Rationalization of Pharmacotherapy of

Chronic Kidney Disease (CKD)

Submitted by

Aamir siddique

15-AUST-F-404

Doctor of Pharmacy

Supervisor

Miss Rashida Bibi

DEPARTMENT OF PHARMACEUTICAL SCIENCES

ABBOTTABAD UNIVERSITYOF SCIENCE AND

TECHNOLOGY

HAVELIAN ABBOTTABAD

SESSION 2015-2020

i
 Rationalization of Pharmacotherapy of
Chronic Kidney Disease (CKD)

A Thesis Presented to

Abbottabad University of Science & Technology, Abbottabad

In partial fulfilment of the requirements for the degree of

Doctor of Pharmacy
By

Aamir siddique

ii
 Rationalization of Pharmacotherapy of
Chronic Kidney Disease (CKD)

A Graduate Thesis submitted to the Department of Pharmacy as partial fulfilment of

the requirement for the award of Degree .

Name Registration Number

Aamir Siddique 15-AUST-F-404

Supervisor

Miss Rashida Bibi

Department of Pharmacy

Abbottabad University of Science & Technology

Abbottabad

iii
 Final Approval

Rationalization of Pharmacotherapy of
Chronic Kidney Disease
By

Aamir siddique

15-AUST-F-404

Has been approved

For the Abbottabad University of Science & Technology, Abbottabad

External Examiner: __________________________________________

Prof. _______________

Supervisor: ______________________________________________

Prof.________________

Department of Pharmacy, Abbottabad University of Science & Technology

Co-supervisor: ______________________________________________

Dr. ________________.

Department of Pharmacy, Abbottabad University of Science & Technology. Head of

Department: __________________________________________

Prof. Dr.______________

Department of Pharmacy, Abbottabad University of Science & Technology.

iv
 Declaration

I Aamir Siddique 15-AUST-F-404 hereby declare that I have produced the work presented
in this thesis, during the scheduled period of study. I also declare that I have not taken any
material from any source except referred to wherever due that amount of plagiarism is
within acceptable range. If a violation of HEC rules on research has occurred in this thesis, I
shall be liable to punishable action under the plagiarism rules of the HEC.

Date: _____________

______________________________

v
 Certificate

It is certified that Aamir siddique 15-AUST-F-404 has carried out all the work related to
this thesis under my supervision at the Department of Pharmacy, Abbottabad University of
Science & Technology, Abbottabad and the work fulfils the requirement for award of
degree.

Date: _________________

Supervisor Head of Department

Department of Pharmacy

________________________ ________________________

vi
 DEDICATIONS

By the grace of Almighty Allah I have completed

my project work and I dedicated it to my beloved
parents who faced alot of problems to serve me
and I am also thankful

to my colleagues my class fellows and specially to

my respected teachers by the effort of whom I
completed my work and spent a lovely time in
university.

vii
 ACKNOWLEDGEMENTS

First of all I like to thanks Almighty ALLAH, The most Beneficial and the most Merciful,
with His grace and blessings upon me for completing thesis. It became possible only with
His help and kindness..

My deep reverence and salam for THE HOLY PROPHET MUHAMMAD (S. A. W) who
is the real code of ethics source and symbol of knowledge and guidance for the entire
mankind.

I am also thankful to HOD, Professor Zia Ahmed who has provided with erudite staff who
has always supported to students in academic pursuit.

I am thankful to Mam Rashida Bibi whose direction and supervision has always soared of
my spirit to perform well.

I am greatly indebted to Medical staff of , Ayub Medical Complex Abbottabad who help me
in collection of histories.

Thanks to my parents, family and friends for their patience over my mistakes and
encouraging me to fulfill my project.

Regards

viii
 Aamir
siddique

Rationalization of Pharmacotherapy of Chronic Kidney Disease

(CKD)

Abstract
Chronic kidney disease (CKD) is characterized by multiple disorders affecting the
morphology and function of kidneys.It is estimated on the basis of a decrease in the number
of nephrons, which ultimately decreases the glomerular filtration rate (GFR) for a period
more than 3 months. Rationalization is a way to ensure safe and effective treatment. The
aim of this study was to evaluate a whether pharmacotherapy of patient suffering from CKD
was rational according to standard or not.
A concurrent, non consecutive , case series type of observational study was adopted to
determine whether a prescribing practice in patients suffering from CKD was rational or
not. Case histories of CKD patients who were in in the Medical ward & urology ward of
the Ayub Teaching Hospital, Abbottabad were included.Subjective, Objective, Assessment,
and Plan (SOAP) format was adopted for data collection and case assessment. Result of this
study showed that disease prevalence was found more in females as compared to male.
Incidence of CKD is high in age group of 55 to 75 years of age. Among different
therapeutic class of the use of Anti hypertensives is very high. Drug related problems were
identified and it was found that majority of drug related problems were prescription of
contraindicated drugs (35%), under prescription of drugs (35),duplication of drugs
(24%)and wrong dose (6%).Drug related problems can interfere with the achievement of
desired therapeutic goals. Medication therapy can be rationalized and above problems can
be solved by placing pharmacist in the health care providing team in hospital and
community level. Pharmacist is the only professional person that can provide information
about the drugs both to the health care team and to patients and knowledge about drug
related problem. Clinical pharmacy services can be valuable to a health care setting and can
potentially lead to a decrease in health care expenses and to an improvement of the standard
of patient care.

ix
Table of Contents

Final Approval…………………………………………………………………………… iv

Declaration……………………………………………………………………….............. v

Certificate……………………………………………………………………………........vi

Dedications……………………………………………………………………….. ….......vii

Acknowledements………………………………………………………………...………viii

Abstract…………………………………………………………………………………...ix

Table of Contents…………………………………………………………………………x

List of Tables……………………………………………………………………………..xii

List of Figures…………………………………………………………………………….xiii

List of Abbreviations...……………………………………………………………………xiv

1.Introduction……………………………………………………………………..............1

1.1 CKD…………………… …………….…..………………………………………2

1.1.1 Background…………………..………………........………….………….2

1.1.2 Definition…………………………….……………………….…….........3

1.1.3 Types of CKD.... ...................................................................................................3

1.1.4 Epidemiology ............................................................................................4

1.1.5 Risk factor…………………………………………..........................................5

1.1.6 Etiology………………………………………………………………. ....6

1.1.7 Pathophysiology………………………………………………………….6

1.1.8 Sign & Symptoms.......................................................................................8

1.1.9 Diagnosis…………………………………………………………………9

x
 1.1.10 Management ..............................................................................................11

1.2 Rational drug use……………………………………………………………….. 15

1.2.1 Definition………………………………………………………………...15

1.2.2 Rational pharmacotherapy………………………………………………..15

1.3 Hypothesis……………………………………………………………………………15

1.4 Aims and objectives……………………………………………………………….....15

2. methodology……………………………………………………………………. ……...17

2.1 Study design……………………………………………………………………...18

2.2 Case histories…………………………………………………………………….18

2.2.1 Inclusion criteria…………………………………………..…….………………..18

2.2.2 Exclusion criteria………………………………….……………….……..18

2.3 Data collection and case evaluation…………..…………………………………………….18

2.3.1 Data (subjective and objective) collection………………………………..19

2.3.2 Case analysis……………………………………………………………...19

2.4 Result interpretation…………………………………………………………….. 20

3 Case analysis…………………………………………………………………………… 26

3.1 Case-wise discussion……………………………………………………………...27

4 Result and discussion……………………………………………………………………45

5 References………………………………………………………………………….........56

xi
List of Tables:

TABLE NO CONTENT PAGE NO

Percentage and frequency distribution of CKD among

4.1 male and female 46

Percentage and frequency distribution of patient

4.2 according to age 47

Percentage and frequency distribution of drug

4.3 interactions in chronic kidney disease 48

4.4 Class wise distribution of drugs given to the patients 49

Percentage and frequency distribution of untreated

4.5 conditions in patients 50

4.6 Percentage and frequency of therapy related problems 51

Proposed plan for achieving desired definite therapeutic

4.7 outcome 52

xii
xiii
List of figures:

FIGURE NO CONTENT PAGE NO

Percentage and frequency distribution of CKD among male and

4.1 female 47

Percentage and frequency distribution of patient according to

4.2 age 48

Percentage and frequency distribution of drug interactions in

4.3 chronic kidney disease 49

4.4 Class wise distribution of drugs given to the patients 50

Percentage and frequency distribution of untreated conditions in

4.5 patients 51

4.6 Percentage and frequency of therapy related problems 52

xiv
 List of Abbreviations:

