This document discusses drug dosing considerations in patients with renal failure or impaired kidney function. It provides information on how the kidneys normally clear drugs from the body and how renal dysfunction impacts drug elimination. Factors that affect renal clearance are described. Methods for assessing renal function, such as creatinine clearance, are outlined. The document also discusses how drug dosages need to be adjusted in patients with renal disease to account for decreased drug clearance and elimination. Equations for estimating glomerular filtration rate and creatinine clearance are presented to aid in renal function determination and dosage adjustment.
Dose Adjustment in Acute Renal Failure and Chronic Kidney Disease. Kevin John
In this presentation, I have tried to explain in brief and precisely about drugs that require renal dose adjustments in Chronic Kidney Disease or Acute Kidney Injury (renal failure).
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)
1)CALCINEURIN INHIBITORS
i. CYCLOSPORIN/ CYCLOSPORINE
ii. SIROLIMUS
iii. TACROLIMUS
iv. EVAROLIMUS
2) ANTIPROLIFERATIVE/ANTIMETABOLIC AGENTS,
i. MYCOPHENOLATE
ii. AZATHIOPRINE
3) BIOLOGICS (ANTIBODIES)
i. MUROMONAB-CD3 (OKT3)
ii. BASILIXIMAB
iii. DACLIZUMAB
iv. ALEMTUZUMAB
v. ANTITHYMOCYTE GLOBULIN
4)GLUCOCORTICOIDS,
clinical pharmacokinetics and therapeutic drug monitoring ----- fifth pharm D notes
Dose Adjustment in Acute Renal Failure and Chronic Kidney Disease. Kevin John
In this presentation, I have tried to explain in brief and precisely about drugs that require renal dose adjustments in Chronic Kidney Disease or Acute Kidney Injury (renal failure).
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)
1)CALCINEURIN INHIBITORS
i. CYCLOSPORIN/ CYCLOSPORINE
ii. SIROLIMUS
iii. TACROLIMUS
iv. EVAROLIMUS
2) ANTIPROLIFERATIVE/ANTIMETABOLIC AGENTS,
i. MYCOPHENOLATE
ii. AZATHIOPRINE
3) BIOLOGICS (ANTIBODIES)
i. MUROMONAB-CD3 (OKT3)
ii. BASILIXIMAB
iii. DACLIZUMAB
iv. ALEMTUZUMAB
v. ANTITHYMOCYTE GLOBULIN
4)GLUCOCORTICOIDS,
clinical pharmacokinetics and therapeutic drug monitoring ----- fifth pharm D notes
Therapeutic drug monitoring (TDM) of drugs used in seizure disordersAbel C. Mathew
Therapeutic drug monitoring (TDM) of drugs used in seizure disorders- Phenytoin, Valproic acid, Carbamazepine are major drugs used in epilepsy disorders. These drug need TDM to ensure their proper usage.
THIS SLIDE GIVES AN INSIGHT TO THE DIFFERENT METHODS THAT COULD BE USED FOR THE DOSAGE ADJUSTMENT IN PATIENTS WITH RENAL DISEASE.
RENAL FUNCTION OF THE PATIENT IS ASSESSED TO DETERMINE THE DOSAGE ADJUSTMENT
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
In this presentation I have tried to explain in brief about the dosage adjustment in renal disorders, how to carry out this process and the important formulae which are used in it.
Therapeutic drug monitoring (TDM) of drugs used in seizure disordersAbel C. Mathew
Therapeutic drug monitoring (TDM) of drugs used in seizure disorders- Phenytoin, Valproic acid, Carbamazepine are major drugs used in epilepsy disorders. These drug need TDM to ensure their proper usage.
THIS SLIDE GIVES AN INSIGHT TO THE DIFFERENT METHODS THAT COULD BE USED FOR THE DOSAGE ADJUSTMENT IN PATIENTS WITH RENAL DISEASE.
