Pharmacist Basic Skill in

Interpreting Laboratory Data

Budi Raharjo
Mengapa Apoteker...?
Px. Lab. rutin dilakukan Dokter utk
dapatkan info yg berguna bagi dokter dlm
Ambil Keputusan Klinik (Tegakan
Diagnosis & Tentukan Terapi)
Penilaian hasil terapi pasien perlu bbrp
indikator: respons klinik pasien,
pemeriksaan fisik, dan data laboratorium
Apoteker dlm memantau proses terapi
mulai dari pemilihan obat, penentuan dosis
obat hingga pemantauan efektivitas dan
keamanan obat pada pasien, butuh hasil
pemeriksaan laboratorium.
Landasan Hukum (medikolegal)
UU Nomor 36 tahun 2009 tentang Kesehatan
UU Nomor 44 tahun 2009 tentang Rumah Sakit
PP Nomor 51 tahun 2009 tentang Pekerjaan
Kefarmasian
PermenPAN Nomor Per/07/M.PAN/4/2008 tentang
Jabatan Fungsional Apoteker & Angka Kreditnya
Peraturan Bersama MenKes & Kepala BKN
Nomor 113/Menkes/PB/XII/2008 dan Nomor
26/2008 ttg Petunjuk Pelaksanaan Jabatan
Fungsional Apoteker & Angka Kreditnya
KepMenKes No. 1027/Menkes/SK/IX/2004
tentang Standar Pelayanan Kefarmasian di Apotek
KepMenKes No. 1197/Menkes/SK/X/2004 tentang
Standar Pelayanan Kefarmasian di Rumah Sakit
Interpretasi-Apoteker,Tujuan:
Menilai Disease Stage dari pasien
Mencegah interpretasi yang salah thd hasil
pemeriksaan
Menilai kesesuaian terapi obat
Monitoring efektivitas terapi obat
Monitoring reaksi obat yg tidak diinginkan
(ROTD)
Menilai toksisitas obat
Monitoring kepatuhan minum obat
Outline
Obat yang mempengaruhi hasil
laboratorium
Pemeriksaan Haematologi
Pemeriksaan Biokimia
Pemeriksaan Fungsi Ginjal
Pemeriksaan Fungsi Hati
Obat vs Hasil Laboratorium
Interaksi Obat-Hasil Lab. Insidens
10-20 %
Mempengaruhi Hasil Diagnosis
Pemberian Terapi yang Kurang
Tepat/Tidak Perlu
Follow-Up Penyakit yang Tidak
TepatHospitalize meningkat
Mekanisme Interaksi Obat-Lab
Invivo/Farmakologi/ Invitro/Analitik/
Toksikologi: Metodologik:
ESO Obat Obat/Metabolit
furosemidhipo Pengaruhi Proses
K+,
Analisis scr in vitro
parastamolsgpt
, fenitoingula Analit struktur
drh kimia mirip dg obat
Biasanya Obat Vit.CGula
Pengaruhi Darah,
Fisiologi Tubuh
Mekanisme Interaksi In-Vitro
Obat + Reagent Kromofor
sefalosporin Kreatinin assay
Struktur Obat mirip dg analite
parasetamol mirip Rx asam urat
Obat mengubah pH spesimen
Obat mengkhelat aktivator enzim
Cystein mengkhelat Mg aktivts
alkaline fosfatase turun
Mekanisme Interaksi In-Vitro
Obat langsung hambat enzim,
mis: teofilin hambat alkalin
fosfatase
Obat langsung aktivasi
enzim,mis: Cystein kreatinin
fosfokinase
Obat panjang gelombang
absorbsi sama dg analit, mis:
MTX pjg glb absorbsi 340-410
nm
Diagnosis Adanya Interaksi (1)
Hasil Tes Lab. Tidak Sesuai dg
Kondisi Klinis/Gejala dari
Pasien,
mis: Bilirubin total 6,0 mg/dL
atau lebih(0,3-1,0 mg/dL),tapi
tidak ada tanda jaundice. Skle
ra ikterik pada kadar Bilirubin
Total 4,0 mg/dL Interaksi
Diagnosis Adanya Interaksi (2)
Bila 2 atau lebih hasil tes yg
menilai anatomi/fisiologi yg sama,
saling bertentangan,
mis: Px 20 th sehat pre-oprasi
Kreatinin Srm 4,2mg/dL (0,7-1,5),
BUN 8,0 mg/dL (5-20)
inj.iv.cefoxitinKreat.Srm
Diagnosis Adanya Interaksi (3)
Bila Hasil Seri Tes Lab. yang
Sama variasinya sangat besar
dalam periode yg dekat,
mis: Px di atas, pemeriksaan
serum kreatinin 1 hari sblm
operasi 1,0 mg/dL (0,7-1,5),
akan ope-rasi mjd 4,2 mg/dL
Diagnosis Adanya Interaksi (4)
Hasil tes tunggal lebih tinggi
atau lebih rendah extrim jauh
dari angka normal atau angka
yang diharapkan,
mis: Gula darah 800 mg/dL
pada Px 75 thn non diabetik
asimtomatik
Action for Drug Interfere
Tes Lab. Diulang, menunggu
Obat tereliminasi smp minimal
(lihat waktu paruh eliminasi)
Obat diganti dengan yang tdk
berinteraksi dengan hasil Lab.
Bila ragu, kondisi klinis pasien
sebagai pedoman pengambilan
keputusan
Pemeriksaan Haematologi
Haematology Test
FULL BLOOD COUNT
Erythrocytes
Platelets
Leucocytes
Lymphocites
Erythrocytes
Produced in bone marrow
Erythropoietin stimulates process of
erythropoiesis
No nuclei
Life span 120 days
Destroyed by the spleen
Carry oxygen (haemoglobin)
Increase Erythrocytes