Abbreviations Meaning

CKD Chronic kidney disease

TDS Three times a day

BDS Two times a day

OD Once a day

IV Intravenous

P/O Oral

S/C Subcutaneous

SOS When needed

IM Intramuscular

Prn Pro Re Nata

STAT At once

RBC Red blood cells

Syp. Syrup

Tab. Tablet

Susp. Suspension

WHO World health organization

Qid Four times a day

G Gram

PO4 Phosphorus

Inf Infusion

QD Once daily

SOB Shortness of breath

xv
 UACR Urine albumin-creatnine ratio

GFR Glomeruler filtration rate

HTN Hypertension

ESA Erythropoiesis stimulating agentt

ARB.s Angiotensin receptor blockers

ACEI Angiotensin converting enzyme inhibitors

DM Diabete mellitus

PTH Parathyroid harmone

PO Per oral

Q8hr Every 8 hour

(16)

xvi
Chapter 1

Introduction

CHAPTER

1
1
1. INTRODUCTION

1.1 CHRONIC KIDNEY DISEASE :

1.1.1 Background:

Chronic kidney disease (CKD) is a global threat to health in general and for developing
countries in particular because of an increasing incidence, poor outcome, and high cost of
treatment. It is a general term for heterogeneous disorders affecting kidney structure and
function.The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National
Kidney Foundation (NKF) defines CKD as either kidney damage or a decreased
glomerular filtration rate of less than 60 mL/min/1.73 m2 for 3 or more
months("National Kidney Foundation Practice Guidelines for Chronic Kidney Disease:
Evaluation, Classification, and Stratification," 2003).CKD is known to be associated with
various complications and comorbidities. Secondary hyperparathyroidism and the
associated homeostatic control of serum calcium, phosphate, and vitamin D is a critical
issue in patients with CKD. Altered mineral metabolism contributes to bone disease,
cardiovascular disease, and other clinical problems in these patients.Results of the
Dialysis Outcomes and Practice Patterns Study clearly demonstrated that uncontrolled
serum concentrations of phosphorus, calcium, and intact parathyroid hormone (iPTH)
were associated with all-cause mortality as well as cardiovascular mortality.Patients with
serum phosphate levels above 6.5 mg/dL have a 27% higher risk of death compared with
those with levels between 2.4 and 6.5 mg/dL. For this reason, one of the main goals in
CKD patients is to maintain serum phosphate in the range recommended in different
guidelines.In CKD patients, if phosphorus or intact PTH levels cannot be controlled
within the target range, despite dietary phosphorus restriction, phosphate binders (PBs)
should be prescribed.Use of the oldest, aluminium-based PBs is currently restricted
because of concerns about tissue accumulation and associated toxic effects of aluminium.
Hence, calcium carbonate and calcium acetate became the most widely used
agents.Patients of CKD are at higher risk of drug-related problems since they need
complex therapeutic regimens that require frequent monitoring and dosage adjustment. In
Pakistan, there is no clear picture of overall medication profile in CKD patients.
Moreover, reports of drug utilisation studies of PBs in these patients are lacking. The
study of prescribing patterns is a component of medical audit that monitors and evaluates

2
prescribing practices, and recommends necessary modifications to achieve rational drug
use.Hence, this study was planned to analyze current prescribing trends in the
management of CKD patients and to suggest ways to rationalize drug use, minimise
medication error, and improve therapeutic outcome("National Kidney Foundation
Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and
Stratification," 2003)

1.1.2 Definition:
A patient is said to have chronic kidney disease (CKD) if they have abnormalities of
kidney function or structure present for more than 3 months. The definition of CKD
includes all individuals with markers of kidney damage or those with an eGFR of less
than 60 ml/min/1.73m2 on at least 2 occasions 90 days apart (with or without markers of
kidney damage)
*Markers of kidney disease may include: albuminuria (ACR > 3 mg/mmol),
Haematuria (or presumed or confirmed renal origin), electrolyte abnormalities due
to tubuler disorders, renal histological abnormalities, structural abnormalities detected
by imaging (e.g. polycystic kidneys, reflux nephropathy) or a history of kidney
transplantation
OR
Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of
kidney function over a period of months to years.

1.1.3 Classification of CKD:

CKD is classified based on the eGFR and the level of proteinuria
Patients are classified as G1-G5, based on the eGFR

G-1:
Kidney damage with normal or increased GFR (>90 mL/min/1.73 m 2)

G 2:
Mild reduction in GFR (60-89 mL/min/1.73 m 2)

G 3a:
Moderate reduction in GFR (45-59 mL/min/1.73 m 2)
G 3b:

3
 Moderate reduction in GFR (30-44 mL/min/1.73 m 2)
G 4:
Severe reduction in GFR (15-29 mL/min/1.73 m 2)
G 5:
Kidney failure (GFR < 15 mL/min/1.73 m 2 or dialysis)

1.1.4 Epidemiology:
In the United States, the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) reports that one in 10 American adults has some level of chronic
kidney disease (CKD).Kidney disease is the ninth leading cause of death in the United
States.
According to the NIDDK, the incidence of recognized CKD in people aged 20-64 years
in the United States rose only slightly from 2000 – 2008 and remains less than 0.5%.In
contrast, the incidence in people aged 65 years or older more than doubled between 2000
and 2008, from approximately 1.8% to approximately 4.3%.
The US prevalence of CKD increases dramatically with age (4% at age 29-39 y; 47% at
age > 70 y), with the most rapid growth in people aged 60 years or older. In the National
Health and Nutrition Examination Survey (NHANES) study, the prevalence of stage 3
CKD in this age group rose from 18.8% during the years 1988 ̶ 1994 to 24.5% during the
years 2003 – 2006. During the same period, the prevalence of CKD in people aged 20-39
years remained consistently below 0.5%.
(O'Hare et al., 2007)
According to 1999 – 2004 NHANES data, the estimated prevalence of CKD by stage was
as follows
Stage 1: 5.7%
Stage 2: 5.4%
Stage 3: 5.4%
Stage 4: 0.4%
Stage 5: 0.4%
The US Surgeon General’s latest report on 10-year national objectives for improving the
health of all Americans, Healthy People 2020, contains a chapter focused on CKD. For
2020, Healthy People lays out 14 objectives concerning reduction of the US incidence,
morbidity, mortality, and health costs of CKD. Reducing renal failure will require
additional public health efforts, including effective preventive strategies and early
detection and treatment of CKD.

4
A systematic review and meta-analysis of observational studies estimating CKD
prevalence in general populations worldwide found a consistent estimated global CKD
prevalence of 11-13%. The majority of cases are stage 3.

Race-related demographics:
Although CKD affects all races, the incidence rate of ESRD among blacks in the United
States is nearly 4 times that for whites.Choi et al found that rates of ESRD among black
patients exceeded those among white patients at all levels of baseline estimated
glomerular filtration rate (GFR).Risk of ESRD among black patients was highest at an
estimated GFR of 45-59 mL/min/1.73 m2, as was the risk of mortality.Schold et al found
that among black kidney transplant recipients, rates of graft loss and acute rejection were
higher than in white recipients, especially among younger patients.Hicks et al looked at
the connection between black patients with the sickle cell trait and their increased risk for
kidney disease; the study found that sickle cell trait was not associated with diabetic or
nondiabetic ESRD in a large sample of black patients.(Choi et al., 2009)

Sex-related demographics:
In NHANES, the distribution of estimated GFRs for the stages of CKD was similar in
both sexes. In the United States Renal Data System (USRDS) 2011 Annual Data Report,
however, the incident rate of ESRD cases at the initiation of hemodialysis in 2009 was
higher for males, with 415.1 per million population compared with 256.6 for females.

1.1.5 Risk factors:

There are certain risk factor which increases the disease occurance probability as below;
• Family history
• Genetic factor
• Gender
• Ethnicity
• Age
• Obesity
• Socioeconomic status
• Smoking
• Nephrotoxins

5
• Diabetes mellitus
• Hypertension

1.1.6 Etiology:-
Causes of chronic kidney disease (CKD) include the following:
• Diabetic kidney disease
• Hypertension
• Vascular disease
• Glomerular disease (primary or secondary)
• Cystic kidney diseases
• Tubulointerstitial disease
• Urinary tract obstruction or dysfunction
• Recurrent kidney stone disease
• Congenital (birth) defects of the kidney or bladder
• Unrecovered acute kidney injury

1.1.7 Pathophysiology:-
Chronic kidney disease is initially described as diminished renal reserve or renal
insufficiency, which may progress to renal failure (end-stage renal disease). Initially, as
renal tissue loses function, there are few noticeable abnormalities because the remaining
tissue increases its performance (renal functional adaptation).
Decreased renal function interferes with the kidneys’ ability to maintain fluid and
electrolyte homeostasis. The ability to concentrate urine declines early and is followed by
decreases in ability to excrete excess phosphate, acid, and potassium. When renal failure is
advanced (GFR ≤ 15 mL/min/1.73 m2), the ability to effectively dilute or concentrate urine
is lost; thus, urine osmolality is usually fixed at about 300 to 320 mOsm/kg, close to that of
plasma (275 to 295 mOsm/kg), and urinary volume does not respond readily to variations in
water intake.

Creatinine and urea:

Plasma concentrations of creatinine and urea (which are highly dependent on glomerular
filtration) begin a hyperbolic rise as GFR diminishes. These changes are minimal early on.
When the GFR falls below 15 mL/min/1.73 m2 (normal > 90 mL/min/1.73 m2), creatinine

6
and urea levels are high and are usually associated with systemic manifestations (uremia).
Urea and creatinine are not major contributors to the uremic symptoms; they are markers for
many other substances (some not yet well defined) that cause the symptoms.

