Pharmacology Definitions, Nomenclature and Pharmacodynamics I

1. General Principles of Drug Therapy
Marc Imhotep Cray, M.D.
BMS / CK-CS Teacher
Definitions, Nomenclature and
Pharmacodynamics I
Integrated Scientific and
Clinical Pharmacology

2. General Principles of Drug Therapy
Definition- pharmacology
Derived from Greek words pharmakon, meaning drug or
poison, and logos, meaning rational discussion or study
rational discussion or study of drugs and their interactions
with body
body of knowledge concerned with action of chemicals on
biologic systems
Also see Integrated Basic and Clinical Pharmacology Course
Syllabus and Digital Guidebook pgs. 9-13
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3. General Principles of Drug Therapy
Definition- pharmacology (2)
Study of drug action at both molecular and whole-organism
levels
 At molecular level, biologic effect of a drug
 At whole-organism level, therapeutic effects of a drug and
unwanted (i.e., adverse or side) effects
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4. General Principles of Drug Therapy
Scope of Pharmacology
a branch of biology, as it is concerned with living organisms
it borrows heavily from physiology and biochemistry for
substantive matter and experimental techniques
MedPharm is related to chemistry, because it deals with
chemical agents
MedPharm is an essential part of medicine
the cornerstone of modern therapeutics is the use drugs
Pharmacology (MedPharm) is:
“So what is pharmacology?” The question is only partially answered by
the term’s derivation.
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5. General Principles of Drug Therapy
mathematics to express its principles in quantitative
terms
behavioral sciences, such as psychology, to
understand actions of drugs that lead to changes in
mood or emotion (eg. psychoactive drugs)
Scope of Pharmacology (cont.)
Pharmacology uses:
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6. General Principles of Drug Therapy
Definition- pharmacology (3)
“Pharmacology is the unified study of the properties of
chemicals and living organisms and all aspects of their
interactions; it is an integrative rather than an autonomous
science, drawing on the techniques and knowledge of many
allied scientific disciplines.”
Levine's Pharmacology: Drug Actions and Reactions 7th ed. Walsh C and Schwartz-Bloom RD
(Eds.) New York, Taylor Francis, 2005. Pg. 18
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7. General Principles of Drug Therapy
“What Is Pharmacology?”
A Summary Statement
…“Medical pharmacology is a bridge between basic science and clinical
medicine. It makes use of all the disciplines that comprise the scientific
foundation of clinical medicine; from anatomy, physiology, pathophysiology,
pathology and immunology to biochemistry, molecular and cell biology,
epidemiology, genetics and genomics. Hence…it is particularly useful for pre-
clinical student to view and engage the subject as a major horizontal and
vertical integrator, as it pulls together all the different strands of the basic
medical science years and simultaneously introduces one to the cornerstone
of modern clinical therapeutics, ie .drugs”…
From: Cray MI. (2015) Integrated Scientific and Clinical Pharmacology:
A Course Syllabus and Digital Guidebook for Medical Students.. Pg.4
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8. General Principles of Drug Therapy
“The broad science of pharmacology.”
four main categories (subdivisions)
1. pharmacodynamics,
2. toxicology,
3. pharmacotherapeutics
4. pharmacy
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Clinical pharmacology =The principles behind the prescribing process
as opposed to
Pharmacotherapeutics =The process of medical treatment

9. General Principles of Drug Therapy
Pharmacology categories defined:
For additional related key terms see: MedPharm Glossary
Pharmacodynamics the study of the actions and effects of
chemicals at all levels of organization of living material and of the
handling of chemicals by the organism.
Toxicology is the study of the toxic or harmful effects of chemicals
as well as of the mechanisms and conditions of occurrence of these
harmful effects.
Pharmacotherapeutics the application of drugs in the prevention,
treatment or diagnosis of disease and their use in purposeful
alteration of normal functions...
Pharmacy concerned with the preparing, compounding and
dispensing of chemical agents for therapeutic use.
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10. General Principles of Drug Therapy
Two major divisions of medical
pharmacology:
pharmacodynamics (PD) & pharmacokinetics (PK)
Pharmacodynamics study of
1) molecular, biochemical and physiologic effects of drugs on cellular
systems
2) Drug-receptor interactions
3) drug mechanisms of action= therapeutic and toxic
 Operationally, what drug does to body
 Processes that determine variability in drug actions despite
equivalent drug delivery to effector sites
 Drug Concentration-Effect relationship
Dose-Response phenomena 10

