dialysis

clearance mechanisms in a renal failure patient

clearance mechanisms in a renal failure patient

only clearance mechanism is non renal
Cl= CLNR

clearance mechanisms in dialysis

non renal routes + dialysis present → can accelerate drug removal from body

CL+CLNR + CLD

what amount of dialysis clearance is considered to be significan

>/=30% of total clearance

OR if the total amount of drug removed by dialysis is enough to warrant a post dialysis replacement dose

is HD or PD more efficient

HD (hemodilaysis)

what is CRRT (continuous renal replacement therapy)

24hr non stop dialysis therapy used for critically ill patients with AKIs, particularly if hemodynamically unstable

important CCRT features that affect drug clearance

characteristics of dialyzer/hemofilter membrane

• high flux membranes have greater permeability for larger molecules (all membranes used for CRRT today are high flux)

modality and operating conditons (ie flow rate settings)

• depending on the specific CRRT modality, drug clearance increases with ultrafiltration, dialysate, or effluent flow rate

list drug characteristics affecting dialysis removal

molecular size

filter size (low flux vs high flux)

solubility

plasma protein binding

VD

what size drugs are readily eliminated by dialysis

MW <500Da

factors that effect small drug removal

blood flow to artificial kidney

dialysis fluid flow rate to artificial kidney

surface area of semipermeable membrane

what type of solubility tends to go into dialysis fluid

water soluble, while lipid soluble drugs tend to remain in the blood

how does plasma protein bidning effect dialysis

only unbound drug can pass thru the pores in the semi permeable membrane

drugs that are not highly plasma protein bound have high free fractions of drug in blood and better dialysis clearance

drugs which are highly PP bound have low FF of drug in blood and worse dialysis clearance

how does Vd affect dialysis

large Vd >2L/kg are principally located at tissue binding sites and not in the blood where dialysis can remove the drug

moderate Vd 1-2L/kg have intermediate dialysis rates

small Vd <1L/kg have high dialysis clearance rates

how to dose an antibiotic/antifungal that is dialyzed (general)

give more frequently at a lower dose POST HD (50% od) or full dose less frequently POST HD (100% 3x/wk) (timing of doses matters)

ex: fluconazole → give 50% of normal dosing daily post HD, or 100% of normal dosing 3x/week post HD

cotrimoxazole important to know

increase K at baseline in HD

septra full dose increases K

so need dose adjustment

what IV cephalosporins/carbapenems are most practical in dialysis (just given post HD)

cefazolin, ceftazadime, ertapenem

meropenem could be just given post dialysis too depending on which dosing regimen you do

half life of aminoglycosides in HD vs PD

3-4hr HD, 36hr PD therefore dose differently

what weight to use in aminoglycosides HD dosing

dose with ABW unless obese

obese ( greater than 30% ideal body weight) use obese body weight

trough target pre vs post dialysis for gentamycin (HD)

target pre dialysis trough is 1.5-3mg/L

assuming 50% removal by HD, the trough is then 0.75-1.5mg/L

how does ESRD change vanco T1/2

ESRD 7.5 days while adults is 4-6hrs without ESRD

PD vancomycin when to get trough

q 5 days for duration of therapy

does PD remove a lot of vancomycin from the body

no, negligible amount

does CRRT remove a lot of vancomycin from the body

yes

how often is vanco trough done with CRRT

oral trough 24hrs post initial dose

when is vanc trough done in HD

pre 3rd dose (i.e at beginning of second dialysis session after loading dose given)

how much vanco does HD remove

3hr session removes 50% of vanc

when is vanco dosed in relation to HD

post HD

how to adjust gentamycin dose in dialyisis

based on pre dialysis levels

levels <1.5 increase dose or decrease interval

levels >3 decrease dose or increase level

(usually change dose bc patients only coming in 3x a week)

if someone on vanc has residiual renal fxn what to do

monitor more frequently, may need higher doses

are HD and PD dialysis vanc dosed same

No- diff monitoring, dosing, troughs

vanc dosing frequency differences in PD, CRRT, HD

PD dosed q 5 days x 14d then R/A

CRRT dosing int ranges from 12-48hrs

dosed post HD

how does renal impairment effect ADME of digoxin

Vd and CL decreases

how does renal impairment effect PK (Vd) of digoxin

mechanism not well understood

it is likely that digoxin is displaced from tissue binding sites in patients with renal dysfxn so drug that would have been bound to tissue becomes unbound

unbound digoxin molecules displaced from tissue binding sites move into blood causing the decreased Vd

is digoxin eliminated by HD or PD

not significantly

how does digoxin dosing change in HD vs normal

not significantly elim by HD/PD therefore dont need an increased maintenance does

decrease LD bc of longer t1/2 and give MD 3x/week during dialysis but doesnt matter when during dialysis bc it is not dialyzed

phenytoin normal protein binding

highly protein bound (90%)

phenytoin considerations in dialysis and renal failure

not dialyzed (HD), dose as in normal renal fxn

decreased protein binding and Vd in renal failure

use corrected phenytoin level for albumin/renal failure (if not on dialysis?)

