OUR LADY OF FATIMA UNIVERSITY OUTCOMES:

COLLEGE OF PHARMACY At the end of the session the

Valenzuela. Quezon City. Antipolo. Pampanga. Cabanatuan. Laguna
students will be able to:
◉ Describe the different branches of
INTRODUCTION TO Pharmacology
◉ Describe what is a drug, its
PHARMACOLOGY characteristics, uses and
PHARMACOLOGY1 classification
◉ Enumerate and describe factors
affecting Absorption, Distribution,
Metabolism and Excretion
◉ Discuss important biological,
Instructor- College of Pharmacy genetic, and pharmacokinetic
Date
COURSE FACILITATOR factors that affect drug disposition
TIME
and response

1 2

OUTLINE: READINGS:
PART 1
• Divisions of Pharmacology • Katzung, B.G. et al. Basic and
• Definition and nature of Drug Clinical Pharmacology, 14th
• Classification of Drug according edition
to use • Wecker, L. (2018). Brody's
Human Pharmacology, 6th
PART 2 Edition. Mechanism-Based
• Review of Pharmacokinetic Therapeutics
principles

3 4

Watch these Videos: PART 1

Introduction to
Pharmacology: Oral Meds Absorption
https://www.youtube.com/watch?v=xiuWdJYyIKs Pharmacology
Enzyme inhibition and Enzyme induction
https://www.youtube.com/watch?v=cKzBpkiOrZg

5 6

1
 What is Pharmacology? DIVISIONS of Pharmacology
• the science of drugs and their effects Clinical
pharmacology
on biological systems Environmental Neuro
pharmacology pharmacology

Pharmacognosy PHARMACOLOGY Pharmacogenetics/

Pharmacogenomics

regulatory Pharmaco-
molecule Posology epidemiology
Toxicology

7 8

HISTORY What is a DRUG?

is any substance that brings about
a change in biologic function
through its chemical actions

It is used in:

Prevention
Diagnosis
Mitigation
1,500 years precursor of Treatment/Cure
17th century pharmacology

9 10

Nature of Drugs Nature of Drugs

1. Size and Molecular Weight 2. Drug-Receptor Bonds
→ Sizes from MW 7 (Lithium) to
over MW 50,000 (thrombolytic
enzymes, other proteins)

→ Majority of drugs have MW

between 100 and 1000.

11 12

2
 Classification of drugs according to use
3. How are drugs named?
 Functional Modifiers
2-(p-isobutylphenyl) propionic acid Chemical name  Replenishers
Ibuprofen Generic name (nonproprietary name)
 Diagnostic Agents
INN or USAN  Chemotherapeutic Agents
Motrin® Trade name
(proprietary name/brand name)

13 14

Classification of drugs according to use Classification of drugs according to use

1. Functional Modifiers 2. Replenishers
➢alter or modulate the normal ➢Supplement endogenous
physiologic functions substances that are lacking or
deficient in the body
➢Examples:
✓Analgesic drugs ➢Examples:
✓Hormones (Insulin)
✓Anti-pyretic drugs
✓IV
Fluids/Electrolyte/ORS
✓Anti-inflammatory drugs
✓Multivitamins
✓Anti-hypertensive drugs

15 16

Classification of drugs according to use Classification of drugs according to use

3. Diagnostic Agents
2. Replenishers
➢ Agents used to determine the presence
➢In the case of pernicious anemia or absence of a condition or a disease
Examples:
(autoimmune disease) that destroys ➢
✓ Edrophonium (Tensilon’s Test)
parietal cells which secretes HCl and
✓ Histamine
intrinsic factor, take Vitamin B12
✓ some Radiopharmaceuticals
✓ Bariumsulfate
Note: Pernicious anemia may also be caused by PPIs, H2 ✓ Dobutamine and Dipyridamole for
Blockers, and Fish Tape worms. “Pharmacologic Stress Testing” for CAD and
MI.
NOTE: Stress Test is an electrocardiographic test of heart
function before, during, and after a controlled period
of increasingly strenuous exercise.

