Case 1

Mrs CD (67 years old) was admitted over the weekend to the acute medical ward you cover as a clinical pharmacist. She was prescribed amoxicillin + clavulanic acid 500/125 one tablet three times 4 days ago by her GP for a suspected UTI. Presenting Complaint (PC) CD now appears very confused, is feverish and complaining of abdominal pain. Past Medical History (PMHx) Type 2 diabetes 15 years Hypertension 5 years On Examination (O/E) Temperature 38.50C Blood pressure 170/105 Weight 65 kg Height 52 Extremely tender abdomen; confused. Medication on Admission Metformin Glipizide Cilazapril 5mg + Hydrochlorothiazide 12.5 mg Lab results WCC CRP Creatinine Potassium Blood glucose HbA1C Urine dipstick 20 x 10 /L 100 mg/L 250 mol/L 4.5 mmol/L 3 mmol/L 6% proteinuria +++
9

500 mg three times a day 5 mg twice a day one daily

(Normal range) (4 11 x 109/L) (< 8 mg/L) (50 - 110 mol/L) (3.5 5.0 mmol/L) (4.2 6.1) (5 8%)

Culture and sensitivity from urine sample taken 4 days ago by her GP are available when CD was admitted to hospital and confirm presence of Escherichia coli in urine resistant to coamoxiclav, amoxicillin and trimethoprim, sensitive to ciprofloxacin and gentamicin. Impression Acute pyelonephritis Plan Stat dose of IV gentamicin given in ED (5 mg/kg) followed by IV ciprofloxacin

When you reach the ward on Monday CD has had 3 doses of IV ciprofloxacin 400 mg. You have a chat with Mrs CD when you are looking at her prescription and she mentions that she occasionally takes diclofenac (50 mg) for pain in her feet and took one tablet 3 times a day for the last week. CD says that she has not told the Drs this as she felt so unwell over the weekend. Problems Outline: current problems that Mrs CD has potential future problems that you think Mrs CD may experience [include objective and subjective evidence] Need to get her IBW (shes overwight) so we can get an accurate creatinine clearance Current problem: o Treatment for acute pyelonephritis o Risk factors were: Diabetes Female Old o Why? Proteinuria WCC and CRP high Fever Abdominal pain Confusion o Renal impairment seen 15 ml/min seen Potential problems: o Chronic renal failure Pyelonephritis (especially recurrent infections) are a risk factor (acute tubular nephritis) Gentamycin and diclofenac may cause renal damage Have diabetes and hypertension (risk factors) Creatinine is currently high o Hypoglycemia Glucose low Glipizide (sulphonurea) may be accumulated Could also be due to just infection Dont eat properly But her glucose control is good, HbA1c is good o Pain in her feet (neuropathy with diabetes?) She also got the triple whammy, a diuretic, NSAIDs and ACEI

Complicated = kidney involvement Check BPAC to see what antibiotic we should choose

Need to know how to calculate GFR by memory, also read NZF stuff on renal impairment Options Outline: possible non-pharmacological treatments possible pharmacological treatments possible pharmacological treatments if her condition changes Non-pharmacological treatments Reduce protein intake Cranberry juice for prevention NOT alkalisers, acute kidney damage makes pH balance hard anyways o Acidosis is common, cant excrete protons Pharmacological treatments Gentamycin stat dose, dont need to adjust (first dose doesnt cause damage, and we need to base loading dose off weight, allows us to know Vd) If continued, then dose reduction and monitoring is required Good because its renally cleared, so its able to enter kidneys easily Follow up with cipro- a good choice o Renally eliminated, so lots would end up in the kidney o Also need dose adjustment as well o IV needed for her, need to be absorbed quickly, and since theyre sick, cant vomit out IV (but can with oral) o Continue IV dosing until her temperature normalises and her symptoms are controlled Renal failure Regular monitoring (daily until stabilised) Adjust for renally cleared drugs Since changes in renal clearance are rapid, need to MONITOR doses of the renally cleared drugs closely o Change in clearance = beware o Tends to overestimates as a result Diabetes management Withhold metformin until greater than 30 ml/min (risk of lactic acidosis) o Or insulin Glipizide- withhold for at least 24 hours and start at a lower dose (maybe it was accumulating, because blood glucose was low) Glicazide is a good choice how, because its partially metabolised by the liver, another pathway for the drugs to leave by Continue cilazapril, renoprotective, but monitor BP, could be accumulating as patient is hypotensive Thiazide diuretics not effective here o Ineffective if GFR is les than 30 ml/min, so withhold Ineffective because they work distally, they cant reach there if they cant get excreted properly

