from the Doxazosin–ramipril study. Heart and vessels, 34(3), pp.484-495.
Knoll, G.A., Fergusson, D., Chassé, M., Hebert, P., Wells, G., Tibbles, L.A., Treleaven, D.,
Holland, D., White, C., Muirhead, N. and Cantarovich, M., 2016. Ramipril versus placebo in
kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled
trial. The Lancet Diabetes & Endocrinology, 4(4), pp.318-326.
Kretzschmar, G., Oehme, J. and Rossen, K., Sanofi-Aventis Deutschland GmbH, 2017. Process
for the preparation of ramipril. U.S. Patent Application 15/317,362.
Krupickova, S., Gatzoulis, M.A., Cheang, M.H., Rigby, M., Fraisse, A., Uebing, A.,
Dimopoulos, K., Swan, L., Alonso-Gonzales, R., Li, W. and Babu-Narayan, S.V., 2016.
Ramipril Efficacy on Left Ventricular Systolic and Diastolic Function in Stable Patients With
Pulmonary Regurgitation After Repair of Tetralogy of Fallot. Circulation, 134(suppl_1),
pp.A14544-A14544.
Krupickova, S., Li, W., Cheang, M.H., Rigby, M.L., Uebing, A., Davlouros, P., Dimopoulos, K.,
Di Salvo, G., Fraisse, A., Swan, L. and Alonso-Gonzalez, R., 2018. Ramipril and left ventricular
diastolic function in stable patients with pulmonary regurgitation after repair of tetralogy of
Fallot. International journal of cardiology, 272, pp.64-69.

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Lawler, A., Reid, C.M., Blombery, P.A. and Kingwell, B.A., 2015. Notice of Retraction:
Ramipril Markedly Improves Walking Ability in Patients With Peripheral Arterial
Disease. Annals of Internal Medicine, 163(11), pp.884-884.
Mietus, C.J., Karvelis, P., Lackner, T., Hernandez, H., DeSpiegelaere, H., Xie, F., Porter, T.,
Pipinos, I. and Casale, G.P., 2017. Microvascular Response to Ramipril in Peripheral Artery
Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(suppl_1), pp.A115-A115.
Nassiri, M., Babina, M., Dölle, S., Edenharter, G., Ruëff, F. and Worm, M., 2015. Ramipril and
metoprolol intake aggravate human and murine anaphylaxis: evidence for direct mast cell
priming. Journal of Allergy and Clinical Immunology, 135(2), pp.491-499.
Sigaroudi, A., Kinzig, M., Wahl, O., Stelzer, C., Schroeter, M., Fuhr, U., Holzgrabe, U. and
Sörgel, F., 2018. Quantification of hydrochlorothiazide and ramipril/ramiprilate in blood serum
and cerebrospinal fluid: a pharmacokinetic assessment of central nervous system adverse
effects. Pharmacology, 102, pp.133-137.
Uduman, S., Thattakudian, M.S., Reddy, R.B., Punuru, P., Chakka, G. and Karunakaran, G.,
2016. Protective role of ramipril and candesartan against myocardial ischemic reperfusion injury:
a biochemical and transmission electron microscopical study. Advances in pharmacological
sciences, 2016.

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