RENAL FUNCTION OF THE PATIENT IS ASSESSED TO DETERMINE THE DOSAGE ADJUSTMENT
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
In this presentation I have tried to explain in brief about the dosage adjustment in renal disorders, how to carry out this process and the important formulae which are used in it.
Variation of Pharmacokinetics in disease states-converted-converted.pdfUVAS
I am a pharmacist. These slides describe biotechnology topic. I hope students get more benefits about it. These slides very helpful for the pharmacy department students.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
3. The conc. of the drug in the urine is the net result of
filtration + secretion (minus the reabsorption).
Rate of excretion = Filtration rate + Secretion rate –
Reabsorption rate
Ac = (Afilt + Asec) – Areabs
ClR = Ac / C
• where, Ac = amt. of drug ‘cleared’ or excreted by the
kidneys
• C = plasma drug conc.; ClR = Renal clearance
Overall Cl = renal Cl + non-renal Cl
4. Factors affecting ClR
• Physico-chemical props. of the drug
• Plasma conc. of the drug
• Urine pH
• Blood flow to the kidneys
• Biological factors
• Drug interactions
• Drug states
5. Disease states
Renal dysfunction: Impairs drug elimination (mainly
those drugs excreted primarily through urine);
Uremia: characterized by impaired GFR; impaired ClR;
accumulation of fluids and proteins in the plasma;
Renal function determination
• By estimating the GFR
• Exogenous and endogenous markers have been used
for this purpose;
• The marker should be entirely excreted unchanged in
the urine; must be physiologically and p’cologically
inert.
6. • Rate at which these markers are excreted in the urine
reflect the status of GFR (possibility of renal
dysfunction or not).
• Inulin (exogenous fructose polysacch.) and Creatinine
Inulin Cl provides accurate estimate of GFR, but the
process is tedious;
Creatinine Clearance (CrCl or Clcr)
• Creatinine: Endogenous amine produced by muscle
catabolism; excreted unchanged by GF only
• Clcr can be correlated to the steady state conc. (Css or
Css) of creatinine in plasma;
• Depends on: age, gender, weight, disease state among
other factors
7.
8. Direct method: determine amt. of creatinine excreted
in urine over a 24 hr. period; and mean of Scr from
blood samples taken before and after urine collection
Normal Clcr value = 120 – 130 ml/min.
Clcr = 20 – 50 ml/min. (moderate renal
impairment)
Clcr = < 10 ml/min. (severe renal impairment)
10. Chronic Kidney Disease
Definition:
A CKD patient has abnormalities of kidney function or
structure present for > 3 months.
The definition of CKD includes…
• all individuals with markers of kidney damage, or
• those with an eGFR of < 60 ml/min/1.73m2 on at least
2 occasions 90 days apart (with or without markers of
kidney damage).
11. Markers of kidney disease:
• Albuminuria (ACR > 3 mg/mmol),
• Haematuria (or presumed or confirmed renal origin),
• Electrolyte abnormalities due to tubular disorders,
• Renal histological abnormalities,
• Structural abnormalities detected by imaging (e.g.
polycystic kidneys, reflux nephropathy)
• H/o kidney transplantation.
12.
13. CKD Classification
Based on the eGFR and the level of proteinuria and helps to
risk-stratify patients.
Patients are classified as…
• G1-G5 (based on the eGFR), and
• A1-A3 (based on the ACR which is albumin:creatinine ratio)
E.g.,
• A person with an eGFR of 25 ml/min/1.73 m2 and an ACR of 15
mg/mmol has CKD G4A2.
• A person with an eGFR of 50 ml/min/1.73 m2 and an ACR of 35
mg/mmol has CKD G3aA3.
14. CKD Classification (contd’.)
Patients with an eGFR of >60 ml/min/1.73m2 should
not be classified as having CKD unless they have
other markers of kidney disease.
