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Case History Mr. RS, a 43yr old male, presented at the Emergency department with a five day history of fevers and coughing and a 3 day history of nausea and vomiting. MrRs had a history of diabetic nephropathy secondary to T1DM and had a kidney and pancreatic transplant in 2000. Mr RS had a history of T1DM since he was a thirteen years old boy. He was started on insulin at diagnosis and remained on it until his transplant in 2000. He had a history of poor control of his diabetes, partly due to heavy alcohol consumption while he was a university student. He had also trouble taking his insulin and monitoring his blood sugar levels regularly. His pancreatic and kidney transplants are believed to be as a result of poor control of his diabetes. RS is a non-smoker and social drinker. He was diagnosed with acute renal failure due to dehydration secondary to flu-like symptoms, and at risk of secondary bacterial infection due to immunosuppressive therapy. No known allergies. Social History: He is divorced and lives alone. Table 1: Medication History Medications Drug prior to admission Tacrolimus Mycophenolate Prednisolone Aspirin Sodibic Dosage Indications √-Continue W- Withhold X- Cease ↑- Increased ↓- Decreased + - Added PO 500mcg bd PO 1gm bd Immunosuppressant for transplantation Immunosuppressant for transplantation Immunosuppressant W Anti-platelet and blood thinning Electrolytes √ PO 25mg OD PO 75mg OD PO 840mg OD W W W Medication in ED Ceftriaxone IV 1gm D Azithromycin IV 500mg D Immunomodulator for community acquired pneumonia Oseltamavir PO 75mg BD Ondansetron IV 4-8mg BD prn prochlorperazine IV 12.5mg q8h prn Morphine IV 2.5mg prn Pantoprazole IV 40mg Daily O2 Table 2: Laboratory Results Blood results on admission Hb 183(H) WCC 12.4(H) Na+ 133(L) K+ 4.5(N) Urea 20(H) Creatinine 229(H) eGFR 27(L) Glucose 8.1(H) Broad spectrum antibacterial, Empirical treatment effective against gram positive and gram negative bacteria. Prophylactic H1N1 Treatment Antiemetic for Nausea and Vomiting Antiemetic for Nausea and Vomiting low dose for Pulmonary Oedema Pain Proton pump inhibitor for GORD and peptic ulceration. To treat hypoxia and low oxygen saturation levels. Most recent blood results 142(N) 14.2(H) 132 14.8(H) 149(H) 45(L) 8.1(H) NormalRange 115-165g/L 4-11/L 135-145mmol/L 3.4-4.5mmol/L 7-18 mg/dL 0.6-1.2 mg/dL 75-190ml/min 3-5.4mmol/L He is not using insulin because has pancreas transplant Acute Renal Failure Acute renal failure (ARF) is a disease in which there is a sudden and fast decrease in renal function resulting in the accumulation of nitrogenous waste in the blood1. ARF rapid decline in glomerular filtration rate (GFR) over hours to days. ARF complicates approximately 5–7% of hospital admissions and up to 30% of admissions to intensive care units. ARF could be classified as pre-renal, intrarenal or post-renal, depending on the causes and locations of the abnormalities.2 Clinical manifestations and symptoms ARF is usually asymptomatic and diagnosed with biochemical monitoring of hospitalized patients reveals a new increase in blood urea and serum creatinine concentrations. In ARF, the 24hr urine production is reduced to 200-400mL. This is called Oliguria, which is the most common symptom of ARF.1 Oliguria results in the accumulation of creatinine, urea, potassium, hydrogen and phosphate ions in the blood which lead to the development of symptoms such as nausea, vomiting, diarrhea, GI hemorrhage and muscle cramps1. Diagnosis and Management of ARF Diagnosis of ARF is through taking the full patient history, physical examination, urinalysis (concentration and volume), blood analysis (WCC, ESR, CR etc.) and radiological examinations1.MrRs above blood analysis (WCC, CR), urine analysis ruled out ARF. Management of ARF should focus on the recovery of kidney functions and keeping patients alive for longer. The management principles should include early identification of patients at risk (e.g. diabetic patients), optimization of renal perfusion via infusion of fluid and electrolyte, diuresis using either loop diuretics or mannitol1. Therapeutic issues and management Immunosuperesents are commonly used to prevent transplant rejection and usually more than one class is used, because of their different mode of action to improve efficacy and reduce side effects.1Immunosuppressants are started immediately or as soon as possible after transplantation. Immunosuppressants are used to preserve transplant function and to prevent organ toxicity and usually prescribed for life time. Infections are more common in patients on immunosuppressants because they diminish the immune system. Treatment has two phases, namely induction and maintenance. In the induction regimen monoclonal antibodies (muromonab-CD3), poly-clonal or anti-CD25 antibodies (basiliximab, daclizumab) are used for 8 weeks post-transplant and had less nephrotoxicity. In maintenance therapy, triple therapy with calcineurin inhibitors, mycophenolate or azathioprine and prednisolone are usually used.3Sirolimus is reserved for those patients who cannot tolerate calcineurin inhibitors. However, the drugs and dosage vary between individual transplant centers and patient requirements. Evidence showed that mycophenolate is more effective than azathioprine in renal transplant patients.3 Immunosuppressant should be maintained at a lower effective dose after 2-6 months to minimize the side effects. In RS case, he is appropriately on three immunosuppressant drugs; namely tacrolimus, mycophenolate and prednisolone. Their dosage and frequency of administration is appropriate taking in to consideration his ARF and other coexisting conditions. However, tacrolimus and prednisolone are known to cause an increase in plasma glucose levels and may compromise his blood sugar control and insulin