physicochemical properties of drugs in relation to drug action roselyn aperocho naranjo, rph, mph...
TRANSCRIPT
Physicochemical Properties of Drugs in relation to Drug Action
Roselyn Aperocho Naranjo, RPh, MPHUSPF, College of Pharmacy
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
Crude extracts
Treatment for medical conditions
History: General
Plant Source Specific Plants are selected
Crude extracts
Treatment for medical conditions
Structure of Natural
products
Selective changes in the molecule
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:
Morphine
Cocaine
Addiction effect
Analgesic effect
Local Anesthetic Effect
CNS effects
reduced
enhanced
reduced
enhanced
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
receptordrug 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
CHLORAMPHENICOL PALMITATE
PRODRUG- inactive form but are easily metabolized in the liver to become active
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
Prepare ¼ sheet of paper for the quiz
