Pharmacologic

Principles (Part 2)
NCM 106 – PHARMACOLOGY
2nd Semester, AY 2021-2022

/mabansig/v.01/02.19.2022
 Learning Objectives
At the end of the session, the students shall be able to:

▪ Differentiate pharmacodynamics from pharmacokinetics

▪ Discuss pharmacodynamic principles

▪ Discuss pharmacognosy and herbal medications

 3
PHARMACODYNAMICS
The actions of a drug on the body,
including receptor interactions,
dose-response phenomena, and
mechanisms of therapeutic and
toxic actions
 PHARMACODYNAMIC PRINCIPLES
DRUG RECEPTOR - A molecule to
which a drug binds to bring about a
change in function of the biologic
system
- must be selective in their
ligand-binding characteristics
- modifiable when they bind a
drug molecule
RECEPTOR SITE (recognition site) -
specific binding region of the receptor
macromolecule
- has a relatively high and selective
affinity for the drug molecule.
TYPES OF DRUG-RECEPTOR INTERACTIONS
Drug (D) + receptor-effector (R) → drug-receptor-effector
complex → effect

D + R → drug-receptor complex → effector molecule → effect

D + R → D-R complex → activation of coupling molecule →

effector molecule → effect

Inhibition of metabolism of endogenous activator → increased

activator action on an effector molecule → increased effect
EFFECTOR
- Component of a system that
accomplishes the biologic
effect after the receptor is
activated by an agonist; often a
channel, transporter, or enzyme
molecule, may be part of the
receptor molecule

eg. sodium-potassium channel

is the effector part of the nicotinic
acetylcholine receptor; tyrosine
kinase effector enzyme is
part of the insulin receptor molecule
GRADED DOSE-RESPONSE RELATIONSHIP & BINDING AFFINITY
GRADED DOSE-RESPONSE CURVE - A graph of the increasing response
to increasing drug concentration or dose
- It is where the efficacy (Emax) and potency (EC50 or ED50) parameters
are derived.
- The smaller the EC50 (or ED50), the greater the potency of the drug.
 GRADED DOSE-BINDING RELATIONSHIPS
GRADED DOSE-BINDING CURVE
- The concentration
of drug required to bind 50% of the
receptor sites is denoted
by the dissociation constant (Kd)
- it is a useful measure of the affinity
of a drug molecule for its binding
site on the receptor molecule. The
smaller the Kd, the greater the
affinity of the drug for its receptor.
GRADED DOSE-BINDING RELATIONSHIPS

Where
[D] = the concentration of free drug,
[DR] = the concentration of bound drug,
[Rt] = the total concentration of receptors and is equal to the
sum of the concentrations of unbound (free) receptors and bound
receptors, and
Kd = the equilibrium dissociation constant for the drug from the
receptor
 QUANTAL DOSE-RESPONSE RELATIONSHIPS
• QUANTAL DOSE-RESPONSE RELATIONSHIP
– defined as the minimum dose required to
produce a specified response is determined in
each member of a population
• QUANTAL DOSE-RESPONSE CURVE - A
graph of the increasing fraction of a
population that shows a specified response at
progressively increasing doses
• QUANTAL DOSE-RESPONSE DATA - provide
information about the variation in sensitivity
to the drug in a given population
- If the variation is small, the curve is steep.
 EFFICACY
- is the greatest effect
(Emax) an agonist can produce if
the dose is taken to the highest
tolerated level

Partial Agonists - have lower

maximal efficacy than full
agonists
 POTENCY
- a measure of the amount of drug necessary to produce an effect of a
given magnitude.
- The concentration of drug producing 50% of the maximum effect (EC50) is
usually used to determine potency.
SPARE RECEPTORS

- exist if the maximal drug

response (Emax) is obtained
at less than 100%
occupation of the receptors
(Bmax)
AGONISTS, PARTIAL AGONISTS, & INVERSE AGONISTS

Agonist - A drug that

activates its receptor upon
binding

Constitutive activity -
Activity in the absence of
ligand is
• Full agonist - If a drug binds to
a receptor and produces a
maximal biologic response that
mimics the response to the
endogenous ligand
• Partial agonist - A drug that
binds to its receptor but
produces a smaller effect (Emax)
at full dosage than a full agonist
• Inverse agonists - A drug that
binds to the non-active state of
receptor molecules and
decreases constitutive activity
 ANTAGONISTS
• Pharmacologic antagonist -
A drug that binds without
activating its receptor and
thereby prevents activation
by an agonist
• Allosteric agonist,
antagonist - A drug that
binds to a receptor molecule
without interfering with
normal agonist binding but
• alters the response to the
normal agonist
A. COMPETITIVE AND IRREVERSIBLE
PHARMACOLOGIC
ANTAGONISTS

