Study Guide I

What are drugs? What are the different ways that drugs can be classified give examples
in each category. What are the features of each kind of classification?

Drugs are chemicals that can react with biological systems and produce a biological response.
Drugs are grouped by:
1. Pharmacological effect--- analgesic, antipsychotic, antibacterial, antibiotic
2. Chemical StructureCompounds with a common skeleton: penicillins, barbiturates, opiates,
steroids. Compounds of a similar structure have similar activities
3. Target Systembased on what they target (chemical messenger): antihistamines (block
histamine release), cholinergic. Different stages can be targeted.
4. Site of action---grouped according to the enzyme or receptor with which they interact.
Anticholinesterases are a group of drugs that act through the inhibition of the enzyme
acetylcholinesterase.

What is Medicinal Chemistry? What are the various fields of study that may be included
in medicinal chemistry?
Science which deals with the discovery or design of new chemicals and their
development into useful medicines.
It may involve any or all of the following:Computational chemistry.
Synthesis of new compounds
Investigation of relationship between structure and biological activity.
Understanding interactions of the chemical with receptors of various kinds: enzymes,
DNA, etc
Absorption, transport, distribution properties.
Metabolism or breakdown

Toxicology

What have been the benefits and consequences of modern drug development?

many life threatening diseases are now minor health concerns (polio, small
pox, TB, gastric ulcers, etc. A decade ago people with HIV infection usually
succumbed to AIDS within 2 years after the infection, while now, with regular
medication, they have a normal life expectancy.
- Increase in life expectancy (more and more people are living into the 100s).
- Improvement in quality of life (Viagra, birth control pills, treatments for
incontinence).
Consequences of drug development
- overuse of antibiotics, bacterial resistance.
- More healthy elderly population, leading to diseases of the elderly
(cancer, autoimmune diseases, neurodegenerative and degenerative diseases
more people with these diseases means increased health care costs)

In your opinion, are drug companies justified in pricing drugs as they currently do? Why
or why not?

What are the various stages in drug development? Describe what is involved in each
stage.

The structures of cocaine, cocaine acetate, and cocaine hydrochloride are shown
below. State which one of these would be most water-soluble, moderately water-soluble, and
least water-soluble. Explain the reasons for your choices.

What are agonists and antagonists?

What are acids and bases? You should be able to recognize acids, bases, conjugate acids
and conjugate bases in an equation.
What do acids and bases have to do with drug ionization? What role does ionization play
in the absorption of a drug?
What are the functional groups that are considered acidic, basic and neutral? Given a
drug molecule, you should be able to identify the various functional groups, classify them
as acidic, basic or neutral, and identify the most acidic and the most basic site in the
molecule.

What are strong acids and strong bases? Give examples. What is the leveling effect of
water?
Given the pKa of an acidic drug or the protonated form of a basic drug, you should be
able to calculate the degree of ionization in different parts of the body (at a specific pH).
You should also be able to indicate where in the body the drug is more likely to be
absorbed.
What are the two kinds of intermolecular forces to be considered when determining the
water or lipid solubility of a molecule?
What is Hydrogen bonding? You should be able to recognize the H bonding nature
(acceptor/donor) of common functional groups. When does hydrogen bonding not
contribute to increased water solubility?
What kinds of ionic compounds (salts) are water soluble and what kinds are not? What
are Zwitterionic compounds? What kinds of zwitterionic compounds have poor water
solubility?
Predict water solubility of drugs based on Lemke's empirical approach (based on
hydrogen bonding potential). You should know the water-solubilizing potential of
common organic functional groups in molecules.

Define partition coeffecient P for drug molecules. Given values for functional groups,
you should be able to calculate logP values for drugs and predict water and membrane
solubility.
Given a set of functional groups (for eg. NO2, COOH, CH3, etc) and a table of their
Hammett constant () and Hansch constant (), you should be able to match the
functional groups to the constants. Given an acidic (phenol) or a basic (aniline)
compound, you should be able to decide what substituent is to be placed in the para (or
ortho) position in order to make it (a) more absorbable, or (b) less absorbable, in the GI
tract (like the examples done in class).

Explain using examples and structures how introducing alterations of alkyl groups can
alter the pharamacologic activity of drug molecules.

What is bioisosterism. What are some common bioisosteric replacements? Given a

molecule, you should be able to suggest a valid bioisosteric replacement for it. Also, for

the examples posted on the website, given a particular drug, you have to be able to draw
the bioisosteric replacements that were used and tested.