o If required for odema, use furosemide o If required for hypertension, use other agents, like ATII antagonist, dihydropyridine CCB or beta blockers Pain Strong opiate on admission o Not NSAID o Fentanyl is good option, no active metabolites o Morphine and pethidine have some accumulation (especially norpethidine which is active and accumulates) o But morphine can be used short term though NSAID to be stopped o Neuropathic pain is likely, need a different type of agent o Gabapentin o TCAs (e.g. amitriptyline, not an approved condition though)

Pharmacological treatments if condition changes Note: options should be broad (AND the co-morbidities) Plans Outline: an initial treatment plan (choosing one of your possible options) a long term treatment plan what expectations you would have for your treatment how you would monitor the outcomes of your treatment plans with Mrs CD Initial Treat the pain o Fentanyl Calculate GFR Check current medications o Withold metformin o Witholg glicazide, consider alternative o Maintain cilazapril, stop thiazide o Stop NSAID o Refer for neuropathic pain Infection o Genta- stat, only once o Cipro- then change to cipro Long term Continue to manage everything What about statin? Shes got diabetes, hypertension. So a statin could be thought about Diretic used could be furosemide, as it works in renal impairment

Expectation Infection should resolve quickly, discharge on oral ciprofloxacin- treatment course should be 10-14 days Monitor temp, BP and blood glucose Monitor renal function (as both inpatient and outpatient)

 Case 2
When Mrs CD was discharged 2 weeks later, her renal function had improved (SCr on discharge 130 mol/l). Unfortunately, over the next 5 years she developed progressively worsening chronic renal failure and had poor diabetic control. Six months ago it was decided that she needed treatment with CAPD and CD has been at home for the last 4 months on this treatment and is a regular visitor to your pharmacy to collect the following medication: Metoprolol CR 95 mg daily Cilazapril 5 mg daily Simvastatin 20 mg daily Humulin N 10 units sc twice a day Calcium carbonate 500 mg 2 tablets three times a day Calcitriol 0.25 g three times a week Erythropoietin Beta 4,000 sc weekly 1. Briefly discuss the advantages and disadvantages of renal replacement therapy using CAPD compared to haemodialysis.

Dialysis is where the filtraction of substances out of the body. Need a semi-permeable membrane Plus with counter current flow to maximise the diffusion gradient Plus with ultrafiltration, which causes a water gradient by osmosis into the dialysis fluid Convection- holes allow solutes and larger molecules to pass through like urea HD= muscle cramps, because elecrylyte balance and moving blood away from the muscles Risk of thrombosis and infection Skin commensuals commonly seen Anticoagulate PD Ultrafiltration and diffusion possible Peritoneal membrane is a continuous single layer of mesothelial cells Dwell time, how long it needs to stay in there, several hours Indwelling catheter is kept in

Advantages Dont need to make the arteriovenous fistulas Dont have to come into the hospital, good for mobility Disadvantages Not recommended for diabetics, glucose used in fluid Risk of infections, because carried out at home The catheter can damage the peritoneal membrane Make sure nothing grows into the cather, can block it 2. Discuss the reasons for the drug treatment that CD has been prescribed.

