NSC2500: Heart Failure - Pathophysiology, Pharmacology & Nursing

This report provides a comprehensive overview of heart failure, its pathophysiology, and the use of Ramipril in its management. It begins by explaining the homeostatic mechanisms responsible for maintaining blood flow and how heart failure disrupts these mechanisms. The report details the changes in the heart due to heart failure, including increased heart rate and alterations in the vascular layer. It then focuses on Ramipril, an ACE inhibitor used to treat heart failure, discussing its pharmacodynamics, pharmacokinetics, indications, contraindications, precautions, side effects, and drug interactions. The report also emphasizes the importance of lifestyle modifications in managing heart failure and concludes with the relevance of this information for nursing professionals, highlighting the need for evidence-based practice to improve patient outcomes. The information is targeted towards nursing professionals to help them effectively deliver care to heart failure patients.

Running head: HEALTHCARE
Pharmacology and pathophysiology in health
Name of the Student
Name of the University
Author Note

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Abstract
Introduction- Three homeostatic mechanisms are accountable for maintaining sufficient flow of
blood namely, the endocrine, neural, and autoregulatory mechanism.
Discussion-Heart failure is characterized by an increase in heart rate, which in turn is mediated
by amplification in the sympathetic activity for maintenance of sufficient cardiac output. This
drug is responsible for inhibition of the angiotensin converting enzyme that leads to a reduction
in production of angiotensin II. While the mechanism through which it stimulates separation of
the renin-angiotensin-aldosterone system is predominantly correlated with reduction in elevated
blood pressure, the drug also creates antihypertensive impacts amid patients who report low-
renin hypertension. Alteration in the vascular layer of the heart is also caused due to an increase
in size of the terminally differentiated fibres of cardiac muscles for enhancing contractility,
which in turn directly contributes to greater stiffness, thereby reducing ability of the heart to
relax and the time of diastole. Ventricle volume increase also brings about reduction in stroke
volume, owing to insufficient heart contraction. Ramipril will be administered for effective
management of the condition. The impact of ramipril on high blood pressure appears to be a
direct consequence of inhibition of both circulating and tissue ACE activity, thus lowering the
formation of angiotensin II in the plasma and tissue.
Target audience- Nursing professionals are the target audience since they come across countless
patients suffering from heart failure.
Conclusion- Thus, information on the medication, its contraindications, and precautions will help
nurses effectively deliver care to heart failure patients.
Keywords: heart failure, ramipril, nursing

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Table of Contents
Homeostasis.....................................................................................................................................3
Pathophysiology..............................................................................................................................3
Medication.......................................................................................................................................4
Drug naming................................................................................................................................4
Pharmacodynamics......................................................................................................................4
Pharmacokinetics.........................................................................................................................5
Indications....................................................................................................................................6
Contraindication..........................................................................................................................6
Precautions...................................................................................................................................6
Side effects...................................................................................................................................7
Drug interaction...........................................................................................................................7
Lifestyle modification......................................................................................................................8
Relevance.........................................................................................................................................8
Conclusion.......................................................................................................................................9
References......................................................................................................................................10

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Homeostasis
The nervous system controls vascular homeostasis through the cardiovascular centres
located in the brain. The autonomic nervous system and neural responses from limbic system
also help in controlling blood flow. The cardiovascular Centre responds to changes in pressure of
blood, in addition to concentrations of carbon dioxide, oxygen, and hydrogen ion. While the
cardiovascular centres trigger cardiac function by controlling stroke volume and regulating heart
rate via sympathetic stimulation, smooth muscle contraction is controlled by the vasomotor
centre, which in turn is controlled by alteration in diameter that affects blood flow pressure and
peripheral resistance (Wood & Valentino, 2017). Receptors present in the heart chambers and
blood vessels transfer impulse and control blood pressure.
An increase in blood pressure leads to stretching of the receptor that initiates action
potential, following which the cardiovascular centre is triggered, and a reflex for maintaining
homeostasis is initiated. The release of catecholamines, norepinephrine, and epinephrine from
the adrenal medulla helps in controlling fight or flight response by increasing heart rate, while
causing construction of the blood vessels, and redirecting flow of blood to the muscles heart and
liver (Hall, 2016). Vasopressin secreted from the hypothalamus also leads to an increase in tissue
fluid osmolarity as a response to blood volume loss. This send signals to the brain cells for water
reabsorption, which prevents additional loss of fluid in urine, and helps in restoring blood
pressure and volume (Lozić, Šarenac, Murphy & Japundžić-Žigon, 2018).