GFR category G2 may be over-diagnosed by eGFR
because sometimes equations used to estimate GFR
may give falsely low results in people with near-normal
function.
15. P’cokinetic considerations in Uremic Patients
May exhibit p’cokinetic alterations in BA, Vd, and Cl.
↓ed oral BA (probable) of a drugs in severe uremia due to
disease-related changes in GI motility and pH (↓ed oral BA
caused by nausea, vomiting, and diarrhea).
Mesenteric blood flow may also be altered.
↑ed Oral BA (probable) of drugs which have a high first-pass
effect (e.g., propranolol ) in patients with renal impairment due
to ↓ in first-pass hepatic metabolism.
The apparent Vd depends largely on drug-plasma protein
binding in tissues and total body water.
16. P’cokinetic considerations in Uremic Patients (contd’.)
Renal impairment may alter the drug distribution due
to changes in fluid balance, drug-protein binding,
among other factors.
↓ed PP binding of weak acidic drugs in uremic patients;
PP binding of weak basic drugs are less affected.
• ↓ed drug-protein binding results in a larger fraction of free drug
and an increase in Vd.
17. P’cokinetic considerations in Uremic Patients (contd’.)
↑ed net elimination t1/2 (generally) due to the dominant
effect of reduced glomerular filtration.
Drug-protein binding may be further compromised due
to the accumulation of drug metabolites and various
biochemical metabolites (FFAs and urea), which may
compete for the protein-binding sites for the active
drug.
18. P’cokinetic considerations in Uremic Patients (contd’.)
↓ed total body clearance of drugs by….
• ↓ in GFR, or
• ↓ed hepatic clearance (ClH)
• active tubular secretion
The appropriate drug dosage regimen in uremic
patients is based on estimation of the remaining
renal function of the patient and a prediction of the
total body clearance.
Drug protein binding in uremic patients is also
dependent on accumulation of urea, nitrogenous
wastes, and drug metabolites.
19. P’cokinetic considerations in Uremic Patients (contd’.)
A complete pharmacokinetic analysis of the drug in the
uremic patients is not possible.
The patient's uremic condition may not be stable and may
be changing too rapidly for pharmacokinetic analysis.
20. Dose adjustment in RF patients
Drugs in pts. with RF have altered p’cokinetic profile:
• ↓ed Clr and elimination rate; ↑ed elimination t1/2;
altered apparent Vd;
Dose adjustment for drugs in uremic or renally
impaired patients should be made in accordance with
p’codynamic and p’cokinetic changes of the drug in
each individual patient.
Active metabolites of the drug may also be formed and
must be considered for additional pharmacologic effects
when adjusting dose.
21. Dose adjustment in RF patients (contd’.)
Dose must be altered (tailored / customized) to each
individual patient.
Drugs excreted by the kidneys require a huge reduction
in doses in order to achieve therapeutic drug conc. in
patients w/ renal dysfunction.
22. Basis for Dose Adjustment in Uremic Patients
Loading dose:
• Is based on the apparent Vd of the patient;
• Is generally assumed that the apparent Vd is not
altered significantly, (implying that the loading dose of
the drug is the same in uremic patients as in subjects
with normal renal function).
Maintenance dose:
• Is based on drug CL in the patient.
• In uremic patients, the ↓ed rate of renal drug excretion
leads to a ↓ed total body CL.
• Most methods for dose adjustment assume non-renal
drug CL to be unchanged.
• The fraction of normal renal function remaining in the
uremic patient is estimated from CrCl.
23. Basis for Dose Adjustment in Uremic Patients (contd’.)
• After the remaining total body CL in the uremic patient
is estimated, the appropriate dosage regimen may
be developed by:
(a) decreasing the maintenance dose,
(b) increasing the dosage interval, or
(c) changing both maintenance dose and dosage
interval.
24. Basis for Dose Adjustment in Uremic Patients (contd’.)
Although total body clearance is a more accurate
index of drug dosing, the elimination half-life of
the drug is more commonly used for dose
adjustment due to it’s convenience.