Sodium and water:

Despite a diminishing GFR, sodium and water balance is well maintained by increased
fractional excretion of sodium in urine and a normal response to thirst. Thus, the plasma
sodium concentration is typically normal, and hypervolemia is infrequent unless dietary
intake of sodium or water is very restricted or excessive. Heart failure can occur due to
sodium and water overload, particularly in patients with decreased cardiac reserve.(Vegter
et al., 2012)

Potassium:
For substances whose secretion is controlled mainly through distal nephron secretion
(eg, potassium), renal adaptation usually maintains plasma levels at normal until renal
failure is advanced or dietary potassium intake is excessive. Potassium-sparing diuretics,
ACE inhibitors, beta-blockers, NSAIDs, cyclosporine, tacrolimus,
trimethoprim/sulfamethoxazole, pentamidine, or angiotensin II receptor blockers may raise
plasma potassium levels in patients with less advanced renal failure.

Calcium and phosphate:

Abnormalities of calcium, phosphate, parathyroid hormone (PTH), and vitamin D
metabolism can occur, as can renal osteodystrophy. Decreased renal production of calcitriol
(1,25(OH)2D, the active vitamin D hormone) contributes to hypocalcemia. Decreased renal
excretion of phosphate results in hyperphosphatemia. Secondary hyperparathyroidism is
common and can develop in renal failure before abnormalities in calcium or phosphate
concentrations occur. For this reason, monitoring PTH in patients with moderate CKD, even
before hyperphosphatemia occurs, has been recommended.
Renal osteodystrophy (abnormal bone mineralization resulting from hyperparathyroidism,
calcitriol deficiency, elevated serum phosphate, or low or normal serum calcium) usually
takes the form of increased bone turnover due to hyperparathyroid bone disease (osteitis
fibrosa) but can also involve decreased bone turnover due to adynamic bone disease (with
increased parathyroid suppression) or osteomalacia. Calcitriol deficiency may cause
osteopenia or osteomalacia.

7
pH and bicarbonate:
Moderate metabolic acidosis (plasma bicarbonate content 15 to 20 mmol/L) is
characteristic. Acidosis causes muscle wasting due to protein catabolism, bone loss due to
bone buffering of acid, and accelerated progression of kidney disease.

Anemia:
Anemia is characteristic of moderate to advanced CKD (≥ stage 3). The anemia of CKD is
normochromic-normocytic, with an Hct of 20 to 30% (35 to 40% in patients with polycystic
kidney disease). It is usually caused by deficient erythropoietin production due to a
reduction of functional renal mass (see Overview of Decreased Erythropoiesis). Other
causes include deficiencies of iron, folate, and vitamin B12.

1.1.8 Sign & Symptoms:

Patients with CKD stages 1-3 are generally asymptomatic. Typically, it is not until stages 4-
5 (GFR < 30 mL/min/1.73 m²) that endocrine/metabolic derangements or disturbances in
water or electrolyte balance become clinically manifest.
Signs of metabolic acidosis in stage 5 CKD include the following:
• Protein-energy malnutrition
• Loss of lean body mass
• Muscle weakness

Signs of alterations in the way the kidneys are handling salt and water in stage 5 include the
following:
• Peripheral edema
• Pulmonary edema
• Hypertension

Anemia in CKD is associated with the following:

• Fatigue
• Reduced exercise capacity
• Impaired cognitive and immune function
• Reduced quality of life

8
• Development of cardiovascular disease
• New onset of heart failure or the development of more severe heart failure
• Increased cardiovascular mortality

Other manifestations of uremia in ESRD, many of which are more likely in patients who are
being inadequately dialyzed, include the following:
• Pericarditis: Can be complicated by cardiac tamponade, possibly resulting in death if
unrecognized
• Encephalopathy: Can progress to coma and death
• Peripheral neuropathy, usually asymptomatic
• Restless leg syndrome
• Gastrointestinal symptoms: Anorexia, nausea, vomiting, diarrhea
• Skin manifestations: Dry skin, pruritus, ecchymosis
• Fatigue, increased somnolence, failure to thrive
• Malnutrition
• Erectile dysfunction, decreased libido, amenorrhea
• Platelet dysfunction with tendency to bleed

1.1.9 Diagnosis:
Screening:
American College of Physicians guidelines on screening for CKD include the following
recommendations:
• Do not screen for CKD in asymptomatic adults without risk factors for CKD (grade: weak
recommendation, low-quality evidence).
• Do not test for proteinuria in adults with or without diabetes who are currently taking an
angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II-receptor blocker
(ARB)(grade: weak recommendation, low-quality evidence).

Laboratory studies:
Laboratory studies used in the diagnosis of CKD can include the following:
• Complete blood count (CBC)
• Basic metabolic panel
• Urinalysis

9
• Serum albumin levels: Patients may have hypoalbuminemia due to malnutrition, urinary
protein loss, or chronic inflammation
• Lipid profile: Patients with CKD have an increased risk of CVS disease

Evidence of renal bone disease can be derived from the following tests:
• Serum calcium and phosphate
• 25-hydroxyvitamin D
• Alkaline phosphatase
• Intact parathyroid hormone (PTH) levels

In certain cases, the following tests may also be ordered as part of the evaluation of patients
with CKD:
• Serum and urine protein electrophoresis and free light chains: Screen for a monoclonal
protein possibly representing multiple myeloma
• Antinuclear antibodies (ANA), double-stranded DNA antibody levels: Screen for systemic
lupus erythematosus
• Serum complement levels: Results may be depressed with some glomerulonephritides
• Cytoplasmic and perinuclear pattern antineutrophil cytoplasmic antibody (C-ANCA and
P-ANCA) levels: Positive findings are helpful in the diagnosis of granulomatosis with
polyangiitis (Wegener granulomatosis); P-ANCA is also helpful in the diagnosis of
microscopic polyangiitis
• Anti–glomerular basement membrane (anti-GBM) antibodies: Presence is highly
suggestive of underlying Goodpasture syndrome
• Hepatitis B and C, human immunodeficiency virus (HIV), Venereal Disease Research
Laboratory (VDRL) serology: Conditions associated with some glomerulonephritides

Imaging studies:
Imaging studies that can be used in the diagnosis of CKD include the following:
• Renal ultrasonography: Useful to screen for hydronephrosis, which may not be observed
in early obstruction or dehydrated patients; or for involvement of the retroperitoneum with
fibrosis, tumor, or diffuse adenopathy; small, echogenic kidneys are observed in advanced
renal failure
• Retrograde pyelography: Useful in cases with high suspicion for obstruction despite
negative renal ultrasonograms, as well as for diagnosing renal stones

10
• Computed tomography (CT) scanning: Useful to better define renal masses and cysts
usually noted on ultrasonograms; also the most sensitive test for identifying renal stones
• Magnetic resonance imaging (MRI): Useful in patients who require a CT scan but who
cannot receive intravenous contrast; reliable in the diagnosis of renal vein thrombosis
• Renal radionuclide scanning: Useful to screen for renal artery stenosis when performed
with captopril administration; also quantitates the renal contribution to the GFR

Biopsy:
Percutaneous renal biopsy is generally indicated when renal impairment and/or
proteinuria approaching the nephrotic range are present and the diagnosis is unclear after
appropriate workup.

1.1.10 Management:
Early diagnosis and treatment of the underlying cause and/or the institution of secondary
preventive measures are imperative in patients with chronic kidney disease
(CKD). These steps may delay, or possibly halt, progression of the disease. Early referral to
a nephrologist is of extreme importance.(Levin et al., 2008)
The medical care of patients with CKD should focus on the following:
1. Delaying or halting the progression of CKD
2. Diagnosing and treating the pathologic manifestations of CKD
3. Timely planning for long-term renal replacement therapy
4. Diet
5.Consultations and Long-Term Monitoring

1.1.10.1 Delaying or halting the progression of CKD :

Measures indicated to delay or halt the progression of chronic kidney disease
(CKD) are as follows:
• Treatment of the underlying condition if possible
• Aggressive blood pressure control to target values per current guidelines
• Treatment of hyperlipidemia to target levels per current guidelines
• Aggressive glycemic control per the American Diabetes Association (ADA)
recommendations (target hemoglobin A1c [HbA1C] < 7%)

11
• Avoidance of nephrotoxins, including intravenous (IV) radiocontrast media,
nonsteroidal anti-inflammatory drugs (NSAIDs), and aminoglycosides
• Use of renin-angiotensin system (RAS) blockers in patients with diabetic kidney
disease (DKD) and proteinuria
• Use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor
blockers (ARBs) in patients with proteinuria

1.1.10.2 Diagnosing and treating the pathologic manifestations of CKD :

Treat these pathologic manifestations of chronic kidney disease (CKD) as follows:
• Anemia:
When the hemoglobin level is below 10 g/dL, treat with an erythropoiesis-stimulating
agent (ESA) such as epoetin alfa or darbepoetin alfa; caution should be exercised in
patients with malignancy
• Hyperphosphatemia:
Treat with dietary phosphate binders and dietary phosphate restriction
• Hypocalcemia:
Treat with calcium supplements with or without calcitriol
• Hyperparathyroidism:
Treat with calcitriol, vitamin D analogues, or calcimimetics
• Volume overload:
Treat with loop diuretics or ultrafiltration
• Metabolic acidosis:
Treat with oral alkali supplementation
• Uremic manifestations:
Treat with long-term renal replacement therapy (hemodialysis, peritoneal dialysis, or
kidney transplantation
• Cardiovascular complications:
Treat as appropriate.
• Growth failure in children:
Treat with growth hormone..

