Pharmacology Fundamentals
What are four major components of pharmokinetics?
Absorption, distribution, metabolism and elimination : Remember pharmokinetics -> What the body does to the drug
In kidney disease, altered elimination is especially important, but changes in distribution, protein binding, and nonrenal metabolism also matters
A patient with advanced CKD is prescribed a medication that is primarily eliminated by the kidneys. Which pharmacokinetic process is most directly affected?
Drug elimination
( other pharmacokinetic processes absorption, distribution, protein binding, metabolism, elimination)
-> reduced renal clearance can prolonged medications half-life and increase the risk of accumulation.
Name three kidney replacement modalities that can have difference effects on drug clearance.
From all three, which modalities removes drugs the slowest?
iHD, PD, and CRRT
A patient with CKD is started on gentamicin for serious infection. What 2 major toxicity should the team monitor for, and how should drug accumulation be minimized?
What are Nephrotoxicity and ototoxicity, and can accumulation be minimized through renal adjusted dosing, therapeutic drug monitoring, and appropriate dosing intervals
-> aminoglycosides have a narrow therapeutic window. Monitor drug levels and kidney function, and reassess dosing as renal function changes.
Jack the Skeleton is a 70 year old man with CKD secondary to hypertension. His eGFR is 24 ml/min/1.73. He is relatively stable and adherent to office visits and medications. What is the recommendation level of dietary protein intake per day
0.55-.60 g/kg body weight per day
Protein intake recommendations in stages 3-5 CKD without diabetes range from .55-.60 g/kg per day to reduce the risk of kidney failure or death.
What primarily determines a drug's loading dose?
The target concentration, volume of distribution and bioavailability ...
Loading dose is often unchanges or sometimes increased to approach therapeutic concentrations quickly. Maintenance dose may need to be reduced depending on drug clearance
A patient with CKD and significant edema is started on vancomycin. Why might a larger initial loading dose be needed despite reduced kidney function?
What is increased volume distribution due to expanded total body water?
Hydrophilic drugs, including vancomycin and aminoglycosides made distribute into a larger volume in patients with edema. A loading dose is determine primarily by volume of distribution were as maintenance dosing depends more on drug clearance.
Name one drug property that generally makes a medicaiton easier to remove by HD
Small molecular size, low protein binding, hydrophilic ,and relatively small volume of distribution ( drugs largely confined to plasma are generally easier to remove than drugs extensively distributed into tissues)
A patient with CKD takes glyburide. what adverse effect is particular concerning ?
prolonged hypoglycemia due to active metabolite accumulation, glyburide is generally avoiding significant CKD.
Sally developed septic shock and AKI. She was placed on CRRT overnight. You are rounding with ICU team and nutrition. What recommendation of protein intake should you recommend
1.7-2.5g/kg/day
This kidney function estimate is reported in mL/min/1.73 m^2, whereas Cockcroft-Gault estimates creatinine clearance in mL/min
What is CKD- EPI eGFR
a patient with CKD, hypoalbuminemia, and uremia is prescribed days highly protein bound medication. Why can the patient be at increased risk of adverse effects even when the total drug concentration appears therapeutic?
What is an increased free pharmacologically active drug fraction
Many medications circulating the blood into forms: bound ( attach to proteins primarily albumin) versus free
Reduced albumin binding and uremic competition can increase the unbound fraction of some medications. Total drug levels may not accurately reflect active drug exposures
A patient with severe AKI is receiving CRRT and is prescribed cefepime. The teamreduces the dose substantially because the patient has kidney failure. Why could this lead to treatment failure, and what factors should guide dosing?
What is inadequate antibiotic exposure due to underdosing?
CRRT continuously removes some drugs including cefepime. Dosing should account for the delivered effluent rate, CRRT interruptions, residual kidney function, infection severity, organism susceptibility, and drug's pharmacokinetics. Excessive dose reduction can result in subtherapeutic antibiotic concentrations while insufficient adjustment can cause accumulation and neurotoxicity.
On patient was CKD is prescribed Bactrim and develops an elevated serum potassium level. Which component of this antibiotic is responsible and how does it cause hyperkalemia?
Trimethoprim blocks epithelial sodium channels in the distal nephron reducing potassium excretion.
Trimethoprim acts similarly to amiloride and can cause clinically significant hyperkalemia, especially in patients with CKD or those taking ACE inhibitors, arbs or spironolactone.