CL allows to predict steady-state drug
concentrations (Css), while elimination half-life
yields information on the time it takes to reach
steady-state concentration.
25. Assumptions of Giusti-Hayton Method and Tozer
approach:
Kidney dysfunction does not affect the non-renal
excretion.
↓ in kidney function….
• proportional ↓ in rate of renal drug elimination;
• does not affect non-renal drug elimination;
• does not affect the drug’s absorption and/or
distribution.
26. UCr x V
CrCl = ________
SCr x t
where,
UCr = urine creatinine conc.;
V = volm. of urine collected;
SCr = serum creatinine (from blood) measured at
midpoint of urine collection;
t = time interval of urine collection
27. Issue with CrCl formula:
Some creatinine found in the urine is due to ‘Tubular
Secretion’.
CrCl formula therefore overestimates GFR at all levels
of renal function.
Dgs. (like amiloride, cimetidine, trimethoprim,
salicylate, triamterene, spironolactone) which inhibit
secretory function may increase SCr, and decrease the
overestimate, without actually affecting the GFR.
28. Note FYI:
Declining kidney function is accompanied by an
increasing contribution of tubular creatinine
secretion to the total creatinine
clearance; secretion may account for as much as 50%
of creatinine clearance in the later stages of chronic
kidney disease (CKD).
29. Dosing adjustment is not usually done unless
GFR < 1 ml/s/70 kg (GFR 60 ml/min/1.73m2)
Dosage regimen need NOT be altered if fraction of drug
excreted unchanged in urine (fu) is ≤0.3% and renal
function is ≥ 0.7% of normal;
• Based on some assumptions: inactive metabolites;
unaltered binding characteristics and drug availability;
kidney function is not greatly reduced;
BUT….
• If fu is almost unity and renal function is almost
zero, dosing should be reduced drastically
(elimination is extremely slowed down);
• The significance of non-renal Cl increases in such
conditions.
30. Dosing adjustment usually includes dose reduction,
increasing dosing interval(s), or both.
Dose reduction more consistent dg. conc. (but
↑es toxicity risk if dosing interval is too short)
↑ ing Dosing interval ↓es toxicity risk (but ↑es risk
of sub-therapeutic effect is concs. fall below MEC)
Loading doses are usually not adjusted.
When rapid effect is needed (in severe infection, etc.),
patient’s response is the most imp. factor to consider.
31. Creatinine Clearance (CrCl) in Adults
• The formula below estimates CrCl from SCr concentration.
• This method considers both the age and the weight of the patient.
• For males,
• For females, use 90% of the Cl Cr value obtained in males.
• FYI: SCr and CCr refer to the same parameter serum creatinine conc.
32. The nomogram method of Siersback-Nielsen et al (1971):
• estimates CrCl based on age, weight, and SCr conc.
33. Homework:
What is the creatinine clearance for a 25-year-old male patient
with C Cr of 1 mg/dL and a body weight of 80 kg?
34. How to use the Siersback-Nielsen nomogram:
• Connect the patient's weight on the 2nd line from the left with the
patient's age on the 4th line with a ruler.
• Note the point of intersection on R and keep the ruler there.
• Turn the right part of the ruler to the appropriate serum creatinine
value and the left side will indicate the clearance in mL/min.
35. Nomogram of Traub and Johnson (1980):
For calculating CrCl in pediatric patients (aged 6–12
years)
37. Subsequent doses should be titrated based on patient’s
response and/or serum conc.
Conventional GFR estimates are not accurate for
children, elderly pts., pregnant women, weight
extremes (‘over’ or ‘under’ weight)
For obese pts. (> 30% over IBW):
Use CG eqn. and use Lean body weight;
Increase the ‘No weight’ CrCl by a factor of 0.3 – 0.4
Use the Salazar-Corcoran eqn.