1.1.10.3 Timely planning for long-term renal replacement therapy:

Indications for renal replacement therapy in patients with chronic kidney disease(CKD)
include the following:

12
• Severe metabolic acidosis
• Hyperkalemia
• Encephalopathy
• Intractable volume overload
• Failure to thrive and malnutrition
• Peripheral neuropathy
• Intractable gastrointestinal symptoms
• In asymptomatic adult patients, a glomerular filtration rate (GFR) of 5-9 mL/min/1.73 m²

Timely planning for long-term renal replacement therapy

Consider the following:
• Early patient education regarding natural disease progression, different dialytic
modalities, renal transplantation, and the option to refuse or discontinue chronic dialysis
• Timely placement of permanent vascular access (arrange for surgical creation of primary
arteriovenous fistula, if possible, and preferably at least 6 mo in advance of the anticipated
date of dialysis for patients in whom transplantation is not imminent
• Timely elective peritoneal dialysis catheter insertion
• Timely referral for renal transplantation

1.1.10.4 Diet :
The following dietary restrictions may also be indicated:
• Protein restrictions
• Salt restrictions
• Phosphate restriction, starting early in CKD
• Potassium restriction
• Sodium and water restriction as needed to avoid volume overload

1.1.10.5 Consultations and Long-Term Monitoring :

Consultations for the management of patients with chronic kidney disease (CKD) may
include the following:
• Early nephrology referral (decreases morbidity and mortality)
• Renal dietitian
• Surgery for permanent vascular access or for peritoneal catheter placement
• Referral to renal transplant center

13
Patients with CKD should be referred to a nephrologist early in the course of their disease
and have continued nephrologic follow-up until initiation of chronic renal replacement
therapy, during dialysis, and after kidney transplantation. Moreover, a multidisciplinary
approach to care, including involvement of the nephrologist, primary care physician, renal
dietitian, nurse, and social worker, should be initiated early in the course of CKD, with
close patient follow-up.

1.2 RATIONAL DRUG USE:

1.2.1 Definition:
WHO defines rational use of drug as:
Rational use of medicines requires that "patients receive medications appropriate to their
clinical needs, in doses that meet their own individual requirements, for an adequate
period of time, and at the lowest cost to them and their community" ( WHO, 1987).

14
 1.2.2 Rational pharmacotherapy:
WHO defines rational pharmacotherapy as:
“Therapeutically sound and cost-effective use of medicines by professionals and
consumers.”
Promoting more rational pharmacotherapy Rohto considers essential to use:
 National evidence-based guidelines.
 Producer-independent information on drugs along with effective distribution.
 Powerful methods for implementation (Centre of pharmacotherapy development, 2008)

1. 3 HYPOTHESIS:
This study was based on evaluation of prescribing practices of pharmacotherapy of
chronic kidney failure. That should be therapeutically sound and cost effective. The
medicines used by professionals and consumer should be rational. We have to consider
that whether the drugs prescribed are rational or irrational. We should also consider
special cases like geriatrics, pediatrics, renal impairment and hepatic impairment for dose
calculation. The factors responsible for low patient compliance are also to be considered.
Mostly the patients in the hospital do not have complete information related to the drugs
and their condition because of
increased patient burden and unavailability of appropriate health-care
professionals, i.e. clinical pharmacists. Information regarding risk factors, complication
of CKD. We have to consider all the risk factors that may worsen the disease.

1.4 AIMS AND OBJECTIVES

The aims and objectives of the study are:
 To rationalize pharmacotherapy of chronic kidney failure.
 To observe rational use of drugs.
 To observe weather the drugs are used rationally or irrationally.
 To get Basic knowledge about the disease i.e. causes, pathology,complications and
management of CKD
 To find out the risk factors for CKD among male and females and also the treatment
related problems to the patients.
 To educate the patients to take medicine in a proper and effective way..
 To study drug – drug interaction in the medicines prescribed for the management of CKD


15
16
 Chapter 2

Methodology

CHAPTER

2
METHODOLOGY

17
2.1.STUDY DESIGN:
A concurrent, non−consecutive, case series type of observational study design was
adopted to determine whether prescribing practices in patients suffering from CKD was
rational in Ayub Medical Complex Abbottabad, Pakistan. Study protocol was approved
by the thesis supervisor. Only verbal consent was obtained from the patients as it was a
non−interventional type of study for educational purpose only. However, patients‟
related information was not shared with anyone without prior permission.

2.2.CASE HISTORIES:
Case Histories of patients having Chronic kidney failure were recorded in this
hospital−based study.

2.2.1.Inclusion Criteria:
Case histories of only those chronic kidney failure patients who attended in patients in
the Medical ward of the Ayub Medical Complex Abbottabad, Pakistan were recorded for
this study. There were no age and gender restrictions.

2.2.2.Exclusion Criteria:
History of patient suffering from disease other than chronic kidney failure was excluded
from study. Incomplete case histories were also excluded from study.

2.3.DATA COLLECTION AND CASE EVALUATION:

The Subjective, Objective, Assessment, and Plan (SOAP) format was adopted for data
collection and case assessment. In this format, the subjective (S) and objective (O) data
are recorded and then assessed (A) to formulate a plan).

2.3.1.Data (Subjective and Objective) Collection:

Subjective data include patient symptoms, things that may be observed about the patient,
or information obtained about the patient. By its nature, subjective information is
descriptive and generally cannot be confirmed by diagnostic tests or procedures. Much of
the subjective information is obtained by speaking with the patient while obtaining the
medical history (chief complaint, history of present illness, past medical and surgical
histories, family history, social history, allergies, and review of systems, etc). Important
subjective information may also be obtained by direct interview with the patient after the

18
initial medical history has been performed (e.g., detail of the previous, hospital and
discharge medications, a description of the drug−related problems such as an adverse
drug effect, etc).A primary source of objective (O) information is the physical
examination. Other relevant objective information includes laboratory values, including
serum drug concentrations (along with the target therapeutic range for each level), and
the results of other diagnostic tests (e.g., ECG, X-rays, Regular and fasting blood glucose
level, biochemical investigations, etc). Risk factors that may predispose the patient to a
particular problem should also be considered for inclusion. The communication note
should include only the pertinent positive and negative findings. Pertinent negative
findings are signs and symptoms of the disease or problem that are not present in the
particular patient being evaluated.
A detailed proforma was designed in consultation with thesis supervisor to record
subjective (S) and objective (O) information as given in the following pages.

2.3.2. Case Analysis (Assessment and Plan):

Each case history was then assessed (A) to determine various patient‟s problems based
upon the subjective and objective information acquired. This portion of the SOAP note
included all of the reasons for the pharmacist‟s assessment
Major problems determined were
 Inappropriate drug product selection.
 Inappropriate administration of drug therapy.
 Inappropriate monitoring of drug therapy.
 Inappropriate drug selections
 Inappropriate drug therapy response.
 Inappropriate drug taking behavior.
Finally, the plan (P) is suggested, if any, to achieve definite outcomes depending upon
patient‟s problem(s), and prevent or resolve drug−related problems, if any. It included
suggesting additional diagnostic/monitoring tests or initiating, revising, or discontinuing
treatment, along with the rational for the specific changes recommended in
pharmacotherapy. The drug, dose, dosage form, schedule, route of administration, and
duration of therapy were included. The plan should be directed toward achieving a
specific, measurable, goal or endpoint, which should

19
be clearly stated in the note. The plan should also outline the efficacy and toxicity
parameters that will be used to determine whether the desired therapeutic outcome was
being achieved and to detect or prevent drug−related adverse events. Ideally,
information about the therapy that should be communicated to the patient should also be
included in the plan. The plan should be reviewed and referred to in the note as often as
necessary.

2.4.RESULT INTERPRETATION:
Microsoft Excel was used to graphically present the data and perform various statistical
calculations like mean, standard deviation, and percentages, etc. The following
calculations were performed:

 Gender distribution of the disease in the recorded cases.

 Age distribution

 Interactions

 Different classes of drugs in per prescription

 Treated and untreated condition; and

 Frequency of different types of problems observed in the recorded cases.