Occurs in:
Stress
Condition causing hypoxia
Policythemia rubra vera
Dehydrated patients
Decrease Erythrocytes
(Anaemia)

Due to decreased production

Excessive destruction
Loss of erythrocytes
Excessive demands for available
materials (ex: pregnancy)
Decrease Erythrocytes
(Anaemia)

Causes
Iron deficiency
Folate deficiency
Vitamin B 12 deficiency
Haemolysis
Chronic inflamatory diseaase
Haemoglobin Concentration
Generally dependent on the number
of erythrocytes
Standard measure of the oxygen
capacity of blood
Concentration men > women
Commonly used to detect anaemia
MCV (Mean Cell Volume), MCH
(Mean Cell Haemoglobin),
Mean Cell Volume (MCV)
Average volume of single red cell
Measured in femtolitres (10-15 litres)
MCV microcytic anaemia
Iron deficiency
Severe vitamin B12 deficiency
MCV macrocytic/megaloblastic anaemia
Vitamin B12 or Folate deficiency
High alcohol intake
Chronic liver disease
Hypothyroidism
Mean Cell Haemoglobin (MCH)
Average weight of Haemoglobin (Hb)
contain in RBC (Red Blood Cell)
Measured in picograms (10-12 gram)
Dependent on the sizes of RBC as well as
concentration of Hb in cells
MCH in iron deficiency anaemia
MCH in macrocytic anaemia
Anaemia: caused by Iron Deficiency
Increase blood loss e.g.
gastric bleeding, menstruation
Increased iron requirement
e.g. pregnancy
Inadequate iron intake (poor
diet)
Erythrocytes appear
microcytic and hypochromic
 Anemia: caused by Folate or
Vitamin B12 Deficiency

In both cases
erythrocytes are
macrocytic and
hypochromic
In severe vitamin B12
deficiency, they may be
microcytic
Anemia: caused by Folate Deficiency
Caused by:
Low dietary intake
Alcoholism
Malabsorption
Pregnancy
Drugs induced:
Methotrexate, phenytoin,
phenobarbitone
Anemia: caused by Vitamin B12
Deficiency
Caused by:
Lack of intrinsic factor
(gastrectomy)
Bacterial over growth
Strict veganism
(vegetarian murni),
because vitamin B12 is
only available from animal
source
Platelets
Produced in bone marrow
Integral part of clotting cscade
Life span in circulation of 8-12 days
Platelets (thrombocytosis)
Decreased destruction after
splenectomy
Increased production in chronic
inflamatory disorder, malignancy,
blood loss & polycythemia
Platelets
Platelets (thrombocytopenia)
Increased consumption in:
Idiopathic
Disseminated Intravascular Coagulation
(DIC)
Splenomegaly
Drugs induced (furosemide, heparin)
Decreased production in:
Bone marrow suppression
Leukaemia
Acquired Immunodeficiency Syndrome
(AIDS)
Macrocytic Anaemia
Systemic Lupus Erythematosus (SLE)
 Leucocytes

