This document discusses dosage adjustments for patients with renal or hepatic failure. It covers:
1) Causes, classification, and measurement of renal failure including glomerular filtration rate (GFR) and creatinine clearance. Dosage adjustments are recommended based on GFR for various drug classes.
2) Causes, classification, and liver function tests for hepatic failure. Considerations for dosage adjustments in patients with hepatic impairment include drug elimination pathways and protein binding.
3) Formulas for estimating creatinine clearance from serum creatinine levels, including the Cockcroft-Gault and modification of diet in renal disease (MDRD) methods.
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
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
Definition, Patterns/types and mechanisms of drug induced liver disorders, assessment of drug induced liver disorders and its treatment (pharmacotherapeutics-3)
Introduction to daily activities of clinical pharmacist.
Drug therapy monitoring,
Medication chart review
Clinical Progress
Pharmacist intervention
Detection and management of ADRs
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.
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).
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
Definition, Patterns/types and mechanisms of drug induced liver disorders, assessment of drug induced liver disorders and its treatment (pharmacotherapeutics-3)
Introduction to daily activities of clinical pharmacist.
Drug therapy monitoring,
Medication chart review
Clinical Progress
Pharmacist intervention
Detection and management of ADRs
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.
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).
This was a review of different guidelines on lupus nephritis from ACR, EULAR, and KDIGO. Goal is appreciate similarities and differences between the different guidelines.
This presentation quotes various pharmaceutical calculations with examples. The following aspects like percentage calculations, alcoholic dilutions, Alligation method, proof spirit calculations, isotonicity adjustment, posology, temperature measurements, dialysis clearance, Pharmacokinetics calculations were covered with examples.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
Dose Adjustment in renal and hepatic failure
1. DOSAGE ADJUSTMENTS OF
HEPATIC, RENAL FAILURE
Presented by:
k.Sowmya
12AB1ROO41
Guided by:
k.Pallavi
Assistant professor
1
vignan pharmacy college,vadlamudi,gunturdist.A.P.
2. Table of contents
Renal failure:
• Causes
• Classification
• Dosing adjustments
• Measurement of GFR-Creatinine clearance
• Dosage adjustments in different drugs
• Serum creatinine concentration
• Formulas
Liver failure:
• Classification
• Etiology
• Liver function tests
• Dosage calculations
2
vignan pharmacy college,vadlamudi,gunturdist.A.P.
3. • Renal failure or kidney failure (formerly called renal insufficiency)
describes a medical condition in which the kidneys fail to
adequately filter toxins and waste products from the blood.
• Renal failure is described as a decrease in glomerular filtration rate
(GFR).
Renal failure
3vignan pharmacy college,vadlamudi,gunturdist.A.P.
4. Causes of renal failure
• Common causes :condition comment
Pyelonephritis Inflammation of pyelonephrons due to infection
Hypertension Chronic overloading of kidney with fluid and
electrolytes lead to kidney insufficiency
Diabetes mellitus The disturbance of sugar metabolism may lead to
degenerative renal disease
Nephrotoxic
drugs/metals
certain drugs like aminoglycosides,
Phenacetin cause irreversible kidney disease
Hypovolemia Any condition that causes a reduction in renal blood
flow leads to renal damage.
4
vignanpharmacycollege,vadlamudi,gunturdist.A.P.
5. Classification
• Renal failure can be divided in to two categories:
Acute renal failure (ARF),
Chronic renal failure(CRF)
5
vignan pharmacy college,vadlamudi,gunturdist.A.P.
6. Acute kidney injury(AKI)
• AKI , previously called acute renal failure (ARF), is a rapidly
progressive loss of renal function, generally charecterized by
oliguria(decreased urine production) and fluid and electrolyte
imbalance.
6vignan pharmacy college,vadlamudi,gunturdist.A.P.
7. Chronic kidney disease(CKD)
• CKD is along term consequence of irreversible acute disease or part
of a disease progression.
• It is a progressive loss of function over several months to years ,
characterized by gradual replacement of normal kidney architecture
with interstitial fibrosis.
