1st Upload - introduction to pharmacology from Katzung's Basic and Clinical Pharmacology

1. Introduction to
Pharmacology
Prepared by:
Abraham Daniel C. Cruz, MD, MS Pharmacology (cand.)

2. Objectives
• By the end of this lecture, the student should be able to:
• Define pharmacology, medical pharmacology and toxicology
• Describe the history of pharmacology
• Explain the basic principles of pharmacogenetics and its clinical
applications
• Describe the different steps in drug development
• Acquire an overview of basic pharmacodynamic and
pharmacokinetic principles

3. What is Pharmacology?

5. HISTORY OF PHARMACOLOGY
PREHISTORY
- Egypt, China, India 
recognize beneficial and toxic
effects from plant and animals
- most were worthless and
harmful
END OF 17TH CENTURY
- Observations & experiments
- Development of materia medica
- lack of methods of purifying
active agents and testing
hypothesis on MOA
LATE 18th & 19th CENTURY
- Francois Magendie and Claude
Bernard develop methods for
experimental pharmacology
and physiology
1940s & 50s
- Introduction of rational
therapeutics and controlled
clinical trial
LAST 30 - 50 YEARS
- receptor pharmacology
- molecular MOA
- orphan receptors
- pharmacogenomics

6. Basic Principle 1

7. Basic Principle 2
Good Evidence  Good Medicine

8. Pharmacology and Genetics

9. Definitions
• Pharmacogenetics
• Genetic differences in metabolic pathways which can affect
individual responses to drugs (therapeutic AND adverse effects)
• Pharmacogenomics
• the technology that analyses how genetic makeup affects an
individual's response to drugs
• deals with the influence of genetic variation on drug response in
patients by correlating gene expression or single-nucleotide
polymorphisms with a drug's efficacy or toxicity

10. Heredity
Hardy Weinberg Law
Harnessing the Power of Pharmacogenetics
Adapted from:
Irma R. Makalinao MD FPPS FPSCOT
Professor of Pharmacology and Toxicology
UP College of Medicine

11. Terminology of Mendelian Genetics
• Parental,F1, and F2
• Dominant and recessive
• Phenotype and genotype
• Monohybrid cross

14. Mendel’s Results
•Principle of Dominance: One form of a
hereditary trait dominates or prevents the
expression of the recessive trait
•Dominant: trait that is expressed in the F1
generation
•Recessive: Trait that is not expressed in the
F1 generation

15. Mendel’s Hypothesis
• For every trait there must be a pair of factors- one maternal,
one paternal  These factors are called genes
• Dominant represented by a capital
• Recessive represented by lower case
• Gene Segregation: genes segregate when gametes are
formed

20. • Genetic polymorphism
• Hereditary variations in which sharply distinct qualities
coexist along side each other in a population
• May refer to genetic loci in which the variants occur with a
frequency of 1-2%
• Twin studies
• Family studies
• Enables the investigator to discriminate:
1. various modes of genetic transmission
2. Dominance – recessivity relationships that characterize
expression of the trait
Genetic Profile of Human Drug Response

21. Estimating Heritability from Twin Studies
• Technique of using twin studies was originally devised
by Francis Galton during the 19th century
• Index of Heritability (Holzinger index)
• If H>1 phenotypic variation due to heredity
• If H =0 attributable to environment

22. Twin Studies in Pharmacogenetics
• Acetylation polymorphism among the first one studied
• Studied first in the German population
• Japanese study showed good correlation (r=0.95) among
identical twin, among fraternal twins (r=0.25)
• Concept of concordance vs. discordance
• Relative importance of heredity and environment to
more complicated pharmacological phenomena can also
be better appreciated from a twin study
• Value of data from identical and fraternal twins

23. Urinary elimination of INH
Identical Twins Fraternal Twin
Sex INH Eliminated Sex INH Eliminated
M
M
8.8
8.3
F
F
12.1
13.7
F
F
26.0
25.2
F
F
10.9
4.6
M
M
11.8
12.4
M
M
11.0
8.5
F
F
12.2
11.5
F
F
3.9
15.2
F
F
4.1
4.4
M
M
10.5
15.6

24. Basic Patterns of Inheritance
• Autosomal Dominant
• Autosomal Recessive
• X-linked
• G6PD deficieny
• Pyridoxine senstitive anemia
• Vasopressin resistance
• Mitochondrial inheritance
• Aminoglycoside induced deafness
• Predominantly maternally inherited