MEDICAL HISTORY (Hx)

Patient Identification Code: Gender: Age:

Weight: Height:

20
 Address:

Chief Complaint(s)

History of Present Illness

Past Medical/Surgical History

Childhood Diseases

Allergies

21
Family Medical History

Personal/Social History

Preventive/Risk Factors

REVIEW OF SYSTEMS & PHYSICAL EXAMINATION

INVESTIGATIONS:

ROUTINE TESTS

22
 Tests Normal values Observed values

Other Major Relevant Diagnostic Tests:

Tests Results

FINAL DIAGNOSIS

MEDICATION HISTORY

(Prescription/OTC/Complimentary)
1. Before Hospitalization (Any Recent Medications)

23
 Medicine Name Indication(s) Dosage Regime Any Problem

2. During Hospitalization:

Name Indications Dosage regimen Problem

Upon Discharge:

Dosage regime (route/dosage

Medicine Name Indications form,dose,frequency,duration)

1. Allergies and Other Problems

24
2. Adherence/Compliance Assessment

25
CHAPTER 03

CASE ANALYSIS

CHAPTER

3
26
CASE ANALYSIS

3.1. CASE-WISE DISCUSSION:

Case # 1:
A female patient of age 60 years was admitted into the hospital with the chief complaints of
SOB(shortness of breath), confusion, fever  Since 3days ,she had a past medical history of
HTN . the clinical and laboratory findings of the patient were found to be
• Temp 100 F
• BP 190/40mmHg
• pulse 85/min
• UACR 550 mg/g
• eGFR 35ml / min
• Hb 10 g/dl
• PO4 8.9 mg/dl
• Calcium 8.2 L
Patient’s data was collected in a profile form .the  patient was diagnosed with chronic
kidney disease with HTN  and the treatment was started with:
• Paracetamol 500 mg PO Q8hr for treatment of fever
• Piperacilin/tazobactam   4.5g IV BD prophylaxis of noscomial inf
• Furosemide 40mg IV  TID for treatment of hypertention
• Nitrofurantoin 100mg P/O Bd prophylaxis of noscomial inf
• Captopril 24 mg PO Q12h for treatment of hypertention
• Calcitriol 0.25 mcg PO Qd for treatment of hyperphosphatemia
Discussion:
• All the drugs were prescribed in right doses.However, duration of treatment was not
mentioned which is important for any successful drug therapy.
• There was over-prescribing of nitrofurantoin which in not needed by patient in addition
to piperacillin-tazobactam.
• No phosphate binder is prescribed although PO4 value is high than normal
• A ESA agent should also be prescribed to increased Hb.
• Absense of patient’s daily food intake record.

27
• 1 interactions found in this prescription. The detail of which is interactions is as
follow:
captopril + furosemide:
Captopril increases the effect of furosemide by pharmacodynamic synergism
Recommended interventions:
1. Addition of PO4 binder to therapy.
2. Addition of ESA (Erythropoiesis-stimulating agent) to therapy.

3. Substitute piperacillin-tazobactam with ceftriaxone

4. Addition of statins to reduce CVS risk.
5. Maintain proper daily calorie intake profile.

Case # 02:
A 66 year-old female presents to the primary care clinic where you are a pharmacist. she has
a past medical history of CKD, hypertension, Type 2 diabetes, dyslipidemia and poor
dentition. the clinical and laboratory findings of the patient were found to be:
• eGFR 25 mL/min/1.73m2
• Calcium 10.1 mg/dL
• Phosphorus 6.0 mg/dL.
• LDL 140 mg/dL.
• Albumin 3.0 g/dL.
• Hemoglobin 12.2 g/dL..
• TSAT 35%.
• HbA1c 6.8 %

Patient medication profile include:

• Lisinopril 10 mg po daily treatment of hypertention
• Atorvastatin 10 mg po at bedtime treatrment of dyslipidemia
• Insulin detemir 10 units SQ at bedtime treatment of diabetes

Discusssion:
• All the drugs were prescribed in right doses.However, duration of treatment was not
mentioned which is very much important for any successful drug therapy.
• None of the phosphate binder is prescribed although PO4 value is high than normal.

28
• Patient daily calorie intake record is not maintained that may lead to progression of
CkD
• 1 interactions found in this prescription. The detail of which is as follow:

Lisinopril + insulin detemir:

Lisinopril increases the effect of insulin detemir by pharmacodynamic synergism,risk of
acute hypoglycemia.
Recommended interventions:
• PO4 binder should be added to therapy.
• Daily calorie intake record should be maintained.

Case # 03
A 55 year old female patient came in for hemodialysis with a complicated past medical
history.she was known case of diabetes mellitus and hypertention.she was diagnosed with
renal failure 3 years back. the clinical and laboratory findings of the patient were found to
be:
• Creatinine 9.8mg/dl
• Hemoglobin 10.4
• Hematocrit 33
• RBC count 3.79
• Potassium 5.8 meq/L
• Calcium 8 mg/dl
• Phosphorus 4.7 mg/dl
Patient medication profile include:
• Erythropoitin 4000iu twice a week treatment of anemia
• Ferrous sulphate iron 200 mg PO Q12h treatment of anemia
• Furosemide 40 mg PO q12h treatment of hypertention
• Metformin 500 mg PO q12h treatment of diabetes mellitus
Discussion:
1 All the drugs prescribed were in right doses.
2 Duration of therapy is not mentioned.
3 Metformin is contraindicated in patients with eGFR < 60 ml/min.
4 None of the drug is prescribed to treat hypocalcemia.

29
 5 Patient daily calorie intake record is not maintained that may lead to progression of
CkD
6 For treatment of hyperkalemia parental form of sodium bicarbonate is
recommended.
Following interactions were present in therapy regimen.
Allopurinol + Sodium bicarbonate:
Sodium bicarbonate decreases levels of allopurinol by in hibition of GI absorption.
Sodium bicarbonate + Ferrous Sulphate:
Sodium bicarbonate decreases levels of allopurinol by in hibition of GI absorption.
Metformin + furosemide:
Metformin decreases levels of furosemide by unspecified interaction.
Recommended interventions:
1.vit-D and calcium supplements should be prescribed.
2. Metformin should be discontinued immediately and substituted by suitable hypoglycemic
agent
3. Interactions should be adressed to promote rational and safe therapy

Case # 04
The patient is 46 year old lady. she was admitted in Hospital for a chief complaint of
general weakness and fever. Her weight is 69 kg with a height of 170 cm.The patient was
diagnosed to have a Chronic Kidney Disease Stage 5. The present physical examination
shows that he has:
• Pale conjunctivae
• Pale nailbeds.
• Elevated blood pressure (180/100 mmHg).
The clinical and laboratory findings of the patient were found to be:
• Creatinine 3202 mmol/L
• RBC 2.25*106/mm3
• Hemoglobin 6g/L
• GFR 2.9ml/min/1.73m2
• Potassium 1.9mmol/L
• Calcium 8.7mg/dl
• Cholestrol 182mg/dl

30
Patient medication profile includes:
• Erythropoitin 4000iu twice a week treatment of anemia
• FeSO4 +FA 1 tablet TID treatment of anemia
• Lisinopril 10 mg OD treatment of hypertention
• Furosemide 20mg BID treatment of hypertention
• Aspirin 81mg PO QD prophylaxis of heart attack
• Ceftriaxone 1 g IV QD prophylaxis of noscomial inf
Discussion:
1. Drugs were prescribed in right doses.
2. Duration of therapy was not mentioned which is important for rational therapy
3. An untreated condition “hypocalcemia” was left,for which no therapy was prescribed
4. Lisinopril, concomitant with NSAID maybe a potential candidate to induce and
worsen hypokalemia.
5. NSAIDS are contraindicated in CKD.
Following interactions are present in regimen:
Aspirin + furosemide:
Both the drugs counter act on serum potassium level.
Ceftriaxone + furosemide:
Ceftriaxone increases toxicity of furosemide by pharmacodynamic synergism.increased risk
of nephrotoxicity.
Recommended interventions:
1. Vit D and calcium supplements should be added to therapy.
2. lisinopril should be replaced by diuretics or ARBs.
3. NSAID should be discontinued immediatly and substituted by appropriate drug.
4. Patient daily calorie intake record should be maintained.

Case # 05:
A 74 year old female with CKD due to diabetic kidney disease was admitted to hospital..
Her most recent labs were
• Calcium 7.4 mg/L
• Phosphorus 5.5 mg/dL
• Albumin 3.2 g/dL
• PTH 550 pg/mL.
• eGFR 25 ml/min/1.73m2

31
Patient medication profile includes:
• Calcium acetate 1334 mg PO TID treatment of hyperphosphatemia
• Paricalcitol 1 mcg PO once daily to reduce PTH level
• Cinacalcet 30 mg PO once daily. to reduce PTH level
• Paracetamol 500 mg PO BID treatment of fever
• Metformin 2.5 mg BID with meals treatment of diabetes mellitus
• Ertugliflozin 1000mg BID with meeals treatment of diabetes mellitus
Discusssion:
1. All the drugs were prescribed in right doses except for paricalcitol which shouldbe
increased to 2 mcg QD. (BP)
2. Duration of drug therapy is not mentioned.
3. Metformin and ertugliflozin are contraindicated in advanced renal disease.
4. Patient daily calorie intake profile is not maintained.
5. Following are drug interactions present in regimen:
Ciprofloxacin + Metformin:
Ciprofloxacin increases effect of metformin by pharmacodynamic synergism.
Calcium acetate + Metfromin:
Calcium acetate decreases the effect of ciprofloxacin by inhibition of GI absorption.
Recommended interventions:
1. Dose of Paricaitol shouldbe increased
2. Metformin and artugliflozin should be substituted by appropriate hypoglycemic agent
3. Atleast one anti hypertensive agent should be added in regimen to slow progress of
disease.
4. Patient daily calorie intake profile should be maintained.

