Physicochemical Properties of Drugs in relation to Drug Action

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Physicochemical Properties of Drugs in relation
to Drug Action

• Roselyn Aperocho Naranjo, RPh, MPH
• USPF, College of Pharmacy
• rose_may26_at_yahoo.com

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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

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History General
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History General
Structure of Natural products
Selective changes in the molecule
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Selected molecules are changed due to

• Reduction of undesirable pharmacologic response
  of the drug (side-effect)
• Obtain better drug response
• Alter drugs metabolism
• Produce more cheaper and competitive supply of
  the product

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Selected molecules are changed due to

• Example
• Morphine
• Cocaine

Addiction effect
reduced
Analgesic effect
enhanced
Local Anesthetic Effect
enhanced
CNS effects
reduced
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Medicinal Chemistry in 1900s

• 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

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Overview
Pharmacologic response
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Overview
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Drug Distribution

• Oral Administration

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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

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Drug Distribution
PRODRUG- inactive form but are easily metabolized
in the liver to become active

• Oral Administration
• Example
• CHLORAMPHENICOL

• CHLORAMPHENICOL PALMITATE

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Protein Binding
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Protein Binding

• Can affect the drugs effective solubility,
  biodistribution, half-life in the body and
  interaction with other drugs.
• Control access to certain body compartments
• Prolong the drugs duration of action
• Limit the amount of drug available for
  biotransformation and interaction with specific
  receptor sites.

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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

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Drug Metabolism Excretion
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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

Quantitative-Structure- Activity relationship
(QSAR)
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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

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QSAR
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Topological Descriptors

• Alternate method in describing molecular
  structure which is based on graph theory using
  the bonds that connects between atoms

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Combinatorial Chemistry

• to be continued
• Prepare ¼ sheet of paper for the quiz

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