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Pathophysiology
Heart failure is associated with the decrease in efficiency of cardiac muscles due to
overloading or damage. This sympathetic activity also leads to abnormal heart rhythms, which
might even prove fatal. This results in hypertension, myocardial infarction, and amyloidosis. An
increase in workload over time results in significant changes to the heart. Overloading in the
ventricle also leads to a decrease in force of constriction. Healthy heart is characterized by an
increase in contraction force due to greater filling of ventricles, which results in a subsequent
augmentation in cardiac output (Francis & Tang, 2019). However, during heart failure the
mechanism fails, and the ventricles become loaded with blood to such an extent that decreases
the efficiency of cardiac muscle contraction. Eventually, it lessens the capability to cross link
myosin and actin filaments in the cardiac muscles that have been overstretched. This increase in
workload is also governed by prolonged activation of the renin-angiotensin system that results in
dilation, fibrosis, and structural modifications in the left ventricle from an elliptical shape to
spherical (Guazzi & Naeije, 2017).
Medication
Drug naming
One drug that will be administered for the management of heart failure is ramipril. The
chemical name is (2S,3aS,6aS)-1[(S)-N-[(S)-1-Carboxy-3phenylpropyl] alanyl]
octahydrocyclopenta [b]pyrrole-2-carboxylic acid, 1-ethyl ester (NCBI, 2020). It belongs to the
category of ACE inhibitors, also referred to as angiotensin converting enzyme inhibitors, and is
typically sold under the trade name of Altace.

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Pharmacodynamics
This drug brings about an inhibition of the angiotensin converting enzyme, which in turn
leads to a decrease in production of angiotensin II. This eventually reduces the degeneration of
bradykinin (Serrano-Rodríguez et al., 2016). Angiotensin II decrease is also responsible
for triggering relaxation of the smooth muscles of the arterial walls, which increases total
peripheral resistance. This eventually results in a reduction in blood pressure, when blood gets
pump through the vessels.
Pharmacokinetics
Administration of the drug results in peak plasma concentration within an hour and
around 50-60% of the drug gets absorbed, which in turn is not affected by food in
gastrointestinal tract. Ramipril gets converted to ramiprilat, through cleavage of ester groups,
which primary occurs in the liver. Ramiprilat reaches a peak plasma concentration within 4
hours of its intake, and ramipril has a serum protein binding of an estimated 73%, in contrast to
56% of ramiprilat. It also gets metabolized to inactive diketopiperazine acid, diketopiperazine
ester, and glucuronides of ramiprilat and ramipril. 44% and 28% are the absolute bioavailability
of ramiprilat and ramipril respectively (Drugbank.ca, 2020).
Ramipril at also reaches a steady state plasma concentration bifold dose, following which
the concentrations deteriorate in a triphasic manner. 60% of ramipril gets eliminated through
urine after its oral administration, with the remaining 40% being eliminated through faecal
matter. The drug that is obtained from faecal matter often represents both biliary metabolic
excretions, and traces of the drug which might have been unabsorbed (NCBI, 2020). Not more
than 2% of the administered ramipril drug is recovered through urine, in any unchanged form.