7vignan pharmacy college,vadlamudi,gunturdist.A.P.
8. Drug dosing incase of ARF:
• Drug therapy optimization in ARF is a challenge confounding
variables include residual drug clearance , and fluid accumulation.
• Volume of distribution for water soluble drugs is significantly
increased due to edema . Use of dosing guidelines for CKD does not
reflect the clearance and volume of distribution in critically ill ARF
patients.
8
vignan pharmacy college,vadlamudi,gunturdist.A.P.
9. Dosing adjustments in CKD:
• Loading doses do not need to be adjusted in patients with CKD.
• Some guide lines suggest methods for maintaining dosing adjustments:
dose reduction , lengthening the dose interval or both.
• Dose reduction maintains more constant drug concentrations but
associated with high risk of toxicities if the dosing interval is inadequate
to allow for drug elimination.
• Lengthening the dosing interval - lower risk of toxicities but a higher risk
of sub therapeutic drug concentrations.
9vignan pharmacy college,vadlamudi,gunturdist.A.P.
10. National Kidney Foundation
Kidney Disease Outcomes Quality
Initiative (K/DOQI)
Stage Description GFR (mL per minute
per 1.73 m2)
1. Kidney damage with normal or
increased GFR
≥90
2. Kidney damage with a mild
decrease in GFR 60 to 89
60-89
3. Moderate decrease in GFR 30 to 59
4. Severe decrease in GFR 15-29
5. Kidney failure < 15 (or dialysis)
10
vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-1
11. Antihypertensive Agents: Dosing
Requirements in patients with
Chronic Kidney Disease
Drug Usual
dosage
Dosage Adjustment based on GFR
>50 10 to 50 <10
ACE
INHIBITORS:
Captopril
10 mg
daily
100% 50 to 75% 50%
BETA
BLOCKERS:
Atenolol
5 to 100 mg
daily
100% 50% 25%
DIURETICS:
Furosemide
No
adjustment
needed
_ _ _
11
vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-2
12. Hypoglycemic Agents:
Dosing Requirements in patients
with Chronic Kidney Disease
DRUG USUAL DOSAGE SPECIAL CONSIDERATIONS
Acarbose (Precose) Maximum: 50 to 100 mg
three times daily
Lack of data in patients with a serum
creatinine level higher than 2 mg per
dL (180 µmol per L); therefore,
acarbose should be avoided in these
patients1
Chlorpropamide
(Diabinese)
100 to 500 mg daily Avoid in patients with a glomerular
filtration rate less than 50 mL per
minute because of the increased risk
of hypoglycemia19
Glipizide (Glucotrol) 5 mg daily Dosage adjustment not necessary in
patients with renal impairment
12
vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-3
13. Antimicrobial Agents: Dosing
Requirements in patients
with Chronic Kidney Disease
Drug Usual dosage Dosage adjustment based on GFR
>50 10 to 50 <10
ANTIFUNGALS:
Fluconazole
200 to 400 mg
every 24 hours
100% 50% 50%
ANTIVIRALS:
Acyclovir
5 to 10 mg per
kg every
100% 100% every 12
to 24 hours
50% every 12 to
24 hours
PENICILLINS:
Amoxicillin
250 to 500 mg
every 8 hours
Every 8
hours
Every 8 to 12
hours
Every 24 hours
TETRACYCLINES
Doxycycline
No adjustment
needed
_ _ _
OTHERS:
Nitrofurantoin
500 to 1,000
mg every 6
hours
100% Avoid Avoid
13
vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-4
14. Other Common Agents: Dosing Requirements
in patients with Chronic Kidney Disease
Drug Usual dosage Dosage adjustment based on GFR
>50 10 to 50 <10
Allopurinol 300 mg daily 75% 50% 25%
Famotidine 20 to 40 mg at bedtime 50% 25% 10%
Metoclopramide 10 to 15 mg three times
daily
100% 75% 50%
omeprazole no adjustment needed _ _ _
Ranitidine 150 to 300 mg at
bedtime
75% 50% 25%
14vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-5
15. Measurement of glomerular
filtration rate:
Several drugs and endogenous substances have been used as
markers to measure GFR.
