P1 Milestone Exam Review Guide

Spring 2011
By Rho Chi Pharmaceutical Honor Society

BLACK BOX WARNING

In order to facilitate preparation for your upcoming Milestone Exam, the Rho Chi
Pharmaceutical Honor Society has attempted to compile fundamental information and
topics that are likelyto appear ontheexam. However,the followingreview should be
usedasstudyaidratherthanaonestopreferenceforallmaterialcoveredduringyour
P1year.ToensuresuccessontheMilestoneExam,usethefollowinglearningobjectives
as a guide to your studies but always consult your notes or textbooks for indepth
explanationsandclarifications.

GOODLUCK!

Milestone Exam Process UTCoP

A Proposal for Milestone Exam Implementation at the UT College of
Pharmacy
Patrick Davis, Sr. Assoc. Dean for Academic Affairs
Developed by the Program Assessment Team (as a result of the AACP Curriculum
Summit, September-09) and approved by the Curriculum Committee (11-9-09).
Question Design: Faculty will be asked to develop 3-4 capstone (big picture) questions
for inclusion on their final exams that map to the stated outcomes of their course. The
intent of these questions would be to not only assess students at the conclusion of the
course (since they are included on the final exam) but to also illustrate to the student the
level of questions that will subsequently be forwarded for inclusion on the milestone
exam(s). During the summer months, faculty will then be asked to provide a comparable
set of questions (not the same questions, since the students saw those on the final) for
inclusion on the relevant milestone exam(s) for the year. Accumulation of these
submitted questions over the years will serve to construct a database of questions that can
be used in subsequent milestone exams.
Question Approval: Questions that are submitted by faculty for inclusion on milestone
exams will be reviewed by the Program Assessment Team (which includes representation
from each division & discipline) for appropriateness (format and level; i.e., truly capstone
in nature rather than at the detail level of a summary exam). If the PrAT excludes
questions or modifies them from what was submitted, the faculty member crafting the
question will be so notified (including being asked to modify their question(s).
Formative Exam #1: This exam will be based on coursework from the P1 year, and
administered at the beginning of the P2 year in Professional Development Convocation
Milestone Exam Process based on 3 questions per semester credit hour. This is simply a
formative assessment to help students identify strengths/deficiencies, and for
programmatic assessment of the P1 year. Students will be required to address how they
will remedy identified deficiencies through reflective assignments with their e-portfolio
early in the PDC.
Formative Exam #2: This exam is similar to that described above, but administered at the
beginning of the P3 year (again in the Professional Development Convocation). Content
is based largely on P2 coursework (~75%; 3 questions per semester credit hour), but also
addressing P1 retention and integration (~25%).

Incentivizing the Formative Exams: As a mechanism to help students focus on the

importance of the formative exams, we will provide the following incentive. On each of
the two formative exams, students will earn the following points towards the Summative
Exam #3 based on their performance: 95-100% = 5 pts; 90-95% = 4 pts; 85-89% = 3 pts;
80-85% = 2 pts; 75-79% = 1 pts. Thus, a student who scores >95% on each of the two
Formative Exams will carry forward 10 pts that will be added to their Summative Exam
#3 results.
Summative Exam #3: The first gatekeeper (must pass) exam is based largely on the P3
year content (~50%), but also addressing retention and integration of P1 and P2 content
(~50%). This exam will be addressed prior to or immediately following final exams in
the Spring P3 semester (to be determined). Students that pass will progress (on time) to
the P4 year and rotation #1 in July. Those who do not pass have time for selfremediation
and a second attempt at the gatekeeper exam. Students that pass this second
attempt will still progress (on time) to the P4 year and rotation #1 in July. Students who
do not pass this second attempt will have time for self-remediation and a third attempt,
but will necessarily be delayed in progressing to the first rotation in the P4 year (and thus
will be delayed in graduation). If the student does not pass this third attempt at the exam,
they will receive a grade of F for the Spring-P3 Professional Development Convocation
course with which this exam is associated .
Summative Exams 4a, 4b, 4c: We will continue with the existing summative exams
(gatekeeper; must pass) currently given in the P4 year (Clinical Exam, Ambulatory Care
Exam, and Institutional Exam). Students who do not pass these exams the first time are
given a second opportunity. These exams are associated with a specific rotation, and
failure on the second attempt at the exam results in failure of the rotation.
NAPLEX: The NAPLEX exam constitutes THE Capstone Summative Exam for entry
into practice.