Case # 06
A 36 year old male was admitted to hospital and diagnosed with CKD after examining his
lab reports (UACR= 800 mg/g).she has a past history of type 2 diabetes with albuminuria.
His more recent labs were:
• UACR 800 mg/g
• A1C 6.5 %
• Albumin 3.0 g/dl
• eGFR 50 ml/min

32
• Calcium 9.2 mg/dl
• Phosphorus 4.0 mg/dl
• LDL 72 mg/dl

His medications profile includes:

• Glyburide 5 mg 2 tab BD treatment of diabetes mellitus
• Metformin 500 mg 2 tab BD treatment of diabetes mellitus
• Fosinopril 10 mg 1tab QD treatment of hypertention
• Lovastatin 20 mg 1tab QD treatment of dylipidemia
• Ranitidine 150 mg 1tab QD prophylaxis of peptic ulcer
• Omeprazol 20 mg 1tab QD prophylaxis of peptic ulcer
Discussion:
1. Medications are prescribed in accurate doses
2. Duration of therapy was not mentioned.
3. Metformin should be use in caution as it is contraindicated in CKD
4. Duplication of medication are present in case of ranitidine and omeprazole.
Recommended interventions:
1. Substraction of one of anti ulcer drug from regimen
2. Substitution of metformin with approprite hypoglycemic agent
3. Use of medications that block the renin-angiotensin-aldosterone system
such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers,blood
pressure control, sodium restriction, weight loss, adequate not excessive protein intake, and
tobacco cessation may lower urine albumin

Case # 07
A 60-year-old lady with a recent diagnosis of chronic kidney disease due to type 2 diabetes.
she was told he is approaching kidney failure. The clinical and laboratory findings of the
patient were found to be:
• HBA1c 9%
• Blood pressure 154/98
• LDL 129 mg/dl
• eGFR 17 ml/min
• UACR 765 mg/g
• Phosphorus 4.9 mg/dl

33
His medication profile includes:
• Insulin glargine 10 units (long acting insulin taken at bedtime)
• Simvastatin 20 milligrams (mg) treatment of dylipidemia
• losartan 50 mg PO QD treatment of hypertention
• Captopril 25 mg PO q8h treatment of hypertention
• Furosemide 80 mg twice a day treatment of hypertention
• calcium carbonate 500 mg TID treatment of hyperphosphatemia
• sodium bicarbonate 650 mg twice a day prophylaxis of stomach acid
• ferrous sulfate 325 mg twice a day treatment of anemia
Discussion:
1.All the drugs was prescribed in appropriate dose.
2. Duration of treatment was not mentioned.
3. Duplication of antihypertensive medication of same therapeutic outcome(captopril and
losartan).
4. Patient daily calori intake record is not maintained.
5. Long acting insulin should be avoided in advanced CKD patients.
6. Following are the interactions found in regimen:
Losartan + captopril
Increase toxicity by pharmacodynamic synergism,increase risk of
hypotention,hyperkalemia.
Captopril + insulin glargine:
Captopril increaes effect of insulin glargine by synergism,increase chance of hypoglycemia
Sodium bicarbonate + ferrous sulphate:
sodium bicarbonate will decrease the absorption of ferrous sulphate by changing PH.
Recommended interventions:
1. long acting hypoglycemic agent should replaced by intermediate or short acting
agents.
2. One of the antihypertensive should be eleminated from regimen.
3. Record of patient daily calorie intake shoould maintain.

Case # 08

34
Patient was a 24-year old obese female ( BMI 33). She was diagnosed with T2DM at 13
years of age and with stage 3 CKD, 2 years ago. Her kidney function has progressively
declined and she was admitted to the hospital for preparation for kidney replacement
therapy. Her lab report indicates:
• serum phosphorus 9.5 mg/dl
• potassium 5.8 mEq/L
• creatinine 4.0 mg/dl
• e GFR 28 ml/min
• Glucose 282 mg/dl
• Calcium 7.8 mg/dl
• Cholestrol 220 mg/dl
which places her at stage 4 CKD.

Her medication profile includes:

• Enalapril 2.5 mg PO Q12H treatment of hypertention
• Epoetin alfa 2000 units/ml 3x weekly for Tx of anemia
• Vitamin/mineral supplement 1tab PO QD . for vit deficiency
• Calcitriol 0.25mcg PO QD for hypovcalcemia
• Metformin 500 mg PO Q12H for diabetes mellitus
• Calcium acetate 1 cap PO treatment of hyperphosphatemia
• Furosemide 40 mg PO treatment of hypertention
Discussion:
1.All the drugs were prescribed in right doses.
2 ACE inhibitor should be substituted by diuretics or ARBs to decrease hyperkalemia.
3. Metformin is contraindicated in advanced CKD.
4. Patient daily calories intake record was not maintained.
5. The interaction reported in regimen are as under:
Enalapril + furosemide:
Pharmacodynamic synergism,increased risk of hypotension and renal insuffiency.
Enalapril + Metformin:
Enalapril increases toxicity of metformin by unknown mechanism.
Furosemide + Calcium acetate:
Furosemide decreases level of calcium acetate by increasing its clearence.

35
Recommended interventions:
1.Metformin should be replaced by appropriate hypoglycemic agent
2. DDI should be adresses to promote safe therapy.
3. Patient daily calories intake record should be maintained.

Case # 09:
A 58-year-old man was admitted in the hospital .he was a diagnosed case of diabetes,
hypertension, and CKD. His physical examination reveals obesity with lower leg edema,
good dentition and no obvious nutrient deficiencies.his lab report revealed:
• HBA1c 5.9 %
• UACR 65 mg/g
• Creatinine 1.2 mg/dl
• eGFR 56 ml/min
• potassium 4.3 mEq/l
• calcium 9.0 mg/dl
• phos 5.3 mg/dl
• LDL 131 mg/dl

His medication record included:

• Simvastatin 5 mg QD treatment of dylipidemia
• Furosemide 20 mg PO Q12h treatment of hypertention
• Lisinopril 10 mg PO QD treatment of hypertention
• Baby aspirin 81 mg PO QD prophylaxis of heart attack
• Metformin 500mg PO Q12h treatment of diabetes mellitus
Discusssion:
1. All the drugs were prescribed in appropriate dose.
2. Duration of drug therapy is not mentioned.
3. A condition of hyperphosphatemia is left untreated.
4. Following are the drug interactions in regimen:
Aspirin + Lisinopril:
Pharmacodynamic anatgonism,co administration may result in a significant decrease in
renal function.avoid or use alternative
Lisinopril + furosemide:
Pharmacodynamic synergism,risk of acute hypotension.

36
Lisinopril + Aspirin:
Pharmacodynamic anttagonism,nephrotoxicity.
Lisinopril + Metformin:
Lisinopril increases toxicity of metformin by unspecified mechanism .
Aspirin + furosemide:
Both counter act on serum potassium concentration.
Metformin + furosemide:
Metformin decreases levels of furosemide by unspcified mechenism
Recommended interventions:
1. Phosphate binder drugs should be prescribed.
2. Interactions should be adressed to promote safe therapy.
3.Patient daily calories intake record should be maintained.
4.Avoid to use lisinopril concomitantly with aspirin.

Case # 10
Patient was a 77-year-old man was admitted to hospital with type 2 diabetes since 1999.on
the basis of his lab reports, he was diagnosed with CKD. His lab findings reveals:
• UACR 550
• Glucose 60
• BUN 43
• Creatinine 3.1
• eGFR 25
• Potassium 5.3
• Phosphorus 5.3
• LDL 104

His medication profile includes

• Enalapril 10 mg PO QD treatment of hypertention
• Lovastatin 40 mg PO QD treatment of dylipidemia
• Aspirin 81 mg PO QD prophylaxis of heart attack
• Furosemide 40 mg PO Q12h treatment of hypertention
• Paracetamol 325 mg POQ8 hr treatment of fever
• Naproxen 250 mg PO Q8hr treatment of fever
Discussion:

37
1. All the drugs were prescribed in appropriate doses.
2. Duration of treatment was not mentioned.
3. Patient daily calorie intake record was not maintained.
4. An abnormal condition “Hyperphosphatema” was left untreated.
5. Duplication of drug with same therapeutic outcome was present.
6. Interactions present in the regimen was:
Aspirin + Enalapril:
aspirin, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug.
Coadministration may result in a significant decrease in renal function.
Naproxen + enalapril:
naproxen, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug.
Coadministration may result in a significant decrease in renal function.
Enalapril + furosemide:
enalapril, furosemide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor.
Risk of acute hypotension, renal insufficiency.
Enalapril + aspirin:
enalapril, aspirin. Either increases toxicity of the other by Other (see comment). Use
Caution/Monitor. Comment: May result in renal function deterioration, particularly with
high dose aspirin, in elderly or volume depleted individuals.
Enalapril + naproxen:
enalapril, naproxen. Either increases toxicity of the other by Other (see comment). Use
Caution/Monitor. Comment: May result in renal function deterioration, particularly in
elderly or volume depleted individuals.
Aspirin + naproxen:
aspirin and naproxen both increase anticoagulation. Use Caution/Monitor.
Aspirin + naproxen:
aspirin and naproxen both increase serum potassium. Use Caution/Monitor.
Aspirin + furosemide:
aspirin increases and furosemide decreases serum potassium. Effect of interaction is not
clear, use caution. Use Caution/Monitor.
Naproxen + furosemide:
naproxen increases and furosemide decreases serum potassium. Effect of interaction is not
clear, use caution. Use Caution/Monitor.
Aspirin + naproxen:

38
aspirin will increase the level or effect of naproxen by acidic (anionic) drug competition for
renal tubular clearance. Minor/Significance Unknown.
Aspirin + furosemide:
aspirin decreases effects of furosemide by pharmacodynamic antagonism.
Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.
Naproxen + furosemide:
naproxen decreases effects of furosemide by pharmacodynamic antagonism.
Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis
Recommmended interventions:
1.Phosphate binder should be added to regimen.
2. Duration of therapy should be mentioned.
3. Duplication of drug should be avoided by eleminating a duplicated drug.
4. Patient daily calorie intake record should be maintained.