These markers carried to the kidney by the blood via the renal artery
and are filtered at the glomerulus.
Therefore, the rate at which these drug markers are filtered from the
blood in to urine per unit of time reflects the GFR of the kidney.
Changes in GFR reflects changes in kidney function.
15
vignan pharmacy college,vadlamudi,gunturdist.A.P.
16. Creatinine clearance
Creatinine clearance may be defined as the volume of plasma
cleared of creatinine per unit time .
It can be calculated by the following formula:
𝑐𝑙
𝑐𝑟=
𝑟𝑎𝑡𝑒 𝑜𝑓 𝑢𝑟𝑖𝑛𝑎𝑟𝑦 𝑒𝑥𝑐𝑟𝑒𝑡𝑖𝑜𝑛 𝑜𝑓 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒
𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
It is expressed in mL/min.
16vignan pharmacy college,vadlamudi,gunturdist.A.P.
18. Measure of GFR-
creatinine clearance
The clearance of creatinine is used most extensively as a
measurement of GFR .
Creatinine is an endogenous substance formed from creatinine
phosphate during muscle metabolism.
Creatinine production varies with age, weight, gender of the
individual.
In humans, creatinine is filtered mainly at the glomerulus, with no
tubular re-absorption.
It tends to be decrease in elderly patient.
18
vignan pharmacy college,vadlamudi,gunturdist.A.P.
20. Serum creatinine concentration
and creatinine clearance:
• Under normal circumstances , creatinine production is roughly equal
to creatinine excretion, so the serum creatinine level remains
constant.
• In a patient with reduced glomerular filtration , serum creatinine will
accumulate in accordance with the degree of loss of glomerular
filtration in the kidney.
• The serum creatinine concentration alone is frequently used to
determine creatinine clearance, 𝑐𝑙 𝑐𝑟 .
• Creatinine clearance from the serum creatinine concentration is a
rapid and convenient way to monitor kidney function.
• Serum creatinine is expressed in mg/dL or mg%.
20vignan pharmacy college,vadlamudi,gunturdist.A.P.
21. Calculation of
creatinine clearance from
serum creatinine concentration:
• Serum creatinine concentration , 𝑐 𝑐𝑟, is related to creatinine
clearance measured routinely in clinical laboratory.
• Therefore , creatinine clearance 𝑐𝑙 𝑐𝑟 , is most often estimated from
the patient’s 𝑐 𝑐𝑟.
• Several methods are available to calculate 𝑐𝑙 𝑐𝑟 from 𝑐 𝑐𝑟, in which
accurate methods are based on the patient’s age, height, weight,
gender.
21
vignan pharmacy college,vadlamudi,gunturdist.A.P.
22. Cockcroft and Gault method:
• Adults:
The method of cockcroft and gault is used to estimate creatinine
clearance from serum creatinine concentration . This method
considers both the age and the weight of the patient.
For males,
𝑐𝑙 𝑐𝑟= 140−𝑎𝑔𝑒 𝑦𝑒𝑎𝑟𝑠 ×𝑏𝑜𝑑𝑦𝑤𝑒𝑖𝑔ℎ𝑡(𝑘𝑔) /72𝑐 𝑐𝑟
For females use 90% of the 𝑐𝑙 𝑐𝑟 value obtained in males.
22
vignan pharmacy college,vadlamudi,gunturdist.A.P.
23. Children:
• There are a number of methods for calculation of creatinine
clearance in children , based on body length , and serum creatinine
concentration.
• It is a method developed by schwartzand associates :
𝑐𝑙
𝑐𝑟=
0.55 𝑏𝑜𝑑𝑦 𝑙𝑒𝑛𝑔𝑡ℎ(𝑐𝑚)
𝑐 𝑐𝑟
Where 𝑐𝑙 𝑐𝑟 is given in mL/min/1.73𝑚2
.