Granulocytes Agranulocytes

Lymphocytes
Monocytes Polymorphonuclear

Neutrophils Basophils Eosinophils

Only small number in blood stream

Huge reserve in bone marrow and tissues
Neutrophils
Most abundant WBC (White Blood
Cell)
Phagocytic destroying bacteria, fungi
and cellular debris
Formed from bone marrow from stem
cells
40 70 % of WBC
Life span 10-20 days
Neutrophils
Caused by
Infection
Tissue necrosis (Myocard Infarc)
Metabolic disorders
Smoking
Oral contraseptive use
Corticosteroids
Late Pregnancy
Neutrophils
Caused by
X-rays
Chronic alcoholism
Bone marrow obliteration
Severe infection
Drugs (cytotoxic)
Eosinophils

Function not well understood

Phagocytic
Reduce inflamatory response in
allergic reactions
Have receptor that bind IgG & IgE
Eosinophils

Occur in
Allergic disorder (e.g. angioedema)
Parasitic infection
Skin diseases (e.g. eczema,
psoriasis)
Asthma
Drug sensitivity (e.g. tryptophan can
induce eosinophilic myalgia
syndrome)
Eosinophils
Caused by
Corticosteroids
Lymphocytes

Second most abundant WBC

Found in the spleen and other
lymphatic tissue
Formed in bone marrow
 Lymphocytes

Lymphocyte :
Childhood viral infections e.g.
rubella, mumps, infectious hepatitis
and infectious mononucleosis
Corticosteroids
Lymphoma
 Monocytes

Monocytes are Macrophages

Monocytes in some infection:
Typhoid
Sub acute bacterial endocarditis
Infectious mononucleosis
Tuberculosis
Pemeriksaan Biokimiawi
Biochemistry Test
Sodium (Na)

Potasium (K)
Sodium
(133-145 mEq/L or mmol/L)

Extracellular ion-which plays an

important part in maintaining serum
osmolality and extracellular fluid
volume
Sources: salt, confenience food, drugs
Excretion: via Kidneys
Hyperosmolality can lead to cerebral
dehydration & intracranial haemorrhage
due to tearing of blood vessels
Hyponatraemia
(Na < 133 mEq/L)
Causes
Deficiency of Na
Na Depletion: Addisons disease,
Renal disease, Drugs (diuretics),
Excessive sweating, Gastro intestinal
disease
Excess of water
Water retention: Cirrhosis with
ascites, Hypergly chaemia, CHF,
Renal disease, Post surgery / injury
SIADH: Neoplasma, Respiratory
disesase, Stroke, Head injury, Drugs
(Carbamazepine)
Hyponatraemia
(Na < 133 mEq/L)
Causes
False Reading
High lipids: TPN
Post opperative: Leaky cell (sick cell
syndrome)
 Hyponatraemia
(Na < 133 mEq/L)
Clinical Consequences:
Nausea, vomiting, weakness, difficulty in
concentrating, headache, anorexia,
lethargy, convultion, coma
125-130 mEq/L symptomless (no
treatment)
< 120 mEq/L patient weaknes
(fluid restrict)
< 110 mEq/L palsy
90-105 mEq/L sever neurological
sign
Hyponatraemia
(Na < 133 mEq/L)
Treatment
Identify underlying causes
Treatment appropriate
Na loss consider increassing water &
salts
Excess water restrict Na, water intake
& con-sider diuretics
SIADH consider fluid restriction 1-1,5
lt/day, If Na < 120 mEq/L consider Na
replacement, Finally consider drug
treatment: demeclocycline
Hypernatraemia
(Na > 155 mEq/L)
Causes
Water depletion
Reduce intake: patient unable to
respond to thirst, e.g. coma, elderly,
babies
Increase water loss: Diabetes
insipidus, Diarhoe in infant, Excess
sweating
Na Excess
Excess Na intake: Administration of
hypertonic salts solution
Na retention: Drug induce (steroid)
Hypernatraemia
(Na > 155 mEq/L)
Clinical Consequences
Cerebral dehydration: Thirst, Mental
confu-sion, lethargy, coma
Brain Haemorhage
> 160 mEq/L is assosiated with a
mortality of 75 % patient
Hypernatraemia
(Na > 155 mEq/L)
Treatment
Identify underlying cause
Treat apprpriate: i.v. fluids (D 5% or 0,45
Saline)
 Drugs known to cause hyponatraemia