17 18

3
 Classification of drugs according to use
4. Chemotherapeutic Agents
PART 2
➢Agents used to kill or inhibit growth
of cells or nucleic acid considered Review of
as foreign to the body. Selective
toxicity is considered Pharmacokinetics
➢Examples:
✓Anti-infectives
✓Antineoplastics

19 20

Two Main Areas of Pharmacology What is Pharmacokinetics?

The study of the fate of drugs in
1.Pharmacokinetics the body :
2.Pharmacodynamics
drug disposition= the way in
which the body handles drugs

21 22

REVIEW OF PHARMACOKINETIC PRINCIPLES LIBERATION

What is the fate of the drug in vivo? The release of active ingredient from
its dosage form.
.... LADME ....
1. Disintegration
2. Dissolution - (rate-limiting step
in absorption of solid dosage forms
and consequently onset, intensity,
and duration of action of the drug).

23 24

4
 LIBERATION LIBERATION
Factors that influence the dissolution rate:  Factors that influence the dissolution rate:
Crystal form or amorphous drug forms
Surface area B
A  → Ex: Choramphenicol palmitate is inactive in
crystalline form but when it is administered in
amorphous form, absorption in the GIT is rapid and
Which one has a larger surface area? with good therapeutic response.
Saltforms - dissolve much readily when → Ex: Insulin
compared to the drugs in its free form a. Short-acting→ Semilente (100% amorphous)
b. Intermediate→ Lente (30% amorphous and 70%
crystalline)
State of hydration
c. Long-acting→ Ultralente (100% crystalline)
Anhydrous vs. Hydrated form

25 26

ABSORPTION FACTORS AFFECTING ABSORPTION:

RATE and EXTENT of DRUG entry into 1. Dose size administered -
the systemic circulation dose = drug absorption
Bioavailability- The proportion of 2.Degree of
a drug that is delivered to its site perfusion of
of action in the body. the absorbing
environment
blood supply =
greater extent/
faster absorption

27 28

FACTORS AFFECTING ABSORPTION

FACTORS AFFECTING ABSORPTION
3. Areas of the absorbing surface
4. pH of the absorbing
environment

29 30

5
 Environmental pH and Ionization
Aspirin is an acidic drug. In the
stomach will it exist mostly in ionized
If we put an acidic drug in an or non-ionized form?
environment with a lot of H+ (low pH)
what will this equilibrium do?

NON-IONIZED
Why?
HA H+ + A-
HA
HA

 HSystem
+
from at
Non-ionized acid environment
Equilibrium
form predominates!

31 32

How will this affect aspirin

Moral of the story...
absorption?
Lipid Bilayer
Acidic drugs are best absorbed
from acidic environments.
Ionized form
A-
(charged)
Basic drugs are best absorbed from
basic environments.

Non-Ionized form
(uncharged) HA HA

33 34

So...
FACTORS AFFECTING ABSORPTION
5. Gastric emptying – time it takes for
To  absorption of an acidic drug… the stomach to empty its contents
acidify the environment.

To  absorption of an acidic drug…

alkalanize the environment.

35 36

6
 37 38

Factors that Increase Gastric Factors that Decrease Gastric

Emptying Time: Emptying Time:
1. Stress 1. Mild Exercise
2. Heavy Exercise 2. Gastrectomy
3. Gastric Ulcers 3. Cold Foods/Drinks
4. Hot Food (Protein Rich, Lipid-Rich 4. Lying on the right side
Foods) 5. Use of motility enhancing drugs
5. Lying on the left side 6. Diabetes mellitus
6. Drugs that inhibit gastric motility

37 38

FACTORS AFFECTING ABSORPTION

FACTORS AFFECTING ABSORPTION
6. Dosage form 7. Drug solubility- for a drug to be
absorbed, its solubility must
correspond to the characteristics of the
absorption site.