Elderly patients:
Usual methods overestimate GFR;
Dosing should be based on risk vs benefit analysis,
patient’s response and clinical judgment.
38. Required dose in patients with renal impairment can be
calculated by:
Normal dose x RF
where, RF = Renal Function
Dosing interval (in hrs.) can be derived by:
Normal interval (in hrs.) / Renal Function
When the drug is excreted by both renal and non-renal
mechanisms, the dose to be administered in RF
patients is:
39.
40. In pts. w/ CKD stages 1 – 5 (pre-dialysis), the
Cockroft-Gault (CG) eqn. is used to estimate the CrCl
in the presence of stable renal function.
(140-age) x (W)
CrCl = ______________
(72) x SCr
CrCl (females) = CrCl (males) x 0.85
where, SCr is in mg/dl and W is in kgs
The IS conversion for males is
1.23 x (140-age) x (W)
CrCl = ___________________
(72) x SCr
41. Weight-corrected (‘No weight’) CG equation:
meta-analysis showed this formula provided the best
estimate of GFR (Park E., et al., 2012)
42. CKD-EPI Equations for calculation of eGFR
CKD-EPI creatinine equation (Levey, et. al.)
eGFR = 141 x min(SCr/κ, 1)α x max(SCr /κ, 1)-1.209 x
(0.993)Age x [1.018 if female] x [1.159 if Black]
• eGFR (mL/min/1.73 m2); SCr = standardized serum creatinine (mg/dL)
• κ = 0.7 (females); 0.9 (males); α = - 0.329 (females), - 0.411 (males)
• min = indicates the minimum of SCr/κ or 1
• max = indicates the maximum of SCr/κ or 1
The CKD-EPI eqns. are mainly used for identifying CKD
and staging the degree of severity.
More accurate than the MDRD4 equation, especially for
patients with higher levels of GFR.
Not yet being used in Malaysia.
43. CKD-EPI Equations for calculation of eGFR (contd’.)
CKD-EPI cystatin C equation (Inker, et. al.)
eGFR = 133 x min(SCys/0.8, 1)-0.499 x max(SCys /0.8, 1)-1.328 x
(0.996)Age x [0.932 if female]
• eGFR (mL/min/1.73 m2); SCys = standardized serum cystatin C
CKD-EPI creatinine-cystatin C equation (Inker, et. al.)
eGFR = 135 x min(SCr/k, 1)-a x max(SCr /k, 1)-0.601 x
min(SCys/0.8, 1)-0.375 x max(SCys /0.8, 1)-0.711 (0.995)Age x
[0.969 if female] x [1.018 if Black]
K = 0.7 (females), 0.9 (males);
a = -0.248 (females), -0.207 (males)
44. MDRD4 equation:
• Where, eGFR = estimated GFR (ml min-1/ 1.73 m2 BSA)
• (Cs)cr = serum creatinine conc.(mg/dl)
If serum albumin (ALB) and BUN values are known,
then the formula can be expressed as:
• (Cs)cr and BUN units is mg%; ALB is %
45. MDRD4 eqn. limitations:
Underestimates eGFR for patients with GFR > 60
ml/min
MDRD4 eqn. is not adjusted for body weight…
• Smaller eGFR values for heavy patients,
• Larger eGFR values for thinner patients
Jelliffe Equation:
CrCl (ml/min) = {[98 – 0.8 × (age – 20)] × [1 – (0.01 × sex)] ×
(BSA/1.73)}/(SCr × 0.0113)
vs CG eqn.
46. Dialysis and Hemoperfusion
For severe renal failure cases
To remove toxic waste products, drugs and
metabolites, which accumulate in the body;
Dialysis: Process in which easily diffusible substances
are separated from poorly diffusible substances by a
semi-permeable membrane.
2 types: Hemodialysis and Peritoneal dialysis
Peritoneal dialysis:
• The semi-permeable membrane is the natural
membrane of the peritoneal cavity.