• Competitive antagonist - A
pharmacologic antagonist that can
be overcome by increasing the
concentration of agonist
• Irreversible antagonist - A
pharmacologic antagonist that
cannot be overcome by increasing
agonist concentration
B. PHYSIOLOGIC ANTAGONISTS
- A drug that counters the effects of another by binding to a
different receptor and causing opposing effects

C. CHEMICAL ANTAGONISTS
A drug that counters the effects of another by binding the
agonist drug (not the receptor)
THERAPEUTIC INDEX & THERAPEUTIC WINDOW
• THERAPEUTIC INDEX (TI)
- the ratio of the dose that produces
toxicity in half the population (TD50) to
the dose that produces a clinically
desired or effective response (ED50) in
half the population:
TI = TD50/ED 50
• THERAPEUTIC WINDOW
- describes the dosage range between the
minimum effective therapeutic
concentration or dose, and the minimum
toxic concentration or dose.
 SIGNALING MECHANISMS
- designed to transmit information from the cell surface to specific
targets within the cell

Types of transmembrane signaling receptors:

1. Intracellular, often steroid receptor-like - Steroids, vitamin D, nitric
oxide, and a few other highly membrane-permeant agents cross the
membrane and activate intracellular receptors

2. Membrane-spanning receptor-effector enzymes - Insulin, epidermal

growth factor, and similar agents bind to the extracellular domain of
molecules that incorporate tyrosine kinase enzyme activity in their
intracellular domains. Most of these receptors dimerize upon activation
3. Membrane receptors that bind intracellular tyrosine kinase enzymes
(JAK-STAT receptors) - Many cytokines activate receptor molecules that
bind intracellular tyrosine kinase enzymes that activate transcription
regulators that migrate to the nucleus to bring about the final effect

4. Ligand-activated or modulated membrane ion channels - Certain Na+/K+

channels are activated by drugs: acetylcholine activates nicotinic Na+/K+
channels, serotonin
activates 5-HT3 Na+/K+ channels
5. G-protein-coupled receptors(GPCRs) - consist of 7 transmembrane (7-TM)
domains and when activated by extracellular ligands, bind trimeric G
proteins at the inner membrane surface and cause the release of activated
Gα and Gβγ units.
 4
PHARMACOGNOSY
The study of the physical, chemical, biochemical
and biological properties of drugs, drug
substances, or potential drugs or drug
substances of natural origin as well as the
search for new drugs from natural sources.”
- American Society of Pharmacognosy
Dietary Supplement Health and Education Act Of 1994
DEFINITION OF SUPPLEMENTS:

• intended to supplement the diet

• Contains one or more dietary ingredients (including
vitamins, minerals, herbs or other botanicals,
amino acids, and certain other substances) or their
constituents
• intended to be taken by mouth ( tablet, capsule, powder,
softgel, gelcap, or liquid)
• labeled as being a “dietary supplement”
5 COMPONENTS REQUIRED ON ALL LABELS :
1. Name of the supplement
2. Amount of the supplement (net quantity)
3. Nutrition labeling
4. Ingredient list
5. Name and place of the manufacturer, packer, or distributor
 ALLOWED CLAIMS
(1) Health claims
(2) Structure and function claims
(3) Nutrient content claim
CURRENT GOOD MANUFACTURING PRACTICES
- FDA proposed standards for
marketing and labeling dietary
supplements in 2003
- Require package labels give the
quality and strength of all contents
and that products be free of
contaminants and impurities
- “Seal of approval” - U.S.
Pharmacopeial Convention (USP),
ConsumerLab.com, National Products
Association, and NSF International
 DEFINITIONS OF HERBAL PREPARATIONS
1. Decoction – A tea made from boiling plant material in water.
May be used therapeutically. Natural dyes are often made this
way.
2. Infusion - A tea made by pouring water over plant material
- the mixture is allowed to steep. The water is usually boiling, but
cold infusions are also an option
- hot tea is an excellent way to administer herbs.
3. Tincture - An extract of a plant made by soaking herbs in a dark
place with a desired amount of either glycerine, alcohol, or vinegar
for two to six weeks.
- The liquid is strained from the plant material
4. Liniment - Extract of a plant added to either alcohol or
vinegar and applied topically for therapeutic benefits.
5. Poultice - therapeutic topical application of a soft moist
mass of plant material, usually wrapped in a fine woven cloth.
6. Essential oils - Aromatic volatile oils extracted from the
leaves, stems, flowers, and other parts of plants.
7. Herb-infused oils - A process of extraction in which
the volatile oils of a plant substance are obtained by
soaking the plant in a carrier oil for approximately 2
weeks and then straining the oil.
8. Percolation - A process to extract the
soluble constituents of a plant with the
assistance of gravity.
- The material is moistened and evenly
packed into a tall, slightly conical
vessel
- The liquid (menstruum) is then poured
onto the material and allowed to
steep for a certain length of time. A
small opening is then made in the
bottom, which allows the extract to
slowly flow out of the vessel. (eg.
tinctures and liquid extracts)
 COMMONLY USED HERBAL REMEDIES
Astragalus (A. membranaceus and A. mongholicus)
- used as an adjunct to boost the immune system, such as for hepatitis and
cancer; limit the effects of cold and flu symptoms