Study Strategies

1.

START EARLY! The entire first-years worth of information cannot be re-learned in

one week. Even if you devote just 3 hours per week of your summer vacation to
reviewing information, the payback will be notable. Remember: learning objectives and
notes can be reviewed just as easily while sitting in a library as while lounging poolside.

2.

Focus on one subject at a time. Rather than studying Anatomys first test material one
day, Medicinal Chemistrys first test material the second, Biochemistrys first test
material the third (and so on), finish one courses workload before moving on to the next.
Many of the concepts presented early in the class notes can be clarified by specific
examples later on the semesters notes.

3.

Pace yourself. Devote one week to each course. That way, you can spread the review
material for the corresponding course over several days rather than losing an entire day of
summer vacation by cramming. Remember: cramming does not ensure long-term recall
of the information!

4.

Refer to your class notes. Use the following compilation of objectives as a study guide
instead of a tutor. If further information or explanation is needed concerning a topic, the
best place to look is your class notes. After all, Milestone Exam questions are submitted
by professors; their respective lecture slides and/or handouts are fundamental to gaining
insight to their idea of key concepts for the course.

5.

Collaborate with friends. If the learning objectives, your own notes, and pharmacy
references are not helpful, ask a classmate. Everybody learns in different ways so perhaps
learning the concept from a new perspective will help resolve any confusion.

6.

Dont stress. The Milestone Exam was created to ensure that pharmacy students acquire
essential knowledge during each year of pharmacy school. You passed your first year
(hopefully with flying colors), so you must have put in the effort to learn the material for
each course the first time around. This summer will just serve as a refresher of the
knowledge you already have!

Table of Contents

Anatomy and Physiology (PHR 343C)

5-6

Anatomy and Physiology (PHR 343C) Sample Questions

7-10

Pharmaceutical Biochemistry (PHR341C)

11-15

Pharmaceutical Biochemistry (PHR341C) Sample Questions

16-19

Biopharmaceutics (PHR 252C

20-24

Medicinal Chemistry (PHR143M)

25-28

Medicinal Chemistry (PHR143M) Sample Questions

29-38

Physical and Chemical Principles of Drugs (PHR 342C)

39-40

Introduction to Pharmacy Practice (PHR 242DA/B)

41

Pharmacy Administration I (PHR 224C)

42-46

Pharmacy Administration I (PHR 244C) Sample Questions

47

Professional Development Convocation (PHR 152H)

48

Pharmaceutics I (PHR 356C / PHR156P)

49-56

Pharmocology Principles (PHR 153M)

57-58

Pharmacology Principles (PHR 153M) Sample Questions

59-61

Anatomy and Physiology (PHR 253C)

62-66

Anatomy and Physiology (PHR 253C) Sample Questions

67

Pathology (PHR 253D)

68-71

Pharmaceutical Biochemistry II (PHR 251C)

72-76

Anatomy and Physiology (PHR 343C)

Detailed Course Objectives
Describe the structural and functional organization of the human organism, beginning
at the cellular and, where appropriate, subcellular levels. Define the basic components
and processes critical for basic cell physiology. Describe how positive and negative
feedback mechanisms allow the body to adapt to changes in the internal and external
environment.
Describe the gross anatomical features of organs in the neural, neuroendocrine,
gastrointestinal and cardiovascular systems in great detail. For all other organ systems,
students should be able to identify their anatomy and functionally define them.
Describe the various passive and specialized forms of transport and explain the
functional significance of each.
Define basic principles and processes controlling and subserving all of the following
cellular functions: osmolarity and control of cell volume, the ionic basis of equilibrium
potentials and membrane potentials as well as active and passive properties of excitable
cells.
Define and explain in detail the basic mechanisms and components which subserve
intercellular communication including synaptic and hormonal information transfer via
ligand-gated ion channels, G-protein coupled receptors, tyrosine kinase and steroid
hormone receptors.
Describe the anatomy and define in detail the functions of all major components of the
gastrointestinal system.
Describe the anatomy and define in detail the functions of all major components of the
central and peripheral nervous systems including the afferent and efferent nervous
systems completely.
Describe and define in detail all anatomic and functional components of the sensory
apparati.
Describe and define in detail all anatomic and functional components of the autonomic
nervous system and its control of homeostasis. Describe central and peripheral
mechanisms regulating the ANS.