Aminoglutethimide Diuretic
Amitriptyline & other Heparin
Tricyclic antidepresant Lithium
Amphotericin Miconazole
Captopril & other ACEI NSAIDs
Carbamazepine Opiates
Chlorpropamide Oxcarbazepine
Cisplatine Tolbutamide
Clofibrate Vasopresin
Cyclophosphamide Vincristine
 Drugs known to cause hypernatraemia

Adrenocorticotropic Diazoxide
hormone Lactulose
Anabolic steroids Methyldopa
Androgens Oestrogens
Carbenoxolone Oral contraseptives
Clonidine Phenylbutazone
Costicosteroids Sodium
bicarbonate
Potassium
(3,5-5,0 mEq/L or mmol/L)
Intracellular ion
Excreted from the body via urine, but may
also be lost via GI tract. During vomitting,
diarrhoe, Nasogasric aspiration or fistulae
Major Function: Maintain excitability of neuro
muscular tissue
Also important in carbohydrate & protein
metabolism and in enzymatic reaction
Intake via food = 100 mmol/day
 Hypokalaemia
(K < 3,5 mEq/L)
Causes
K+ depletion
GI tract. loss: Vomiting, diarrhoe, vistulae
Renal loss: Renal disease, Post trauma
Drug induce: Diuretics, steroids
Redistribution K+
Acid-base disorder: Alkalosis
Drug induce: Insulin, steroid, beta agonis
 Hypokalaemia
(K < 3,5 mEq/L)
Causes
Redistribution of K+ continued
Megaloblastic anemia
Inadekuat intake
NBM (Nil By Mouth)
Diet
 Hypokalaemia
(K < 3,5 mEq/L)
Clinical Consequences
(usually when K+ < 2,5 mEq/L)
Neurological disturbance
Fatigue, depression, confusion
Musculosceletal disturbance
Muscle weakness, paralysis, cramps
Cardiac disturbance
Cardiac aritmia, hypotension,
exacerbates digoxin toxicity
 Hypokalaemia
(K < 3,5 mEq/L)
Treatment
Identify underlying cause
Treat appropriate
Oral replacement therapy (mild
hypokalaemia)
Intravena replacement tx. (severe
hypokalaemia)
Check max. concentration & rate of
administration
Monitor for phlebitis
Hyperkalaemia
(K+ > 6,5 mEq/L
life threatening)
Causes
Excess intake of K+
Inappropriate i.v. infusion
Reduced elimination of K+
Renal Failure
Addisons disease
Drug induce: Diuretics, ACE inhibitor
Redistribution of K+
Acid-base disorder: Acidosis
Hyperkalaemia
(K+ > 6,5 mEq/L
life threatening)
Causes
Blood transfusion
False reading
Haemolysed sample
 Hyperkalaemia
(K+ > 6,5 mEq/L
life threatening)
Clinical consequences
Cardiac disturbance
Tachicardia, Ventricular
fibrilation, Cardiac arrest
Muscular disturbance
Muscle weakness
 Hyperkalaemia
(K+ > 6,5 mEq/L
life threatening)
Treatment
Identify underlying cause
Treat appropriate
Oral ion exchange resins
I.V. calcium gluconate
Soluble insulin and 5 % glucose
 Drugs known to cause hypokalaemia

Amphotericin Benzylpenicillin
Aspirin (penicillin G) Na
Corticosteroids Piperacillin+
tazobactam
Diuretics
Salicylates
Gentamicin
Sod. bicarbonate
Insulin
Sod. Chloride
Laxatives
Ticarcillin+
Terbutaline
clavulanate
 Drugs known to cause hyperkalaemia