39 40

FACTORS AFFECTING ABSORPTION 9. Enterohepatic recycling- some drugs

8. First-pass effect- some
drugs are partially metabolized
in the liver or portal vein before
passing into circulatory system.
travel intact through the biliary tract after
initial absorption and are then reabsorbed
into bloodstream through the intestine

41 42

7
 ABSORPTION
Factors That Affect Absorption
ABSORPTION
10. Routes
→A drug’s route of administration affects its rate
11. TRANSPORT MECHANISMS
and extent of absorption.
 Enteral- oral, sublingual, buccal, rectal
 Parenteral- IV (fastest), IM, SC, ID, others - means of movement of drug molecule
 Topical- Skin (including transdermal patch), eyes,
ears, nose, lungs (inhalation), vagina
across cell membrane

NOTE: In enteral route, a drug is absorbed into the systemic

circulation through the oral or gastric mucosa, the small
intestine, or rectum.

43 44

Specific Modes of Drug Transport

(Permeation)

1.Passive Diffusion
2.Carrier-mediated Transport
3.Convective (Pore) Transport
4.Vesicular Transport
5.Ion-Pair Transport
Passive
diffusion Carrier Mediated Transport
45 46

Examples
Inorganic and organic electrolytes up Ion-pair Transport
to 150 to 400 MW
Ions of opposite charge of pore lining
Ionized sulfonamides  QUATERNARY AMMONIUM COMPOUND (+) AND
MUCIN (-) = UNIONIZED (no charge) SO IT CAN EASILY
Convective (Pore) Transport PASS THROUGH THE CELL MEMBRANE
Examples
Fats, glycerin, starch
Parasite eggs
Plastic particles, hairs
and yeast cells
Ferritin and insulin

Endocytosis Exocytosis
Griseofulvin
bulk transport Fat-sol vitamins
Vesicular Transport

47 48

8
 DISTRIBUTION DISTRIBUTION
 The transport of a
drug in the body by Parameters
the bloodstream to ▪ Volume of Distribution
its site of action.
▪ Protein Binding
 The extent to which ▪ BBB and Placental Barrier
the drug passes into
different tissues and
fluid compartments
in the body.

49 50

DISTRIBUTION DISTRIBUTION
Physiologic Factors Affecting Distribution Physiologic Factors
▪ Cardiac Output- Affecting Distribution
Normal=2.2-3.5 liters/min/square meter ▪ Regional Blood Flow-
*Low CO in the case of CHF→ low distribution= fraction of cardiac output
slower onset of action of drugs
that is delivered to
*Liver, kidneys, and Brain 25% CO; Lungs 100% CO;
Adipose tissues and Bones <1 % CO specific tissues/organs
*Pneumonia 7-14 days treatment because 100% →Areas of high blood
CO flow: heart, liver, kidneys,
*Osteomyelitis 6 weeks to 6 months Tx (very low CO) brain
→Areas of low blood flow:
muscle, skin, fat, bone

51 52

DISTRIBUTION DISTRIBUTION
1. Volume of Distribution (VD)
➢ The hypothetical volume of body fluid
necessary to dissolve a given amount or
dose of a drug to achieve a concentration
equal to that of the drug plasma
concentration.
High VD Low VD
-basic drugs -acidic drugs
-examples: -examples:
-atropine, chloroquine -chlorpropamide
-raloxifene -tolbutamide

53 54

9
 DISTRIBUTION Protein binding
2. Protein Binding
albumin
➢ Itis the phenomenon that occurs when a
drug combines with plasma (particularly acidic drugs
albumin) or tissue protein to form a Alpha acid
complex. erythrocytes glycoprotein
Exogenous/endog Protein basic drugs
enous compounds

lipoproteins globulin

Lipids or proteins hormones

inactive
55 56

DISTRIBUTION
Factors Affecting Protein Binding
1. The drug itself
2. The protein itself
3. Affinity between the drug & the protein
4. Drug Interactions
5. Physiologic Condition of the patient.

