Drug Use in Dialysis

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1 (Last Updated: 08/22/2018) Created by: Socco, Samantha Drug Use in Dialysis Drambarean, B. (2017). Drug Use in Dialysis. Lecture presented at PHAR 503 Lecture in UIC College of Pharmacy, Chicago. DIALYSIS Kidney can t function on it s own anymore o Need to turn to dialysis or transplant When kidney fails, get increase in BUN and SCr uremia o Pt. feels tired, lethargic, nauseous o Electrolyte abnormalities Decrease in bicarbonate and increase in K + metabolic acidosis when kidneys are failing o Fluid build-up edema Lower extremities and abdomen Get dialysis when: o End stage renal disease (GFR<15) usually outpatient o Acute kidney injury (AKI) = a rapid decline in kidney fxn usually inpatient o Emergent removal of toxic substances or elevated metabolic abnormalities K + >6.5 cardiac abnormalities Hemodialysis outpatient o Moves blood out and goes back in by moving opposite directions through a semi-permeable membrane o The dialysate is a buffer that restores homeostasis of electrolytes Creates concentration gradient to allow solutes/toxins to come out of blood Give bicarb and removes K + Also gives K + because intracellular stores can t give back in an adequate time and the pt. can get hypokalemia o Pt. needs permanent access: Arteriovenous (AV) fistula = gold standard. Most stable because decreased chance of infection and thrombosis and most effective AV graft Catheter = high risk of infection, not best clearance o Usually done three times a week in 4 hour sessions depends on characteristics of the pt. o Dialyzer = filter. Is usually hi-flux (large pore size)

2 Diffusion = solutes go from high concentration to low concentration Removes uremic toxins Depends on: o Concentration difference between blood and solute compartments o Solute molecular size and charge o Membrane qualities: surface area, high/low flux, porosity Convection = solutes dragged across membrane with water Removes fluid with larger molecules Higher hydrostatic pressure in blood compartment drives the solute movement Peritoneal dialysis outpatient, in pt. home o Better for patients with hypotension, residual renal fxn, large fluid gains This is because its everyday, several times a day Can monitor fluid build-up Fluid build-up causes heart failure o The dialyzing filter is the patient s own peritoneal membrane o Catheter goes into the abdominal wall Cuffs in the catheter serve as barriers to infection and to stabilize the catheter o Types of peritoneal dialysis CAPD (continuous ambulatory peritoneal dialysis) = pt. manually does the exchanges throughout the day APD (automated peritoneal dialysis) = a cycler does the exchanges overnight, with hours of daytime dwell (no exchange) NIPD (nocturnal intermittent peritoneal dialysis) = pt does not carry excess dialysate during the day, unlike APD Continuous flow peritoneal dialysis = fixed peritoneal volume o Dialysate is a solution of electrolyte concentrations Usually has barrier separating the electrolytes and this must be removed to the solution mix Dextrose solutions = hyperosmolar Better ultrafiltration Icodextrin = iso-osmolar used for long dwell times (APD, CAPD) o Solute movement guided by diffusion and convection Urea, creatinine, potassium go from peritoneal capillaries across peritoneal membrane into peritoneal cavity (into dialysate) Bicarbonate and lactate go into the serum o Dwell time = how long the dialysate stays in the peritoneal cavity 2

3 At one point, pt. reaches an equilibrium Aren t removing anymore toxins/solutes Need to do another exchange To increase the osmotic gradient and maximize fluid and solute removal: o Use larger dialysate volume o Smaller dwell time o More exchanges per day o Peritoneal equilibrium test (PET) = gives idea of rate of transport Higher the dialysate-plasma creatinine ratio, the more rapid the clearance, the less exchanges the pt. needs o Peritonitis = infection of peritoneal cavity Usually at catheter site Antibiotics can be infused with the dialysate Continuous renal replacement and hybrid hospital only o CVVH = continuous veno-venous hemofiltration Substitution fluid comes before or after the filter o CVVHD = continuous veno-venous hemodialysis Guided by diffusion o CVVHDF = continuous veno-venous hemodiafiltration Guided by diffusion and convection o SLEDD = slow extended daily dialysis Daily, longer duration of treatment o Flow rate is slower If pt. BP and HR goes down too much with hemodialysis, pt can use this instead PHARMACOKINETICS IN RENAL FAILURE Bioavailability o There is reduced GI absorption in renal failure. Due to: Concurrent meds phosphorous binders can bind other meds Alkaline environment if med (like iron) needs to acid to be absorbed, bioavailability will be decreased Volume of distribution 3

4 o Between sessions there is extracellular volume and an increase in volume of distribution o In patients with wasting muscle, there is a decrease in volume of distribution Protein binding o b/c lower protein (since filtered out) there is more free drug and a seemingly lower volume of distribution Metabolism o Hydrolysis is slower but oxidation is faster Clearance = volume from which drug is removed per unit time (ml/min) o For drugs that are not eliminated renally, elimination can increase/decrease/stay the same Loading dose adjusted based on Vd Maintenance dose can be decreased or interval between dosing can be increased (or both) Dosing in dialysis: Depends on molecular weight of drug, protein binding, Vd, proportion of drug renally eliminated, dialysate/blood flow rates o Depends on type of dialyzer o Small MW molecules have larger clearance b/c can be dialyzed out easier o Large MW molecules have smaller clearance b/c can too big to really be dialyzed out o If drug is highly protein bound, less chance it will be dialyzed out o Large Vd drugs less dialyzable and vice versa o If drug more likely to be dialyzed out, you can dose before dialysis and then supplement after o Dialysance = way meds get cleared by hemodialysis o Peritoneal dialysis typically has minimal drug removal More exchanges, more chance drug will be removed Ionized drugs will diffuse slower o Continuous renal replacement From high to low drug clearance: CVVH>CVVHDF>CVVHD Dosing based on drug characteristics Anti-hypertensive drugs that are dialyzable or not : KNOW THESE o ACE-I Yes o ARB No o Beta-blockers Yes o Calcium channel blockers No o Hydralazine Yes (dose after) o Clonidine not likely (dose after) 4

5 o Minoxidil Yes Antibiotics dialyzable or not o Amoxicillin yes, dose after o Cephalexin yes dose after o Most fluoroquinolones are (so dose after) except moxifloxacin o Sulfamethoxazole/trimethoprim yes, dose after o The -mycins (macrolides) no data, so dose after to be safe o Metronidazole no data, so dose after Dose carefully with: o Narcotics o Meperidine o Lithium (easily dialyzed out) o Phenytoin = seizure med that is highly protein bound (monitor the free levels) 5

End-Stage Renal Disease. Anna Vinnikova, M.D. Associate Professor of Medicine Division of Nephrology

End-Stage Renal Disease. Anna Vinnikova, M.D. Associate Professor of Medicine Division of Nephrology End-Stage Renal Disease Anna Vinnikova, M.D. Associate Professor of Medicine Division of Nephrology ESRD : Life with renal replacement therapy CASE: 18 month old male with HUS develops ESRD PD complicated