THERAPEUTIC DRUG

MONITORING and
TOXICOLOGY
JANNICA DOMINIQUE C. CLAROS, RMT ※ CLINICAL CHEMISTRY 3 ※ LPU-ST. CABRINI SCHOOL
OF HEALTH SCIENCES
 TOPIC
OUTLINE
ROUTES OF ADMINISTRATION
DISTRIBUTION AND ELIMINATION
SAMPLE COLLECTION
TOXICOLOGY
 The essence of therapeutic drug
monitoring with drug
concentration

 relationship between the pharmacological activity

and drug concentration in blood or in other available
biological material
 Therapeutic Drug Monitoring – TDM

 action leading to achieve such a dosage of

the drug in a patient that the obtained

levels of concentration remain within the

therapeutic range
Factors conditioning Criteria for the
the efficacy of selection of drugs
therapeutic drug for monitoring
monitoring  low therapeutic index
 the use of  dangerous toxic effects
pharmacokinetic rules of the drug and
 combined analysis of unnoticeable clinical
obtained results and effect
clinical status of the  close interrelationship
patient between the drug
 verification of concentration and its
pharmacological activity activity
of  administration in a
administered drugs by long-term therapy
means of other
methods
 Therapeutic index
 concentration range
Criteria for the selection of characterized by a
drugs high efficacy of action and
for monitoring – continuation low risk of
 the use in life-threatening upper toxic symptoms
diseases
 significant individual
differences in the
range of pharmacokinetics
 non – linear
pharmacokinetics
 high distribution coefficient
ROUTES OF DRUG
ADMINISTRATION
Oral refers to two methods of administration:
 applying topically to the mouth
 swallowing for absorption along the gastrointestinal
(GI) tract into systemic circulation
 po (from the Latin per os) is the abbreviation used
to indicate oral route of medication administration

Advantages
 Convenient - can be self- administered, pain free,
easy to take
 Absorption - takes place along the whole length of
the GI tract
 Cheap - compared to most other parenteral routes
Disadvantages Disadvantages cont.
 Sometimes inefficient -  destruction of drugs by
only part of the drug may gastric acid and
be absorbed digestive juices
 effect too slow for
 First-pass effect - drugs emergencies
absorbed orally are  unpleasant taste of some
initially transported to the drugs
liver via the portal  unable to use in
vein unconscious patient
 irritation to gastric mucosa
- nausea and vomiting
Sublingual administration is where the
dosage form is
placed under the tongue
rapidly absorbed by sublingual
mucosa
SUBLINGUAL ROUTE
ADVANTAGES
 ECONOMICAL
 QUICK TERMINATION
 FIRST-PASS AVOIDED
 DRUG ABSORPTION IS QUICK
DISADVANTAGES
 UNPALATABLE & BITTER DRUGS
 IRRITATION OF ORAL MUCOSA
 LARGE QUANTITIES NOT GIVEN
 FEW DRUGS ARE ABSORBED
Buccal administration is where the dosage form is placed
between gums and inner lining of the cheek (buccalpouch)
absorbed by buccal mucosa
BUCCAL ROUTE
ADVANTAGES DISADVANTAGES
– Avoid first pass effect – Inconvenience
– Rapid absorption – lost if swallowed
– Drug stability – Small dose limit
RECTAL ROUTE

ADVANTAGES
 USED IN CHILDREN
 LITTLE OR NO FIRST PASS EFFECT
 USED IN
VOMITING/UNCONSCIOUS
 HIGHER CONCENTRATIONS RAPIDLY ACHIEVED
DISADVANTAGES
 INCONVENIENT
 ABSORPTION IS SLOW AND ERRATIC
 IRRITATION OR INFLAMMATION OF RECTAL
MUCOSA CAN OCCUR
SYSTEMIC-PARENTERAL
 Parenteral administration is TYPES:
injection or infusion by means of  INJECTABLES
a needle or catheter inserted into I. INTRAVENOUS
the body II.INTRAMUSCULARIII.SU
 The term parenteral comes from BCUTANEOUS
Greek words IV. INTRAARTERIAL
 para, meaning outside V.INTRAARTICULAR
 enteron, meaning the intestine VI. INTRATHECAL
 This route of administration VII. INTRADERMAL
bypasses the alimentary canal
I
ADVANTAGES DISADVANTAGES
 BIOAVAILABILITY 100%  IRRITATION &
 DESIRED BLOOD CELLULITIS
CONCENTRATIONS  THROMBOPHELEBITIS
ACHIEVED  REPEATED INJECTIONS
 LARGE QUANTITIES NOT
 VOMITING & DIARRHEA ALWAYS FEASIBLE
 EMERGENCY  LESS SAFE
SITUATIONS  TECHNICAL ASSISTANCE
 FIRST PASS AVOIDED REQUIRED
 GASTRIC  DANGER OF INFECTION
MANUPALATION  EXPENSIVE
AVOIDED  LESS CONVENIENT AND
PAINFUL
 Topical Routes of Dose forms for topical
Administration administration include:
 Skin:
 Topical administration is  creams
the application of a drug  ointments
directly to the surface of the  lotions
skin  gels
 Includes administration of  transdermal patches
 disks
drugs to any mucous • Eye or ear:
membrane – solutions
 eye , vagina, nose, – suspensions
urethra – ointments
ears, colon, lungs • Nose and lungs:
– sprays and powders
Advantages and Disadvantages of the
Topical Route
 Local therapeutic effects
 Not well absorbed into the deeper layers of
the
skin or mucous membrane
lower risk of side effects
 Transdermal route offers steady level of drug
in
the system
sprays for inhalation through the nose
may be for local or systemic effects
TIME OF EFFECT OF DRUGS
• intravenous 30-60 seconds
• intraosseous 30-60 seconds
• endotracheal 2-3 minutes
• inhalation 2-3 minutes
• sublingual 3-5 minutes
• intramuscular 10-20 minutes
• subcutaneous 15-30 minutes
• rectal 5-30 minutes
• ingestion 30-90 minutes
• transdermal (topical) variable (minutes to
hours)
Pharmacokinetics
“What the body does to the drug?”
“How the body handles the drug?”