26. Hardy-Weinberg Law
• Developed in 1908
• algebraic formula to estimate the frequency of a dominant or recessive
gene in a population based on the frequency with which the trait or
condition is found in that population
p2 + 2pq + q2 = 1
• p2 = frequency of homozygous dominant population
• 2pq = frequency of heterozygous population
• q2 = frequency of homozygous recessive population
• p = frequency of the dominant allele in a population
• q = frequency of the recessive allele in the population, and
• p + q = 1

27. Population studies

28. Population studies

34. Rx +  = 
Rx +  = 
Rx +  = 

35. Imagine
being able to
walk into your doctor’s office
and present
a “smart card” encoded either with the
sequence of your genome itself
or with an access
code granting permission to log on to a secure
database
containing your genomic information.

37. Pharmacogenomics significantly impacts this
development model by identifying people whose
genetic profiles or "bar codes" predict that they are
inappropriate for a given medication, whether due to
poor efficacy and/or adverse side effects.

38. Pharmacogenomics
“Drugs by Design?”
“In the very near future, primary care
physicians will routinely perform
genetic tests before writing a
prescription because (they will) want to
identify the poor responders.”
F. Collins
(AAFP Annual Meeting, 1998)

39. Environmental Health Perspectives • VOLUME 111 | NUMBER 11 | August 2003

40. The Benefits of Personalized Medicine
Experts believe that minimizing adverse
drug reactions are likely to be the first
area in which Pharmacogenomics will
benefit patients

41. Anticipated Benefits of Pharmacogenomics
• More Powerful Medicines
• drugs based on the proteins, enzymes, and RNA molecules associated with genes
and diseases.
• facilitate drug discovery and allow drug makers to produce a therapy more
targeted to specific diseases.
• maximize therapeutic effects and decrease damage to nearby healthy cells

42. Anticipated Benefits of Pharmacogenomics
• More Accurate Methods of Determining Appropriate Drug Dosage
• Current methods
• of based on weight and age  replaced with dosages based on a person's genetics
• maximize value of therapy's value and decrease the likelihood of overdose

43. Anticipated Benefits of Pharmacogenomics
• Better Vaccines
• Vaccines made of genetic material, either DNA or RNA, promise all
the benefits of existing vaccines without all the risks.
• activate the immune system without causing infections.
• inexpensive, stable, easy to store, and capable of being
engineered to carry
• several strains of a pathogen at once

44. Anticipated Benefits of Pharmacogenomics
• Better and safer medications the first time
• Instead of the standard trial-and-error method  prescribe the best available drug
therapy from the beginning
• take guesswork out of finding the right drug
• speed recovery time
• increase safety as the likelihood of adverse reactions is eliminated

45. Anticipated benefits of Pharmacogenomics
• Decrease in the Overall Cost of Health Care
• Decreases in:
• ADRs
• failed drug trials
• time to get a drug approved
• time patients are on medication
• medications patients must take to find an effective therapy
• effects of a disease on the body (through early detection)
• An increase in the range of possible drug targets will promote a net decrease in
the cost of health care

46. GENETIC
POLYMORPHISMS
Pharmacokinetic Pharmacodynamic
•Transporters
•Plasma protein binding
•Metabolism
•Receptors
•Ion channels
•Enzymes
•Immune molecules

47. Genetic Polymorphisms of Drug Metabolizing Enzymes are
significant if:
• The enzyme changes the
way the drug is metabolized
in the human body
(quantitative disposition)
• Active metabolites are
formed

48. Genetic Polymorphisms of Drug Metabolizing Enzymes are significant if:
• Therapeutic index is narrow and the risk for
toxicity is high with small changes in the
concentration
(Ex. Phenytoin)
• There are significant interactions with other
drugs, food or disease

49. From: Evans WE, Relling MV. Pharmacogenomics: Translating functional genomics
into rational therapeutics. Science 286:487-491, 1999.
Genetic polymorphisms in human drug
metabolizing enzymes

50. Succinylcholine Induced Paralysis

51. N-acetyltransferase Polymorphism
• Acetylation polymorphism of Isoniaizd was first
discovered in 1950s
• Trait and mode of inheritance correlated with adverse
reactions

52. Inherited Variations in
Pharmacodynamics

53. Warfarin Resistance
• Discontinuous variation in response to warfarin
• Resistance to anticoagulation
• Present theory:
• Decreased sensitivity of liver enzyme or receptor sites to
anticoagulants
• Increased sensitivity to Vitamin K1
INDEX CASE: HM, 73 year old male with MI
Warfarin dose: 145 mg/day as maintenance dose
Vitamin K1: 1/2 mg to increase prothrombin
time to 25-43% activity

