Transcript Physicochemical Properties of Drugs in relation to Drug Action

Physicochemical Properties of
Drugs in relation to Drug Action
Roselyn Aperocho Naranjo, RPh, MPH
USPF, College of Pharmacy
[email protected]
Understanding the
Modern Drug Design
 Modern chemical techniques
 Recent knowledge on disease mechanisms & receptor
properties
 Transportation of drugs in the body
 Distribution of drug through different compartments
 Metabolism of drugs in the liver and other organs
 Structural characteristics of the receptor
 Acid-base chemistry
 Availability of the computer software that determines
the three-dimensional shape of the receptor in order
to design new molecules that will give optimum fit to
the receptor
History: General
Plant Source
Specific Plants are
selected
Treatment
for medical conditions
Crude
extracts
History: General
Plant Source
Structure of
Natural
products
Specific Plants are
selected
Selective changes in
the molecule
Treatment
for medical conditions
Crude
extracts
Selected molecules are changed
due to:
 Reduction of undesirable
pharmacologic response of the drug
(side-effect)
 Obtain better drug response
 Alter drug’s metabolism
 Produce more cheaper and
competitive supply of the product
Selected molecules are changed
due to:
Example:
Addiction effect
Morphine
reduced
Analgesic effect
enhanced
Cocaine
Local Anesthetic
Effect
enhanced
CNS effects
reduced
Medicinal Chemistry in 1900’s
 Phenothiazines –
first synthesized as ANTIHISTAMINES
- Careful investigation led to discover its
TRANQUILIZING PROPERTY for the
mentally ill patient.
 Benzodiazepines –
originated from an expected ring
enlargement which resulted it to
become a CNS RELAXANT
Overview
drug
receptor
Drug-receptor complex
Pharmacologic response
Overview
Drug Distribution
 Oral Administration
Drug Distribution
 Oral Administration
 Solubility depends on:
 Chemical Structure
 Size of particles
 Surface area
 Nature of crystal form
 Type of tablet coating
 Type of tablet matrix
Drug Distribution
 Oral Administration
 Example:
 CHLORAMPHENICOL
PRODRUG- inactive form
but are easily metabolized
in the liver to become
active
CHLORAMPHENICOL PALMITATE
Protein Binding
Protein Binding
 Can affect the drug’s effective solubility,
biodistribution, half-life in the body and
interaction with other drugs.
 Control access to certain body
compartments
 Prolong the drug’s duration of action
 Limit the amount of drug available for
biotransformation and interaction with
specific receptor sites.
Tissue Depot
 Fats in the body which can be a
storage for drugs
 The more Lipophilic the drug is, the
more it will stay in the tissue
 Example:

Thiopental
Drug Metabolism & Excretion
Statistical Prediction of
Pharmacological Activity
 Mathematical Model will explain many
chemical processes
Three goals in Drug Design
• Predict biological activity in untested
compounds
• define the structural requirements required
to fit to a specific receptor
• design a test set of compounds
QSAR
 Proposed by Crum-Brown and Fraser
in 1865 to 1870
 Certain modification in the molecular
structure of a poisonous compound
produces an important differences in
their action
QSAR
Topological Descriptors
 Alternate method in describing
molecular structure which is based on
graph theory using the bonds that
connects between atoms
Combinatorial Chemistry
…to be continued
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