Mary Anne Sarmiento

Marjorie Sendin
Ralph Justin Sicat
Maricar Soliman
Ilishah Zuniega
THERAPEUTIC DRUG MONITORING (TDM)
• It involves the analysis, assessment and evaluation of circulating
concentrations of drugs in serum, plasma or whole blood. It allows
for the safe use of drugs that would otherwise be potentially toxic.

DEFINITION OF TERMS:
• PHARMACOLOGY is the study of drugs including their origins,
history, uses, and properties. It mainly focuses on the actions of
drugs on the body.
• DRUG is a substance that is used to treat, cure, or prevent a
disease or otherwise enhance physical or mental health.
• Bioavailability is the rate and relative amount at which the intact
form of a drug appears in the systemic circulation following
administration.
• When prescribing for older patients, it is important to
consider pharmacokinetic and pharmacodynamic changes
observed in normal aging, the likely effects of the
individual's genetics and intercurrent disease, as well as
evidence for therapeutic efficacy, and safety and the
patient's total exposure to medications.

2 Branches of Pharmacology
• PHARMACODYNAMICS is how the drugs does to the body
• PHARMACOKINETICS is how the body does to the drugs
• SYMPTOMATIC: Used to relieve disease symptoms
• PREVENTIVE: Used to avoid getting disease
• DIAGNOSTIC: Used to determine the presence or
absence of disease
• CURATIVE: Used to eliminate disease
• HEALTH MAINTENANCE: Used to keep body
functioning normally
• (or Absorption) The entry of drug into the systemic circulation from the
site of administration.

1. Surface area of the GIT

• Stomach (not an organ for absorption)
• Weak acids are absorbed in the stomach
• Small Intestine (Most important site for drug absorption)
• Large Intestine (Site of absorption for slowly absorbed drugs)

2. Gastric Emptying Rate

• Rate at which the drug solution leaves the stomach and enters the
duodenum (small intestine).
• Decrease GER = Decrease Absorption = Decrease onset of action
• The drug leaves the bloodstream and distribute into
the interstitial and intracellular fluids.
• Drugs from the systemic circulation to organs and
tissues.
• Distribution Space- the relationship between tissue and
blood levels.
• A large distribution space indicates that much of the
drug moves into the tissues that stays in
• Metabolism is an essential pharmacokinetic process
which converts lipid soluble and non-polar compounds
to water soluble and polar compounds so that they are
excreted.
• * Liver - is the main site of metabolism
• *also includes: Kidney, Liver, Lung, Skin, Brain
• It is the process whereby drugs are transferred from
the internal to external environment
• Principal organs involve: KIDNEY(main), LUNG, BILIARY
SYSTEM, INTESTINE, SALIVA, MILK
CARDIOACTIVE DRUGS
• ANTIBIOTICS
• ANTIEPILEPTIC DRUGS
• PSYCHOACTIVE DRUGS
• BRONCHODILATOR
• IMMUNOSUPRESSIVE DRUGS
• ANTINEOPLASTIC DRUGS
• ANTI-INFLAMMATORY/ ANALGESICS
• NEUROLEPTICS
• TDM is based on the principle that for some drugs
there is a close relationship between the plasma level
of the drug and its clinical effect.
• If such a relationship does not exit TDM is of little
value.
• The clinical value of plasma level monitoring depends
on how precisely the treatment outcome can be
defined.
• When a precise therapeutic end point is difficult to
define, monitoring of drug levels may be of
considerable therapeutic assistance.
Toxicity
• Diagnosing toxicity when the clinical syndrome is undifferentiated (unexplained nausea in a
patient taking digoxin)
• Avoiding toxicity (aminoglycosides, cyclosporin)

Dosing
• After dose adjustment (usually after reaching a steady state)
• Assessment of adequate loading dose (after starting phenytoin treatment)
• Dose forecasting to help predict a patient's dose requirements1 (aminoglycosides)