carbamazepine considerations in dialysis

unknown dialyzabiility (HD)

normal dose

titrate to target level (can monitor drug levels)

administer post HD if q 12hr dosing but may require supplemental dose post HD

sodium valproate (divalproex) considerations in dialysis

may be dialyzed in high flux dialysis to unknown extent

dose as normal (based on indication and target free VPA level)

administer post HD

administer q 12hr but may require supplemental doses

phenobarb considerations in HD

dialyzed

dose as in GFR <10mL/min → reduce dose by 25-50% and avoid very large single doses

lamotrigine dialysis considerations

depends on resource

BC renal says 17% dialyzed, dose normal, administer post HD (no supplemental dose required)

renal handbook says unknown dialyzability, dose as in <10 GFR

in general: start low and dose based on indication

levetiracetam considerations in dialysis

dialysed

51% of dose is removed with 4hr of HD- therefore need supplemental dose post HD of 50%

dosed post HD? bid?

immunosuppresant considerations in dialysis

renal failure does not change PK

not significantly removed by HD or PD (admin anytime)

dose adjustments are not needed for HD or PD

dose based on levels

lithium dosing in HD patients

reduce to 25-50% of normal dose if new med (if already on dont adjust right away wait to see levels)

titrate based on target serum level (0.4-1mmol/L in levels taken 12hr post dose, taking 4-7 days to get to SS)

administer post HD

replacement doses determined based on serum Li levels

how can lithium clearance be altered in renal failure

Li CL decreases proportionally to CrCl

renal clearance of Li is influenced by state of sodium balance and fluid hydration in that individual

Lithium is reabsorbed in the proximal tubule of the nephron via the same mechanisms used to maintain sodium balance

if a pt gets a negative sodium balance or becomes dehydrated the kidney increases sodium reabsorption (compensatory) and lithium reabsorption increases - leads to decreased clearance

how to approach pain management in musculoskeletal/nociceptive pain score 1-4/10

non opioids first line

start with acetaminophen and optimize dose (4g/day)

if tylenol not enough try topical NSAIDs (diclofenac) tid-qid for localized pain

or try capsaicin cream bid-qid for localized pain (may take >2wks for onset)

pain management if pain is not controlled on first line meds for score of 4 or less OR pain score is 5/10 or greater

add an opioid to non opioid analgesic and/or adjuvant

avoid morphine and meperidine

start with IR hydromorphone and may transition to CR when patient achieves adequate pain control

in some cases may start with tramadol/tramacet but it is not recommended due to unpredictable PK

why is codeine/morphine not used in renal impairment

accumulation of active metabolites which can cause fatal respiratory depression

(codeine is met by 2D6 to morphine and therres highly variably polymorphism so cant rly predict how much active )

neuropathic pain 1st line med

gabapentin (or pregabalin) with max doses due to accumulation (gabapentin max dose 300mg)

or capsaicin cream but prob not

2nd line neuropathic pain meds

1st line was gabapentin so if intolerable AE or fail, taper off and try an alternative:

TCAs- nortriptyline/desipramine

topiramate

venlafaxine

THC:CBD (Sativex)

chronic vs intermittant PD dosing

intermittant PD it is less likely that replacement doses will need to be given (bc its less efficient)

drug doses need to be increased in chronic PD

what way does dialysis fluid flow vs blood flow

counter current (opposite)

its more efficient at moving waste vs parallel

what size drugs are only really removed with a high flux filter

>1000Da

how to change vancomycin dosing in PD

adjust based on trough

how to change vanco dosing in CRRT

based on levels

every time it falls below target range for indication being treated give 15mg/kg

How to adjust vancomycin dosing in HD

based on level, in increments of 250mg

so if level is 13.1 (target 15-20) and dose is 500 IV post HD, increase to 750 IV post HD

if level is 23, decrease to 250 IV post HD

what dosing weight is used for vanc

actual body weight

T1/2 digoxin normal vs ESRF

30-40hr normal, 100hrs ESRD