Case # 11
A 50 year old male is diagnosed case of CKD along with hypercholesterolaemia and
hypertension.On step down to medical ward.his lab reports revealed:
• Sodium 132
• Potassium 5.0
• Urea 24 (from 8)
• Creatinine 390 (from 60)
• Clinically he is mildly dry
• BP 135/83.
• HR(heart rate) 90 beats per min.

His medication record included:

• Furosemide 20mg PO q12h treatment of hypertention
• Enalapril 1.25 mg/dose IV ,5 min q6hr treatment of hypertention
• Aspirin 81 mg PO QD prophylaxis of heart attack
• Clopidogrel 75 mg PO qDay treatment of diabetes mellitus
• Simvastatin 5 mg qDay initially treatment of dylipidemia
Discusssion:
1. All the drugs were prescribed in appropriate dose.
2. Duration of drug therapy is not mentioned.

39
3. Following are the drug interactions in regimen

aspirin + enalapril:
aspirin, enalapril. pharmacodynamic antagonism.Coadministration may result in a
significant decrease in renal function NSAIDs may diminish the antihypertensive effect of
ACE inhibitors.
enalapril + furosemide:
enalapril, furosemide. Mechanism: pharmacodynamic synergism.risk for renal
insufficiency.
aspirin + furosemide:
aspirin increases and furosemide decreases serum potassium. Effect of interaction is not
clear.
Recommended interventions:
1. Interactions should be adressed to promote safe therapy.
2.Patient daily calories intake record should be maintained.

Case # 12
A 55 year old male patient was admitted in medical ward.He was diagnosed with Type 2
diabetes at 13 years old.He was non-compliant with prescribed treatment for diabetes.he
was diagnosed with CKD based upon his lab reports.His physical examantion revealed:
• Muscle Weakness
• 3+ pitting edema to the knees
• High blood pressure

His lab findings are :

• Albumin 3.7 g/dl
• Sodium 130 mEq/l
• Potassium 5.8 mEq/l
• Phosphorus 9.5 mEq/l
• Glucose 282 mg/l
• eGFR 45 ml/min
• UACR 800 mg/dl
• Creatinine 12 mg/2dl
• LDL 166 mg/dl

40
His medication profile contain:
• Lisinopril 10 mg PO QD treatment of hypertention
• Aspirin 81 mg PO QD prophylaxis of heart attack
• Calcitriol 0.25 mcg PO QD treatment of hypocalcemia
• Metformin 500 mg PO Q12h treatment of diabetes mellitus
• Simvastatin 40 mg QD treatment of dylipidemia
Discussion:
1.All the drugs were prescribed in approprate dose
2. Duration of treatment was not mentioned.
3. A pathological condition hyperphosphatemia was left untreated.
4. Interactions identified in the regimen were:
Aspirin + lisinopril:
aspirin, lisinopril. pharmacodynamic antagonism. Coadministration may result in a
significant decrease in renal function
Lisinopril + Aspirin
lisinopril, aspirin. Either increases toxicity of the other. Use Caution/Monitor. Comment:
May result in renal function deterioration,
Lisinopril + Metformin:

lisinopril increases toxicity of metformin by unspecified interaction mechanism. Increases

risk for hypoglycemia and lactic acidosis.

Recommended interventions:
1.Phosphate binder should be prescribed to treat hyperphosphatemia.
2. Patient daily calories intake should be maintained.
3. Interactions should be adressed to promote safe therapy.

Case # 13
A 65 year old Male patient was admitted in medical ward with the complaints of abdominal
pain for 10 days.swelling, difficulty in breathing,frequent urination at night,fatigue and
fever.He was a diagnosed case of diabetes mellitus and hypertention.His lab findings were:
• RBCs 67 mg/dl
• Blood urea 46 mg/dl

41
• Creatinine 2.2 mg/dl
• eGFR 40 ml/min
• Phosphate 7.5 mg/dl
• UACR 500 mg/dl
• A1C 8.5 %

His medication profile contained:

• Cefotaxime 2mg IV bd prophylaxis of noscomial inf
• Ranitidine 150 mg PO QD prophylaxis of peptic ulcer
• Paracetamol 650 mg PO bd treatment of fever
• Furosemide 40 mg PO bd treatment of hypertention
• Epoetin alpha 100 mg IV QD treatment of anemia
• Propranolol 40 mg PO Q12hr treatment of hypertention
• Sitagliptin 100mg PO QD treatment of diabetes mellitus
• Pitavastatin 2mg PO QD treatment of dylipidemia
Discussion:
1. All the drugs were prescribed in appropriate doses.
2. Duration of treatment was not mentioned.
3. Beta blockers are sometime contraindicated in patient having
difficulties in breathing.
3. Interactions present in the regimen are discussed as follows.
calcium carbonate + propranolol:
calcium carbonate decreases effects of propranolol by unspecified interaction mechanism.
Use Caution/Monitor.
calcium carbonate + propranolol:
calcium carbonate decreases levels of propranolol by inhibition of GI absorption. Applies
only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.
propranolol + furosemide:
propranolol increases and furosemide decreases serum potassium. Effect of interaction is
not clear, use caution. Use Caution/Monitor
furosemide + calcium carbonate:
furosemide decreases levels of calcium carbonate by increasing renal clearance.

42
Recommended interventions:
1. Phosphate binder shouldbe included in therapy
2. Patients daily calorie intake should be maintained.
3. Beta blockers can be switch to other classes of drugs such as ACE INHIBITORS and
ARBs drugs.
4. Patient daily calorie intake profile should be maintained.

Case # 14
A patient ,49 years old lady was admitted in medical ward with chief complaints of Type 2
diabetes, Hypertension, Dyslipidemia, Retinopathy.his lab test were carried out and she
was diagnoed with CKD. Her lab values reveals:
• HB A1c,% 10.1 %
• Blood pressure 180/110 mmHg
• LDL 146 mg/dl
• eGFR 53 ml/min
• UACR 500 mg/g
The medication profile includes:
• Insulin NPH/REG 70/30 45 units treatment of diabetes mellitus
• Lisinopril 40 mg daily treatment of hypertention
• Simvastatin 40 mg daily treatment of dylipidemia
• Furosemide 20 mg daily treatment of hypertention
• Aspirin 81 mg daily prophylaxis of heart attack
Discussion:
1. All the drugs were prescribed in appropriate dose.
2. Duration of the treatment was not mentioned.
3. Patient daily calorie intake profile was not maintained.
4. Following was the interactions in regimen.
Aspirin + lisinopril:
aspirin, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug.
Coadministration may result in a significant decrease in renal function. NSAIDs may
diminish the antihypertensive effect of ACE inhibitors.
Lisinopril + aspirin:
lisinopril, aspirin. Either increases toxicity of the other by Other .

43
Aspirin + insulin NPH:
aspirin increases effects of insulin NPH by pharmacodynamic synergism.

Case # 15:
A 62-year-old man was admitted in the hospital .he was a diagnosed case of diabetes,
hypertension, and CKD. His physical examination reveals lower leg edema, good dentition
and no obvious nutrient deficiencies.his lab report revealed:
• HBA1c 5.9 %
• UACR 65 mg/g
• Creatinine 1.2 mg/dl
• eGFR 56 ml/min
• potassium 4.3 mEq/l
• calcium 9.0 mg/dl
• phos 5.3 mg/dl

His medication record included:

• Furosemide 20 mg PO Q12h treatment of hypertention
• Baby aspirin 81 mg PO QD prophylaxis of heart attack
• Metformin 500mg PO Q12h treatment of diabetes mellitus
• Calcium acetate 1 cap PO every meal treatment of hyperphosphatemia
Discusssion:
1. All the drugs were prescribed in appropriate dose.
2. Duration of drug therapy is not mentioned.
3. Following are the drug interactions in regimens
Aspirin + furosemide
Both counter act on serum potassium concentration.
Metformin + furosemide:
Metformin decreases levels of furosemide by unspcified mechanism
Recommended interventions:
1. Interactions should be adressed to promote safe therapy.
2.Patient daily calories intake record should be maintained

44
CHAPTER 04

RESULTS
AND DISCUSSION

45
 CHAPTER

4
RESULT AND DISCUSSION

STATISTICAL INTERPRETATION:
The study was conducted during December 2019 to March 2020, in medical ward.
Among thirteen histories prevalence among male and female and different age groups
were determined. With the detailed study therapy related problems, treated and untreated
condition of patient were also observed.