11. General Principles of Drug Therapy
Two major divisions of med pharm (2)
Pharmacokinetics study of ADME
Absorption
Distribution
Metabolism
Excretion
Movement of drug molecules through various
physiologic compartments drug deposition
Operationally, what body does to drug
Processes that determine drug delivery to (in)
and removal from (out) molecular targets
Drug Concentration-Time relationship
drug in
drug out = Elimination
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12. General Principles of Drug Therapy
Drug deposition
Tissue
reservoirs
Bound Free
Absorption
Biotransformation
Free drug
Systemic
circulation
Bound drug Metabolites
The summation of these processes will determine plasma
drug concentrations (Cp) at any point in time
Excretion
Locus of
action
“receptors”
Bound Free
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13. General Principles of Drug Therapy
Third emerging division of medical
pharmacology
Learn more: Ritter JM, Lewis LD, Mant TG, Ferro A. Ch.14 Pharmacogenetics. In: A Textbook of Clinical
Pharmacology and Therapeutics 5th-ed. Hodder Arnold, 2008; Pgs. 79-85.
Pharmacogenomics study of how genetic makeup affects
PD and PK
affects drug selection and application to individual
patients
“Pharmacogenomics may hold the opportunity of allowing practitioners to
integrate a molecular understanding of the basis of disease with an individual's
genomic makeup to prescribe personalized, highly effective, and safe
therapies.”
From: Roden DM. (2012) Ch. 5 Principles of Clinical Pharmacology. In: Longo DL, Fauci AS, et al. Harrison's
Principles of Internal Medicine,18th Ed., McGraw-Hill 2012, Pg. 33
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14. General Principles of Drug Therapy
Relationship between PK and PD
Pharmacokinetics Pharmacodynamics
Dose of drug
Drug concentration
in target organ
over time
Mechanism and
magnitude of
drug effect
Absorption
Distribution
Biotransformation
Excretion
Receptor binding
Signal transduction
Physiological effect
Redrawn after Brenner GM and Stevens CW. Pharmacology 4th ed. (Sanders, 2014) 14

15. General Principles of Drug Therapy
Definition-Drug
No precise uniformly accepted definition
 commonly accepted -drug is any exogenous non-nutritive
substance that affects bodily function
In medicine drug is a chemical agent used in
prevention, diagnosis, treatment or cure of disease (or
affect fertility)
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16. General Principles of Drug Therapy
Drug- cardinal features:
 modify communication system within organism
[humans and (or) animals]
 modification should not interfere with fidelity of
biochemical and physiologic signal
 should not activate unwanted compensatory
response
 should selectively target specific cellular components
that Fx in normal signaling process
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17. General Principles of Drug Therapy
Properties of an ideal drug
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 Safety
Fewer side effects or lower toxicity
 Effectiveness
Better therapeutic effects
 Selectivity
Target to desired sites or molecules
NB Due to the multiple variations in patient profiles and drug
variables and the interaction between the two, the ideal drug
“Does not exist”

18. General Principles of Drug Therapy
Clinical Pharmacology
A complex interaction between patient and drug
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Patient profile
Age
Weight
Sex
Race
Allergies
Smoking history
Alcohol history
Diseases
Pregnant/lactating
Current therapy
Intelligence
Drug profile
Name (generic)
Class
Action
Pharmacokinetics
Indications
Contraindications/
precautions
Interactions
Side effects
Dosing regimen
Monitoring
Overdose
Patient profile
 The patient is a unique individual,
with many distinguishing features that need
to be taken into account during prescribing
Drug profile
 The drug, likewise, is unique,
with its own distinguishing features
 Good prescribing involves tailoring drug
and dosing regimen to unique patient
 Clinical pharmacology provides basis of
this pharmacotherapeutic principle