54. G6PD Deficiency Drug-induced Hemolysis
• X-linked trait affecting nearly 400 M people
• Predisposes an individual to hemolytic anemia induced by a specific
drug
• G6PD catalyzes the first step in HMP oxidation pathway of carbohydrate
metabolism leading to the oxidation of NADP to NADPH
• NADPH needed by to maintain reduced GSH
INDEX CASE:
Among Blacks who developed hemolytic anemia after
treatment with PRIMAQUINE an antimalarial

55. Drugs and other agents causing clinically significant hemolysis in
G6PD deficiency
Acetanilid
Phenylbutazone
Sulfanilamide
Sulfacetamide
Sulfapyridine
Sulfamethoxazole
Thiazolesulfone
Diaminodiphenylsulfone
Trinitrotoluene
Nitrofurazone
Nitrofurantoin
Furazolidone
Furaltoldone
Pamaquine
Primaquine
Pentaquine
Naphthalene
Fava beans

56. Inherited Variations in Pharmacodynamics
Condition Abnormal
Enzyme
Inheritance
Frequency
Drugs
Inability to
taste
phenylthiourea
Unknown Autosomal
recessive
Approx.
30% of
Caucasians
Drugs containing N-
C-S group
Phenylthiourmethyl
Propylthiouracil
Glaucoma due
to abnormal
intraocular
pressure to
steroids
Unknown Autosomal
recessive
Approx. 5%
of USA
population
Corticosteroids

57. Inherited Variations in Pharmacodynamics
Condition Abnormal
Enzyme
Inheritance
Frequency
Drugs
Malignant
Hyperthermia
with muscular
rigidity
Unknown  Autosomal
dominant
 Approx. 1 in 20000
anesthetized patients
 Halothane
 Other
general
anesthetics
Methemoglobin
Reductase
deficiency
Methemo-
globin
Reductase
 Autosomal recessive
 Heterozygous
(HZG) carriers
affected
 Approx. 1 in 100
HZG carriers
Many
different
drugs

58. Specific Applications of
Pharmacogenetics

59. Personalizing cancer chemotherapy
• Thioupurine S-methyltransferase (TPMT)
• essential for the metabolism of thiopurine medications used to
treat acute lymphoblastic leukemia (ALL)  most common form of childhood
cancer

60. Application of pharmacogenetics to cancer therapy
• There is now a commercially available diagnostic test measuring a
patient’s ability to produce the metabolic enzyme thiopurine S-
methyltransferase (TPMT)

61. TPMT deficiency screening
• Genetic testing gives clinicians the ability to classify ALL patients
according their TPMT genotype, which allows for optimized
dosing.

62. Why do you need to screen?
• Doses in patients with alleles rendering them deficient in TPMT
(who are thus less tolerant of thiopurine medications) are reduced
by as much as 95%.

63. Cytochrome p450 enzymes

64. Ecogenetics and cancer
• Genetic differences in the metabolic activation or detoxification of
carcinogenic chemicals as determinants or risk
• Increased risk of cancer associated with the following polymorphism
• CYP (2A1, 1A2, 2E1)
• Gluthathione transferases (GSMT1, GSTT1)
• Epoxide hydrolase
• NAT2
Neurotoxicology, 21(1-2) 2000

65. Issues related to ecogenetic research
• Functional significance of the polymorphism
• Interaction/combination of susceptibility genotypes
• Increased risk of Lung cancer (Hayashi et al)
• CYP 1A1 Val/Val genotype = 2.0
• GSTM (-) = 1.44
• CYP + GSTM = 5.58
• Ethical, legal, social issues surrounding studies of susceptible
individuals

67. Environmental Genome Project
• The mission of the EGP is to improve understanding of
human genetic susceptibility to environmental exposures

68. The power of pharmacogenetics
• These new tools must be used for the purposes of identifying and
controlling harmful exposures rather than to exclude the genetically
predisposed
(Eaton et al 1998)

69. DRUG DEVELOPMENT

70. Drug Development and Evaluation
• Possible therapeutic value  drug development
• DOH-BFAD  FDA
• Ensure safety and reliability
• Must undergo pre-clinical trials and clinical
trials (phase I, II, III)