ACE Inhibitor Heparin

Antineoplastic Isoniazid
agent Lithium
(cyclophosphamid,
vincristine Penicillins (garam
NSAIDs kalium)
-blocking agents Potassium suppl.
Ciclosporine Succynilcholin chlor
Potassium sparing Tetracycline
Diuretics
Renal Function Test
Renal Function Test
Serum Creatinine

Creatinine Clearance

Urea (Blood Urea Nitrogen)

Miscellaneous
Function of Kidney
Excretion of waste product
e.g.Hydogen ion, Water
Biosynthesis and Metabolim of hormone
e.g. Renin, Insulin
Regulation of homeostasis
e.g. Fluid, Electrolyte and Acid-base balance
Serum Creatinine
(Male 0,6-1,2 mg/dL; Female 0,2-0,4 mg/dL)
By product of muscle metabolism
Rate of formation proportional to muscle mass
Freely filtered by glomerolus (little secretion or
reabsorption by tubule)
Indicator of renal function, but..
Factor affecting serum creatinine:
Diet, time of day, age, sex, exercise, drugs
Caution in unstable renal function or acute renal
disease
Creatinine Clearance
Measurement of creatinine clearance give an
estimate of GFR (Glomerular Filtration Rate)
Creatinine clearance varies with age, sex, and size
Measurement:
Urine collection
Cockroft and Gault Equation
Creatinine Clearance
Normal reference = 120 ml/min
Renal disorder if: 60 < CrCl < 120 ml/min
symptomless
Renal insuficiency:
Mild 20 50 ml/min
Moderate 10 20 ml/min
Severe < 10 ml/min
 Urine Collection
Accurate collection of over 24 hour periode (note
problems with patient compliance)
Plasma sample midway through 24 hour periode
U x V
Clcr = -------------
S
U = Urine Creatinine concentration (mg/dL)
V = Urine flow rate (ml/min)
S = Serum Creatinine concentration (mg/dL)
Cockroft & Gault Equation
F x (140 age) x IBW
CrCl = ml/min
Serum Cr (mg/dL) x 72
F = 1,23 (males) F = 1,04 (females)
IBW (Ideal Body Weight)
Males
TB > 152,5 cm IBW = 50 + [(TB - 152,4) x 0,89]
TB < 152,5 cm IBW = 50 - [(152,4 - TB) x 0,89]
Females
TB > 152,4 cm IBW = 45,5 + [(TB - 152,4) x 0,89]
TB < 152,4 cm IBW = 45,5 - [(152,4 - TB) x 0,89]
 Limitation of
Cockroft & Gault Equation

Cannot be used if
Age < 15 years old or age > 90 years old
Renal function is changing rapidly
Pregnancy (GFR + 20 %)
Serum creatinine > 3 x normal range
Amputated limb
 Blood Urea Nitrogen
(8 18 mg/dL)
Urea Nitrogen is an end product of protein metabolism
Produced by the liver, transported in blood and excreeted
by the kidney
Freely filtered by glomerolus, partly reab-sorbed by the
tubules
use as a screening test for renal disfunction, not quantify
the extend of renal disease
 Blood Urea Nitrogen
BUN in:
Acute or chronic renal failure
High protein intake in diet
Increased catabolism (infection, surgery)
Uper GI bleeding or esophageal varices (blood converted
to ammonia by bacteria)
Dehydration or water depletion
BUN in:
End state of liver disease ( formation)
Water axcess (dilution)
Miscellaneous
Increased potassium
Decreased bicarbonate
Increased phosphate
Decreased calcium
Altered sodium levels
Disturbed fluid balance
 Implications for Clinical Pharmacy
Practice
Drug choice in patient with renal disease
Pharmacokinetics

