Transcript 1 Pharmacology

ISHIK UNIVERSITY
FACULTY OF DENTISTRY
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Pharmacology
The science of drugs 
 Greek: Pharmacos (drug) + logos (study)
 The study of substances that interact with living
system through chemical processes, especially by
binding to regulatory molecules and activating or
inhibiting normal body processes.

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 Pharmacotherapeutics: is to achieve a
desired beneficial effect with minimal adverse
effects. When a medicine has been selected for a
patient, the clinician must determine the dose
that most closely achieves this goal.
 Clinical
Pharmacology : Is carried out
for evaluation of efficacy and safety of drugs, and
provides data for optimum use of drugs in human.
The science that deals with materials and drugs
used to prevent, diagnosis and treat diseases.
 Pharmacognosy:
Identification and
preparation of drugs from natural sources.
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

Chemotherapy : Deals with treatment of systemic
infection, malignancy with spesific drugs. Usually,
these drugs have selective toxicity for the infecting
organisms, malignant cell with no minimal effects on
the host cells.
Toxicology : Is the branch of pharmacology that
deals with the undesirable effects of chemicals on
living systems, from individual cells to humans to
complex ecosystems
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
Biotechnology: this was the production of drugs
or other useful products by biological means
(antibiotic production from microorganisms or
production of monoclonal antibodies).
 Pharmacogenetics: Is the study of genetic
influences on responses to drugs.
 It is focused on drug reactions, where affected
individuals show an abnormal response to a
class of drug .
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
Pharmacogenomics : It describes the use of
genetic information to guide the choice of
drug therapy on an individual basis.

Pharmacoeconomics : Is branch of health
economics aims to quantify in economic
terms the cost and benefit of drugs used
therapeutically.
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
Pharmacovigilance : The pharmacological
science that deals with detection, assessment ,
understanding and prevention of adverse effects
particularly long term and short term side effects
of medicine.
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Drug
A chemical substance of known structure, other than a
nutrient or an essential dietary ingredient, when
administered to a living organism, produces a
biological effect.
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Drug------dried herbs
 They are chemical substances which modify the
activity of living system or
 They are compounds that used to diagnos ,
prevent and treat a disease.

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SOURCES OF DRUGS
Animal: Insulin, thyroid, heparin,
gonadotrophins..
 Mineral: zinc, Aluminium hydroxide..
 Microorganisms: Important sources of
antibacterials (penicillins and other antibiotics)
 Synthetic : Paracetamol..
 Drugs produced by genetic engineering:
HGH, HI
 Plant : Oil, alkaloids..

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
Side effects of drug: Production of other effects rather
than original effects.
Adverse effect: Undesired effect of drug.
 Contraindication: Is a situation I which application of
a particular drug not advisable because it may
increase the risk on the patient.

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ROUTES OF DRUG ADMINISTRATION
Routes of drug administration depends on the
site of effect that we want to get from the drug :
 Local Drug Administration : When a
superfacial effect is needed. To increase the effect
of the drug, absorption should be avoided.
 Systemic Drug Administration: When a wide
effect is desired, or when local effect could not be
achieved and is not possible,

Drug absorption should be fast and complete
 Undesired effects of the drug beside its main effect

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A) Enteral
1. Oral Administration :Most drugs are taken by mouth
and swallowed. Little absorption occurs until the drug
enters the small intestine.
2. Sublingual : Placement under the tongue allows a
drug to diffuse into the capillary network and,
therefore, to enter the systemic circulation directly.
 Administration of an agent, sublingually, has several
advantages including rapid absorption, convenience of
administration, low incidence of infection, avoidance of
the harsh GI environment, and avoidance of first-pass
metabolism.
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3. Rectal: Fifty percent of the drainage of the rectal
region bypasses the portal circulation; thus, the
biotransformation of drugs by the liver is
minimized. Like the sublingual route of
administration, the rectal route of administration
has the additional advantage of preventing the
destruction of the drug by intestinal enzymes or
by low pH in the stomach.
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B) PARENTERAL

