Dosing in AKI Flashcards
True or False
Drug Dosing is equal to CKD Staging
False
What equation is used for dosing of most drugs?
Cockroft - Gault
Newer drugs are beginning to use what equation?
eGFR
Equation for Obesity
Salazar
Equation for Elderly
Sanaka
Equation for Acutely changing SCr
Jelliffe
Equation for Pediatrics
Schwartz
No change in regimen in kidney dysfunction patient if a drug…
- has a large therapeutic index
- fraction excreted unchanged in urine is ≤ 30%
- metabolites are inactive (or no metabolites)
Changes in Pharmacokinetics: Absorption
largely unchanged
Changes in Pharmacokinetics: Distribution
can be increased, decreased, or unchanged depending on drug
Changes in Pharmacokinetics: Metabolism
decrease phase I enzyme capacity
no change in phase II
-phase II metabolites eliminated by kidney
Changes in Pharmacokinetics: Elimination
decrease renal elimination
Changes in Pharmacodynamics in renal dysfunction
Increase BBB Permeability
- increase CNS effects
Decrease platelet aggregation
- increase bleed risk
Non - Renal Clearance Effects
- Uremic toxins inhibit CYP enzymes and drug transporters in gut and liver (accumulation)
- increased bioavailability
- increased systemic exposure
changes in hepatic metabolism
decrease metabolism to inactive metabolites
- increase active drug
increase bioavailability
decrease in phase I
no change in phase II
How do you deal with drugs regarding metabolite accumulation?
AVOID drugs with toxic metabolites
USE CAUTION with drugs with pharmacologically active metabolites
MONITOR drugs with inactive metabolites
Opioids changes in PK
Opioids - Phase II
- conjugated metabolites kidney eliminated
- morphine and meperidine (neurotoxic)
**Dose relates to peak conc - max pain relief
**interval - duration of pain relief
Opioid changes in PD
renal dysfunction increases therapeutic and toxic effects
increased opioid receptor sensitivity
increased BBB permeable - increase CNS effects
Good opioids in kidney dysfunction
Fentanyl
Methadone
Okay opioids in kidney dysfunction
Hydromorphone
Oxycodone
Hydrocodone
Bad opioids in kidney dysfunction
Morphine
Codeine
Meperidine
***neurotoxic
Renal Clearance Equation
(GFR x Fu) + (CLsecretion - CLreabsorption)
Renal dysfunction does what to GFR and protein binding?
Decrease GFR
Decrease Protein binding
Opioids of choice in kidney dysfunction
Fentanyl
Hydromorphone
Hemodialysis patient GFR?
<15 ml/min
Loading dose is affected by?
Volume of distribution
**Decrease in Vd = decrease in dose
**LD for kidney dysfunction = LD for normal kidney function
**Vd reduced in kidney dysfunction w/ Digoxin (by 50%)
**Hydrophilic ABx - higher doses in AKI
Maintenance dose is affected by?
Clearance
***Decrease in CL = extend interval (tau)
Antimicrobial agents that do no need dose adjustment in kidney dysfunction
Moxifloxacin
Metronidazole
Ceftriaxone
Clindamycin
Azithromycin
Doxycycline
Linezolid
***My mother can cook a damn lasagna
ABx Clinical Pearls
Dose adjustment depends on
- site of infection, illness severity, renal stability
Vd is the same or higher in CKD/AKI
**Should not be reduced
**24 - 48 hrs of aggressive dosing
kidney dysfunction PK changes in distribution
- Increase Vd in edematous states
- Decrease in drug concentration
- Decrease Vd with muscle wasting/volume depletion
- increase in drug concentraton
- Hypoalbumin - decrease protein binding
- increase drug free fraction
- increase toxicity
Altered tissue binding
Phenytoin Xtics
K channel block
Antiepileptic
Narrow Therapeutic index
Numerous DDIs
Non-Linear PK (Michaelis Menten)
Phenytoin in renal dysfunction
Uremia
hypoalbuminemia
***Concentration is obscured
Phenytoin total target concentration
10 - 20 mcg/ml
Phenytoin free drug target concentration
1 -2 mcg/ml
When should you correct phenytoin?
If total trough is collected
AND
if serum albumin <3.3 mg/dl
Corrected phenytoin in CrCl <20
Measured conc/[(0.2 x albumin) + 0.1]
Corrected Phenytoin in CrCl >20
Measured conc/[(0.275 x albumin) + 0.1]
Factor Xa inhibitors
Apixaban
Rivaroxaban
Edoxaban
Fondiparinux
Direct Thrombin Inhibitors
Dabigatran
Bivalirudin
Lepirudin
Desirudin
LMWH
Enoxaparin
Tinzaparin
Dalteparin
Anticoagulant changes in PK
Reduced kidney elimination
Anticoagulant changes in PD
Increased bleeding risk
-Kidney dx >uremia>plate dysfunction>bleed
***uremic toxins > no plate aggregation
Anticoagulants that don’t need renal dose adjustment
Heparin
Warfarin
DOAC’s order of least kidney clearance
Apixaban
Rivaroxaban
Edoxaban
Dabigatran
Parenteral’s order of least kidney clearance
Tinzaparin
Bivalirudin
Dalteparin
Desirudin/Enoxaparin
Fondiparinux
Best DOAC in renal dysfunction
Apixaban
Best parenteral in renal dysfunction
Tinzaparin
Oral AntiDiabetics in kidney dysfunction
Metformin
Sulfonylureas
DPP4i
Metformin Dosing
eGFR >45: no dose adjustment
eGFR 30 - 45: 50% dose reduction
eGFR <30: Contraindicated
***risk of lactic acidosis
Sulfonylurea dosing
Glipizide - preferred
Glyburide - bad
DPP4i’s
All renal dose adjustments except linagliptin
Diuretics in kidney dysfunction
No AntiHTN effect w/ CrCl <30
- risk of HyperK
some diuresis w/ loop diuretic
decrease in GFR -> increase in dose
Analgesics in kidney dysfunction
*****AVOID NSAIDs in CKD
* Caution in ESRD
APAP preferred
Adjunctive analgesics in kidney dysfunction
Duloxetine
TCA’s
Anticonvulsants
Gabapentin/Pregabalin
