Ahmed Ibrahim Nouri

Introduction.. Pharmacists participate with the health care team and share responsibility for

ensuring safe and effective drug therapy.

Laboratory (lab) data is among the information that pharmacists may consider in

determining the safety and effectiveness of patients’ treatment regimens.

Statistical background ..

In a recent review article, Schiff et. al stated that:

In the U.S., 54% of ADE that caused hospitalizations was due to drugs that need

regular monitoring.

16% of ADEs resulted from ignoring clinical lab results.

Monitoring-related ADEs were almost 50% more frequent than ADEs from

inappropriate initial prescriptions.

(J Am Geriatr Soc 2011;59:1513–1520)

Introduction (cont.)

Lab results performed for multiple purposes, including:

- Discovering disease progression.

- Confirm or differentiate diagnosis.

- Monitor effectiveness of therapy. …etc

Pharmacists must use their professional judgment to review, interpret, and

consider lab data.

However, it may not be practical or necessary to review lab data every time

you monitor patients’ care, or before dispensing or prescribing medications.

So ..

Introduction (cont.)

Pharmacists usually monitor laboratory tests for several reasons:

1. Ensuring that the drug and the dose ordered is

appropriate for each patient.

E.g.

- Review of culture and sensitivity results to determine an appropriate

antibiotic for treatment

- Review of INR for patients taking warfarin

- Review of blood levels for drugs such as anticonvulsants, digoxin, lithium.

- Review of serum creatinine (and calculation of estimated creatinine

clearance) for drugs that are cleared renally (e.g., metformin)

2. Monitoring for adverse effects to ensure patient safety.

E.g.

- Review of liver function for patients with HMG-CoA reductase inhibitors.

- Review of INR for warfarin patients started on medications that are likely to

effect INR results (i.e. amiodarone, metronidazole).

- Review of electrolytes for patients taking diuretics

(cont.)

3. Assess the need for additional or alternative drug therapy.

4. Monitoring patients’ response to therapy.

5. Prevent mis-interpretation resulted from drug interference

(false-positive results)

(cont.)

Definition of Normal Values Normal laboratory test results fall inside a predetermined range of values, and

abnormal values fall outside that range.

BUT.. When the “abnormal” is abnormal?!

1. Values outside normal range not always indicates disease or need for treatment.

(e.g., asymptomatic hyperuricemia, ALT).

2. Patient specific factors (e.g., age, sex)

3. Values vary from lab to lab and may depend on the method used to perform the test.

4. The goal is NOT to make all laboratory values normal;

“TREAT THE PATIENT NOT THE LAB VALUE”

SI Units .. In 1970, the world tried to standardize the presentation of lab data by using the

International System of Units (SI units).

But the United States resisted to use this system and uses their American system.

The difference between both is in measurement of chemical concentration.

the basic unit of the SI is the mole.

Technically and pharmacologically, the mole is more meaningful than the gram

because each physiological reaction occurs on a molecular level.

so we need to pay attention for the units provided

with lab values.

Medications Effect on Lab Results Interpretation

Clinician usually aware of the main therapeutic effects of drugs, but other changes in

biochemical parameters often neglected and unexpected.

Because they may be unrelated to the main action of a drug.

This may lead to incorrectly manage the patient, by wrong diagnosis, inadequate

treatment, additional lab data, or extended hospitalization and hence increase cost.

Mechanisms for drug interference in laboratory data can be classified as

in-vivo and in-vitro.

1. In-vitro drug effect:

- analytical or methodological that occur in the lab.

- Ascorbic acid is a common source of interactions in the estimation of glucose,

hemoglobin and nitrite in urine. Ascorbic acid supplement can interfere with the

reagent used. Therefore, patients should avoid consumption of high doses of

ascorbic acid 24 hours before urine collection for routine examinations.

2. in-vivo interference

It is biological interference and can be classified as

pharmacological or toxicological.

It is an actual change in the substance concentration occurred inside the patient.

prior to sample collection and analysis,

in-vivo interference will always change the lab result, regardless of the assay

method used, even if repeated.

1. Pharmacological effects interference.

-Thiazide and loop diuretics cause increased renal excretion of potassium.

So we will have decreased serum potassium levels in the patients.

- Increased blood urea nitrogen (BUN) can occur as a result of excessive fluid loss

during treatment with thiazide and loop diuretics.

2.Toxicological effects interference.

When drug damages certain organ system, abnormal lab tests will be one of the first

sign of the problem. E.g.:

- Isoniazid and Rifampin produce hepatotoxicity.

elevated hepatic transaminases will be sign of liver inflammation.

- Prolonged course of high dose aminoglycoside antibiotic causes acute renal failure,

serum creatinine and serum trough AG levels will increase steadily.

- Cyclophosphamide induced bone marrow suppression, neutropenia will appear 10 to

14 days after the dose administration.

Lab-Pharmacy Partnership The Canadian Pharmacists Association (CPhA) introduced a new continuing

professional development program in March/2014 to train pharmacists in ordering,

monitoring and interpreting lab tests. In a response to some provinces increasing

pharmacist authority to order lab tests or access lab results.

Pharmacists having access to lab values and the skills to interpret them will benefit

their patients and other health care system.

