BASIC

PHARMACOLOGY

dr. Kartini Lidia, MSc

Faculty of Medicine, Nusa Cendana University
2015
 REFERENCES

BASIC AND CLINICAL PHARMACOLOGY

by Bertram G.Katzung

MANUAL OF PHARMACOLOGY AND

THERAPEUTICS
by Goodman and Gilmans

A TEXTBOOK OF CLINICAL PHARMACOLOGY

AND THERAPEUTICS
By James M ritter et al

PHARMACOTHERAPY PRINCIPLES AND PRACTICE

by Marie A Chisholm Burns et al
 PHARMACOLOGY
The study of substances that interact with living
systems through chemical processes, especially by
binding to regulatory molecules and activating or
inhibiting normal body processes.

Medical pharmacology, the science of substances used to

prevent, diagnose, and treat disease.

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
 DRUG
Drug :
Any substance that
brings about a change in
biologic function through
its chemical actions
 General Principles of
Pharmacology

Drug
Agonist (activator)
Antagonist (inhibitor)
Receptor
Drugs may be synthesized within the body (eg, hormones ) or
may be chemicals not synthesized in the body
(ie,xenobiotics, from the Greek xenos, meaning "stranger").
Poisons are drugs that have almost exclusively harmful effects.
Paracelsus (14931541) famously stated that "the dose makes
the poison,
Toxins are poisons of biologic origin, ie, synthesized by plants or
animals
 DRUG ACTION

a
D+R DR E
drug receptor effect

Drugs works on the molecular levels

Generally, drug will work as :
- Stimulant increase cellular activity increased function
- Depressant decrease cellular activity decreased function
- Iritation effects on food, growth, morphology of living tissue
- Replacement subtitution effect
- Anti-infection eliminate or to obstruct the growth of certain
micro-organisms.
 DRUG MOLECULE

To interact chemically with its receptor, a drug molecule must

have : - the appropriate size
- electrical charge
- shape and
- Atomic composition
A drug is often administered at a location distant from its
intended site of action

SITE OF ADMINISTRATION SITE OF ACTION

A drug should be inactivated or excreted from the body at a

reasonable rate so that its actions will be of appropriate duration
 DRUG BODY INTERACTION

Pharmacodynamic
The actions of the drug on the body = the study of effects of
drugs on biological processes.
Ex : PPI dan H2 antagonist (peptic ulcer treatment)

Pharmacokinetic
The actions of the body on the drug
Absorbsi
Distribusi
Metabolisme
Ekskresi
Pharmacokinetic
 Absorbtion
The movement of a drug from its site of
administration into the central compartment

Influencing factors :

Route of administration
Solubility
Physical state of drug (solution, suspension, or solid dosage
form
Concentration
Absorption site
Circulation
Drug interactions
 BIOAVAILABILITY

Bioavailability indicates the fractional extent to which a dose of

drug reaches its site of action, taking into account, for example,
the effects of hepatic metabolism and biliary excretion that may
occur before a drug taken orally enters the systemic circulation. If
hepatic elimination of the drug is large, bioavailability will be
reduced substantially (the first-pass effect).
This decrease in availability is a function of the anatomical site
from which absorption takes place; other anatomical,
physiological, and pathological factors can influence
bioavailability
 BIOAVAILABILITY

pH partition
Stomach :
Weak acid nonionized quick absorption
Weak bases ionized slow absorption
Intestine :
Weak acid ionized slow absorption
Weak bases nonionized quick absorption
Motility
Intestine motility high slow absorption
Food
Empty stomach quick absorption
Soluble
Lipid soluble quick absorption
Water soluble slow absorption
 ROUTE OF DRUG ADMINISTRATION
ENTERAL
Oral Ingestion,
Sublingual,Transdermal, Rectal

PARENTERAL INJECTION
Intarvenous, Subcutaneous,
Intramuscular, Intrathecal

PULMONARY
ABSORPTION/INHALATION

TOPICAL APPLICATION
Mucous membrane : conjunctiva,
nasopharynx, oropharynx,vagina,
colon, urethra, and urinary bladder
primarily for their local effects.
 Distribution
Following absorption or systemic administration into the
bloodstream, a drug distributes into interstitial and intracellular
fluids depending on the particular physicochemical properties of
the drug.

Influencing Factors :
Cardiac output
Regional blood flow
Capillary permeability, and
Tissue volume determine
Compartments for drug distribution
 Distribution

An absorpted drug will be distributed through blood

circulations to the whole body.
Some drug shows affinity to specific tissue and being
heaped, such as :
- Iodium Thyroid glands
- Chloroquin, emetin Liver
- Glycoside digitalis Myocard
Protein plasma, fat tissue and bone could act as a
drug storage depot
To reach the central nervous system & fetus, drug
must be able to penetrate the blood brain barrier &
placenta barrier. Usually a lipofillic drug could be
easier to penetrate through the barrier.
DRUG CONCENTRATION IN PLASMA
illustrations

PEAK LEVEL

HALF
LIFE
(t1/2)

half life steady state

a steady-state concentration eventually will be achieved when
a drug is administered at a constant rate
Dosing rate = CL Css
 Volume of distribution

The volume of distribution (V) relates the amount of drug in the

body to the concentration of drug (C) in the blood.