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However, patients suffer from impaired renal function and report a decrease in urinary
excretion. Its general route of administration is through the mouth.
Indications
Ramipril is primarily indicated for the management of hypertension or congestive heart
failure, in order to decrease an elevated blood pressure, which in turn increases the risk of
suffering from non fatal cardiovascular complications, myocardial infarction or strokes. It is also
used for improving survival of a patient after a cardiac attack.
Contraindication
Contraindications to the administration of ramipril comprise of impaired flow of blood in
the kidneys, also referred to as renovascular disease. Some additional side effects are dizziness,
shakiness, chest pain, and fever. Severe renal impairment occurs particularly in patients who
suffer from renal artery stenosis, patients having a history of angioedema, volume depleted
patients, those suffering from hypertension, or pregnant patients (Drugbank.ca, 2020). Ramipril
should not be administered in combination with aliskiren, in patients suffering from diabetes
mellitus (Chen et al., 2017). Additionally, if suffering from hyperkalemia, patients should not be
given this drug since it might result in a further elevation in the level of potassium in circulating
bloodstream (Chauhan & Ahmad, 2019).
Precautions
Elderly patients have the likelihood of suffering from age-associated kidney, liver, or
heart disease, which might necessitate an adjustment in dosage of the drug, prior to its
administration. Studies conducted among pregnant females have also reported an increased risk
to the foetus during all trimesters (Drugbank.ca, 2020). Owing to the fact that these inhibitors

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create an impact on metabolism of polypeptides and eicosanoid, together with androgynous
bradykinin, the patients might report signs and symptoms of angioedema and anaphylactoid
reactions, at the time of desensitization. During its administration, a healthcare professional must
check for allergic symptoms in the patient to other ACE inhibitors.
Side effects
Some commonly reported adverse effects of the drug are dry cough, shakiness, light-
headedness due to hypertension, dizziness, fatigue, dryness of mouth, chest pain, nausea,
painting, signs of infection like chills, fever, and persistent sore throat, neutropenia or decrease in
white blood cell, hypokalemia and erectile dysfunction (Meyer, 2016). Although serious
hypersensitive reactions are unlikely, they require immediate medical attention, and are
characterized by swelling of throat and mouth, in addition to rash or itchiness.
Drug interaction
Patients who are administered diuretics, particularly those who have been recently been
subjected to diuretic therapy, might occasionally report signs of an abrupt decrease in blood
pressure, following initiation of ramipril therapy. The probability of occurrence of hypertensive
impact can be reduced by the discontinuing or decreasing the diuretic, or augmenting the intake
of salt prior to administration of ramipril. Under most circumstances, a combined therapy of
ramipril along with RAS inhibitors should be avoided. An increase in levels of serum lithium,
and signs and symptoms of lithium toxicity have also been found amongst several patients who
are administered this drug, in combination with lithium (Hommers et al., 2019). This calls for the
need of frequent patient monitoring. If there is usage of diuretic, the risk of suffering from
lithium toxicity increases manifold. Nitride reactions that are characterized by nausea, facial
flushing, hypertension, and vomiting are also reported by patients who are administered ramipril,

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in combination with sodium aurothiomalate or injectable gold (Brampton, 2017). The risk of
angioedema also remains for patients who are administered mTOR inhibitors or neprilysin
inhibitors.
Lifestyle modification
The risk of an individual to develop heart failure demonstrates an inverse correlation to
the amount of physical activity that the person participates in. It has been reported by Jeong et al.
(2019) that 500 MET-minutes/week physical activity is associated with a 7% and 14% reduction
of risk in primary and secondary prevention groups, respectively. People diagnosed with
cardiovascular diseases get maximum benefits from 500 MET-minutes/week physical
activity, in comparison to healthy subjects. The risk of heart failure can also be decrease by
reducing elevated blood pressure and high blood cholesterol, in addition to taking necessary
efforts for controlling blood glucose level. Maintaining a healthy body weight, in addition to
decreasing the consumption of sugar and alcohol, besides reducing sodium intake will also
provide help. Moreover, smoking cessation has also been found to reportedly decrease the risk of
suffering from heart failure.
Relevance
The findings are relevant to clinical practice and nursing professionals since an estimated
300,000 Australian adults, aged more than 45 years suffer from chronic heart failure with 30,000
diagnoses of new cases every year (AIHW, 2003). Since nursing professionals act as frontline
healthcare workers, and have to spend maximum time delivering care to patient, a
comprehensive idea on the mechanism of action of ramipril will help them in participating in

