1.

1 INTRODUCTORY CONCEPTS PHARMACOLOGY

Dr. Garcia | June 19, 2013 1st 2013-2014

OUTLINE - bind to proteins particularly α1 acid glycoprotein

I. Definition of Terms
II. Branches of Pharmacology
C. Prototype Drugs
III. Major Branches of Pharmacology  Typify the most important characteristics of a class or group
IV. Drug Development of drugs
V. Placebo
 Representative drug of every family that has almost all the
VI. Types of Drug Action
characteristics (2015B trans)
OBJECTIVES
1. To understand the terminologies, basic principles of Pharmacology, the Prototype drug Group Use for treatment
different branches, different phases of drug development, and to Cimetidine H2 blockers Peptic ulcer
differentiate the different types of drug action. Propranolol Beta blockers Hypertension
References: Erythromycin Macrolides Antibiotic
Dr. Garcia’s PPT
Omeprazole Proton pump inhibitor Peptic ulcer
Katzung, B.G.(2012). Basic and Clinical Pharmacology: 12th Edition.New York :
McGraw-Hill Medical. Table 1. Examples of Prototype drugs
2015B Trans D. Drug Names
Legend: Italicized – quoted from the lecturer; bold – emphasis, or from references
 Chemical name – chemical structure of the drug
 Nonproprietary name – generic name, the international name
I. DEFINITION OF TERMS (must know to be able to understand, used in prescription)
 Proprietary name – brand name, given by drug manufacturer
A. Pharmacology
 Example:
 The Science that deals with the study of substances that interact o Nonproprietary name: Paracetamol
with the living system through chemical processes especially by o Chemical name: N-acetyl-para-aminophenol
binding to regulatory molecules and activating or inhibiting o Proprietary name: Tylenol/Tempra/Biogesic
normal body processes. E. Pharmaceutical Preparations
 These substances may be chemicals administered to achieve a
beneficial therapeutic effect on some process within the patient  Tablets and capsules
or for their toxic effects on regulatory processes in parasites  Drug solutions and particle suspensions
infecting the patient (Katzung)  Skin patches
 GOAL: to understand the mechanisms by which drugs interact  Aerosols, nasal sprays
with biologic systems in the diagnosis and treatment of disease.  Ointments and creams
(2015B trans)  Suppositories (vaginal, urethral, rectal suppositories)
B. Drug
 A natural product, chemical substances, or pharmaceutical
preparation to be used in the diagnosis or treatment of a disease.
II. BRANCHES OF PHARMACOLOGY
 Varies in terms of: A. Pharmacy
o Molecular size  Compounding, preparation, collection, standardization and
 Usually within100-1,000 MW dispensing of the drug
 Lower limit of 100 – set by the requirements for specificity B. Pharmacognosy
of action.  Study of crude drugs
- To have a good “fit” to only one receptor, a drug molecule  Recognition of the drugs: desctiption, sources, chemical
must be sufficiently unique in shape, charge, and other copmostion, nature of doing, etc
properties to prevent its binding to other receptors.
 Study of the physical and chemical properties of the drugs with
(Katzung)
the description and identification of their sources and nature
 Upper limit of 1,000 – determined primarily by the ability to
 Ex: sources can be animals(epinephrine, insulin), plants
move within the body (from site of administration to the site
(alkaloids - organic substances/compounds made up of
of action) (Katzung)
carbon, oxygen, nitrogen), minerals (Iron, Iodine)
 Drugs with greater than 1,000 MW would not diffuse readily
between compartments of the body thus, it must be
C. Biochemorphology
administered directly into the compartment where they  SAR (Structure Activity Relationship)
have their effect. (Katzung)  How the chemical structure of the drug is related to physiological,
o Shape of the receptor biological, and biochemical effects
 Receptors can be enzymes, neurotransmitters, ion channels EXAMPLES:
 Drug molecule should be complementary to the shape of its  Endogenous Catecholamines: synthesized in the body
receptor o Norepinephrine – affects α1, α2, β1 receptors
o Chemical nature o Epinephrine – affects α1, α2, β1, β2receptors
 Weak acids (e.g. aspirin, mefenamic acid, NSAIDs) o Dopamine
- bind to a protein (most of the time, albumin) o Tyrosine
 Weak bases (e.g. acetazolamide, antacids, Mg or Al
hydroxide, beta blockers)