71. Drug Development and Evaluation
Pre -clinical

72. Pre-Clinical Trials
 In vitro and animal studies
 Purpose
 Evaluate toxicity
 Determine presumed effects
 Reasons for dropping
 Lack therapeutic activity
 Toxic to living animals
 Teratogenic (adverse effect on fetus)
 Small or narrow margin of safety

73. Phase I
 20-50 HEALTHY volunteers (young men)
 Clinical investigators evaluate:
 Safety (adverse effects)
 Pharmacokinetics
 Therapeutic effects (?)
 Reasons for dropping
 Lack therapeutic effect
 Unacceptable adverse effects
 Highly teratogenic
 Too toxic

74. Phase II
 20 – 300 subjects; patients WITH DISEASE
 Evaluate
 Efficacy – does it work?
 Safety
 Reasons for dropping
 Less effective than anticipated
 Too toxic, unacceptable adverse effect
 Low benefit-t0-risk ratio
 No more effective than other available drugs

75. Phase III
• Randomized, controlled multicenter trials
• Double blind
• Large patient groups (300 – 3000)
• Patients WITH DISEASE
• Usually compared with “gold standard” and placebo
• Most expensive, time consuming, difficult trials to design and run

76. Phase IV
• Post marketing surveillance
• Pharmacovigilance
• Detect any rare or long term adverse effects
• Report any untoward or unexpected adverse effect not seen during
pre-clinical and phases I – III
• After prolonged use and wide distribution
• Risk of malignancy
• Thrombotic events
• Idiosyncratic side effects in special populations

77. Drug Development and Evaluation

78. Drugs Withdrawn from the Market
• Troglitazone (Rezulin) – liver failure
• Rofecoxib (Vioxx) – thrombotic events
• Dexfenfluramine (Redux)– cardiotoxicity

79. Further Drug Classification
• Pregnancy Category
• A, B, C, D, X
• Controlled drugs
• Closely monitored by the Dangerous Drugs Board of the DOH
• Need S-2 license
• Prescription in triplicate

80. FDA Pregnancy Categories
• A- Adequate studies in pregnant , no risk
• B- Animal studies no fetal risk, but human not adequate
OR Animal toxicity but human studies no risk
• C- Animal studies show toxicity, human studies inadequate
but benefit of use may exceed risk
• D- Evidence of human risk, but benefits outweigh risks
• X- Fetal abnormalities in humans, risk greater than benefit

81. GENERAL PRINCIPLES IN
PHARMACOLOGY

82. Nature of Drugs
• Drug - any substance that brings about a change in biologic
function through its chemical action
• interacts as a (pharmacologic) agonist (activator) or
antagonist (inhibitor) with a specific molecule in the biologic
system that plays a regulatory role (receptor)
• Chemical antagonists - interact directly with other drugs
• Osmotic agents - interact almost exclusively with water
molecules; concept of receptor pharmacology does not
apply.

83. Sources of Drugs
Source Example Generic/Trade Name Classification
Plants Cinchona bark
Purple Foxglove
Poppy Plant
Quinidine
Digitalis
Morphine
Codeine
Anti-arrhythmic
Inotrope
Analgesic
Analgesic, Antitussive
Minerals Magnesium
Zinc
Gold
Milk of Magnesia
Zinc Oxide Ointment
Aurafonin
Antacid, Laxative
Suncreen, Skin Protectant
Anti-inflammatory; used
in RA
Animals Pancreas (Cow,
Pig)
Stomach (Cow,
Pig)
Thyroid Gland
Insulin
Pepsin
Thyroid, USP
Antidiabetes
Digestion
Hormone
Synthetic Meperidine
Diphenoxylate
Co-trimoxazole
Demerol
Lomotil
Bactrim, Septa
Analgesic
Antidiarrheal
Anti-infective

84. Nature of Drugs
• Poisons - drugs that have almost exclusively harmful effects
• Paracelsus (1493–1541) - "the dose makes the poison"  any
substance can be harmful if taken in the wrong dosage
• Toxins - poisons of biologic origin (from plants or animals);
different from inorganic poisons (heavy metals)
• Requirements for drug – receptor interaction
• Appropriate size, electrical charge, shape, and atomic composition
• Permeation - Can be transported from its site of administration to its site of
action  absorption and distribution
• Appropriate duration of action  inactivation or excretion

85. Physical Nature of Drugs
• State at room temperature - determines best route of
administration
• solid (aspirin, atropine); liquid (nicotine, ethanol); gas (nitrous
oxide)
Organic drugs
• carbohydrates, proteins, lipids, and their constituents
• weak acids or bases  implications on kinetics and
compartmentalization (ion trapping)
Inorganic drugs
• lithium, iron, and heavy metals