The parenteral route introduces drugs directly
across the body's barrier defenses into the
systemic circulation or other vascular tissue.
Parenteral administration is used for drugs that
are poorly absorbed from the GI tract (for
example heparin) and for agents that are
unstable in the GI tract (for example, insulin).
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PARENTERAL
1. Intravenous (IV): Injection is the most common
parenteral route. For drugs that are not absorbed
orally, such as the neuromuscular blocker
atracurium, there is often no other choice. With IV
administration, the drug avoids the GI tract and
therefore, first-pass metabolism by the liver.
 Intravenous delivery permits a rapid effect and a
maximal degree of control over the circulating
levels of the drug.
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2. Intramuscular (IM): Drugs administered IM can be
aqueous solutions or specialized depot preparations.
3. Subcutaneous (SC): This route of administration,
like that of IM injection, requires absorption and is
somehow slower than the IV route. Subcutaneous
injection minimizes the risks associated with
intravascular injection.
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OTHER ROUTES OF ADMINISTRATION
Intranasal
 Topical
 Transdermal
 Buccal (inside mouth)
 Intravaginal
 Intraplevral
 Intracardiac

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DISADVANTAGES OF ORAL
ADMINISTRATION COMPARED TO
PARENTERALS
Inactivation after the absorption (First pass
effect)
 Incomplete absortion of the drugs from the GIS
(digestion enzymes, stomach acid)
 The drug-food interaction that affects drug
absorption
 Patient cooperation

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PHARMACOKINETIC
THE PHARMACOKINETIC PROCESSES OF
ABSORPTION, DISTRIBUTION, AND
ELIMINATION DETERMINE HOW RAPIDLY
AND FOR HOW LONG THE DRUG WILL
APPEAR AT THE TARGET ORGAN.
THE PHARMACODYNAMIC CONCEPTS
OF MAXIMUM RESPONSE AND
SENSITIVITY DETERMINE THE
MAGNITUDE OF THE EFFECT AT A
PARTICULAR CONCENTRATION.
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
Pharmacokinetics can be defined as the
measurement and formal interpretation of
changes with time of drug concentrations in one
or more different regions of the body in relation
to dosing ('what the body does to the drug'). This
distinguishes it from pharmacodynamics ('what
the drug does to the body
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
Pharmacodynamics deals with physiological
and biochemical effects of drugs and their
meachanism of action at macromolecular ,
subcellular, organ, system level.
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DRUG ABSORPTION
Absorption is the transfer of a drug from its site
of administration to the bloodstream.
 The rate and efficiency of absorption depend on
the route of administration.

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 For
IV delivery, absorption is complete; that is,
the total dose of drug reaches the systemic
circulation.
 Drug delivery by other routes may result in
only partial absorption and, thus, lower
bioavailability.
 For example, the oral route requires that a
drug dissolve in the GI fluid and then
penetrate the epithelial cells of the intestinal
mucosa, yet disease states or the presence of
food may affect this process.
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FACTORS AFFECTING ABSORPTION RATE
1.
2.
Drug: type, physicochemical characters,
dissolution, concentration, and pharmacological
function.
Route of administration and the biological
effect: blood flow rate , and the permeability
and width of the surface that the drug is
absorbed.
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1. DRUG FACTOR

The physicochemical properties of the drug
Molecular weight : The absorption rate increases
with decreasing the MW of the drug.
 Lipophilicity: The ratio of concentration of the drug
dissolved in lipophilic phase to the hydrophilic phase
 lipid/water partision coefficient
 The physical properties of the pharmaceutical form of
the drug and its dissolver (suspension, strong acid,
tablet)

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

The concentration of the drug: The same amount
of the drug absorption can be increased by
increasing the concentration.
Pharmacological properties of the drug.
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2. ROUTE OF ADMINISTRATION AND THE
BIOLOGICAL EFFECT:
Blood flow rate at the site of the drug that
applied to the body surface or tissue.
 The permeability and width of the area of
administration.