• The value 0.55 represents a factor used for children ages 1 to 12
years.
23
vignan pharmacy college,vadlamudi,gunturdist.A.P.
24. Cockcroft-Gault equation-
IBW AND ABW:
• For obese patients , generally defined as patients more than 20%
over ideal body weight(IBW) creatinine clearance should be based
on ideal body weight .
• Males : IBW=50 kg+2.3 kg for each inch over 5 feet
• Females : IBW=45.5kg+2.3 kg for each inch over 5 feet.
• ADJUSTED BODY WEIGHT(ABW):
• Studies have shown ABW is the best approach for calculating
creatinine clearance in the elderly patients.
𝑐𝑙 𝑐𝑟=[(140-age)× 𝐴𝐵𝑊)/(𝑆𝑐𝑟 × 72) × 0.85 𝑓𝑜𝑟 𝑓𝑒𝑚𝑎𝑙𝑒𝑠
ABW=IBW+0.3*(TBW-IBW).
24vignan pharmacy college,vadlamudi,gunturdist.A.P.
25. Estimated GFR(e GFR) using
modification of diet in
renal disease(MDRD):
• Various approaches for the estimate of GFR from serum creatinine
have been derived .
• For example,
eGFR(mL/min/1.73𝒎 𝟐)=175× 𝒔 𝒄𝒓.std)-
1.154×age(years)-0.203×(0.742 if female)×(1.212 if
African or American.
Where eGFR is estimated GFR using the MDRD equation.
25
vignan pharmacy college,vadlamudi,gunturdist.A.P.
26. LIVER FAILURE
• Liver failure or hepatic insufficiency is the inability of the liver to
perform its normal synthetic and metabolic function as part of
normal physiology.
• Two forms are recognized;
Acute liver failure,
Chronic liver failure
26
vignan pharmacy college,vadlamudi,gunturdist.A.P.
27. ACUTE LIVER FAILURE
• It is defined as the rapid development of hepatocellular dysfunction,
specifically coagulopathy and mental status changes
(encephalopathy) in a patient without known prior liver disease.
CHRONIC LIVER FAILURE
• It usually occurs in the context of cirrhosis , itself potentially the
result of many possible causes, such as excessive alcohol intake,
hepatitis B or C , auto immune , hereditary and metabolic causes.
27
vignan pharmacy college,vadlamudi,gunturdist.A.P.
28. ETIOLOGY
• The liver can be damaged in a variety of ways:
Cells can become inflamed(such as hepatitis).
Bile flow can be obstructed (such as cholestasis).
Cholesterol or triglycerides can accumulate (steatosis).
28
vignan pharmacy college,vadlamudi,gunturdist.A.P.
29. Considerations in
dosing patients
with hepatic impairment
ITEM COMMENTS
Drug elimination Drugs eliminated by the liver >20% are less
likely to be affected by liver disease.
Protein binding Drug protein binding may be altered due to
alteration in hepatic synthesis of albumin.
Therapeutic range Drugs with a wide therapeutic range will be
less affected by moderate hepatic impairment.
29
vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-6
30. Liver function tests
and hepatic metabolic
markers
Drug markers used to measure residual hepatic function may correlate
well with hepatic clearance of one drug which correlate poorly with
substrate metabolized by a different enzyme with in the same
cytochrome p-450 subfamily .
30
vignan pharmacy college,vadlamudi,gunturdist.A.P.
32. Useful hepatic marker
compounds
1.Aminotransferase (AST):Normal AST value for males is 10-55 U/L;
and for females is 7-30 U/L.
2.Alkaline phosphatase (AP):Normal AP values for males is 45-115
U/L and for females is 30-100 U/L ,
Marked AP elevations may indicate hepatic tumors or biliary
obstruction in the liver.
3. Bilirubin : Normal value is 0-1mg/dl
Unconjugated hyperbilirubinemia results from increased bilirubin
production.
Conjugated hyperbilirubinemia results from defects in hepatic
excretion.