Monitoring
• Assessing compliance (anticonvulsant concentrations in patients having frequent seizures)
• Diagnosing under treatment (particularly important for prophylactic drugs such as
anticonvulsants, immunosuppressants)
• Diagnosing failed therapy (therapeutic drug monitoring can help distinguish between
ineffective drug treatment, non-compliance and adverse effects that mimic the underlying
disease).
• The following are important considerations to ensure an
optimum TDM service in any setting:
• Measurement of patient’s serum or plasma drug concentration
taken at appropriate time after drug administration
• Knowledge of pharmacological and pharmacokinetic profiles
of the administered drugs
• Knowledge of relevant patient’s profile like demographic
data, clinical status, laboratory and other clinical
investigations, and
• Interpretation of SDC after taking into consideration all of the
information and individualizing drug regimen according to the
clinical needs of the patient.
• The circulatory system is convenient route that
can effectively deliver most drugs to its site of
action.
• IV – 100% bioavailability
• Orally Administered drug should achieved 0.7
bioavailability fraction.
• When drugs are IV administered, the
distribution and elimination rates are constant.
• Specimen of choice: Serum or Plasma
• Whole blood EDTA sample is required for cyclosporine and
tacrolimus tests.
• Timing of specimen collection is the single most important factor
in TDM.
• TDM samples should not be collected in tubes with gel
separators or SSR – some gels absorb certain drugs causing a
falsely low result.
• No changes occurred in Theophylline and salicylates levels when
blood is collected in serum separator tube (SST).
• Measurement of serum concentrations should be done only after
steady state has been achieved.
• ASSAY
An investigative procedure for qualitatively
assessing or quantitatively measuring the
amount or functional activity of the target
entity.
• COLORIMETRIC ASSAY
This uses the quantitative estimation of colors. The
substance binds woth color forming chromogens. The
difference in color results in difference in absorption
of light.
• FLUOROMETRIC ASSAY
An analytical technique for characterizing minute
amount of substance by excitation of the substance
with a beam of light and detection and
measurement of the characteristic wavelength of the
fluorescent light emitted.
• Chromatographic immunoassay
Is a technique in which an antibody or antibody-related
agent is used as part of a chromatographic system for the
isolation or measurement of a specific target.
Are based on the indirect detection of an analyte by
observing how it reacts with labeled binding agent or
prevents a labeled analog of the analyte from interacting
with an antibody.
Various binding agents, detection methods, supports and
assay formats have been developed for this group of
methods, and applications have been reported that range
from drugs, hormones and herbicides to peptides, proteins
and bacteria.
Two types of chromatographic immunoassays:
• Competitive binding Immunoassay
Can be used for either large or small analytes

• Homogenous Immunoassay
Involves a size separation that restricts their use to
low-mass analytes
• Contains Amino sugars
• Linked by Glycosidic bond
• Protein synthesis inhibitors
• Bactericidal
• Used to treat infectious caused by Gram
Negative Bacteria
• Derived from the soil Actinomycetes
• Suffix: Mycin and Micin
Pharmacokinetics
• Highly polar
• No absorption from GIT
• Not used orally, but only used orally in surgical
prophylaxis
• For Meningitis, used parentally I/V, I/M, and I/T
• It may cause damage to the 8th cranial nerve at toxic
levels
• Given combination with other drugs for synergistic effect
• Toxic Level:
• >30 µg/ml (Amikacin and Kanamycin)
• 12-15 µg/ml (Gentamicin and Tobramycin)
• Genus: Streptomyces
Streptomycin
• First drug (Waksman=1944)
• To treat a number of bacterial infections such as tuberculosis,
mycobacterium avium complex, rat bit fever and others
Kanamycin
• To treat severe infections and tuberculosis orally or injection
Tobramycin
• To treat various types of infections especially Gram- negative
infections
Neomycin
• Has been used as preventive measure for hepatic
encephalopathy and hypercholesterolemia
•Genus: Micro-Monospora
Gentamicin
• To treat bone infections, pelvic
inflammatory
• Genus: Semisyn
Amikacin
• To treat bacterial infections such as
joint infections, intra-abdominal
infections, sepsis and urinary tract
infections
• Adverse Effect
> 5 days
High doses
Pre- existing renal insufficiency
Elderly