Heart/BP Metoprolol o Hepatically cleared Cilazapril o Renoprotective as well Simvastatin o Hepatically cleared o Recommended due to high CVD risk (diabetes + hypertension) Diabetes Removed everything, only on insulin o Better idea due to renal failure Renal failure Calcium o Soft tissue calcification causes the drop in calcium o This is due to phosphate retention Reduce phosphate in the diet Or consider a phosphate binder o A part of preventing hyperparathyroidism Calcitriol o The activation step of calcidiol to calcitriol occurs in the liver o Obviously, cholecalciferol wont work o Prevents osteomalacia (soft bones) o Also prevent hypterparathyroidism EPO o Normally produced by the kidneys as well o Required for normal red cell production One year after staring CAPD CD is admitted to your ward with suspected peritonitis. She has had abdominal pain and a slight temperature over the last day or two and noticed last night that the volume she drained was much less than normal and the drained fluid has become cloudy. The medical team looking after CD asks for your advice on appropriate antibiotic treatment. 3. What treatment would you recommend? Quick empirical treatment with broad coverage o Cefazolin (G+) and cefotaxine (G-)/gent (G-) o OR vancomycin + gent Give into peritoneal fluid, not IV to achieve high local concentrations Think about dwell time, can give it intermittently to prevent too much absorption into systemic circulation o But need to have a long enough well time to get enough into the systemic circulation o Higher dose if intermittent, low dose if continuous Also think about renal clearance, they cant clear it!

o Higher doses if they have urine output Should take a few days (48h), monitor symptoms o Peritoneal fluids should become clear Catheter related infections: oral? 4. Should CDs regular medication be altered while she is receiving your recommended treatment? Monitor glucose and adjust insulin as required

Case 3
Mr RT is a 45 year old has been just discharged home from a renal transplant unit. He comes into your community pharmacy and tells you that although he has pain from his operation he is feeling well and getting his energy back. He is attending a transplant clinic three times each week for review and adjustment of his medication. His discharge medication card notes that he is taking the following medicines. Ciclosporin Mycophenolate Mofetil Prednisone Valganciclovir Co-trimoxazole Allopurinol Cilazapril Diltiazem CD Humulin N Humalog Simvastatin Ferrous sulphate Codeine phosphate Paracetamol 1. 450 mg twice a day 1 g twice a day 40 mg daily 450 mg every second day 480 mg once daily 50 mg daily 5 mg daily 120 mg daily 10 units sc twice a day 10 units sc three times a day 20 mg daily 200 mg twice a day 30 mg four times daily as required 1 g four times daily as required

Using the list of mediation above identify RTs main medical problems (other than his renal transplant). Diabetes Iron depletion o Probably caused due to renal failure o Probably exacerbated by blood loss during surgery o Short term Hypertension/CVD Recurrent gout Identify the medicines which will have been started after his operation. Discuss the function of each, any special precautions relating to use and side effects which RT is likely to experience? Ciclosporin Mycophenolate Prednisone Valganciclovir o Cytomegalovirus (especially with allograft) Cotrimoxazole o PCP prophylaxis Pain o Short term treatments

2.

See www.kidney.org.uk/Medical-Info/transplant/txinfect.html 3. Are there any changes to his medicines that you anticipate or would recommend? How should these be managed? He uses a medication tray. 4. Add laxative (codeine) Need to slowly taper down the rejection drugs quite regularly (especially with prednisone) o Blister packing is a very good idea Even if they use their own tray, its probably a good idea for us to pack them Ciclo can be changed to tacrolimus (also a good idea for a second kidney after reject, its stronger) Beware of pregnisone, changes diabetes (down titration) o Especially important for long term kidney survival Monitor kidney function, and make dose adjustments on a regular basis Oxypurinol build up needs to be accounted for in renal failure. Dose adjustments may be required Mr RT asks to receive an influenza vaccination in your pharmacy. What is your recommendation?

Its not going to work, your immune system is currently being suppressed. Cant produce a response against it. (its an attenuated vaccine, wont cause infection at least) Note: diltiazem can be used as a ciclosproin sparer, this is via CYP inhibition (plus good for addon for hypertension)