Laboratory Tests for Disease Diagnosis and Treatment

DRUG LAB INTERACTION Diploma (Clinical Chemistry) Dr. Basma Al- Sudani Lecture 1

Laboratory Tests involved in the diagnosis and treatment of disease Purposes: 1. reliable for proper decision making 2. measures chemical changes in the body 3. detection of any dysfunctions in the body 4. monitor drug therapy

Features that describe the following aspects of the Drug laboratory effects: o o o o o o o onset of effect after starting the medication o duration of effect after stopping the medication o clinical significance of effect nature of effect route of administration direction and strength of effect level of documentation sex of patient age of patient

o CLASSIFICATION Screening Test - Used in patient with no signs and symptoms of a disease eg. Serum cholesterol for assessing cardiovascular disease risk Diagnostic Test - Done in patient with signs and symptoms of disease or with an abnormal screening test

MONITORING DRUG THERAPY o Laboratory Test Results: Assess the therapeutic and adverse effects of a drug Determine the proper drug dose Assess the need for additional or alternate drug therapy Prevent test misinterpretation resulting from drug interference

Laboratory Test Results NORMAL VALUES Usually determined range by applying statistical methods to result from a representative sample of general population NORMAL LAB TEST RESULT Fall within a predetermined range of values ABNORMAL LAB TEST RESULT Fall outside a predetermined range of values

oFALSE POSITIVE -indicates a given condition is present when it is not oFALSE NEGATIVE -it appears negative when it should not

oQUANTIATIVE TEST Test with normal values reported in ranges oQUALITATIVE TEST Test with positive or negative outcomes oSEMIQUANTITATIVE TEST Those with varying degrees of positivity

The quality of Quantitative assay is measured in terms of accuracy. oACCURACY -Extent to which mean measurement is close to the true value oPRECISION -Refers to the reproducibility of the assay

DRUG LABORATORY TEST INTERACTION 1. SERUM BILIRUBIN

Bilirubin H N 21 H N 24 H N 23 H N 22 O CH CH2 CH O 18 17 13 12 8 3 2 7 H3C H3C CH3 CH CH2 CH2 CH2 CH2 CH3 H2C CH HOOC H2C COOH Is a bile pigment. Bilirubin Results from the degradation of heme, one of the breakdown products of red blood cells It is thought to be a toxin because it is associated with neonatal jaundice, possibly leading to irreversible brain damage due to neurotoxicity.

Bilirubin H N 21 H N 24 H N 23 H N 22 O CH CH2 CH O 18 17 13 12 8 3 2 7 H3C H3C CH3 CH CH2 CH2 CH2 CH2 CH3 H2C CH HOOC H2C COOH It is extracted and biotransformed Bilirubin mainly in the liver, and excreted in bile and urine.

Formation of Bilirubin 1. Hemoglobin from senescent or hemolyzed red cells is broken down, releasing heme. 2. Heme is then degraded in humans by the enzyme heme oxygenase (HO), which is the rate-limiting step in the formation of bilirubin. 3. HO converts heme to biliverdin IX.

Formation of Bilirubin 4.Biliverdin is a hydrophilic compound that is reduced by biliverdin reductase into the hydrophobic compound bilirubin

Formation of Bilirubin 5. HO catalyses an oxidase reaction opening the heme ring to convert one of the bridge carbons to carbon monoxide. This step releases iron from the now linear tetrapyrrole yielding biliverdin. 6. Biliverdin reductase reduces the double bond on nitrogen inside one of four of the pyrrole rings leading to the formation of bilirubin.

Formation of Bilirubin Primary site of synthesis: -SPLEEN Secondary site of synthesis: - LIVER & BONE MARROW

Two Types of Bilirubin o Prehepatic o Posthepatic

TYPES SYNONYMS CHARACTERISTICS Prehepatic Unconjuganted Does not cross glomerular filtrate Free Harmful to neonatal nervous system Indirect-reacting Formed in reticuloendothelial system (peripheral) requires organic solvent for diazo rx

TYPES SYNONYMS CHARACTERISTICS Posthepatic Conjuganted Freely crosses glomerular filtrate Glucoronide Formed by enzymatic activity, in liver Direct-reacting Gives diazo rx in aqueos medium

Unconjugated Conjugated In water In alcohol normal In bile In urine Absorption gut Diffusion into tissues Van den bergh insoluble soluble 0.2-0.9mg/dl Absent Always absent Absorbed Diffuses yellow colour Indirect + soluble soluble 0.1-0.4mg/dl Present Normally absent Not absorbed Doesn t diffuse Direct +

Serum Bilirubin o A break down product of porphyrin ring of heme containing proteins , found in blood in 2 fractions conjugated/unconjugated

Serum Bilirubin ( indirect ) Protein bound and is associated with the increased destruction of RBCs Indirect bilirubin= total- directbilirubin Reference Values Adult and Children: - 0.1-1.0 mg/dL, - 1.7-17.1 mol/L

Serum Bilirubin (direct and total ) oDirect or conjugated bilirubin is frequently the result of obstructive jaundice, either from extrahepatic or intrahepatic origin.