Pharmacokinetic Processes
♦ Absorption
♦ Distribution
♦ Metabolism / Biotransformation
♦ Excretion
Factors that Affect the ABSORPTION
Drug Passage ♦ is the movement of a drug
Across Membranes
from its site of administration to
1. molecular size and
shape
the systemic circulation and the
2. degree of ionization extent to which this occurs
3. relative lipid solubility of
its ionized
and nonionized forms
4. binding to serum
Routes of Administration, Bioavailability, and General Characteristics
Route Bioavailability (%) Characteristics

Intravenous (IV) 100 (by definition) most rapid onset

Intramuscular (IM) 75 to ≤ 100 large volumes ; may be painful
Subcutaneous (SC) 75 to ≤ 100 smaller volumes than IM; may be painful
Oral (PO) 5 to <100 most convenient; first-pass effect significant
Rectal (PR) 30 to < 100 less first-pass effect than oral
Transdermal 80 to ≤ 100 usually very slow absorption
Excretion Half- life (T½)
♦ process by which a drug ♦ time required to decrease the
or its concentration
metabolites is eliminated of the drug in the plasma by 50%
from the body ♦ often used to determine
♦ main organ of elimination frequency of
is the administration
kidneys ♦ determines the time to attain
♦ other organ of excretion steady-state
include the concentration
biliary system, GIT, skin and
lungs
SAMPLE COLLECTION
• Timing of specimen collection is the single most important
factor
• peak concentrations are drawn 1 hour after an orally
administered dose
• determination of serum concentrations should bedone only
after steady state has been achieved
• Serum or plasma is the specimen of choice
• Care must be taken that the appropriate container is used when
collecting specimens. DO NOT USE GEL SEPARATOR
TUBES
• Heparinized plasma is suitable for most drug analysis
• The calcium-binding anticoagulants add a variety of anions and
cations may interfere with analysis or cause a drug to distribute
differently between cells and plasma.
• EDTA and citrated and oxalated plasma are usually
UNACCEPTABLE specimens.
TOXICOLOGY
BASIC DEFINITIONS
• Toxin
• Toxic substances that are produced naturally (nature
origin)
• Toxicants
• Any chemical that can injure or kill humans, animals,
or plants; (poison)
• Toxicity
• Describes the degree to which a substance is
poisonous or can cause injury.
• Factors: dose, duration and route of exposure, shape
and structure of the chemical itself, and individual
human factors
Toxicology
• The study of how natural or man-made poisons cause
adverse effects in living organisms.
• It involves observing and reporting symptoms,
mechanisms,
detection and treatments of toxic substances.
• It includes environmental agents and chemical
compounds,as
well as pharmaceutical compounds that are synthesized for
medical use. These substances may produce toxic effects
leading to , discomfort, disease and even death in living
organisms
IMPORTANCE OF DOSE
• The dose is an important factor in toxicology
• All substances have the potential to be toxic if given to
living organisms in the right conditions and dose

PURPOSE OF TOXICOLOGY:
• It provides protection to humans and environment from
toxic effects of toxicants.
• This study will ultimately lead toward the development
of newer, innovative and more selective drug therapies to
treat different diseases such as cancer having reduced
toxic potential to human body
ROUTES OF EXPOSURE
• Skin & mucous membrane
• Lung (Inhalation)
• Ingestion
• Eye (Occular)

SKIN• Chemicals that can penetrate healthy intact skin –

aniline• hydrogen cyanide,• organophosphate, etc.
INGESTION
• Mostly we can control
(unlike airborne)
• Depends on :
• • Concentration
• • Time
a) • Continuous
b) • Intermittent
• • Sometimes can
accumulate and cause harm
in later life e.g. Lead
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