1. health and fitness
2. drugs

What is Pharmacology?
• derived from the Greek word for drug
• A science that studies drug effects within
a living system, biochemical and
physiological aspects
• Deals with all drugs used in society
today, legal or illegal, including street,
prescription, and non-prescription or
over –the-counter medications
Drug
• A drug is defined as any substance;
chemical agent; used in the
• Diagnosis
• Cure
• Treatment
• prevention of a disease or condition
Drug Names
• Chemical Name
• Generic Name
• Trade Name
Chemical Name
• Describes its molecular structure
and distinguishes it from other
drugs
Generic name
• Determined by the pharmaceutical
company along with
a special
organization known as the U.S. Adopted
Names Council (USAN)
Trade Name
• Or brand name- the manufacturer
selects alone…can become a registered
trademark.
• They are the only one who can advertise
and market the drug under that name.
How is the Trade Name Chosen?
• The particular spelling of a brand name
drug is proposed by a manufacturer for
one of several reasons.
1. To indicate the disease process
being treated
• Azmacort- treats asthma
• Rythmol- treats cardiac arrhythmias
2. To simplify the generic name
• Pseudoephedrine to Sudefed
• Haloperidol to Haldol
• Ciprofloxacin to Cipro
3. To indicate the duration
• Slow-K slow release potassium
supplement
Prescription Drugs
• Or legend drugs
• Means in order to obtain drug, you must
have a legal prescription
Non-Prescription Drugs
• Or Over-the-Counter (OTC) drugs
• Drug that may be purchased without a
prescription
Sources of Drugs
Drugs have been identified or derived from
four main sources:
• Plants
• Animals
• Minerals and Mineral Products
• Synthetic or Chemical Substances Made in
the Laboratory
Routes of drug administration
Routes of Drug Administration
Important
Info
The route of administration (ROA) that
is chosen may have a profound effect
upon the speed and efficiency with
which the drug acts
• The main routes of drug entry into the
body may be divided into two classes:
–Enteral
–Parenteral
Enteral Routes
• Enteral - drug placed directly in the GI tract:
– sublingual - placed under the tongue
– oral - swallowing (p.o., per os)
– rectum - Absorption through the rectum
Sublingual/Buccal
Some drugs are taken as smaller tablets which
are held in the mouth or under the tongue.
• Advantages
– rapid absorption
– drug stability
– avoid first-pass effect
Sublingual/Buccal
• Disadvantages
– inconvenient
– small doses
– unpleasant taste of some drugs
Oral
• Disadvantages
– Sometimes inefficient - only part of the drug may
be absorbed
– First-pass effect - drugs absorbed orally are initially
transported to the liver via the portal vein
– irritation to gastric mucosa - nausea and vomiting
Oral
• Disadvantages
– destruction of drugs by gastric acid and digestive juices
– effect too slow for emergencies
– unpleasant taste of some drugs
– unable to use in unconscious patient
First-pass Effect
• The first-pass effect is the term used for the
hepatic metabolism of a pharmacological agent
when it is absorbed from the gut and delivered to
the liver via the portal circulation.
• The greater the first-pass effect, the less the agent
will reach the systemic circulation when the agent
is administered orally
First-pass Effect
Magnitude of first pass hepatic effect:
Extraction ratio (ER)
ER = CL liver / Q ;
where Q is hepatic blood flow (usually about
90 L per hour.
Systemic drug bioavailability (F) may be
determined from the extent of absorption (f)
and the extraction ratio (ER):
F = f x (1 -ER)
First-pass Effect
RECTAL ADMINISTRATION:
• Absorption across the rectal mucosa occurs by passive
diffusion.
• This route of administration is useful in children, old
people and unconscious patients.
• Eg., drugs that administered
acetaminophen,
theophylline,
promethazine & certain barbiturates.