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evidence based practice, thereby enhancing health outcomes of heart failure patients, besides
decreasing mortality rate.
Conclusion
Thus, it can be concluded that inability of the heart to pump adequate amount of blood
results in a failure in meeting the needs of the human body, consequently causing congestive
heart failure. Ramipril is an ACE inhibitor and has been found effective in the management of
the condition. However, prior to its administration, the contraindications with other drugs must
be taken into consideration.

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References
Australian Institute of Health and Welfare. (2003). Heart failure. . . what of the future?.
Retrieved from https://www.aihw.gov.au/reports/heart-stroke-vascular-diseases/heart-
failure-future/contents/summary
Brampton, O. N. (2017). PrRANTM-RAMIPRIL HCTZ. Retrieved from
https://pdf.hres.ca/dpd_pm/00047217.PDF
Chauhan, M., & Ahmad, F. (2019). Ramipril. Retrieved from
https://europepmc.org/article/NBK/NBK537119
Chen, Y., Meng, G., Bai, W., Ma, Y., Xie, L., Altaf, N., ... & Ji, Y. (2017). Aliskiren protects
against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase
dependent manner. Clinical and Experimental Pharmacology and Physiology, 44(2),
266-274. https://doi.org/10.1111/1440-1681.12692
Drugbank.ca. (2020). Ramipril. Retrieved from https://www.drugbank.ca/drugs/DB00178
Francis, G. S., & Tang, W. W. (2019). Pathophysiology of congestive heart failure. Reviews in
cardiovascular medicine, 4(S2), 14-20.
https://rcm.imrpress.com/EN/2153-8174/abstract915.shtml
Guazzi, M., & Naeije, R. (2017). Pulmonary hypertension in heart failure: pathophysiology,
pathobiology, and emerging clinical perspectives. Journal of the American College of
Cardiology, 69(13), 1718-1734. DOI: 10.1016/j.jacc.2017.01.051

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Hall, J. E. (2016). Guyton and Hall Textbook of Medical Physiology, Jordanian Edition E-Book.
Elsevier. Retrieved from https://books.google.co.in/books?
hl=en&lr=&id=qyfRDwAAQBAJ&oi=fnd&pg=PP1&dq=guyton+and+hall&ots=r16H99
zfem&sig=04LF3VKophTAnt4VnGYe0s65mWM&redir_esc=y#v=onepage&q=guyton
%20and%20hall&f=false
Hommers, L., Fischer, M., Reif-Leonhard, C., Pfuhlmann, B., Deckert, J., & Unterecker, S.
(2019). The Combination of Lithium and ACE Inhibitors: Hazardous, Critical,
Possible?. Clinical drug investigation, 39(5), 485-489. https://doi.org/10.1007/s40261-
019-00768-7
Jeong, S. W., Kim, S. H., Kang, S. H., Kim, H. J., Yoon, C. H., Youn, T. J., & Chae, I. H.
(2019). Mortality reduction with physical activity in patients with and without
cardiovascular disease. European heart journal, 40(43), 3547-3555.
https://doi.org/10.1093/eurheartj/ehz564
Lozić, M., Šarenac, O., Murphy, D., & Japundžić-Žigon, N. (2018). Vasopressin, central
autonomic control and blood pressure regulation. Current hypertension reports, 20(2),
11. https://doi.org/10.1007/s11906-018-0811-0
Meyer, N. (2016). Clozapine/ramipril/sodium-valproate/spironolactone. Reactions, 1583, 338-9.
Retrieved from
https://search.proquest.com/openview/3777bc2a259738bc6fb8705281a5f6fe/1?pq-
origsite=gscholar&cbl=43703
National Center for Biotechnology Information. (2020). Ramipril. Retrieved from
https://pubchem.ncbi.nlm.nih.gov/compound/Ramipril