Penggunaan Obat pada Pasien

dengan Kondisi Khusus

Drs. Budi Raharjo, Apt.SpFRS.

Aim & Objectives

Aim
To anable students to understand, interpret and

act upon data laboratory results

Objecttives
List common causes of abnormal results

(including drug related)

Describe common symtoms resulting from
abnormal results
Describe how abnormal level affect drug therapy
Suggest appropriate treatment to alleviate
symptoms or correct the abnormal level

Content
Biochemistry

Test
Haematology Test
Renal Function Test
Liver Function Test

Application
Confirm

diagnosis made on clinical

grounds
Assess

the severity of a disease

Monitor

the respons to treatment

Implication for Practice

Advice

on the choice of drugs & dosage

Advice on appropriate monitoring parameters to ensure safe and effective
drug treatment
Detect and prevent adverse drug
reactions and interactions

Interpretation of Test Result (1)

Reference

Range

Based on assumption that 95 % of the

population are normal

Vary from one laboratory to another
Single

vs Series of test results

Caution in interpreting single result

Series of results will identify significant

change or trends

Interpretation of Test Result (2)

Factor

influencing test results:

Drugs
Race
Exercise
Male / Female
Posture
Diet
Time of day
Laboratory/Ward Error
Age of patient
Inappropriate sample

Biochemistry Test

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 confusion, 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

Heparin

& other
Tricyclic antidepresant
Amphotericin
Captopril & other ACEI
Carbamazepine
Chlorpropamide
Cisplatine
Clofibrate
Cyclophosphamide

Lithium
Miconazole
NSAIDs
Opiates
Oxcarbazepine
Tolbutamide
Vasopresin
Vincristine

Drugs known to cause hypernatraemia

Adrenocorticotropic

Diazoxide

hormone
Anabolic steroids
Androgens
Carbenoxolone
Clonidine
Costicosteroids

Lactulose
Methyldopa
Oestrogens
Oral

contraseptives
Phenylbutazone
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
Aspirin
Corticosteroids
Diuretics
Gentamicin
Insulin
Laxatives
Terbutaline

Benzylpenicillin

(penicillin G) Na
Piperacillin+
tazobactam
Salicylates
Sod. bicarbonate
Sod. Chloride
Ticarcillin+
clavulanate

Drugs known to cause hyperkalaemia

ACE

Inhibitor
Antineoplastic agent
(cyclophosphamid,
vincristine
NSAIDs
-blocking agents
Ciclosporine
Potassium sparing
Diuretics

Heparin
Isoniazid
Lithium
Penicillins

(garam

kalium)
Potassium suppl.
Succynilcholin chlor
Tetracycline

Haematology Test

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

(thrombocytopenia)
Increased consumption in:

Platelets

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

Monocytes

Neutrophils

Only

Agranulocytes

Polymorphonuclear

Basophils

Lymphocytes

Eosinophils

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

Renal Function Test

Renal Function Test

Serum

Creatinine

Creatinine
Urea

Clearance

(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
Moderate
Severe

20 50 ml/min
10 20 ml/min
< 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
ml/min
CrCl =
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 reabsorbed 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

disease

adjusment in patient with renal

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

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

Drugs in Renal Disease:

Clinical Pharmacy Practice Point
Identification

of patient with renal

disease
Monitoring of renal function
Assessment of current and
proposed drug treatment

Liver Function Test

Liver Disease
Function

of The Liver

Assesment
Causes

of Liver Disease

of Liver Disease

Implication

for Clinical Pharmacy Practice

Functions of The Liver

Storage
Vitamin (Vit K)

Homeostasis
Glucose

Secretion
Bile salts

Excretion
Cholesterol

Synthesis
Albumin

Metabolism
Vitamin D

Filtration
Antigens

Clearance
Drugs

Cause of Liver Disease

Viral

infection*
Alcohol*
Immune disorders
Vascular
abnormalities
Inherited metabolic
disorder

Billiary

tract disease
Infectious disease
Drugs & toxin
Gilberts synrome

* 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
Weakness
Weight loss
Nausea
Abdominal
discomfort
Low grade fever
Confusion

Signs
Jaundice
Ascites
Pruritus
Oedema
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

Methyldopa

Rosiglitazone

Sulfasalazin

Sodium

Statin

Valproate

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
Monitoring

of liver function

Assessment

treatment

of patien with liver disease

of current & proposed drug