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Group 9: Cabili, Cabrera, Cabuang, Cabuguason, Cabungcal, Caldozo, Calingo, Calma, Calubayan

 Exogenous (Synthetic) Catecholamines: synthesized outside the
body
o Isopoterenol – affects β1, β2 receptors
 Ephedrine – mixed - acting symphatomimetic agent; CNS
stimulation; not a catecholamine but its effects on bronchi and
other smooth muscles are quantitatively similar to those of
epinephrine
 Amphetamine - acts indirectly by releasing norepinephrine; also
a CNS stimulant; depresses the appetite by affecting the feeding
center in the hypothalamus
NOTE: ephedrine and methamphetamine are NOT catecholamines
D. Toxicology
 Study of the harmful effects of drugs and other chemicals on
human, animals, and plants
 There is no safe drug
 Examples:
o NSAIDs – should be taken after, or with meals, otherwise can
cause ulcer
o Diphenhydramine – H1 receptor antagonist; Drowsiness as a
toxic effect
o Aspirin– should not be given to pediatric patients, can cause
nose bleeding or vertigo
o Organophosphate (i.e. Baygon) ‐ they are highly lipid soluble
thus easily absorbed by skin. Increased levels could lead to
poisoning
o Paracetamol - overdose can lead to liver necrosis
o INH (isoniazid) – for treatment of TB; overdose may lead to
hepatotoxicity
D. Posology
• Deals with the dosage of the drug required to produce a
therapeutic response or effect (Recommended dosage, dosage
regimen)
 Example:
o elderly – dosage is reduced to half
o children – liver and kidneys are not yet developed, dosage is
computed using their weight in kilograms
 Recomended doseper kg body weight (Pediatric)
o Amoxicillin: 30-50mg/kg body weight
o Ampicilline: 50-70mg/kg body weight
E. Molecular Pharmacology
• Studies the mechanism of action of a drug at enzymatic level
o Gene Therapy – insertion, alteration or removal of genes w/in
an individual’s cells to treat a disease
o Genetic Engineering– produces products called
“biopharmaceuticals” insertion of artificial gene to produce
certain effects
 Almost related to pharmacogenetics, pharmacogenomics,
ethnopharmacology
F. Development Pharmacology
• Deals with drugs given to a mother as it affects the fetus during
natal, prenatal, perinatal & neonatal periods.
• Several drugs are not safe for pregnant mothers especially during
the 1st trimester, harmful effects to fetus (even vitamins; usually
st
given after 1 trimester)
• Examples:
o Anti-epileptic drugs: teratogenic
 Phenobarbital – for seizures
 Dilantin/Phenitoin –produces cleft lip in babies
o Anti-malarial drugs: teratogenic and fetotoxic
PHARMACOLOGY Lec#1.1
 Quinine – for malaria
o Aminoglycosides
 used in the treatment of bronchopneumonia, pneumonia,
used in combination with beta-lactam drugs
 causes irreversible ototoxicity (deafness), neurotoxicity, and
nephrotoxicity
o “Sulfa-” drugs
 cannot be given during the last trimester of pregnancy
o Chloramphenicol
 for typhoid fever but can cause “Gray Baby Syndrome”
 side effects: bone marrow depression thus aplastic anemia
 neonates lack or have decreased levels of the liver enzyme:
glucoronyl transferase
 Chloramphenicol levels = Increased
 Clinical manifestations: abdominal pain, diarrhea, cyanosis,
cardiovascular collapse
G. Pharmacogenetics
• studies the influence of heredity on the pharmacokinetic and
pharmacodynamic response of the drug
• mainly theoretical
• depends on genetic makeup of individual
• Example: Isoniazid (INH)
o Anti-TB drug
o Reaction of patients to INH depends on whether the person is
a slow or fast acetylator (dependent on one’s genes)
o Metabolism depends on N-acetylation:
 FAST acetylator = shorter INH half-life
- Half-life: 1 hour
- Faster Excretion
- Toxic effect: hepatotoxicity
- Ex: Asians
 SLOW acetylator = longer INH half-life;
- Half-life: 3 hours
- Slower Excretion
- Toxic effect: peripheral neuropathy
- Vitamin B is taken alongside to prevent this toxicity
H. Pharmacogenomics
 pertains to the use of genetic information to aid in determining a
specific drug therapy program for a particular individual
 determines the specific gene variations that may respond well or
poorly to a particular drug
 may be considered as a branch of pharmacogenetics
I. Pharmacoepidemiology
 involves the observation of the adverse or beneficial responses of
pharmacologic events in a particular population at a given time
and place, through the use of epidemiology techniques
 such observations may include:
o variation of the effects of particular drugs among individuals
and between populations
o responses of the people to the drugs
 allows authorities to obtain information for the evaluation of new
drugs (BFAD/FAD decides whether to approve or provide license
to new drugs in the market)
J. Pharmacoeconomics
 study of the cost effectiveness of drug treatments
 follows RATIONAL DRUG USE (4 parameters: ESSC criteria)