19. General Principles of Drug Therapy
Drug Nomenclature
Several names refer to the same drug:
 Chemical Name
 Based on a drug's chemical and molecular constituents and structure
 Generic Name (Nonproprietary, Approved)
 Assigned by manufacturer after approval by regulatory body in country of
origin (e.g., United States Adopted Names Council)
 Trade, Brand, or Proprietary Name
 Assigned by manufacturer, copyrighted and therefore can be used
commercially only by originating pharmaceutical company
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20. General Principles of Drug Therapy
Clinical Connection:
Drugs can have many different names:
For example, a prototypical calcium channel blocker of dihydropyridine class has
 Chemical name 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-
dihydropyridine-3,5-dicarboxylate
 Generic name nifedipine, and is available in U.S.under several
 Trade names including Adalat, Nifedical, and Procardia
Drug Nomenclature (2)
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21. General Principles of Drug Therapy
How drugs work
Drug effects are produced by altering normal functions of cells and
tissues via one of four general mechanisms:
1. Interaction with receptors
Ligand-activated ion channels
G-protein–coupled receptors
 Gαs-coupled receptors
 Gαi (Ginhibitory)-coupled receptors
 Gq (and G11)-coupled receptors
Intracellular nuclear receptors
Receptor-activated tyrosine kinases
2. Nonspecific chemical or physical interactions
 e.g., antacids
3. Antimetabolite action
 e.g., ChemoTx agents
4. Alteration of the activity of enzymes
 increasing or decreasing
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Note:
 Drugs do not produce new function
 No drug has a single action, but have both therapeutic and
adverse actions or have multiple therapeutic effects
 Drug vs poison dose related

22. General Principles of Drug Therapy
Receptors*
 Specialized proteins that are binding sites for
neurotransmitters and hormones
 Postsynaptic cell membranes (neurotransmitters)
 Cell nucleus (steroid hormones)
 Linked to one of many signal transduction mechanisms
“Receptor” (According to Rang & Dale Pharmacology):
A target or binding protein for a small molecule (ligand), which
acts as an agonist or antagonist.
Rang HP etal. Rang & Dale's Pharmacology, Churchill Livingstone; 7th edition 2011
*“not to be confuse with other drug targets such as enzymes etc.”
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23. General Principles of Drug Therapy
Ligand-Receptor Interactions
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 Complementary conformations in 3 dimensions
 Similar to enzyme-substrate interactions
 Physiologic interactions are weak attractions
 H-bonding, van der Waal’s forces
 Drug mechanisms
– Agonists - bind and activate receptors
– Antagonists - bind but DO NOT activate receptors
"Receptor" according to IUPHAR (International Union of Basic and Clinical Pharmacology):
A cellular macromolecule, or an assembly of macromolecules, that is concerned directly and specifically
in chemical signaling between and within cells. Combination of a hormone, neurotransmitter, drug, or
intracellular messenger with its receptor(s) initiates a change in cell function.

24. General Principles of Drug Therapy
Steps in Signal Transduction Process
 There are three general classes of signal transducing receptors:
 G-proteins are one and are referred to as serpentine receptors
Binding of the neurotransmitter, hormone or
drug to receptor> signaling of G-protein>
enzyme activation> production of a second-
messenger> protein kinase activation >
phosphorylation of specific proteins
(effect)> termination
See: GPCRs-Signal Transduction Toolkit (& Other Receptor Mechanisms)
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25. General Principles of Drug Therapy
The neurohormone epinephrine and its receptor (pink) is used in this example: The activated
receptor releases the Gs alpha protein (tan) from the beta and gamma subunits (blue and green) in
the heterotrimeric G-protein complex. The activated Gs alpha protein in turn activates adenylyl
cyclase (purple) that converts ATP into the second messenger cAMP
Mechanism of cAMP dependent signaling
GPCR structure & function (simplified)
G-Protein Coupled Receptor
Binding of neurotransmitter, hormone
or drug to receptor> signaling of G-
protein> enzyme activation>
production of a second-messenger>
protein kinase activation
>phosphorylation of specific proteins
(effect)>termination
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26. General Principles of Drug Therapy
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Neal, MJ Medical Pharmacology at a Glance.

27. General Principles of Drug Therapy
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28. General Principles of Drug Therapy
Further study:
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 eNotes: GP- General Principles of Drug Action
 Drug-Receptor Interactions, Morris ZS, Golan DE and (or) Brody’s Human
Pharmacology: Ch.1 Pharmacodynamics- Receptors and Concentration-
Response Relationships
 Enzyme kinetics Notes
 MedPharm Wiki| PK and PD, Pgs. 73-88
 Integrated Scientific & Clinical Pharmacology Course Website