C P J / R P C • MAY /JUNE 2 0 1 4 • V O L 1 4 7 , N O 3

You can’t fix what you don’t know about!

Almost every condition and most medications has lab value that will tell about the

status of the condition and the effects or side effects of the drug.

TDM LFT CBC LDH

BMP

HbA1c

TFT

Complete Blood Count (CBC) RBC count

Total WBC count

Hemoglobin (Hb)

Hematocrit (Hct)

Mean cell volume (MCV)

Mean cell Hb (MCH)

Mean cell Hb concentration (MCHC)

Reticulocyte count.

Platelet count.

Basal Metabolic Panel (BMP) Liver Function Test

o Albumin

o Bilirubin

o Alanine Aminotrasferase (ALT)

o Aspartate Aminotransferase (AST)

o Alkaline Phosphatase (ALP)

o ɣ-Glutamyl-transferase (GGT)

o PT, INR

Electrolytes and minerals

o Sodium (Na+)

o Potassium (K+)

o Chloride (Cl-)

o Magnesium (Mg)

o Calcium (Ca)

Kidney Function Test

o Blood Urea Nitrogen (BUN)

o Creatinine

o BUN/Cr ratio

Other Lab test

Immune/inflammatory marker

o C-reactive protein

o Erythrocyte sedimentation rate (ESR)

o Anti-nuclear anti-body (ANA)

Cardiac markers

o Troponin (T,I,c)

o Creatine kinase (CK)

o Beta-natruretic peptide (BNP)

Glucose

o Fasting blood glucose

o HbA1c

Creatinine clearance Impairment of kidney function will have a significant impact on the

pharmacokinetic properties of renally excreted drugs.

The relationship between creatinine clearance and drug elimination can be

used to predict an optimum dose for a patients.

There is controversy to which equation is better for estimating CLcr, and what

weight to use, and whether to round up the serum creatinine in the geriatrics.

Cockroft-Gault equation Jelliffe equation

Therapeutic Drug Monitoring (TDM)

The measurement of drug plasma concentration level and relate this level

with therapeutic range to optimize dosing for individual patients.

It is a tool that guides clinicians

to provide effective and safe drug

therapy in patients.

TDM History The science of TDM came from the recognition that:

– Certain drugs have a narrow therapeutic range.

– In conc. above the upper limit of the range, the drug can be toxic.

– In conc. below the lower limit of the range, the drug can be ineffective.

- Therapeutic effect cannot always be assessed by the clinical observation.

– Not all patients have the same response at similar doses

Some believed that TDM testing provided little or no value.

But .. studies were initiated to determine the clinical value of TDM testing, and in certain cases clear clinical value was obvious.

Today there are over 20 therapeutic drugs which are routinely monitored.

Indications for TDM 1. Low therapeutic index.

2. Poorly defined clinical end point.

3. Non compliance.

4. Therapeutic failure.

5. Drugs with saturable metabolism.

6. Individual variation drug metabolism.

Indications cont. 7. Suspected toxicity or drug abuse.

8. Drugs with sharp dose response curve (small increase in dose can result in a marked increase in desired/undesired response e.g. theophylline)

9. When another drug alter the relationship between dose & plasma concentration e.g. plasma concentration of lithium is increased by thiazide.

10. Renal disease (alters the relationship between dose & the plasma concentration. Important in case of digoxin, lithium & aminoglycoside antibiotics.)

There are several classes of drugs commonly

monitored to ensure correct blood concentration:

Antiepileptics (Phenytoin, Valproic acid etc.)

Antiarrythmics (Digitalis, lignocaine etc.)

Antibiotics (Gentamycin, amikacin, vancomycin)

Antineoplastics (Methotrexate)

Antimanics (Lithium)

Bronchodilators (Theophylline)

Immunosuppressives (Cyclosporine)

TDM: Pharmacoeconomics The measurement of drug levels in body fluids must be cost

effective.

Studies showed that TDM service offered benefits like fewer

adverse reactions, shorter intensive care unit stay and shorter

overall hospital stay.

Finally .. Many ADE can be prevented by checking lab results.

You don’t have to memorize the normal level,

but you need to know how to use them properly.

We treat the individual patient not the lab value.

References New program helps pharmacists give better patient care with lab tests, Canadian Pharmacy Journal/RPC

MAY/JUNE2014 VOL147,NO3.

Guidelines for Pharmacists Ordering Lab Test & Using Lab Data, July 1 2011, Alberta College of Pharmacists.

THERAPEUTIC DRUG MONITORING – CONCEPTS, METHODOLOGY, CLINICAL APPLICATIONS AND

LIMITATIONS, Health Administrator Vol : XIX Number 1: 22-26.

Overview of Therapeutic Drug Monitoring Ju-Seop Kang1 and Min-Ho Lee, Departments of Pharmacology

and Clinical Pharmacology Laboratory and Internal Medicine, Hanyang University, College of Medicine,Seoul,

Korea.

Therapeutic drug monitoring: which drugs, why, when and how to do it, RA Ghiculescu, Senior Clinical

Pharmacology Registrar, Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane,

Australian prescriber, Volume 31,NUMBER 2,APRIL 2008

Comprehensive pharmacy review: Leon Shargel ,Alan H. Mutnick, FASHP, Paul F. Souney, Larry N. Swanson, seventh edition,