use.1Regular blood sugar monitoring and insulin dose adjustment may be required to control his diabetes. RS is also taking 75mg of aspirin to protect him from blood clots. However, aspirin is mainly cleared through the kidneys, and in ARF there may be an increased risk of bleeding due to reduced clearance. On admission to hospital Mr RS had dehydration secondary to flu-like symptoms, and at risk of secondary bacterial infection due to immunosuppressive therapy. The common viruses involved in influenza are influenza A and B (these viruses cause flu-like symtoms). Therefore, he was started on antibiotics. Antiboitics: Ceftriaxone belongs to the antibacterial group Cephalosporins and it is one of the broad spectrum antibiotics. This group of antibiotics contain a beta-lactam ring that interferes with the bacterial peptidoglycan synthesis.It is therefore bactericidal and effective against gram-negative and gram positive organisms. Azithromycin is macrolide antibiotic. This is Bacteriostatic and inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. They also have immunomodulatory and anti-inflammatory effects. Osltamavir used as prophylactic for H1N1. Ondanseton and prochorperazineare antiemetic for nausea and vomiting. This patient had history of excessive alcohol consumption and diabetes, which were more prevalent in the ARF .The studies have been reported that long-term alcohol use of alcohol is associated with renal dysfunction4 and patients with diabetes are more susceptible to damage to the kidneys and more prone to infections.5 Drugs that require Therapeutic Drug Monitoring and Precautions Aspirin and prednisolone When administered together, corticosteroid drugs decrease the serum concentration of salicylates6. Therefore monitoring of anti-platelet effect and increasing aspirin dose may be required. Patients are advised to take these medications with food to avoid gastrointestinal bleeding. Prophylactic anti-ulcer treatment such as proton pump inhibitors and H2antagonists can also be used.6 Aspirin and tacrolimus Co-administration of aspirin and tacrolimus may increase the risk of renal impairment due to synergistic effect on the kidney. Renal function should be monitored when using this combination both during and after treatment.6 Morphine and prochlorperazine Moderate interactions have been found between Morphine and prochlorperazine, creating a synergistical depressant affect and therefore monitoring is required.6 Aspirin & Sodium Bicarbonate Alkalinisers (i.e. sodium bicarbonate) increase aspirin renal elimination – monitor for possible dose adjustment.7 Tacrolimus& Sodium Bicarbonate Sodium bicarbonate reduces tacrolimus absorption and plasma level when taken together, therefore separate doses by at least 2 hours8. Immunosuppressed patients are more prone to get infection and require annual pneumococcal and influenza vaccinations.1Mycophenolate is more prone to cause infection, monitor complete blood count each week for one month then every 1-3 months. Tacrolimus is renally cleared; renal function test is recommended every 2-3 months. Blood concentration drug monitoring is recommended because of its low therapeutic index and variable bioavailability.9 Immunosuppresant drugs increase the risk of malignancy and other proliferative disordersespecially of the skin.Regular examination for skin cancers and avoiding sun exposure by using SPF 30+ sunscreen and protective clothing is recommended.1 Continuation of care: The role of the pharmacist is to watch the right dosage, strength and if there is any interaction between the drugs, should discuss with patients. Based on the patient’s previous medication history, Pharmacist should assist this patient after discharge from hospitaleducate the patient about the immunosuppressant medication and about that he is more prone to infections. Patient is divorced and single. For future care we may want to ask the patient how long ago this happened and how he is coping. We may think about depression and patient’s compliance towards his medications. He may also benefit from a home medicine review. Educate the patient how to use blood glucose monitoring and keep the readings of them. This would help to establish if the medication non-compliance and educate the patient on the role of her medications to prevent further complications. Educate the patient on the importance of regular blood test, renal function test, followed by regular visit to the doctor. Promote healthy eating habitse.g increase the intake of green vegetables and fruits. References: 1. Walker R and Whittlesea C, editors. Clinical Pharmacy and Therapeutics 4thed, Edinburgh: Churchill Livingstone; 2007. 2. Acute renal failure The Merck Manual of Diagnosis and Therapy; last reviewed 25 March 2011. [Online www.merck.com/mmpe/sec10/ch111/ch111b.html 3. Australian Medicines Handbook (AMH), 2009, Australian Medicines Handbook Pty Ltd, Adelaide. 4. Cecchin E, De Marchi S. Alcohol misuse and renal damage. Addict Biol 1996; 1(1): 7–17. 5. Weisberg LS, Kurnik PB, Kurnik BR. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus. Kidney Int 1994; 45(1): 259–26 6. MIMS Online MIMS Australia Pty Ltd 2003. [Online] 2008 [Cited 2011, march19]: Available from: http://www.mims.com.au. 7. Vicari-Christensen M, Repper S, Basile S, and Young D.Tacrolimus. Review of pharmacokinetics, pharmacodynamics, and pharmacogenetics to facilitate practitioners' understanding and offer strategies for educating patients and promoting adherence. Prog Transplant. 2011 Sep;19(3):277-84 8. Shastri RA. Effect of antacids on salicylate kinetics,International Journal of Clinical Pharmacology Therapy & Toxicology. (1985) 23, 480–84. 9. Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, McMichael J, Lever J, Burckart G, Starzl T. Clinical pharmacokinetics of tacrolimus, Clinical Pharmacokinetics (1995) 29, 404–30.