4. Prothrombin time : Normal value is 11.2-13.2 sec , with the
exception of factor 8 , all coagulation factors are synthesized by the
liver ; therefore hepatic disease can alter the coagulation.
32
vignan pharmacy college,vadlamudi,gunturdist.A.P.
33. Effect of hepatic
disease on
pharmacokinetics
• Drugs are often metabolized by one or more enzymes located in
cellular membranes in different parts of the liver
• Drugs and metabolites may also be excreted by biliary secretion.
• Liver disease may also alter kidney function, which can lead to
accumulation of a drug and its metabolite's even when the liver is
not primarily responsible your elimination.
• Hepatic disease can alter the pharmacokinetics of a drug including
the absorption and disposition and the pharmacodynamics including
efficacy and safety.
33
vignan pharmacy college,vadlamudi,gunturdist.A.P.
34. Hepatic blood flow
and
intrinsic clearance:
• Blood flow changes can occur in patients with chronic liver disease.
• Hepatic arterial venous shunts may lead to reduced drug fraction of
drug excreted and an increase in the bio avilability of drug.
• In other patients , resistance to blood flow may be increased as a
result of tissue damage and fibrosis , causing a reduction in intrinsic
hepatic clearance. The following equation may be applied to
estimate hepatic clearance of a drug after assessing changes in blood
flow and intrinsic clearance (𝑐𝑙𝑖𝑛𝑡): 𝑐𝑙ℎ=Q.𝑐𝑙𝑖𝑛𝑡/Q+𝑐𝑙𝑖𝑛𝑡
• Alternatively, when both Q and the extraction ratio ER, are known in
the patient , clearance(cl) may also be estimated : cl=Q(ER)
Where Q=Amount of blood flows to liver.
34
vignan pharmacy college,vadlamudi,gunturdist.A.P.
38. Hepatic impairment and
dose adjustment
• The drug is metabolized in the liver to a small extent (<20%) and
the therapeutic range of the drug is wide so that modest impairment
of the drug directly or by increasing its interaction with other
drugs.
• The drug is gaseous or volatile , and the drug and its active
metabolites are primarily eliminated via the lungs.
• For each drug case , the physician needs to assesses the degree of
hepatic impairment and consider the known pharmacokinetics and
pharmacodynamics of the drug.
• Starting therapy with low doses and monitoring response or plasma
levels provides the best opportunity for safe, efficacious treatment
38
vignan pharmacy college,vadlamudi,gunturdist.A.P.
39. Dosage considerations in hepatic failure:
:
• Several physiologic and pharmacokinetic factors are relevant
in considering dosing of a drug in patients with hepatic
disease.
• Chronic disease and tissue injury may change the accessibility
of some enzymes as a result of re-direction of hepatic blood
circulation.
• Drugs with flow dependent clearance are avoided otherwise
the dose of those drugs need to be reduced to as low as one-
tenth of conventional dose , for an orally administered agent.
• Starting therapy with low doses and monitoring response or
plasma levels provides the best opportunity for safe,
efficacious treatment.
39vignan pharmacy college,vadlamudi,gunturdist.A.P.
40. Dosing in liver disease
• For severe liver dysfunction (albumin<30g/L, INR > 1.2):
(a) If the drug is a high clearance drug (liver blood flow dependent)
reduce dose by 50%:
High Clearance Drugs Example
Antipsychotics Opioids (most)
Beta-blockers (most) Tricyclic antidepressants
Lignocaine statins
Nitrates SSRIs
40vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-10
41. Dosing in liver disease
(b) If the drug is low clearance (flow-independent - includes all
other metabolised drugs) reduce dose by 25%:
Low clearance drugs Examples
Anticonvulsants (most) Sulphonylureas
Spironolactone Theophylline
Paracetmol Warfarin
NSAID’s Steroids
41
vignan pharmacy college,vadlamudi,gunturdist.A.P.
