Drugs Used in the Management of M Green - Case Study Example

Names of medication and Dosage Mode of Action & why is it ordered for this patient Pharmakinetics related to the patient Main side-effects related to patient Contraindications and Drug interactions related to patient Frusemide A loop diuretic which inhibits the Na+/K+/Cl- co-transporter at the loop of Henle preventing the re-arbsoption of water and salt thus enhancing excretion. This was to regulate the hypertension that the patient had developed . . Frusemide is rapidly absorbed from the gastrointestinal tract. The onset of diuresis following oral administration is within one hour. The peak effect occurs within 1-2hours. The duration of diuretic effect is six to eight hours. . Peak plasma concentrations increase with increasing dose. Frusemide is extensively bound to plasma proteins, mainly to albumin.. Is decreased due to the liver disease since its glucuronidation occurs in the liver Urinary excretion occurs for frusemide Dehydration due to excessive loss of water. Loop diuretics can cause postural hypotension by reducing the circulating volume Excessive diuresis may result in dehydration and reduction in blood volume with circulatory collapse and with the possibility of vascular thrombosis and embolism, Known hypersensitivity to frusemide or sulfonamides or any of the inactive ingredients (see Composition). Patients allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may show cross sensitivity to frusemide. Complete renal shutdown, impaired renal function or anuria. If increasing azotaemia and oliguria occur during treatment of severe progressive renal disease, discontinue frusemide. Severe hypokalaemia, hyponatraemia, hypovolaemia or hypotension must be regarded as contraindications until serum electrolytes, fluid balance and blood pressure have been restored to normal levels. In hepatic coma or precoma and conditions producing electrolyte depletion, frusemide therapy Lactulose A bulk laxative that was prescribed because the patient had constipation . the Osmotically active laxative which has   lactulose which is degraded by saccharolytic bacteria in the colon into lactic acid. Thus acidification of the intestinal content takes place and the osmotic pressure is markedly raised. Stool volume increases by moderate water retention in the intestine, resulting in softer faeces. Furthermore, intestinal peristalsis is enhanced leading to shorter transit time and eased bowel movement. The lactulose enhances excretion andprevents ammonia accumulation and enhance its excretion in liver diseases through the production of the lactic acid and acetic acid which acidify the colonic contents thus formation of the non-absorbable NH4+ from NH3, traps NH3 in the colon and effectively reducing plasma NH3 concentrations lactulose is poorly absorbed from the gastrointestinal tract and no enzymes capable of hydrolysis of lactulose into its component monosaccharides are known to be present in human gastrointestinal tissue. Lactulose reaches the colon unchanged. There it is metabolised by colonic bacteria to low molecular weight acids, i.e. lactic acid and other short chain carboxylic acids. . Dehydration Due to excessive loss of water in the faecal matter. electrolytic disturbances such as hypernatremia. diarrhea and constant flatulence are associated with lactulose administration Known hypersensitivity to any content of the lactulose solution Metoclopramide (Maxolon) Was prescribed to reduce the nausea and vomiting . The mode of action is that it - Stimulates motility of upper GI tract; also increases lower oesophageal sphincter tone & blocks dopamine receptors at chemoreceptor trigger zone. Also relaxes pyloric sphincter & duodenal bulb & increases peristalsis of duodenum & jejunum to increase gastric emptying. Tardive diskinesia hypertension ,hypotension and constipation, depression, headache, Phaeochromocytoma because the drug may cause a hypertensive crisis, probably due to release of catecholamines from the tumour. Known hypersensitivity or intolerance to the drug. tardive dyskinesia. Omeprazole reduces the secretion of gastric acid by irreversibly inhibiting the primary agent for gastric acid production, gastric enzyme H+ K+ -ATPase (proton pump) within the parietal cells of the stomach omeprazole may cause damage to liver cells since its metabolized by the liver,leading to the inflammation of the liver. is completely metabolized by the CYP 450 system, mainly in the liver AND excreted as metabolites in the urine and the remainder is found in the feces, primarily originating from bile secretion. Hepatitis. Inflammation of liver cells Omeprazole is a liver enzyme inducer hence interacts with many other drugs administered concurrently increasing the metabolism ,reduce their bioavailability 5. How BMI of 40 will impact on the pathophysiology and/or pharmacology in Mrs Greens case. Pierre et al (2008, p. 523) asserts that just as heart rate, temperature, breathing rate and blood pressure are vital signs that aid in indicating underlying pathology, as diagnostic criteria, prognostic factors and as indicators for treatment initiation, body mass index (BMI) is also a vital sign. Subsequently, in Mrs Green case, a BMI of 40 is an indication of acute obesity (considering BMI of > 30 is a sign of obesity) and this may impact on the pathophysiology and pharmacology of the Mrs Greens liver failure leading to risk of further morbidity and increased mortality. Rutherford et al (2006, p. 1544) assert that BMI influences the outcome of acute liver failure. The risk of mortality and morbidity is higher in obese patients with risk of odds of death at a rate of 1.63 times in transplantation than non obese individuals and 3.4 times after transplantation (Rutherford et