86. Drug Size
• 100 – 1000 MW  range of molecular weight of most
drugs
• 100 – lower limit; minimum molecular weight of drug
to achieve selective binding
• upper limit – determined by the need of the of the
drug to traverse membranes
• drugs larger than 1000 MW do not diffuse readily diffuse between
compartments of the body
• implication – very large drugs (proteins) must be administered
directly in their site of drug action

87. Drug Reactivity and Drug-Receptor Bonds
BOND TYPE MECHANISM BOND STRENGTH
van der Waals Shifting electron density in areas of a molecule, or in a molecule as a
whole, results in the generation of transient positive or negative charges.
These areas interact with transient areas of opposite charge on another
molecule.
+
Hydrogen Hydrogen atoms bound to nitrogen or oxygen become more positively
polarized, allowing them to bond to more negatively polarized atoms such
as oxygen, nitrogen, or sulfur.
++
Ionic Atoms with an excess of electrons (imparting an overall negative charge
on the atom) are attracted to atoms with a deficiency of electrons
(imparting an overall positive charge on the atom).
+++
Covalent Two bonding atoms share electrons. ++++

88. • DRUG SHAPE
• Chirality – molecule has a non-superposable mirror image
• chiral center (asymmetric carbon)  S)(-) isomer - “left-oriented” or
(R)(+) isomer – “right-oriented” per chiral center
• Implications: potency, toxicity, metabolism
• most drugs are administered as racemic mixtures (50% or more is less
active, inactive, or actively toxic)
• RATIONAL DRUG DESIGN
• based on SARs and info about receptors
• computer models + Human Genome Project
• RECEPTOR NOMENCLATURE
• IUPHAR Committee on Receptor Nomenclature and Drug
Classification

89. DRUG-BODY INTERACTIONS
Pharmacodynamics and Pharmacokinetics

90. Pharmacodynamics
1. Drug (D) + receptor-effector (R)  D-R-effector complex 
effect
2. D + R  D-R complex  effector molecule  effect
3. D + R  D-R complex  activation of coupling molecule 
effector molecule  effect
4. Inhibition of metabolism of endogenous activator 
increased activator  increased effect
*effector may be part of the receptor molecule or may be a
separate molecule

91. Types of Drug-Receptor Interactions

92. Drugs That Inhibit Their Binding Molecules
• “indirect agonist” - mimic agonists by
inhibiting molecules responsible for
terminating the action of an endogenous
agonist
• amplify effects of physiologically released
agonists
• effects are more selective and less toxic than
those of exogenous agonists

93. Agonists, Partial Agonists, Inverse Agonists
• Receptor status
• Ri - inactive, nonfunctional
• Ra - activated
• constitutive activity  (-) agonist; some of the
receptors are activated; produce same
physiologic effect as agonist-induced activity
• Agonists - ↑ affinity to Ra = ↑ effect
• full agonists vs. partial agonists
• Antagonists – Ri = Ra  blocks access of agonists to
receptor  prevent usual agonist effect  no
change
• Inverse agonists - ↑ affinity to Ri = produce
opposite effects when compared with agonists

94. Receptors and Inert Binding Sites
Receptor
• Selective in “choosing” ligands
to bind  avoid constant
activation of the receptor by
many different ligands
• Function changes upon ligand
binding  alters biologic system
 pharmacologic effect
Inert Binding Site
• ex. Albumin
• bind drugs but (-) regulatory
function  no detectable change
• Significant in pharmacokinetics
• Distribution
• Bioavailability

95. Pharmacokinetics
• drug should reach its site of action; scenarios:
• Drug is active, lipid soluble, stable  given as such
• Prodrug  absorbed and distributed  converted to the active drug by
metabolic processes
• Apply drug directly to target tissue
• (most common) administer drug in one compartment  move to site of
action in another compartment; requires:
• Permeation – perfusion-rate limited versus permeability-rate limited
• absorption
• distribution
• Elimination
• metabolic inactivation
• excretion

96. Permeation
• Aqueous diffusion
• Through aqueous pores
• Not present in some tissues
• Driven by concentration gradient
• Does not occur if drug is protein-bound
• Lipid diffusion
• Most important factor for drug
permeation
• lipid: aqueous partition coefficient
• for weak acids and bases
• Charged molecules attract water
• Dissociation depends on pH of medium and
pKa of drug
• Henderson-Hasselbalch equation –
determines ratio of lipid-soluble form to
water-soluble form
• Special carriers
• peptides, amino acids, and glucose
• via active transport or facilitated
diffusion
• selective, saturable, and inhibitable
• Endocytosis
• Vit B12
• Iron
• Exocytosis
• Neurotransmitters
• Thyroid hormones

