History of Pharmacology

Question 1

What is Pharmacology?

Answer 1

The study of substances that act via chemical processes to affect biological organism.

Question 2

What is Medicinal Chemistry?

Answer 2

Medicinal Chemistry is the field of design, development,

and synthesis of pharmaceutical substances.

Question 3

Main principles of pharmacology:

Answer 3

Biological interactions with drugs: Endogenous - xenobiotic - poison/toxin

Phamacogenomics: genetic response to drugs

System/Organ/Tissue/Cellular structure:
Transporters / Enzymes
Membranes, organelles, signaling processes

Pharmacodynamics
Biological Targets
Mechanism of Action

Pharmacokinetics
ADME - absorption, distribution, metabolism, excretion
Biotransformation

Question 4

Main principles of medicinal chemistry:

Answer 4

Physical-chemical properties of drugs
Drug structure and functional groups
Ionization and lipophilicity
Size

Types of drugs
Natural product, synthetic molecule
Peptide/proteins, antibodies, nucleic acid derivatives

Modifications to drugs
       Pro-drugs
       Pegylation -> impacts drug half-life
       Selectivity for biological target
       Reduce off-target effects

Question 5

How pharmacology is dependent upon other disciplines such as physiology?

Answer 5

Must know both physiology and pathophysiology to understand how substance or drug will affect the functions within a human.

Question 6

Mechanism of Action

Answer 6

Specific biochemical interaction through which a drug substance produces its pharmacological effect

Question 7

Physiological Effect

Answer 7

Physiological change drug exhibits on the body

Question 8

What is toxicology?

Answer 8

The toxicological effect on an infective organism affecting patient.

Question 9

What are the 5 key concepts of pharmacology?

Answer 9

1) You must know normal physiology to understand how the pharmacology of drugs/substances work in the body.
2) Understanding the Mechanism of Action (MOA) for a drug is key to understanding its clinical usefulness, some PK parameters, prediction of side effects, and some DDIs.
3) Drug structure including functional groups contribute to MOA, PK parameters (ADME), potency, selectivity, formulations, and interactions.
4) Knowledge about the biological target (pharmacophore) and the SAR of the drug will help to understand the MOA, the physiological outcome, and PK parameters.
5) All exogenous substances/drugs have side effects; the type and degree mostly depends upon the drug’s mechanism of action, concentration, and length of treatment.

Question 10

Describe the relationship between pharmacology, medicinal chemistry as they pertain to drug structure, MOA, PK parameters, side effects, and DDIs

Answer 10

1. Drug Class (generic name – required)
2. Drug structure
   • Key functional groups, physico-chemical properties 3. Mechanism of Action
   • Biological Targets / pharmacodynamics (PD)
3. Pharmacokinetics (PK)
   • A: Bioavailability, first pass effect, enterohepatic circulation
   • D: Volume of distribution
   • M: Phase I or II biotransformation; fast acetylator; half-life (t1/2)
   • E: Renal versus hepatic
4. Adverse/side effects
   • Extension of physiological effects from drug
5. Drug – drug interactions
   • Interferes with other drugs or additive effects via different MOA