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are: aspirin,
indomethacin,
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Rectal
Advantages:
1. Suitable for unconscious patients and
children
2. suitable if patient is nauseous or vomiting
3. easy to terminate exposure
4. good for drugs affecting the bowel such
as laxatives
Disadvantages:
1. absorption may be variable
2. irritating drugs contraindicated
Parenteral Routes
– Intravascular (IV, IA)- placing a drug directly into the
blood stream
– Intramuscular (IM) - drug injected into skeletal muscle
–
– Subcutaneous - Absorption of drugs from the
subcutaneous tissues
– Intrathecal : into CSF
Intravascular
Absorption phase is bypassed
(100% bioavailability)
1.precise, accurate and almost immediate onset of
action,
2. large quantities can be given, fairly pain free
Disadvantages
a-. greater risk of adverse effects
b- high concentration attained rapidly
C- risk of embolism
Intramuscular
1. very rapid absorption of drugs in aqueous
solution
2. Slow release preparations
Disadvantages
pain at injection sites for certain drugs
Subcutaneous
1. slow and constant absorption
2. absorption is limited by blood flow,
affected if circulatory problems exist
3.
concurrent
administration
vasoconstrictor will slow absorption
of
Inhalation
1. gaseous and volatile agents and aerosols
2. rapid onset of action due to rapid access to
circulation
a. large surface area
b. thin membranes separates alveoli from
circulation
c. high blood flow
Topical
•Mucosal membranes (eye drops, antiseptic)
•Skin
a. Dermal - rubbing in of oil or ointment
(local action, sun screen, an callus removal)
b. Transdermal - absorption of drug through
skin (systemic action)
i. stable blood levels
ii. no first pass metabolism
iii. drug must be potent or patch becomes too large
o Intra nasal administration
• Drugs generally administered by intra nasal route for
treatment of local condition such as perennial
rhinitis, allergic rhinitis and nasal decongestion etc.
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Route for administration
-Time until effect•
•
•
•
•
•
•
•
•
•
intravenous 30-60 seconds
intraosseous 30-60 seconds
endotracheal 2-3 minutes
inhalation 2-3 minutes
sublingual 3-5 minutes
intramuscular 11-30 minutes
subcutaneous 14-30 minutes
rectal 5-30 minutes
ingestion 30-90 minutes
transdermal (topical) variable (minutes to hours)
Aspects of Drug
Pharmacokinetics (ADME)
Drug at site
of administration
Absorption
Drug in plasma
Distribution
Drug/metabolites
in tissues
Metabolism
Drug/metabolites
in urine, feces, bile
Elimination
Absorption
• Definition :
The process of movement of unchanged
drug from the site of administration to systemic
circulation.
• The ultimate goal is to have the drug
reach the site of action in a concentration
which produces a pharmacological effect.
• No matter how the drug is given (other
than IV) it must pass through a number of
biological membranes before it reaches
the site of action.
LIPID BILAYER
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the Rate dependent on polarity and size.
Polarity estimates partition coefficient.
The greater the lipid solubility – the faster the rate of diffusion
Smaller molecules penetrate more rapidly.
Highly permeable to O2, CO2, NO and H2O .
Large polar molecules – sugar, amino acids, phosphorylated
intermediates – poor permeability
These are essential for cell function – must be actively transported
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MOVEMENT OF SUBSTANCES ACROSS
CELL MEMBRANES
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MECHANISMs OF DRUG ABSORPTION
1) Passive diffusion
2) Carrier- mediated transport
a) Facilitated diffusion
b) Active transport
3) PINOCYTOSIS
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1) PASSIVE DIFFUSION
• Also known as non-ionic
diffusion.
• It depends on the difference
in the drug concentration
on either side of the
membrane.
• Absorption of 90% of drugs.
• The driving force for this
process is the concentration
or electrochemical gradient.
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2) CARRIER MEDIATED TRANSPORT MECHANISM
• Involves a carrier (a component of the membrane)
which binds reversibly with the solute molecules to be
transported to yield the carrier solute complex which
transverses across the membrane to the other side
where it dissociates to yield the solute molecule
• The carrier then returns to its original site to accept a
fresh molecule of solute.
• There are two types of carrier mediated transport
system:
a) facilitated diffusion
b) active transport
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a) Facilitated diffusion
• This mechanism driving
force is concentration
gradient.
• In this system, no use of
energy is involved (downhill transport), therefore
the process is not
inhibited by metabolic
poisons that interfere
with energy production.
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b) Active transport
• More important process than
facilitated diffusion.
• The driving force is against
the concentration gradient or
uphill transport.
• Since the process is uphill,
energy is required in the
work done by the barrier.
• As the process requires
energy, it can be inhibited by
metabolic
poisons
that
interfere
with
energy
production.