57 58

DISTRIBUTION
DISTRIBUTION Prediction of Extent of Distribution

3. Special Barriers: BODY FLUID % BODY

WEIGHT
70 KG BODY
WEIGHT
❑Placental: Most small molecular Total Body Fluid 60% 42 Liters
weight drugs cross the placental 1. Intracellular 40% 28 L
barrier, although fetal blood levels
2. Extracellular 20% 14 L
are usually lower than maternal.
2.a. Intravascular (High MW 5% 3-4 L
and high protein bound drugs
❑Blood-Brain: It is permeable only like Heparin)
to lipid-soluble drugs or those of 2.b. Interstitial (Low MW and 15% 10-11 L
very low molecular weight. hydrophilic drugs like
Aminoglycosides

59 60

10
 METABOLISM
“Biotransformation”
“Inactivation” Why is drug biotransformation
necessary?
“Detoxification”

61 62

63 64

Drug Biotransformation Reactions

Active Drug to Reactive Metabolite
Polar Metabolite

Inactive Metabolite
ACTIVE DRUG
Active Metabolite
Reactive Metabolite

PRODRUG Active Metabolite

63 64

65 66

Where do drug Biotransformations occur?

OTHER SITES:
MAJOR SITE: CNS

Skin Lungs

GIT
Prostate

65 66

11
 67

First Pass Metabolism

• the phenomenon whereby drugs may be
metabolized following absorption before reaching
systemic circulation.
• a.k.a. “First Pass Effect” What are enzyme
• Examples:
➢ Morphine
inducers and inhibitors?
➢ Meperidine
➢ Pentazocine
➢ Catecholamines
➢ Propranolol
➢ Beta Blockers

67 68

Enzyme Inducers 70

• Examples: Enzyme Inhibitors

✓Carbamazepine  Examples:

✓Phenobarbital ✓ Cimetidine
✓ Ketoconazole
✓Phenytoin
✓ Chloramphenic
✓Rifampicin
✓ Disulfiram
✓Smoking
✓ Grapefruit Juice
✓Chronic ✓ Acute Alcoholism
Alcoholism
✓ decrease the metabolic activity
of an enzyme, increase the
✓ increase the metabolic activity pharmacologic action of co-
of an enzyme, decrease the administered drugs
pharmacologic action of co-
administered drugs

69 70

Phases of Drug Metabolism

Possible routes for metabolism of drugs

71

71 72

12
 73 74
Phase 1 Reactions
reactions that convert the parent drug to a Phase 1
more polar (water-soluble) or more reactive
product by unmasking or inserting a polar a. Oxidation
functional group such as -OH, -SH, or –NH2.
a.k.a. “ Functionalization Reaction”. 1. CYP 450 Mediated
a. Oxidation 2. Non CYP 450 Mediated
b. Reduction
c. Hydrolysis

73 74

75

75 76

77 78

13
 80

Types of Reaction:
➢Hydroxylation (Phenytoin)
➢N-Dealkylation (Morphine)
➢O-Dealkylation (Codeine)
➢N-Oxidation (Nicotine)
➢S-Oxidation (Thioridazine)
➢Deamination (Amphetamine)

79 80

81
b.Reduction 82

2. Non CYP 450 Mediated

Carbonyl reduction
Eg .Acetohexamide
a. Xanthine Oxidase
b. Flavin Monooxygenase (Ziegler’s
enzyme)
c. Amine Oxidases (Epinephrine)
Azoreduction
d. Dehydrogenation(Ethanol) -Sulfasalazine

Nitroreduction
-Clonazepam

81 82

83 84

Types of Reactions:
c.Hydrolysis
 is the splitting up of a molecule with ➢ Ester Hydrolysis
water, the –OH group of water becoming (Cocaine, Aspirin, Enalapril)
part of one molecule and the hydrogen
atom becoming part of the other. ➢ Amide Hydrolysis
(Lidocaine, Procainamide,
Indomethacin)

83 84

14
 PHASE II or
CONJUGATION REACTIONS
1. Convert the Phase I metabolites to more
polar and water-soluble products.
Conjugated products
relativelywater soluble and readily
excretable
biologically inactive and nontoxic

Attachmentof small,polar and ionizable Other phase II reactions, such as

endogenous molecules, such as:
methylation and acetylation
sulfate glycine do not generally increase water solubility but
mainly 2. serve to terminate or attenuate
glucuronic acid glutamine pharmacological activity.

