Pharmacy Practice And Therapeutics Essay

Question:

Discuss about the Pharmacy Practice and Therapeutics.

Answer:

Introduction:

The kidney contributes as significant function in the management of different body fluids and control of blood pressure. Earlier studies have shown that disruption in the function of the renal system can lead to the development of hypertension. Factors mainly responsible for the development of hypertensive state are: functional augmentation of renal vascular tone like elevated renal vascular resistance, renal arterial vasoconstriction due to increased angiotensin II , deficiency in control of renal blood flow like decreased renal blood flow, increased sympathetic activity by increasing level of noradrenalin, altered response of angiotensin II to renal vasculature leads to vasoconstriction and decreased dopaminergic activity.

Change in the renal vascular tone results in the vascular resistance and consequent increase in the blood pressure. Alteration in the vascular tone is due to unusual sympathetic system reaction to the increased level of sodium which is due to the increased secretion of aldosterone hormone release.

In hypovolemia condition there is the decreased blood flow and it is detected by barorecptors in the blood vessels, macula densa cells present in the loop of henle and sympathetic nervous system. This decrease in blood flow leads to the renal ischemia condition. In response to the sympathetic stimulation like increase noradrenaline release there is the increased release of rennin in the granular cells of juxtaglomerular apparatus. Renin detects alteration in the renal perfusion pressure through stretch receptors present in the renal vascular walls. Increased level of rennin leads to the conversion of angiotensinogen in the liver into angiotensin I. Angiotensin-converting enzyme plays important role in the conversion of angiotensin I to angiotensin II and this enzyme mainly found in the lung and also found in the endothelial and kidney epithelial cells. Angiotensin II acts on the adrenal gland to secret aldosterone which leads to the tubular Na+ Cl- reabsorption and K+ excretion, which leads to the increase in the blood pressure. Angiotensin II acts on the AT1 receptor which releases Ca++, this results in the decreased level of cAMP and increased blood pressure (Holechek, 2003).

Raynaud's syndrome is a condition which affects extremities of the body like fingers and toes. This condition is painful and color changes of the extremities occur. This painful condition of the extremities is due to effect of extreme conditions like very high and low temperature and also emotional stress plays role in this condition. Due to these external factors there is narrowing of the blood vessels in the extremities. This condition also occurs as a complication of disease like rheumatoid arthritis, lupus and scleroderma (Marshall et al., 1976).

Peripheral artery disease is complication of the circulatory system and it occurs due to decreased blood flow to the limbs, heart and brain due to the narrowed arteries. This results in the pain in the leg which is also called as claudication. This narrowing of the arteries occurred mainly due to the deposition of plaque in the arteries which is called as atherosclerosis. This plaque is formed by fat, calcium, cholesterol, and fibrous tissue in the blood. Peripheral artery disease is a risk factor for other cardiovascular disease like heart attack, coronary heart disease, stroke, and ischemia.

Beta blockers are mainly used for the cardiovascular disease like coronary artery disease, hypertension and arrhythmias. In these diseases, this effect is due to antagonism of both beta 1 and 2 receptors. These beta blockers produce effects like reduced cardiac output and unchecked alpha adrenergic action. These effects results in the reduced blood supply to the extremities and vasoconstriction. In both the diseases Raynaud's syndrome and peripheral artery disease, there is the vasoconstriction which increases the blood pressure and also there is the reduced supply of blood to the extremities like figures, toe and limbs. This leads to the painful condition like claudication. If beta blockers administered to these patients of Raynaud's syndrome and peripheral artery disease, there is the possibility of exaggerating these disease conditions and patient may deteriorate. Evidences are available for the increase in frequency of Raynaud's syndrome and peripheral artery disease due to administration of beta blockers (Paravastu et al., 2013).

Airway airway remodelling comprises of injury to the epithelial cells, goblet cell hyperplasia and nucus secretion, subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis.

Tyrosine kinase inhibitors:

Several receptor tyrosine kinases like epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR) are responsible for the airway remodeling in the lung diseases. Above mentioned growth factors are the main ligands for these kinase enzymes and these growth factors plays important role in the remodeling of lung in respiratory diseases. These growth factor inhibitors exhibited reduced collagen deposition, reduced goblet cell proliferation and reduced airway smooth muscle contraction (Manuyakorn et al., 2013).

Biological therapies:

Biological therapies like Omalizumab, Mepolizumab, Etanercept etc. act on the inflammatory cytokines in the lung diseases. Increased level of inflammatory cytokines leads to the airway remodeling in the patients with lung diseases. It has been well established that epithelium plays significant part in the beginning of the airway remodeling. Epithelium mesenchymal transformation (EMT) initiated by these cytokines and environmental factors needs to be prevented. These biological therapies inhibit these cytokines and consequently prevent airway remodeling maintenances property of EMT. These biological therapies help in alleviating airway remodeling by preventing eosinophils recruitment, angiogenesis, by preventing formation of fibroblasts, by prevention smooth cell differentiation and by acting on endothelial cells and alveolar macrophages. Effect of the biological therapies in airway remodeling is evident from positive effect of these therapies on forced expiratory volume (FEV1), asthma exacerbations, airway obstruction, collagen deposition and bronchoconstriction (Cho, 2001).

Inhaled corticosteroids (ICS): Inhaled corticoids like flunisolide, budesonide, fluticasone and beclomethasone are mainly used as anti-inflammatory drugs in respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Inflammatory cells and cytokines are mainly responsible for the structural airway changes and the airway remodeling. These inhaled corticosteroids produce its effect in airway remodeling by reducing angiogenesis in the lamina propria below the epithelium. Inhaled corticosteroids showed effect on airway remodeling by reducing bronchial hyperresponsivness (Riccioni et al., 2004).

References:

Cho, J.Y. (2001). Recent advances in mechanisms and treatments of airway remodeling in asthma: A Message from the bench side to the clinic. Korean Journal of Internal Medicine, 26(4), 367–383.

Holechek, M.J. (2003). Renal hemodynamics: an overview. Nephrology Nursing Journal, 30(4), 441-6.

Marshall, A.J., Roberts, C.J., and Barritt, D.W. (1976). Raynaud's phenomenon as side effect of beta-blockers in hypertension. British Medical Journal, 19(1), 1498–1499.

Manuyakorn, W., Howarth, P.H., and Holgate, S.T. (2013). Airway remodelling in asthma and novel therapy. Asian Pacific Journal of Allergy and Immunology, 31, 3- 10.

Paravastu, S.C., Mendonca, D.A., and Da Silva, A. (2013). Beta blockers for peripheral arterial disease. Cochrane database of systematic reviews, 11(9), CD005508. doi: 10.1002/14651858.CD005508.

Riccioni, G., Di Ilio, C., and D’Orazio, N. (2004). Pharmacological treatment of airway remodeling: inhaled corticosteroids or antileukotrienes?. Annals of Clinical & Laboratory Science, 34(2), 138-142.

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