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TRANSPORT OF A DRUG FROM
THE GI TRACT
Depending on their chemical properties, drugs may be
absorbed from the GI tract by either passive diffusion or
active transport:
1)Passive diffusion: The driving force for passive
absorption of a drug is the concentration gradient across
a membrane separating two body compartments; that
is, the drug moves from a region of high concentration
to one of lower concentration
 Lipid-soluble drugs readily move across most biologic
membranes due to their solubility in the membrane
bilayers. Water-soluble drugs penetrate the cell
membrane through aqueous channels or pores
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2)Active transport: This mode of drug entry also involves
specific carrier proteins that span the membrane. A few
drugs that closely resemble the structure of naturally
occurring metabolites are actively transported across
cell membranes using these specific carrier proteins.
 Active transport is energy-dependent and is driven by
the hydrolysis of adenosine triphosphate .
 It is capable of moving drugs against a concentration
gradient that is, from a region of low drug concentration
to one of higher drug concentration.
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4) Endocytosis and exocytosis: This type of drug delivery
transports drugs of exceptionally large size across the
cell membrane.
Example: Transport of B12 across the gut wall by
endocytosis.
 Exocytosis is the reverse of endocytosis and is used by
cells to secrete many substances by a similar vesicle
formation process
 Norepinephrine is stored in membrane-bound vesicles
in the nerve terminal and are released by exocytosis.
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Most drugs are either weak acids or weak
bases. Acidic drugs (HA) release an H+ causing
a charged anion (A-) to form

HA ↔ H⁺ + A⁻
 Weak bases (BH+) can also release an H+.
However, the protonated form of basic drugs
is usually charged, and loss of a proton
produces the uncharged base (B):
 BH ↔ B + H⁺

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A drug passes through membranes more readily if it is
uncharged .
 Thus, for a weak acid, the uncharged HA can permeate
through membranes, and A⁻ cannot.
 For a weak base, the uncharged form, B, penetrates
through the cell membrane, but BH+ does not.
 Therefore, the effective concentration of the permeable
form of each drug at its absorption site is determined by
the relative concentrations of the charged and
uncharged forms.

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The ratio between the two forms is, in turn,
 determined by the pH at the site of absorption and by
the strength of the weak acid or base, which is
represented by the pKa.
 The pKa is a measure of the strength of the interaction
of a compound with a proton. The lower the pKa of a
drug, the more acidic it is.
 Conversely, the higher the pKa, the more basic is the
drug.


Highly lipid-soluble drugs rapidly cross
membranes and often enter tissues at a rate
determined by blood flow
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
The relationship of pKa and the ratio of acid-base
concentrations to pH is expressed by the HendersonHasselbalch equation:

stomach (pH 1.0-1.5) , and blood plasma (pH 7.4).
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Absorption of drugs from the intestine, as a function of pKa, for
acids and bases. Weak acids and bases are well absorbed; strong
acids and bases are poorly absorbed.
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BIOAVAILIBILITY
 Bioavailability
is the fraction of administered
drug that reaches the systemic circulation.
 Bioavailability is expressed as the fraction of
administered drug that gains access to the
systemic circulation in a chemically unchanged
form.
 For example, if 100 mg of a drug is administered
orally and 70 mg of this drug are absorbed
unchanged, the bioavailability is 70%.
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Bioavailability relates to
the total proportion of
the drug that reaches
the systemic circulation
and neglects the rate of
absorption
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Bioequivalence
 Two related drugs are bioequivalent if they show
comparable bioavailability and similar times to achieve
peak blood concentrations.
 Two related drugs with a significant difference in
bioavailability are said to be bioinequivalent.
Therapeutic equivalence

Two similar drugs are therapeutically equivalent if they
have comparable efficacy and safety.
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FACTORS THAT EFFECTING
BIOAVAILABILITY
1. First-pass hepatic metabolism: When a drug is absorbed across the
GI tract, it enters the portal circulation before entering the systemic
circulation. If the drug is rapidly metabolized by the liver, the
amount of unchanged drug that gains access to the systemic
circulation is decreased. Many drugs, such as propranolol or
lidocaine, undergo significant biotransformation during a single
passage through the liver.
2. Solubility of the drug: Very hydrophilic drugs are poorly absorbed
because of their inability to cross the lipid-rich cell membranes.
Drugs that are extremely hydrophobic are also poorly absorbed,
because they are totally insoluble in aqueous body fluids and,
therefore, cannot gain access to the surface of cells.
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FACTORS THAT EFFECTING
BIOAVAILABILITY
3. Chemical instability: Some drugs, such as penicillin G,
are unstable in the pH of the gastric contents. Others,
such as insulin, are destroyed in the GI tract by
degradative enzymes.
4. Nature of the drug formulation: Drug absorption may
be altered by factors unrelated to the chemistry of the
drug. For example, particle size, salt form, crystal
polymorphism, enteric coatings and the presence of
excipients (such as binders and dispersing agents) can
influence the ease of dissolution and, therefore, alter
the rate of absorption.
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