DRUG DESIGN STRATEGY

Medicinal Chemistry devoted to discovery

and development of new agents to treat
diseases
Drugs- agents intended for use in diagnosis,
mitigation, cure, and prevention of diseases
in humans/ other animals
Receptor- a substance to which a drug must
interact with to elicit a pharmacological
response
Affinity an act in which a drug binds to a
receptor

Efficacy/ response- this is when a drug exerts

its pharmacological action
Drug design- based on modern
computational chemical technique; requires
sophisticated knowledge of disease
mechanisms and receptor properties
-

Requires understanding on how the

drug:
o Transported into the body
o Distributed throughout the
other body compartments
o Metabolically altered by the
liver and other organs
o Excreted by the patient

Drug distribution
-

Following introduction of the drug into

the body
Drug must pass through many
membrane barriers
Survive alternate sites of attachment
and storage
Avoid significantly metabolic
destruction before it reaches to the
site of action

Oral administration
-

The drug must go into solution to pass

through the GIT.
Any drug passing the GIT will
encounter digestive enzymes which
will metabolized it either to its active
form or into a metabolite which will
then be secreted out of the body.
Factors governing drug dissolution
o Chemical structure

o Variation in particle size

o Particle surface area
o Nature of the crystal form
o Type of tablet coating
o Type of tablet matrix
o Dosage matrix
o Physical characteristics
Sodium phenytoin- used to treat
epilepsy
Chemical modification- used to a
limited extent to facilitate a drug
reaching its desired target
Olsalazine- a prodrug of mesalamine
( 5-aminosalicylic acid); is activated
pass through the intestinal tract to
reach the colon to elicit its effect
against ulcerative colitis (inflammation
in the colon); it is a dimer of
mesalamine; once it reaches the GIT,
digestive enzymes/ bacteria will
cleaved the olsalazine into two
mesalamine
Chloramphenicol palmitate a prodrug
of chloramphenicol; a product of
chloramphenicol + palmitic acid
Prodrug- inactive compounds that
require metabolic biotransformation to
convert it to its active form
Prodrug approach enhances the
absorption of a drug that is poorly
absorbed in the GIT
Enalapril a prodrug of enalaprilic
acid, an active inhibitor of angiotensin
converting enzyme

Parenteral administration
-

Intraspinal spine ; intracerebral

brain
These routes prevent the drug from
passingan epithelial tissue, bloodbrain barrier, which protects the brain
from metabolites and other chemicals
Local anesthetics- drugs directly to the
desired nerve
Spinal block a form of anesthesia
perform by injecting a local anesthetic
into the spine blocking transmissions
alog specific neurons
SQ and IM produces a tissue depot

Protein binding

Profound effect on the drugs effective

solubility, biodistribution, interaction
with other drugs, half-life in the body
Drugs enter the systemic circulation
and bind to serum proteins usually
albumin

Drug + albumin = albumin-drug

complex
Albumin-drug complex acts as a
reservoir by providing large
concentrations of free drug to elicit its
pharmacologic effect at its receptor