• Common Toxic Effects

Nephrotoxicity
Ototoxicity
• Nephrotoxicity
Kidney damage
• Neomycin
• Gentamicin
• Tobramycin

• Ototoxicity
Disruption of inner ear
• Cochlea (Amikacin and Kanamycin)
• Vestibule (Gentamicin and Streptomycin)
• Mechanism Of Action
• The overall process consists of two main steps:
• Transport of aminoglycosides into the cell
wall and cytoplasmic membrane
• Irreversibly binding of ribosomes
• Uses
Aerobic Gram Negative Bacteria
Infections
Complicated Urinary Tract
Infections
Complicated Skin And Soft
Tissue Infections
Infective Endocarditis
Intra-abdominal Infections
Severe Pelvic Inflammatory
Tuberculosis (Streptomycin)
Sepsis
• CHROMATOGRAPHY IMMUNOASSAY
The primary methods used for
aminoglycoside determinations
• CARDIOACTIVE DRUGS
• used for treatment of arrhythmias and congestive heart failure

• CLASSIFICATION OF CARDIO DRUGS

• Class I - rapidly sodium channel blockers
• Example: Quinidine, Procainamide, Lidocaine
• Class II - beta receptor blockers
• Example: Propanolol
• Class III - Potassium Channel blockers
• Example: Amiodarone
• Class IV - Calcium channel blockers
• Example: Verampil
• Cardiac glycoside for treatment of Atrial
arrhythmia and CHF
• Elimination: Renal filtration of plasma free
form
• Peak serum level: 8 hrs after an oral dose
• Half-life: 38 hours (average adult)
• Therapeutic level: 0.5-2ng/mL
• Toxic level: >2ng/mL
• Used to correct ventricular arrhythmia for
treatment of AMC
• Administered by continuous IV infusion
after a loading dose
• Can be used as Local anaesthetic
• Elimination: By hepatic metabolism, changes in
renal function have little effect
• Primary product of hepatic metabolism:
Monoethylglycinexylidide (MEGX)
• Therapeutic level: 1.5-4.0 ug/mL
• Toxicity level: >4.0 ug/mL
• CNS depression: >4-8 ug/mL
• Seizure and ↓bp and cardiac output: >8ug/mL
• Toxic effect: CHF and Heart block
• Naturally occurring drug for the treatment of
arrythmias
• 85% protein bound; GIT absorption is complete
and rapid for the sulfate

• Elimination: Hepatic metabolism

• Route of delivery: Oral administration
• Common formulations: Quinidine sulfate and
quinidine gluconate
• Peak serum level: 2 hours after an oral
dose (sulfate); 4-5 hours (gluconate)
• Therapeutic level: 2.3-5 ug/mL
• Toxic level: >5 ug/mL
• Toxic effects: Cinchonism, blood dyscrasia
and hepatitis
• Used to treat ventricular arrythmia
• GIT absorption is rapid and complete
• 20% protein bound; eliminated by renal
filtration and hepatic metabolism

• Common route: Oral

• Hepatic metabolite: N-acetyl procainamide
(NAPA)
• Peak serum level: One hour after the
dose
• Therapeutic level: 4-10 ug/mL
• Toxic level: >12 ug/mL
• Toxic effects: Reversible upus-like
syndrome (ANA), nephrotic syndrome,
urticaria
• Used to treat cardiac arrythmias
• Used as substitute for Quinidine
• Has anticholinergic effects – dry mouth and
constipation (>4.5 ug/mL)
• Elimination: Renal filtration
• Therapeutic level: 3-5 ug/mL
• Toxic level: 10ug/mL
• Toxic effects: Bradycardia and atrioventricular
node blockage
• A beta-receptor blocking drug
• Used in the treatment of angina pectoris,
hypertension, coronary artery disease
• Suppresses the conversion of T4 to T3 – Used in
the treatment of thyrotoxicosis
• Therapeutic range: 50-100 ng/mL
• Toxic effects: Bradycardia, arterial insuffiency
(Raynauds type), platelet disorder and
pharyngitis