You are scheduled for outpatient HD rounds today. You see your continuity patient, George. After evaluating his labs you start talking to him about diet. How much protein do you recommend and why?
Common target is about 1-1.2 g/kg/day
Dialysis related amino acid and protein losses, inflammation, and catabolic stress increase protein intake
A drug label recommends dosing based on Cockcroft Gault creatinine clearance but the patient's lab report provides CKD-EPI eGFR. Why might these values differ and what should you do before choosing the dose
The equations estimate different measures of kidney function and use different inputs. eGFR is indexed to a standard body surface area while Cockcroft- Gault estimates CrCL in (mL/min). Check the medications prescribing info. and use the renal function estimate specified or validated for that drug, accounting for the patient factors such as body mass and muscle mass.
A patient with diabetic gastroparesis and advanced CKD takes an oral antibiotic at the same time as a phosphate binder containing calcium. What two factors could reduce the amount of antibiotic reaching systemic circulation?
What are delayed or impaired GI absorption and chelation with calcium
-> Gastroparesis can daily absorption, while calcium combined certain antibiotics especially tetracyclines and fluoroquinolones reducing their absorption. Separate administration of coordinate a specific drug instructions.
A patient receiving iHD is prescribed an antibiotic that is substantially removed during dialysis. The patient receives the medication before dialysis and drug levels may fall during the session. What dosing strategy may be needed to maintain adequate antibiotic exposure?
Supplemental post HD dose...
The need for supplemental dosing depends on the type of antibiotic, its dialyzability, the timing of administration, and the organism being treated.
( vancomycin, cefazolin, ceftazidime, gentamicin, ampicillin)
patient with CKD stage 5 she's coming into the ED for confusion, lethargy and myoclonus. After reviewing her medication list, patient is taking gabapentin 300 mg t.i.d.. What medication related complication should you suspect and why?
for patients with CKD stage pharynx, what is the recommended gabapentin dose?
Gabapentin neurotoxicity due to renal clearance and drug accumulation..
Gabapentin is primarily renally eliminated and requires dose adjustment CKD. In severe toxicity hemodialysis can reported to drug
Recommended dose for CrCl<15 100-300 mg daily. After HD a supplement dose of 125-350mg can be given.
Mario has CKD And has been restricting potassium, phosphorus, sodium and protein. And now has unintentional weight loss and muscle wasting. What nutritional complication should you suspect and what should be prioritized in his management
what is protein energy wasting, requiring assessment of nutritional status and adequate energy and protein intake
overly restrictive diets can worsen malnutrition. Nutrition plans should be individualized to laboratory values kidney replacement therapy status and overall nutritional needs rather than imposing blanket restrictions.
Why might a patient with septic shock and AKI still require a full loading dose of a renally cleared antibiotic
Loading dose is driven mainly by volume of distribution and target concentration, maintenance dosing is adjusted for clearance
Two patient's with the same estimated GFR received the same renally cleared medication. One has stable CKD, while the other has rapidly worsening AKI. Why might the same maintenance dose be inappropriate for both patient's ?
The difference between stable and changing drug clearance, with serum creatinine lagging behind actual kidny function during AKI
Creatinine based estimates assume relatively stable kidney function. During evolving AKI, drug clearance may change faster than serum creatinine reflects. So dosing requires reassessment and clinical judgement
A patient with septic shock and severe AKI is receiving CRRT. The CRRT circuit clots, and therapy is interrupted for several hours. Why might continuing he same medicaiton regimen during this interruption increase the risk of drug toxicity?
What is reduced extracorporeal drug clearance?
CRRT clearance Dependence on the deliver treatment intensity and up time. When CRRT stopped, drugs normally removed by the circuit may accumulate, particularly if residual kidney function is poor. Dosing should be reassess when CRRT is interrupted or restarted.
A patient with advanced CKD and atrial fibrillation is started on an anticoagulant. Why is anticoagulation particularly challenging in patients with kidney failure, and what factors should guide anticoagulant selection and dosing?
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Reducing foods with inorganic phosphate additives especially process and packaged foods.
phosphate additives are highly bioavailable. Choosing fresh foods and checking ingredients list for ingredients containing phosphorus can reduce phosphorus intake while preserving adequate protein.