Gender wise prevalence of CKD in Abbottabad medical complex:

case histories of selected patients having CKD were divided into two groups on basis of
gender, such as group A(Male), group B(Female).Percentage and frequency distribution of
CKD among males and females is given in table 4.1

TABLE 4.1: Percentage and frequency distribution of CKD among

Gender Frequency Percentage

MALES 06 40%

FEMALES 09 60%

46
All PATIENTS 15 100%
males and females: ( n=15)

FIGURE 4.1: : Percentage and frequency distribution of CKD amongmales and

females: ( n=15)

70

60

50

40
FREQUENCY
PERCENTAGE
30

20

10

0
MALE FEMALE

DISCUSSION:
As seen by the data female patients are more in numbers who have been affected from CKD
as compared to male patients. Male patients were 6 in number and female patients were 9 in
number who suffered from chronic kidney disease.

TABLE 4.2: Percentage distribution of patients acccording to age: (n=15)

47
 PATIENTS FREQUENCY PERCENTAGE

15-35 1 6.6%

35-55 5 33.3%

55-75 8 53.3%

75-95 1 6.6%

Figure 4.2 : Percentage distribution of patients acccording to age: (n=15)

60

50

40

30 FREQUENCY
PERCENTAGE

20

10

0
15-35 35-55 55-75 75-95

DISCUSSION:
According to the age as seen by the data, that disease progresses more in 55-75
years.The causative factors are mostly diabetes and hypertention.

TABLE 4.3: Percentage and frequency distribution of interaction of Chronic Kidney

Disease(CKD): ( n=15)

NO OF FREQUENCY PERCENTAGE

48
 INTERACTIONS
0 1 6.6
1 2 13.3
2 3 20
3 6 40
4 1 6.6
6 1 6.6
11 1 6.6
Figure 4.3 :Percentage and frequency distribution of interaction of Chronic Kidney
Disease(CKD): ( n=15)

45

40

35

30

25
FREQUENCY
20 PERCENTAGE
15

10

0
0 1 2 3 4 6 11

TABLE 4.4: Class wise distribution of drugs given to the patients: (n=15)

49
 CLASS OF DRUGS FREQUENCY
Antibiotics 5
Antidiabetics 14
Analgesics 11
Antihypertensives 25
Antacids 3
Antihyperlipidemics 9
Antianemic 8
Vit D analogues 5
Calcimimetic 1
H2-Antagonist 1
Proton pump inhibitors 1
Xanthine oxidase inhibitors 1
Vitamins/Supplements 2
PO4 Binders 3
Figure 4.4 : Class wise distribution of drugs given to the patients: (n=15)

FREQUENCY
24
22
20
18
16
14
12
10
8 FREQUENCY
6
4
2
0
ive tic sic ic ic tic ue ids ins er tic ist PI's
ens iabe alge idem nem bio alog tac tam Bind ime gon P
ert ti d An lip ti
a nti
an A n Vi 4 cim nta
hy
p
An er An A D PO Cal 2 A
ti hyp Vit H
An n ti
A

DISCUSSION:
In CKD, The most occuring pathological menifestation is uncontrolled
hypertension,uncontrolled glucose level and hyper lipidemia so most of the drugs are
prescribed to control these conditions to halt progression of CKD.As patients were also

50
suffering from some other diseases so for the treatment of those complications other
medications were also prescribed.

Table 4.5: Percentage distribution of untreated condition in patients:

Patient condition Frequency Percentage

Treated 12 80%

Untreated 3 20%

Figure 4.5: Percentage distribution of untreated condition in patients:

100
95
90
85
80
75
70
65
60
55
50 FREQUENCY
45 Percentage
40
35
30
25
20
15
10
5
0
Treated Untreated

DISCUSSION:
Above data shows that most of conditions of patient are treated and few remain untreated
it is either due to the incomplete examination of the patient by the physician due to
patient overload or some time due to uncooperative patient.

51
 TABLE 4.6: Frequency and percentage of therapy related problems:

Therapy related problems

Frequency Percentage
Under prescribing

6 35%
Dose error
1 6%
Duplication of drug

4 24%
Contraindications

6 35%

Figure 4.6: Frequency and percentage of therapy related problems:

40

35

30

25

20

15 FREQUENCY
Percentage
10

0
se
s

s
n

ug
ug

tio

do
dr

dr
rip

ng
of
d

sc
te

ro
re

n
ca

W
tio
rp
di

ica
in

de

pl
ra

Un

Du
nt
Co

52
DISCUSSION:
Above data shows that most of problem associated with therapy are prescription related
problems including prescription of congtraindicated drugs,under prescription of
adrug,duplication of drugs. Some major problems occurs due lack of grip of physician
about drug-disease and drug-drug interactions.that shows the importance of pharmacist
being a drug specialist to monitor drug therapy.

TABLE 4.7: Proposed plans for achieving desired definite therapeutic

outcomes and resolving drug related problems among 15 patients:

Drug Related Recommended Case #

Problems interventions
Contraindicated drugs

Metformin is Metformin should be

contraindicated in patients discontinued immediately
3,5,6,8
with eGFR < 60 ml/min and substituted by suitable
hypoglycemic agent
Long acting insulin should long acting hypoglycemic
be avoided in advanced agent should replaced by
CKD patients intermediate or short 7
acting
agents
long acting hypoglycemic Beta blockers should be
agent should replaced by switch to other classes of
intermediate or short drugs such as ACE
acting INHIBITORS
agents long acting and ARBs drugs
13
hypoglycemic agent
should replaced by
intermediate or short
acting
agents

53
 Under prescription

No phosphate binder is Addition of PO4 binder to 1

prescribed although PO4 therapy ,
value is high than normal. 2
,
9
,
1
0
,
1
2
An untreated condition Vit D and calcium 4
“hypocalcemia” was supplements should be
left,for which no therapy added to therapy
was
prescribed
Duplication of medications

over-prescribing of One of the antibiotic 1

nitrofurantoin which in should be eliminated.
not needed by
patient in addition to
piperacillin-tazobactam.
Duplication of medication Substraction of one of anti 6
are present in case of ulcer drug from regimen
ranitidine and omeprazole
Duplication of One of the 7
antihypertensive antihypertensive should be
medication of same eleminated from regimen
therapeutic
outcome(captopril
and losartan)
Duplication of drug with Duplication of drug should 1
same therapeutic outcome be avoided by eleminating 0

54
 was a duplicated drug
present(paracetamol+Nepr
oxen)
Wrong dose

Paricalcitol is not paricalcitol shouldbe 5

prescribed in right dose. increased to 2 mcg QD

Conclusion

Chronic kidney disease (CKD) is characterized by multiple disorders affecting the

morphology and function of kidneys.It is estimated on the basis of a decrease in the
number of nephrons, which ultimately decreases the glomerular filtration rate (GFR) for
a period more than 3 months.Hypertension and diabetes, recurrent infections along with
an inappropriate prescription of drugs are the leading factors resulting in the increasing
incidence of CKD. This study was conducted to identify any irrational therapy problem
in pharmacotherapy of diabetes.Result of this study showed that disease prevalence was
found more in females as compared to male. Incidence of CKD is high in age group of 55
to 75 years of age. Among different therapeutic class of the use of Anti hypertensives is
very high. Drug related problems were identified and it was found that majority of drug
related problems were prescription of contraindicated drugs (35%), under prescription of
drugs (35),duplication of drugs (24%)and wrong dose (6%).Drug related problems can
interfere with the achievement of desired therapeutic goals. Medication therapy can be
rationalized and above problems can be solved by placing pharmacist in the health care
providing team in hospital and community level. Pharmacist is the only professional
person that can provide information about the drugs both to the health care team and to
patients and knowledge about drug related problem. Clinical pharmacy services can be
valuable to a health care setting and can potentially lead to a decrease in health care
expenses and to an improvement of the standard of patient care.

55
CHAPTER 05

REFERENCES

56
 References

1. Choi, A. I., Rodriguez, R. A., Bacchetti, P., Bertenthal, D., Hernandez, G. T., & O'Hare, A.
M. (2009).

2. White/Black Racial Differences in Risk of End-stage Renal Disease and Death. The
American Journal of Medicine, 122(7), 672-678. doi:10.1016/j.amjmed.2008.11.021

3. Levin, A., Hemmelgarn, B., Culleton, B., Tobe, S., McFarlane, P., Ruzicka, M., . . . Tonelli,
M. (2008). Guidelines for the management of chronic kidney disease. Canadian Medical
Association Journal, 179(11), 1154-1162. doi:10.1503/cmaj.080351

4. National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation,
Classification, and Stratification. (2003). Annals of Internal Medicine, 139(2), 137-147.
doi:10.7326/0003-4819-139-2-200307150-00013 %m 12859163

5. O'Hare, A. M., Choi, A. I., Bertenthal, D., Bacchetti, P., Garg, A. X., Kaufman, J. S., . . .
Landefeld, C. S. (2007). Age Affects Outcomes in Chronic Kidney Disease. Journal of the
American Society of Nephrology, 18(10), 2758-2765. doi:10.1681/asn.2007040422

6. Vegter, S., Perna, A., Postma, M. J., Navis, G., Remuzzi, G., & Ruggenenti, P. (2012).
Sodium Intake, ACE Inhibition, and Progression to ESRD. Journal of the American Society of
Nephrology, 23(1), 165-173. doi:10.1681/asn.2011040430

57
7. Walker, R., & Whittlesea, C. (2012). Clinical pharmacy and therapeutics. Edinburgh:
Churchill Livingstone

8. Katzung, B. G., Masters, S. B., & Trevor, A. J. (2015). Basic & clinical pharmacology. New
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