 Describe and define in detail the anatomy and physiology of the cardiovascular system
with a focus upon cardiac electrophysiology and hemodynamics (at both the organ and
systems levels).
Establish a theoretical knowledge base for a better understanding of human anatomy
and physiology in preparation for the Doctor of Pharmacy career in the context of lifelong learning.
Detailed and specific learning objectives for each topic are found in the textbook and
study guides provided by the instructor.

Anatomy and Physiology (PHR 343C) Sample Questions

1. An elderly patient has taken an excess of their potassium-sparing diuretic resulting in a
plasma concentrations as follows: osmolarity = 270 mOsm, Na+ = 100 mM and K+ = 10
mM whereas intracellular concentrations of these ions are normal. All other ions are
unchanged as well. Which of the following statements about the patient is correct? The
patient is
A. hypoosmotic but hypernatremic with an equilibrium constant for K+ of about -72 mV
and therefore is at risk for neuronal hyperexcitability resulting in hallucinations
and/or seizures.
B. hyperosmotic but hypokalemic with an equilibrium constant for K+ of about +72 mV
and therefore is at risk for neuronal hypoexcitability resulting in sedation and/or
dyspnea.
C. hypoosmotic and hyponatremic with an equilibrium constant for K+ of about +72 mV
and therefore is at risk for neuronal hypoexcitability resulting in sedation and/or
dyspnea.
D. hypersmotic and hyperkalemic with an equilibrium constant for K+ of about -72 mV
and therefore is at risk for neuronal hypoexcitability resulting in sedation and/or
dyspnea.
E. hypoosmotic but hyperkalemic with an equilibrium constant for K+ of about -72
mV and therefore is at risk for neuronal hyperexcitability resulting in
hallucinations and/or seizures.
2. The steps involving initiation and termination of action potentials involve IN ORDER:
A. a hyperpolarizing current triggers the electrostatic inward movement of the S2
segment on a voltage-gated K+ channel to initiate K+ influx which drives the
membrane potential negative and initiates the downstroke of the action potential.
K+ channels then spontaneously inactivate terminating the action potential and the
cell repolarized by the delayed activation of voltage-gated Na+ efflux.
B. a depolarizing current triggers the electrostatic outward movement of the S4
segment on a voltage-gated Na+ channel to initiate Na+ influx which drives the
membrane potential positive and initiates the upstroke of the action potential.
Na+ channels then spontaneously inactivate terminating the action potential
and repolarization completed by the delayed activation of voltage-gated K+
efflux.
C. a hyperpolarizing current triggers the electrostatic inward movement of the S4
segment on a voltage-gated Na+ channel to initiate Na+ influx which drives the
membrane potential negative and initiates the downstroke of the action potential.
K+ channels then spontaneously inactivate terminating the action potential and
repolarization completed by the delayed activation of voltage-gated K+ influx.
D. a depolarizing current triggers the electrostatic outward movement of the S4 segment
on a voltage-gated Na+ channel to initiate Na+ influx which drives the membrane
potential negative and initiates the downstroke of the action potential. K+ channels

then spontaneously inactivate terminating the action potential and repolarization