monetary value for health and longevity
 does not compromise health with cost
 tendency of doctors now to prescribe generic drugs so patients
have the option to buy generic or branded drugs
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K. Ethnopharmacology
 Deals with interethnic differences in response to metabolism of
chemical substances, and the presence and absence of enzymes
in different geographic regions and ethnic races.
 Also called pharmacoanthropology
 E.g. A certain group in Panay has G6P Dehydrogenase deficiency
L. Clinical Pharmacology
 deals with rational development of drugs, their safe and effective
use, and other proper evaluation of drugs in humans for the
prevention, diagnosis, treatment, alleviation or cure of a disease.
 ESSC Criteria – refers to the rational use of drugs; patient
management
o E fficacy
 Considers pharmacodynamics, pharmacokinetics, of the
different drug groups and its ability to accomplish what it is
intended to do. (mechanism of action
 Most important factor to consider is the effectiveness of the
drug
o S afety
 Side effects, toxicity, frequency and severity
o S uitability
 convenience, compliance, practicality,
contraindications and possible interactions
o C ost
III. MAJOR BRANCHES OF PHARMACOLOGY
A. Pharmacokinetics
 movement of the drug in the body and how the body acts
on the drug
 fate of drug in the body and how the body handles the drug
 involves four processes: (ADME)
o Absorption: Small Intestines
 from site of administration to systemic circulation
o Distribution: Blood
 blood is the main transport of the drug
o Metabolism (biotransformation): Liver
 liver enzymes are responsible for converting drugs into
active or inactive form (ex. Hepatic Nitro Reductase,
Cytchrome p450)
o Excretion: Kidneys
 elimination of drugs in the system
 may also occur via lungs, skin, bile, saliva, urine
B. Pharmacodynamics
 biochemical and physiological effects of drugs and their
mechanism of action (includes enzymatic or molecular level
and also toxicological or adverse effects.)
 effects of drug in the body
 drug interactions, which may also deal with receptors and drug
potency, efficacy
PHARMACOLOGY Lec#1.1
Fig 1. Diagram of Pharmacology in relation to other Disciplines
IV. DRUG MANUFACTURING
A. Pre-Clinical Phase (Animal Testing)
 Tested in at least 2 rodent and 1 non-rodent species
 1 to 3 years
 Acute toxicity – observation of animal 1-2 wks using a simple
dosage of the drug being tested
 Subacute toxicity – 2 wks to 3 mos.
 Chronic toxicity – 6 mos. to 2 yrs
B. Food and Drug Administration
 30 days
C. Clinical Testing
 Includes humans (healthy adult volunteers)
 2-10 years (average of 5-6 years)
 The lowest effective dose given to humans because we can
react differently to the drug
 Pediatric patients not included in the testing because some
drugs can have adverse effects on the development of the
patient
 Consent is needed
 Looking for the short term and long term effects (chronic
toxicity, reproduction, teratogenicity), toxicity of the drug
 Phase 1: Establish Safety
- Involves normal healthy adult males; to measure the
initial drug safety, biological effects; done by clinical
pharmacologista
 Phase 2: Establish Efficacy and Dose
- Involves selected patients needing the treatment; to
measure therapeutic efficacy, dosage range, metabolism,
kinetics; done by clinical pharmacologists