Chamomile (Matricaria recutita and Chamomilla recutita)

- used primarily to treat sleeplessness, anxiety, and stomach or intestinal
ailments

Cinnamon (Cinnamomum zeylanicum and C. cassia)

- use as a treatment for bronchitis, gastrointestinal (GI) problems,
anorexia, and diabetes
Echinacea (Echinacea purpurea)
- commonly used for colds, flu, and infections
- has been used for skin problems such as acne
- It is thought to stimulate the immune system to fight infection.

Garlic (Allium sativum)

- reported to lower cholesterol, decrease blood pressure, and reduce heart
disease
- also used to prevent cancer of the stomach and colon.

Ginger (Zingiber officinale)

- used to treat postoperative, pregnancy-related, and chemotherapy-related
nausea as well as motion sickness and diarrhea

Ginkgo (Ginkgo biloba)

- treat asthma, bronchitis, fatigue, and tinnitus
Ginseng (Panax ginseng)
-used to boost the immune system, increase a person’s sense of well-being, and
increase stamina

Hawthorn (Crataegus laevigata and C. monogyna)

- predominantly used in the treatment of heart disease (e.g., heart failure and
angina)
- also used to treat digestive issues and kidney disease.

Licorice Root (Glycyrrhiza glabra and G. uralensis)

- used to treat stomach ulcers, bronchitis, sore throat, and viral hepatitis

Milk Thistle (Silybum marianum)

- used widely to treat cirrhosis, chronic hepatitis, and gallbladder disorders
Peppermint (Mentha x piperita)
- treat a wide variety of ailments like nausea, indigestion,
irritable bowel syndrome (IBS), cold symptoms, headaches, and muscle and
nerve pain

St. John’s Wort (Hypericum perforatum)

- used extensively throughout history to treat mental disorders and nerve pain,
treatment for malaria, sleep disorders, and wounds

Turmeric (Curcuma longa)

- used for heartburn, stomach ulcers, gallstones, inflammation, and cancer

Valerian (Valeriana officinalis)

- widely used in the treatment of insomnia, anxiety,
headaches, depression, irregular heartbeat, and tremors
 POTENTIAL HAZARDS OF HERBS
• Herbs are natural substances, natural does not mean safe.
• Possible herb-drug interactions
• Examples:
Asian ginseng - induces the drug-metabolizing enzyme
CYP3A
Goldenseal – potent inhibitor of CYP3A4 and CYP2D6
St. John’s wort - potent inducer of CYP-450 enzymes and
intestinal p-glycoprotein
- significant documented interactions with
cyclosporine, indinavir, oral contraceptives, warfarin,
digoxin, and benzodiazepines
REFERENCES:

Katzung, B. (2015). Basic and Clinical Pharmacology 12/E (LANGE Basic

Science) 12th (twelve) edition (13th ed.). Mc Graw Hill.

Msn, P. L. M. E., Msn, D. K. R., Acanp-Bc, W. M. P. R. B., & Aprn, R. P. J. Y. J.

(2022). Pharmacology: A Patient-Centered Nursing Process Approach,
11e (11th ed.). Saunders.

Whalen, K. (2015). Pharmacology Lippincott Illustrated Reviews (6th ed.) [E-

book]. Wolters Kluwer.