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Drug Absorption
Active vs. Passive
•
•
•
•
•
Active transport:
Carrier-mediated
Energy-dependent
Against conc gradient
Shows carrier saturation
kinetics
 Passive transport
• Energy-independent
• No carrier involved
• Along conc gradient
• No saturation kinetics
ATP
ADP
+ Pi
Carrier-mediated
energy-dependent
active transport
Passive diffusion of a
water-sol drug via
aqueous channel
AH
B
ABH+
Passive diffusion of a
lipid-sol drug
3) Pinocytosis
• This
process
is
important
in
the
absorption
of
oil
soluble vitamins & in
the
uptake
of
nutrients.
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PHYSICOCHEMICAL FACTORS
• Drug transported by passive diffusion depend
upon:
 dissociation constant, pKa of the drug
 lipid solubility, K o/w
 pH at absorption site.
•
• Most drugs are either weak acids or weak
bases whose degree of ionization is depend
upon pH of biological fluid.
• For a drug to be absorbed, it should be
unionized and the unionized portion should
be lipid soluble. Only non-ionized fraction of
drugs (acids or bases is absorbed
• The fraction of drug remaining unionized is a
function of both
• Dissociation constant (pKa) and pH of
solution.
HENDERSON HASSELBATCH EQUATION
For acid,
pKa - pH = log[ Cu/Ci ]
For base,
pKa – pH = log[ Ci/Cu ]
Eg. Weak acid aspirin (pKa=3.5) in stomach (pH=1) will have >
99%of unionized form so gets absorbed in stomach
Weak base quinine (pKa=8.5) will have very negligible unionization
in gastric pH so negligible absorption
Several prodrugs have been developed which are lipid soluble to
overcome poor oral absorption of their parent compounds.
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Factors Affecting GIT Absorption
• Blood Flow To Absorptive Site:
o Greater blood flow raises absorption
o Intestine has greater BF than stomach
• Total Surface Area of Absorptive Site:
 Intestinal microvilli increases surface area to 1000-fold that of
the stomach favoring intestinal absorption
• Contact Time at Absorptive Site:
 Diarrhea reduces absorption
 Accelerated gastric emptying→ faster delivery to intestinal
large surface → increased absorption
Factors Affecting GIT Absorption
• Food:
Presence of food in the gut reduces/delays drug
absorption from GIT
 Increased splanchnic blood flow during eating increases drug
absorption
 Ionized drugs as tetracycline can form insoluble complexes
with Ca2+ in food/milk.
• Formulation Factors:
 Solid dosage forms dissolution & solubility are essential
 Aqueous solutions are absorbed more quickly than tablets or
suspensions
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Factors affecting absorption from GIT
Stomach:
 The surface area for absorption of drugs is
relatively small in the stomach due to the absence
of macrovilli & microvilli.
 Extent of drug absorption is affected by variation in
the time it takes the stomach to empty, i.e., how
long the dosage form is able to reside in stomach.
 Drugs which are acid labile must not be in contact
with the acidic environment of the stomach
PHYSIOLOGICAL FACTORS:
Gastrointestinal (Gi) Physiology
Influence Of Drug Pka And Gi Ph On Drug
Absorbtion
Git Blood Flow
Gastric Emptying………………..contact time
Disease States
Total surface area
Intestine
• Major site for absorption of most drugs due to its large
surface area (0.33 m2 ).
• It is 7 meters in length and is approximately 2.5-3 cm
in diameter.
• These folds possess finger like projections called Villi
which increase the surface area 30 times ( 10 m2).
• From the surface of villi protrude several microvilli
which increase the surface area 600 times ( 200 m2).
• Blood flow is 6-11 times that of stomach.
• PH Range is 5–7.5 , favorable for most drugs to
remain unionized.
• Peristaltic movement is slow, while transit time is long.
• Permeability is high.
All these factors make intestine the best site for
absorption of most drugs.
Large intestine :
 The major function of large intestine is to
absorb water from ingestible food residues
which are delivered to the large intestine in a
fluid state, & eliminate them from the body as
semi solid feces.
 Only a few drugs are absorbed in this region.
Bioavailability
• the proportion of the drug in a dosage
form available to the body
i.v injection gives 100% bioavailability.
BIOAVAILABIITY
Serum Concentration
 Fraction of a drug reaching
systemic
circulation
in
chemically unchanged form
after a particular route
 First pass metabolism, i.e., rapid
hepatic metabolism, reduces
bioav. (lidocaine, propranolol,
nitrates)
 Drug solubility
 Chemical instability in gastric
pH (penicillin G, insulin)
 Drug formulation: Standard &
SR formulations
• Bio = AUC oral/AUC IV x 100
Injected Dose
Oral Dose
Time
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