85 86

Phase II reactions
3.Detoxification
can be regarded as detoxifying
pathways

The role of GSH is to combine with

chemically reactive compounds to
prevent damage to important
biomacromolecules such as DNA, RNA
and proteins.

87 88

Glucuronidation
90

In neonates and children,

neonatal hyperbilirubinemia
glucuronidating processes are
inability of newborns to conjugate
often not developed fully. bilirubin with glucuronic acid

gray baby syndrome

accumulation of drug
inability to metabolize
chloramphenicol
toxicity

89 90

15
 91

2. Acetylation
 Examples: Sulfonamides, Isoniazid,
Hydralazine, Procainamide
What are the processes
involved in the metabolism of
Aspirin and Paracetamol?

91 92

Acetaminophen
In adults:
Major metabolite: O-glucuronide
conjugate
O-sulfate conjugate formed in small
amounts

In infants and young children (ages 3 to 9

years)
0-sulfate conjugate is the main urinary
product

93 94

95 96

Factors Affecting Drug Metabolism Genetic factors

Isoniazid metabolism - acetylation
1. Chemical Structure of Drug
plasma Effect
2. Genetic Differences half-life

3. Diet & Environmental Factors Slow Egyptians 140 t0 peripheral neuritis

acetylators Western 200 and drug-induced
4. Physiologic Stress or Disease Europeans systemic lupus
minutes erythematosus
5. Age syndrome)

6. Gender
7. Drug Interactions Fast Eskimos 45 to 80 develop isoniazid-
acetylators Asians minutes associated hepatitis
(acetylhydrazine.)

95 96

16
 Genetic Polymorphisms in Drug Metabolism Genetic Polymorphisms in Drug Metabolism

97 98

Genetic Polymorphisms in Drug Metabolism Genetic Polymorphisms in Drug Metabolism

99 100

101 102

Diet Diet
Charcoal broiled foods Grapefruit juice
Fur
an
oc
ou
m
Inhibit CYP3A
ari
ns

Metabolism of
CRUCIFEROUS coadministered
vegetables drug

Induce CYP1A enzymes

101 102

17
 103

Enzyme induction
Diseases affecting drug
metabolism
Cigarette smoking
Workers exposed to some pesticides

103 104

EXCRETION
▪ The removal of drugs from the body EXCRETION
▪ A drug or metabolite must be polar or
water-soluble. Half-Life
 The time it takes for
one half of the original
amount of a drug in
the body to be
removed.
 A measure of the rate
at which drugs are
removed from the
body.
https://www.google.com/search?q=excretion+of+drugs&tbm=isch&ved=2ahUKEwiH98uK9brsAhWGAKYKHZRIDL0Q2-
cCegQIABAA&oq=excretion+of+drugs&gs_lcp=CgNpbWcQAzICCAAyAggAMgIIADICCAAyAggAMgYIABAFEB4yBggAEAUQHjIGCAAQBRAeMgYIABAFEB4y
BggAEAUQHjoECAAQQzoFCAAQsQM6BwgAELEDEENQl68FWPrHBWDGyQVoAHAAeACAAbcBiAHNEpIBBDAuMTiYAQCgAQGqAQtnd3Mtd2l6LWltZ8AB
AQ&sclient=img&ei=yIOKX4fzAYaBmAWUkbHoCw&bih=657&biw=1366#imgrc=48EKSCIMQQyLiM

105 106

ACTIVITIES for next meeting

Thank you!
1. Take Quiz no. 1 Any questions?
Topic:
You can find me at:
General Principles in Pharmacology username@fatima.edu.ph
Review of Pharmacokinetics
2. Attend Online Lecture via Zoom Meeting
Topic: Review of Pharmacodynamics
#RisetotheTop
107
Duration: 90 minutes
3. Submit Assign no. 1

107 108

18