Serum Bilirubin (direct and total ) Reference Values: ADULT: Total: 0.1-1.2 mg/ Dl, 1.7-20.5 mol/L Direct: 0.1-0.3 mg/dl, 1.7-5.1 mol/L

Serum Bilirubin (direct and total ) Reference Values: CHILDREN: Newborn: Total: 1-12mg/dl, 17.1-20.5 mol/L (SI) Child: 0.2-0.8 mg/dl

How Do I Prepare for the Bilirubin Blood Test o you will need to fast (not eat or drink anything other than water) for four hours before you have the test performed. o Drink a normal amount of water before going to the laboratory or collection site. o You may have to stop taking certain medications before the test is performed, but only if your doctor tells you to do this

How the test is Performed A blood sample is needed. This may be taken from a vein. The test is called a venipuncture. And heelstick. Venipuncture heelstick

Procedure o Collect 5 to 10 ml of venous blood in a red-top tube o Hold the medication that would increase or decrease serum bilirubin for 24 hrs. o Do not eat or drink (NPO) except for water Take note: If a hematoma develops at the venipuncture or heelstick site, apply warm soaks. o

Caution Whenever blood is drawn for liver function tests, avoid self contamination to prevent possible infection Protect drug specimen from light Blood should be sent to the laboratory immediately

Clinical Implications DECREASED LEVEL: - Iron deficiency anemia Drug influence: aspirin, penicillin, prednisone,asthma medication(theophylline) INCREASED LEVEL: -Obstructive jaundice caused by stones or neoplasms -Hepatitis -Liver cirrhosis -Metistatic cancer -Wilson s disease

Clinical Implications Drug Influence: hydralazine, allopurinol, probenicid,diuretics(Furosemide),antibiotic(Penicillin G) Interfering Factors: High fat dinner Carrots and yam Hemolysisof blood specimen Blood specimen exposed to sunlight certain drugs

Aspirin Is a weak organic acid that is unique among the NSAIDs in that it irreversibly acetylates (and thus, inactivates) cyclogenase.

Aspirin o TYPE OF DRUG INTERACTION: - Drug- laboratory interaction o MECHANISM OF INTERACTION: -Decrease serum bilirubin level -Reduction of the level of platelet TXA2, resulting in the inhibition of platelet aggregation and prolonged bleeding.

Aspirin -inhibits thromboxane A2 synthesis from arachidonic acid in platelets by irreversible acetylataion of a serine, resulting in a blockade of arachidonate to the active site and thus, inhibition of COX1 o EFFECT: -Iron deficiency anemia (false negative value) o MANAGEMENT: -Avoid taking aspirin prior to laboratory test.

Hydralazine -this drug cause direct vasodilation, acting primarily on arteries and arterioles.

Hydralazine o TYPE OF DRUG INTERACTION: - Drug-laboratory interaction with serum bilirubin o MECHANISM OF INTERACTION: -increase the bilirubin serum level

Hydralazine o EFFECT: - Changes in the liver function test (false positive value) o MANAGEMENT: -Complete chemical and biochemical recovery occurs after discontinuation.

Allopurinol -purine analog. -the primary metabolite is alloxanthine, which is also xanthine oxidase inhibitor. -its active metabolite are excreted in the feces and urine.

Allopurinol o TYPE OF DRUG INTERACTION: - Drug-laboratory interaction with serum bilirubin. o MECHANISM OF INTERACTION: -increases the bilirubin serum level.

Allopurinol o EFFECT: - Obstructive jaundice caused by stones or neoplasms, hepatitis, cirrhosis of the liver, infectious mononucleosis. o MANAGEMENT: -close monitoring of serum bilirubin levels is important -avoid taking allupurinol prior to laboratory test

DRUG LABORATORY TEST INTERACTION 2. GLUCOSE LEVEL

What is Glucose? oTHE PRINCIPAL FUEL FOR ALL BODY ACTIVITIES. oPRINCIPAL AND ALMOST EXCLUSIVELYCARBOHYDRATE CIRCULATING IN BLOOD. oMost important simple sugar in human metabolism.

Formation of Glucose oGlycogenesis(glucose-glycogen) oGlycogenolysis(glycogen glucose) oGluconeogenesis(monocarbohydrate like glycerol-glucose) oGlycolysis(glucose lactate and pyruvate)

Definition of Terms oLiver THE CLEARING HOUSE FOR GLUCOSE METABOLISM; IT CONVERTS EXCESS GLUCOSE TO STORAGE FORMS FOR LATER USE oGlycogen primary storage form of glucose oElevated level- caused by the disorders of the pituitary gland and certain brain lesions. oHyperglycemia may cause shock and severe hemmorhaage

oDepressed level(hypoglycemia) is characterized of hyperinsulinism due either to endogenous pancreatic lesions or to exogenous over dosage. oDiabetes mellitus A disorder of carbohydrate metabolism characterized by state of hyperglycemia due to insulin deficiency.

o Glucose Tolerance Test(GTT) Analyzing blood glucose at timed intervals following ingestion of a standard glucose dose; oral glucose tolerance test(OGTT) o Hyperglycemia Blood glucose concentration above normal o Hypoglycemia Blood glucose concentration below normal

oGlycogenolysis Conversion of stored glycogen to glucose o Glycogen Storage form of glucose found in high concentration in the liver o Glycolysis Energy production as a result of metabolic breakdown of glucose oGlycosuria Glucose in the urine;glucosuria

o Glucagon Pancreatic hormone that increases blood glucose concentration by promoting the conversion of glycogen to glucose oFalse positive Result that indicates that a given condition is present when it is not. oFalse negative Result that appears negative when it should no oRenal threshold Blood concentration above which a substance not normally excreted by the kidneys appears in the urine. oGluconeogenesis Formation of glucose

2 Types of Disorders of Glucose Metabolism oHyperglycemia oHypoglycemia

Diseases or disorders associated hyperglycemia Harmful to the body when it is so high that the increased extracellular osmotic pressure causes cellular dehydration; coma can be produces by severe dehydration of brain cells. And also acidosis.(uncontrolled diabetes mellitus)