97. Permeation, Blood Flow, and Protein Binding
Perfusion-Rate Limitation
• Membrane offers no resistance
• Drug in the blood leaving the
tissue is in equilibrium with that
of the tissue  blood and tissue
viewed as one  equilibrium
achieved instantaneously
• Alteration in protein content is
NOT expected to affect rate of
transport at a given
concentration
Permeability-Rate Limitation
• Membrane resistance to drug
movement is high
• Movement is slow and
insensitive to changes in
perfusion  equilibrium is not
achieved by the time the blood
leaves tissue  view blood and
tissue as separate
• Altered protein-binding
influences rate of transport by
affecting unbound concentration

99. Fick’s Law of Diffusion
• Where:
• C1 = higher concentration
• C2 = lower concentration
• Area = cross-sectional area of the diffusion path
• Permeability coefficient = measure of the mobility of the drug molecules in the
medium of the diffusion path
• thickness = length of the diffusion path
• lipid diffusion
• lipid: aqueous partition coefficient - major determinant of drug mobility

100. Ionization of Weak Acids and Bases
• Many drugs are weak acids or bases
• ionized molecules attract water dipoles  polar, relatively water –
soluble, lipid – insoluble complex
• lipid diffusion depends on relatively high lipid solubility  drug
ionization may markedly reduce the ability to permeate membranes

101. Henderson-Hasselbach Equation
Weak Acid Weak Base
• REMEMBER:
• neutral  uncharged/unionized/non-polar  more lipid soluble
• law of mass action  reactions move to the:
• left in an acid environment (low pH, excess protons available)
• right in an alkaline environment
• the lower the pH relative to the pKa , the greater will be the fraction of drug in the protonated form
unprotonatedprotonated

102. Ion Trapping

103. Weak Bases

104. APPLICATIONS

105. Case
• A 12 year old child has bacterial pharyngitis and is to receive an oral
antibiotic. Ampicillin is a weak organic acid with a pKa of 2.5. What
percentage of a given dose will be in the lipid soluble form in the
duodenum at a pH of 4.5?
• A. about 1%
• B. about 10%
• C. about 50%
• D. about 90%
• E. about 99%

106. Case
• A 12 year old child has bacterial pharyngitis and is to receive an oral
antibiotic. Ampicillin is a weak organic acid with a pKa of 2.5. What
percentage of a given dose will be in the lipid soluble form in the
duodenum at a pH of 4.5?
• A. about 1%
• B. about 10%
• C. about 50%
• D. about 90%
• E. about 99%

107. Explanation
• Ampicillin is an acid, so it is more ionized in an alkaline pH and less
ionized in an acidic pH. The Henderson-Hasselbach equation predicts
that the ratio changes from 50/50 at the pH equal to the pKa, to 1/10
(protonated/unprotonated) at 1 pH unit more alkaline than the pKa,
and 1/100 at 2 pH units more alkaline. For acids, the protonated form
is the non-ionized, more lipid-soluble form

108. Computation
• log (protonated/unprotonated) = pKa - pH
• substituting the values, we get log (protonated/unprotonated) = 2.5 -
4.5
• log (protonated/unprotonated) = -2
• to get the actual value of (protonated/unprotonated), you need a
scientific calculator and get the antilog of -2
• if u remember a little bit of calculus, the antilog of -2 is also equal to
10 raised to the exponent of -2
• 10 raised to the exponent of -2 is equal to .01
• .01 = 1/100 = 1%

109. Drug Groups
• one or more prototype drugs can be identified that typify
the most important characteristics of the group
• Study in detail
• permits classification of other drugs as variants
• study differences from prototype

110. Sources of Information
• Pharmacology: Examination and Board Review, by Trevor, Katzung, and Masters (McGraw-Hill,
2010)
• USMLE Road Map: Pharmacology, by Katzung and Trevor (McGraw-Hill, 2006)
• references at the end of each chapter of Katzung
• Periodicals/journals
• The New England Journal of Medicine
• The Medical Letter on Drugs and Therapeutics
• Drugs
• Physicians’ Desk Reference
• Package inserts
• Micromedex
• Drug Interactions: Analysis and Management
• US and Philippine FDA

111. THANK YOU!!!