General guidelines regarding drug choice in patient with

renal disease

Dosage adjusment in patient with renal disease

 Pharmacokinetics
Absorption
Oral absortion reduce by vomitting, nausea, diarrhoea, GI
oedema & changes in blood pH
Little clinical significance
Distribution
Volume distribution (Vd) due to oedema/ascites; Vd
due to dehydration (Little clinical significant:
Aminoglycoside, Lithium)
Protein binding (Pb) due to protein loss or Pb due to
uraemia; increase free drugs; temporary effect; caution in
interprete drug level (Clinical Significant: Phenytoin,
Warfarin)
 Pharmacokinetics
Metabolism
Hepatic metab. unaffected in renal impairment
Clinical significant of impaired renal metabolism:
Accumulation of active metabolite
Vitamin D replacement
Insulin requirement
Excretion
Elimination of drug or its metabolites may be decreased
Most important parameter to consider when making
dosage decissions
 General Guidelines
Only use drugs if a definite indication
Choose drugs with minimal nephrotoxic effect and avoid
potentially nephrotoxic drugs
Increased sensitivity to certain drug effects
Monitor and act on plasma levels
Check appropriate dosage adjustment
Avoid prolonged courses of potentially toxic drugs
Monitor for clinical efficacy and evidence of toxicity
 Drugs in Renal Disease: Clinical
Pharmacy Practice Point
Identification of patient with renal
disease (Acute/Chronic Renal
Disease)
Monitoring of renal function
(including dose adjustment)
Assessment of current and
proposed drug treatment
 Acute Renal Failure

Pre-Renal ARF Intra-Renal ARF Post-Renal ARF

Hipovolemia Acute Tubular Necrosis (ATN) ichaemic

sweating,vomiting,diarho & toxin
e,blood loss (aminoglycosid,cyclosporin,contrast
Cardiac Output media)
AMI, CHF Interstitial nephritis drug hypersensitive:
Renal hypoperfu- penicillin,cepha-
siondrug induce losporine,allopurinol,azathioprin
ARF:Diuretic,ACEI Glomerular lession (glo-merulnephritis)
NSAID (PgE2D2I2)
Post-renal obstruc-tion:
urinary stone,
neoplasm,BPH
 Examination of ARF
1. Full history, including medication history
2. Physically Examination:
Postural hypotension & skin turgor Pre-Renal
Drug rashes / vasculitic lession Intra-Renal
Sizes of bladder & kidneys Post Renal
3. Examination of The Urine:
Concentrated urine Pre-Renal
Intra-Renal Isotonic urine,Epithel cell (ATN);Protein-uria &
Haematuria (Glomerulonephritis)
4. Examination of Blood
5. Radiological Study
 Dosage Adjustment
Loading dose is usually unchanged (except for digoxin and
gentamycin)
The most common maintenance dosage changes are to
decrease the dosage or increase the dosage interval or
both
Refference sources:
BNF
Data Sheet / Drugs leaflet
Bennett: Drugs and renal desease
 Dosage Adjustment

DRrf = DRn x [(1 - Feu) + (Feu x RF)]

Patient creatinine clearance (ml/mnt)
RF =
Ideal creatinine clearance (120ml/mnt)
DRrf = Dosing Rate in renal failure
DRn = Dosing Rate in normal state
RF = the extent of Renal Failure
Feu = Fraction of drugs normally excreting unchage
in the urine
Exsample : RF = 0,2; Feu = 0,5
 Treatment of ARF
1. Early Management:
Correction of fluid & Electrolide imbalance
If not respons Loop diuretic & Manitol; or Dopamine
2. Establish ARF:
a.Uraemia protein intake + Fat & CH Catabolism
b.Hyperkalaemia (K excresion + Cell damage) Cardioto-xic K
supplement; Ca gluconate i.v.; Soluble insulin + glucose; Ca resin ion
exchange
c.Acidosis H+ excresion Na bicarbonate
d.Hypocalcaemia (Ca malabsorption) Ca Suppl.
e.Hyperphosphataemia
3. Haemodialysis, Peritonial Dialysis
Liver Function Test
 Liver Disease
Function of The Liver

Assesment of Liver Disease

Causes of Liver Disease

Implication for Clinical Pharmacy Practice

 Functions of The Liver

Storage Synthesis
Vitamin (Vit K) Albumin
Homeostasis Metabolism
Glucose Vitamin D
Secretion Filtration
Bile salts Antigens
Excretion Clearance
Cholesterol Drugs
 Cause of Liver Disease