Amount of drug in body / V = C,

Or
V = amount of drug in body / C
Metabolism/bio-transformation

A biochemical reactions which cause an alteration of

subtance on human body
Biochemical reactions are classified as :
Non-synthetic reactions, such as oxidation, reduction,
hidrolysis, etc.
Synthetic reaction, such as conjugation.

The result of the reactions itself its what we called

metabolite. Metabolite could be more active, less
active or non-active compared to its original form.

Liver is the main organ for human metabolism.

Excretion

Drugs are driven out from the body by the process of

excretions. The form will either unchanged or
already been converted to metabolites.
Kidney is the most important organ for excreting
drug and its metabolites. But also aware that drugs
and metabolites can also be excreted through breast
milk, faeces, gall bladder, lung, sweat, tears and
hair.

Two important factors regarding excretion :

- Drug Characteristics :
Initial dose,
Maintenance dose
- Excretion organs function
 Clearance

Clearance is the most important concept to consider when

designing a rational regimen for long-term drug administration.
Dosing rate = CL Css
CL is clearance of drug from the systemic circulation
Css is the steady-state concentration of drug.
CL = rate of elimination/C
CLrenal+ CLhepatic+ CLother = CL
On Set of Action
Amount of time from the drug is being administered
until the drug start working
Duration of Action
The amount of time while the drug effect last.
The best way to measure duration of action its by
determining the drug half-life
Half Life - t1/2
The amount of time from the concentration of drug in
the plasma divided by half
 Therapeutic Index

Therapeutic Index Ratio LD50

Also known as Margin of Safety =
ED50

Influencing factors :
- Age and weight
- Sex
- Time and route of administration
- How to administer
- Excretion time
- Drug combination
- Species or Race
dosage
Specific amount of drug that
required to generate a therapeutic
effect
- Minimal Dose
- Maximal Dose
- Therapeutic Dose (Effective Dose) = ED
- Toxic Dose
- Lethal Dose = LD
factors affecting drug activity

factors that can affect the drug activities :

Dose
Tolerance
Idiosyncracy & Hypersensitivity
Pathologic Conditions
Cumulative work
TOLERANCE

Resistance toward drug could happened

due to chronic use of drug. Dose must be
increased to attain the same effect.
Acquired Tolerance
Invidual Tolerance
Cross Tolerance
Species Tolerance

Tachyphylaxis :
Acute tolerance (several minutes/hours)
habituations craving
Desperate need for certain medicine
(emotional dependence)

addiction
Tolerance
Habituation
Dependence Withdrawal Symptoms
- Emotional (Abstinentia
- Physical Syndrome)
IDIOSYNCRACY

Abnormal effects of a drug for an

individual (genetic)
Example :
Morphine Excitation
Pentaquine Anemia Hemolitik (Afrika)
HYPERSENSITIVITY

Allergic reactions due to antigen-antibody reaction. Could

be happened on various body system. Such as :
Allergic rhinitis
Allergic conjunctivity
Asthma bronchialis
Skin disorders, such : urticaria, dermatitis, angioneurotik dedem
Gastrointestinal allergics : nausea, vomit, diarhrea
Blood disorders, such : agranulosytosis, aplastic anemia
Drug Fever
Anaphylactic Shock treatment :
Anaphylactic Shock Adrenaline
Corticosteroid
Anti-hystamine
UNWANTED EFFECTS

Overdose
Consist of absolute overdose and relative overdose

Side effect
For example : anti-histamine cause drowsiness

Tolerance
Idiosyncration & Hypersensitivity
Adverse Drugs Effect
OVER DOSAGE :
The drug is administered in a higher dose than is required
for the principal effect; this directly or indirectly affects
other body functions.

Ex :Morphine
Appropriate dose pain relief by influencing nociceptive
pathways inthe CNS.
Excessive dosesinhibits the respiratory center and makes
apnea imminent.
 Increased sensitivity .
If certain body functions develop hyperreactivity, unwanted
effects can occur even at normal dose levels.

Ex :Increased sensitivity of the respiratory center to morphine is

found in patients with chronic lung disease, in neonates,or
during concurrent exposure to other respiratory depressant
agents.
 Lack of selectivity.
Despite appropriate dosing and normal sensitivity, undesired
effects can occur because the drug does not specifically act on
the targeted (diseased) tissue or organ

Ex : Cutaneous reactions are a common form of drug adverse

reaction.
 ADVERSE DRUG REACTION

Toxic erythema
Urticaria
Fixed eruptions (drug exanthemas) with mostly few demarcated,
painful lesions,usually located in intertriginous skin regions
(genital area, mucous membranes).With repeated exposure,
these typically recur at the same sites.
StevenJohnson syndrome (SJS, erythemamultiforme) and toxic
epidermal necrolysis (TEN or Lyell syndrome)
 TERIMAKASIH
SELAMAT BELAJAR
DAN
SUKSES