Table-11
42. Formulas:
• Model for end stage liver disease(MELD):
MELD=3.78× 𝑠𝑒𝑟𝑢𝑚 𝑏𝑖𝑙𝑖𝑟𝑢𝑏𝑖𝑛(𝑚𝑔/𝑑𝑙)+
11.20× 𝑙𝑛𝐼𝑁𝑅 + 9.57 ×
ln serum creatinine (mg/dl)+
6.43(constant for liver disease etiology).
Where INR=International normalized ratio,
NOTE : If the patient has been dialyzed twice with in the last 7 days ,
then the value for serum creatinine used should be 4.0.
vignan pharmacy college,vadlamudi,gunturdist.A.P. 42
43. • Pediatric end stage liver disease(PELD):It is a disease severity
scoring system for children under 12 years of age .
PELD=4.80× [𝑙𝑛 𝑠𝑒𝑟𝑢𝑚 𝑏𝑖𝑙𝑖𝑟𝑢𝑏𝑖𝑛(𝑚𝑔/𝑑𝑙]+
18.57[ ln INR]-6.87[ln albumin(g/dl)+
4.36(<1 year old)+6.67(growth failure)
• A higher score correlates with a more critical condition . Thus , liver
donations are allocated by UNOS(United network for organ sharing)
according to the PELD score to maximize the life aving capability
of each donated liver.
vignan pharmacy college,vadlamudi,gunturdist.A.P. 43
44. Hepatic vs Renal failure:
• Dose adaptation for patients with liver disease is more difficult than
for patients with impaired renal function.
• Unlike creatinine clearance for the kidney ,for liver there is no
invivo surrogate to predict the drug clearance.
44vignan pharmacy college,vadlamudi,gunturdist.A.P.
45. conclusion
• The liver and kidneys are important for the body’s ability to break
down and excrete medication.
• Diseases of the liver or the kidneys, in addition to aging , often
require doses to be lowered in order to avoid adverse drug reactions.
• Patients with markedly reduced liver function should avoid certain
medications and dietary supplements.
• Moderately impaired kidney function may require lower
medication doses; severely impaired function requires avoidance of
certain medications.
45
vignan pharmacy college,vadlamudi,gunturdist.A.P.
46. RFERENCES:
1. Leon shargel, susanna wu-pong,Andrew Yu,Applied
biopharmaceutics and pharmacokinetics, 6th edition,617-653.
2.Fisher MB, Paine MF, Strelevitz TJ, Wrighton SA (2001) The role of
hepatic and extrahepatic UDP-glucuronosyltransferases
inhumandrug metabolism. Drug Metab Rev 33:273–297.3.
3. National Kidney Foundation. K/DOQI clinical practice
guidelines for chronic kidney disease: evaluation, classification,
and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1-266.
4.Clinical pharmacology and pharmacotherapeutics by
K.Ravishankar,G.V.N.Kiranmayi , page no:345-352.
46
vignan pharmacy college,vadlamudi,gunturdist.A.P.
47. RFERENCES:
4.Palmer BF. Managing hyperkalemia caused by inhibitorsof the
reninangiotensin-aldosterone system. N Engl J Med 2004;351:585-92.
5. Palmer BF. Angiotensin-converting enzyme inhibitors
and angiotensin receptor blockers: what to do if the
serum creatinine and/or serum potassium concentration
rises. Nephrol Dial Transplant 2003;18:1973-5.
6.Kappel J, Calissi P. Nephrology: 3. Safe drug prescribing
for patients with renal insufficiency. CMAJ
2002;166:473-7.
7. Snyder RW, Berns JS. Use of insulin and oral hypoglycemic
medications in patients with diabetes mellitus and
advanced kidney disease. Semin Dial 2004;17:365-70.
47
vignan pharmacy college,vadlamudi,gunturdist.A.P.
48. vignan pharmacy college,vadlamudi,gunturdist.A.P. 48
I would like to express my gratitude to all those
who gave me the possibility to complete this seminar .
A special thanks to the principal sir and seminar
committee.
I express deep and sincere gratitude to my guide
whose encouragement , suggestion have contributed
immensely to complete my seminar.
ACKNOWLEDGEMENT