al, 2006, p. 1544). Obesity and diabetes are also involved in development of non-alcoholic fatty liver disease (NAFLD), which is also a feature of type 11 diabetes, hypertension, and hyperlipidemia (Rutherford et al, 2006, p. 1545). Besides diabetes, obesity is known to be the strongest predictor of fibrosis in non alcoholic fatty liver disease and a risk factor for steatosis, steatohepatitis, and cirrhosis. How BMI of 40 will impact on the pathophysiology of Mrs Greens Liver failure Insulin is crucial in metabolism of glucose with its main targets including adipose tissue, liver and muscles. Besides hormones, the response of these tissues to insulin determines the concentrations of fatty acids, glucose and other metabolites. The levels of blood glucose are largely determined by the balance of hepatic glucose output by the liver, which is suppressed by insulin and glucose uptake by muscle, which is stimulated by insulin (Olefsky and Glass, 2010, p. 220). Insulin further promotes uptake and storage of fatty acids in form of triglycerides and inhibits lipolysis of stored triglycerides (Olefsky and Glass, 2010, p. 220). Obesity impacts on the three target tissues by inducing insulin-resistance resulting to reduction in insulin-stimulated uptake of glucose, increased fatty acid release from the adipose tissue and impaired glucose suppression in liver. Spillovers of free fatty acids to the liver (steatosis) and of other inflammatory mediators from the expanded adipose tissue in obese individuals further contribute to liver damage. This spillover contributing to increased dyslipidemia, atherosclerosis, and insulin resistance may also cause non-alcoholic fatty liver disease (Pierre et al, 2008, p. 524). The increased intrahepatic amounts of free fatty acids in the liver are a key source of oxidative stress (free electrons, H202, and reactive oxygen species) from increased beta oxidation of fatty acids by hepatocyte mitochondria (Rutherford et al, 2006, p. 1545). The oxidative stress stimulates production of cytokine, which inhibits hepatic regeneration and is also a cause of hepatocyte injury. Fatty livers are therefore more vulnerable to oxidative stress, endotoxin/cytokine-mediated injury, ischemia, sudden increase in free fatty acid supply and other factors that cause ATP depletion (Pierre et al, 2008, p. 524). Mrs Green would be at increased susceptibility to further liver damage and severe liver failure compared to the average population. The BMI may also increase as a result of dilutional hyponatremia, and these occurs where there is reduction of serum concentrations of sodium to below 130mEq/l due to impairment of renal secretion of free water (McDonald et al, 2010, p. 628). This often occurs with presence of ascites as in Mrs. Green’s case and is occasioned by severe retention of sodium. Renal retention of free solute-free water occurs and is disproportionate to the sodium retained and subsequently the levels of sodium levels decrease increase in the total levels of sodium. The high level of hormone vasopressin in the circulation is considered a major factor in the impairment of solute-free water excretion. How BMI of 40 will impact on Mrs Green’s pharmacology The link to neurological and non neurological symptoms frequently seen in patients with dilutional hypnoatremia contributing to higher BMI due to water retention also determines and influences treatment outcomes. One of the pharmacological outcomes is that patients experience poor or no response to diuretics (McDonald et al, 2010, p. 629). This may require that Mrs. Green fluid intake is restricted to levels that are similar to urine output so as to prevent fluid imbalance. McDonald et al 2010 (p. 629) suggests that from a pathophysiological perspective, administration of saline sodium concentrations does not make sense since total body sodium and extracellular fluid volume increases with increase in patients with dilutional hypnatremia and invariably leading to increase in edema and ascites. Albumin infusion and oral active drugs such as vaptans, which selectively antagonize vasopressin V2 receptor (responsible for water reabsoprtion in nephron) is recommended as alternative treatment option. These drugs selectively antagonize the effects of vasopressin in the kidney so that solute-free water excretion is increased resulting to restoration of the abnormal water balance, reducing the body water and normalizing sodium water concentration with the subsequent reduction in the BMI. For instance, in studies where Tolvaptan was used for treatment, there was marked improvement in the serum sodium, fluid balance ad significant reduction in weight was observed with no impact on the patients renal function (McDonald, 2010, p. 630). The reduction in ascites, which is marked by reduction in body weight and subsequently in the BMI is also accompanied by reduction in abdominal girth through the action of the V2 receptor antagonists with its contribution to ascite control and increase in serum sodium in patients (McDonald et al 2010, p. 630). References Pierre, Singer, Joelle. Attal, Haim, Shapiro. Body mass index and weight change: The sixth vital sign. IMAJ, Vol 10. 2008. 523-25 Arroyo, Vicente, Colmenero, Jordi. (2003). Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. Journal of Hepatology 38, 69-89. Olefsky, Jerrold and Glass, Christopher. 2010. Macrophages, inflammation and insulin resistance. Annual review of physiology, vol 72: 219-246. Garcia, Jorge, Julio, Martinez, Jose, Estradas, Aldo, Torre, and Isael, Uribe. 2007. Pathophysiology of ascites and dilutional hyponatremia: contemporary use of aquaretic agents. Annals of Hepatology 2007; 6(4). 214-221. McDonald et al. 2010. Evidence based gastroenterology and hepatology. New York: Wiley. Read More