47. Hemodialysis(HD)
• Artificial, semi-permeable membrane, outside the body
(extracorporeal dialysis);
• Equipment is Hemodialyzer (Artificial Kidney);
• Removes toxic wastes from the body;
• Very useful in treatment of overdose or poisoning
situations;
• Patients require hemodialysis every 2-3 days; each
session lasts 3-4 hrs. (average).
48. Factors governing HD
• Water solubility: only water-soluble drugs; lipophilic
drugs (e.g., glutethimide) cannot be dialyzed;
• Mol. Size: only those drugs < 500 Da; larger sized
drugs (e.g., vancomycin) cannot be dialyzed;
• Protein binding: PP-bound drugs cannot be dialyzed as
this process is a passive diffusion process;
• Vd or V: Drugs with large Vd easily distributed
throughout the body difficult to remove by
dialysis (e.g., digoxin)
49. Rate of drug removal by dialyzer depends on:
• Blood flow rate to the machine
• Dialyzer’s performance
Dialysance (Dialysis Cl): Ability of the dialyzer to
clear the drug from the blood.
• where, Cld = Dialysance
• Q = blood flow rate to dialyzer
• Cin = drug conc. in blood entering the dialyzer
• Cout = drug conc. in blood exiting the dialyzer
50. Dosage regimen adjustment for hemodialysis pts.
1° objective: To design an appropriate dg. regimen for
admn. on dialysis days such that the dose given at the
end of dialysis is sufficient to achieve the desired max.
drug conc.
Prospective individualization of dosage regimen is
recommended for dgs. with narrow therapeutic index
(aminoglycosides, vancomycin, etc..).
Why is this imp. in ambulatory care patients on chr.
hemodialysis?
Avoid admn. of dgs. in the hrs. just before HD to
prevent excessive removal of the dgs. during the HD
process.
51. Admn. of higher doses just prior to HD has been
recommended for certain drugs to compensate the
removal of drugs during HD (Mohamed et al., 2007;
Scott MK et al., 1997).
Use simple consistent admn. schedules that minimize
the need for variable drug doses to be administered on
dialysis and non-dialysis days.
Dose to be administered post-HD:
DpostHD = V x (Cmax – C postHD)
CpostHD = CpreHD x (e-kt + e-kHDt)
• where, V = volm. of distribution for the drug of interest
• e-kt = fraction of drug that remains post-HD, as a result of
the patient’s residual total body Cl.
• e-kHDt = fraction of drug that remains post-HD, as a result
of the elimination by the dialyzer.
52. ClHD = {Cart – Cven/Cart} x [Qb (1 – Hct)]
• where, Cart = drug conc. in plasma entering the dialyzer
• Cven = drug conc. in plasma exiting the dialyzer
• Qb = blood flow through the dialyzer
• Hct = patient’s hematocrit value
Dosage individualization for patients on CRRT
CRRT is a viable management approach for
hemodynamically unstable patients with or without
AKI.
The dosage regimen for patients receiving CRRT can be
individually ascertained by adding the estimated or
measured drug Cl by CRRT to the patient’s residual
drug Cl.
53. Roles of the pharmacist
Identify patients who are at high risk for CKD (DM,
HTN, Glomerulonephritis).
Verify the renal functional status of the patient based
on the lab values (incl. of the latest test results).
Identify the medications which require dosage
adjustment, and determine the dosage adjustment
(use BANND CAMP, among others).
Check medication profile for DIs which could …
• affect serum levels of renally-excreted drugs (p-gp
inhibitors);
• ↓ renal function (nephrotoxic dgs.)
Communicate the recommendations regd. patient’s
medication(s) to the doctor.
Set up monitoring plan for the medications.
54. FYI
The K/DOQI classification of CKD
K/DOQI = Kidney Disease Outcome Quality Initiative;
(by the National Kidney Foundation)