 Phase 3: Verify Efficacy and Detect Adverse Drug Reactions
- Involves large sample of selected patients; to measure the
safety and efficacy; done by clinical investigators
- Participants should sign Informed Consent and meet other
co-participants
 Phase 4: New Drug Application
- Marketing approval by the FDA
 Phase 5: Post-Marketing Surveillance
- Looking for chronic effects even if drug is available in the
market
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- Example: Coxicb Drugs (pain relievers) were found to have 3. Pharmacodynamic Phase
cardiotoxic effects after it was released in the market o Drug-Drug Interaction
D. Placebo  Simultaneous intake of two different drugs, where one drug
may reduce or displace the metabolism of the other
 Latin: “I shall please” o Individual Sensitivity
 Phenomenon wherein patients tend to respond in a positive way  Inter-patient variability for hyper- and hypo-active people
to any therapeutic intervention by interested, caring, and o Pathologic Conditions
enthusiastic medical personnel.  Ailments, conditions, and dysfunctions that affect drug
 May involve objective physiologic and biochemical changes as metabolism
well as changes in subjective complaints associated with the
disease
 Quantitated by administration of an inert material, with exactly
the same physical appearance, odor, consistency, etc., as the
active dosage form.
 Two types:
a) For negative control: Do not contain pharmacologically active
ingredients
b) For positive control: Contain some compound with
pharmacological activity different from the test drug
V. DRUG ACTIONS
A. Stimulants
 Enhances specialized tissues
 Ex. Epinephrine  increased heart rate
B. Depressants
 Diminishes activity of specialized tissues
 Ex. Proton pump inhibitors, Beta blockers, Anxiolytics
C. Irritants
 Either stimulate or depress non-specialized tissues
 Ex. Macrolides  GI irritation, NSAIDs  Peptic ulcer disease
(2nd major cause only. 1st major cause: H. pylori)  post prandial
administration of NSAIDs
D.Others
a) Replacement Therapy
o Replaces what is sufficient/deficient
o Ex. Hormone Replacement Therapy, ORS to replace lost fluids
in patients with diarrhea
b) Anti-infective
o antimicrobials(ex: macrolides, sulphonamides)
c) Action in Relation to Specific Effect
o Cathartic – Promote rapid evacuation of bowels, with
noticeable alteration in consistency (ex: Castor Oil)
o Laxative – For easier evauation of bowels; soft but formed
feces (ex: Bisacodyl)
o Hypnotic – Induces sleep (ex: Sedatives)
o Diuretic – Promotes Urination (ex: Flurosemide)
o Antacid – buffering action; neutralizes HCl (ex: Calcium
Carbonate)
o Vasodilator – relaxes vascular smooth muscles (ex: Ca Channel
Blockers)
d) Local – Topical; produces effect only on area applied onto (ex:
ointments, creams, gels)
e) Systemic – applied in one area, then produces systemic effect (ex:
patches for cardiac ailments)

E. Variables Involved In Drug Activity

1. Pharmaceutical Phase
o Disintegration of dosage form; generally water soluble
o Dissolution of active ingredients; lipid soluble
2. Pharmacokinetic Phase
o Involves Absorption, Distribution, Metabolism, and Excretion
o Bioavailability – fraction of the drug that remains unchanged in
circulation
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VI. APPENDIX

 Summary of Phases of Drug Development/Manufacture

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