Viral infection* Billiary tract disease

Alcohol* Infectious disease
Immune disorders Drugs & toxin
Vascular Gilberts synrome
abnormalities
Inherited metabolic
disorder * Common Cause
 Assessment of Liver Disease
LIVER FUNCTION TEST
Billirubin
Aspartate aminotransferase (AST/SGOT)
Alanine aminotransferase (ALT/SGPT)
Alkaline Phosphatase (ALP)
Gamma glutamyl transferase (GGT)
Albumin
Prothrombin Time (PT)
 Assessment of Liver Disease
Clinical Assessment
Symptoms Signs
Weakness
Jaundice
Weight loss
Nausea Ascites
Abdominal discomfort Pruritus
Low grade fever
Oedema
Confusion
Encephalopathy
Oesophageal
varices
 Pruritus

Distressing
Deposition of bile salts under skin
Treatment:
Anion exchange resin: cholestyramine
Non-sedating antihistamine: cetirizine
Ursodeoxycholic acid
Topical treatment: calamine lotion, menthol 2% in
aqueous cream
 Clotting Abnormalities
Liver produces clotting factors
Prothrombin time is an indicator of synthetic capacity of
liver
INR > 1,2 (abnormal)
Treatment:
Oral vitamin K (menadiol)
Intravena vitamin K (phytomenadiol) 10 mg daily for 3
days
 Clotting Abnormalities
Risk of causing gastric ulceration and bleeding using drugs
:
Aspirin
NSAIDs non steroidal anti-inflammatory drugs
Anti-coagulants
COX-2 inhibitors ?
 Ascites
Aim to mobilise intra-abdominal fluid
Treatment:
Bed Rest
Reduce sodium intake 40-60 mmoles/days
Improve renal perfusion
Fluid Restriction
Ideal weight loss 0,5 kg/day
 Management
Diuretics combination of spironolactone and furosemide
Paracentesis-refractory patient
Transjugular intrahepatic portpsystemic shunting
Complication spontaneous bacterial peritonitis
cefotaxime
 Hepatic Encephalopathy
Neuroactive and neurotoxic compounds pass directly to
brain causing cerebral disfunction: ammonia
Sign & symptoms:
Dearranged judgement
Personality changes
Drowsiness
Confusion
Cerebral oedema
 Management
Identify and remove the cause
Protein restriction reduce ammonia in circulation
Treatment:
Lactulose ionisation of nitogenous products
Antibiotics (metronidazole, neomycin) kill colon bacteria
that metabolize protein, reduce ammonia production
 Oesophageal varices
Portal hypertension
Highly mortality
Massive upper gastrointestinal bleeding
Management:
Stop or slow blood loss
Endoscopic treatment-sclerotherapy, variceal banding,
ballon tamponade
Drug: Terlipressin, Octreotide
Treat hypovolemic shock
Fluid replacement: colloid, packed red cell
 Drug induced liver disease
Dose dependent (intrinsic)
Predictable, Involves ingestion of large amount of drugs
Example: Paracetamol
Dose independent (idiosyncratic)
Drug hypersensitivity or metabolic abnormality
Not dose related
Damage is less predictable: Cholestasis caused by
flucoxacillin or clavulanic acid
Implication for Clinical Pharmacy Practice
Altered drug handling in liver disease
Pharmacokinetics
Drug choice in patients with liver disease:
Drugs to avoid
Dosage alteration
 Pharmacokinetics
Absorption
Cholestasis
Distribution
Protein binding: cholestasis, hypoalbuminaemia
Metabolism
Hepatic blood flow
High extraction vs Low extraction drugs
Collateral circulation
Reduction in hepatic cell mass
 Drugs which require reguler monitoring of
liver enzymes

Amiodarone Cyproterone
Methotrexate
Dantrolene
Rifampicin
Rosiglitazone Methyldopa
Sodium Valproate Sulfasalazin
Statin
 Drugs to avoid in patients with liver
disease
Sedatives
Benzodiazepins, Opiates
Drugs which induce electrolyte disorders
Diuretics
Drugs associated with haemorrhage or alterations in
platelet function
NSAID, Warfarin, Aspirin
 Drugs to avoid in patients with liver
disease
Drugs affecting liver enzymess
Enzyme Inducers:
Carbamazepine, Phenytoin, Rifampicin
Enzyme Inhibitors:
Cimetidine. Erythromycin, Isoniazid
Hepatotoxic drugs:
Paracetamol, Halothane, Isoniazid
Summary
Clinical Pharmacy Practice Point:
Identification of patien with liver disease

Monitoring of liver function

Assessment of current & proposed drug treatment