completed by the delayed inactivation of voltage-gated Na+ influx.
E. a depolarizing current triggers the electrostatic outward movement of the S4 segment
on a voltage-gated Na+ channel to initiate Na+ influx which drives the membrane
potential negative and initiates the downstroke of the action potential. K+ channels
then spontaneously inactivate terminating the action potential and repolarization
completed by the delayed re-activation of voltage-gated Na+ influx.
3. Which of the following statements is correct?
A. Glutamate may activate LGICs or GPCRs, whereas norepinephrine, which arises
from the ventral tegmental area, can only activate LGICs.
B. GABA may activate LGICs or GPCRs, whereas serotonin, which arises from the
ventral tegmental area, can also activate LGICs or GPCRs
C. Glutamate may activate LGICs or GPCRs, whereas norepinephrine, which arises
from the locus coerulus, can only activate LGICs.
D. Glutamate activates only LGICs, whereas dopamine, which arises from the ventral
tegmental area, can activate only GPCRs.
E. Glutamate LGICs or GPCRs, whereas receptors for serotonin, which arises only from
the locus coerulus, can activate only LGICs.
4. Which of the following is a correct statement concerning the sequence involving the
activation of a GPCR-coupled pathway?
A. A hormone is released into the blood and circulates to the target tissue where it
activates a receptor possessing 7 transmembrane regions coupled to a protein subunit
that dissociates and moves within the cell to activate protein kinase A which then
synthesizes cyclic AMP, the second messenger.
B. A neurotransmitter is released into the blood and circulates to the target tissue and
activates a receptor possessing 4 transmembrane regions and 5 subunits which are
coupled to a protein subunit that dissociates and moves within the cell to activate
protein kinase C which then synthesizes IP3, the second messenger.
C. A neurotransmitter is released into the synapse and activates a receptor, assembled from
4 or 5 subunits each possessing 4 or 5 transmembrane regions, that activates calcium
flux into the cell which then activates adenylyl cyclase and synthesizes cyclic AMP,
the second messenger.
D. A hormone is released into the blood and circulates to the target tissue where it
activates a receptor possessing 7 transmembrane regions and coupled to a protein
subunit that dissociates and moves within the cell to inhibit protein kinase A which
then decreases the synthesis of cyclic AMP, the second messenger.
E. A hormone is released into the blood and circulates to the target tissue and
activates a receptor possessing 7 transmembrane regions and coupled to a
protein subunit that dissociates and moves within the cell to activate adenylyl
cyclase which then synthesizes cyclic AMP, the second messenger.

5. Temporal summation of glutamatergic epsps will promote

A. NMDA receptor translocation from intracellular sites to the presynaptic membrane
thereby increasing glutamate release and producing LTP.
B. removal of the Mg++ block of presynaptic AMPA channels which results in the
generation of NO causing more the synaptic insertion of AMPA channels
postsynaptically and producing LTP.
C. Ca++ influx through NMDA channels which then activates both insertion of
additional AMPA receptor subunits into the postsynaptic membrane as well as
local release of a paracrine which increases glutamate release presynaptically
thereby producing LTP.
D. inhibition of v-SNARE and t-SNARE proteins thus causing long-term upregulation of
glutamate release thereby causing LTP.
E. de-phosphorylation of AMPA subunits with their internalization thereby causing longterm depression of synaptic transmission.
6. The lateral corticospinal tract
A. crosses at the level of the vertebra where it enters the dorsal root to carry afferent
discriminative touch information into the somatosensory cortex located just anterior
to the central sulcus.
B. crosses at the level of the vertebra where it exits at the ventral root and it carries
efferent voluntary motor commands from the motor cortex, located just lateral to
the central sulcus, to the skeletal muscles.
C. does not cross the spine after it enters to carry efferent spinocerebellar propioceptive
information to the spinocerebellum.
D. crosses at the level of the medulla then travels to the ventral root where it exits
the spine and carries efferent voluntary motor commands from the motor
cortex, located just anterior to the central sulcus, to the skeletal muscles.
E. crosses at the level of the medulla where it exits the dorsal root to carry afferent
discriminative touch information into the somatosensory cortex located just medial
to the central sulcus.
7. During an extremely stressful event, the autonomic nervous system will
A. increase HR due to the synaptic release of NE onto the SA node where it stimulates
alpha-adrenergic receptors to increase the rate of SA nodal diastolic depolarization.
B. decrease HR due to the synaptic release of NE onto the SA node where it inhibits
muscarinic receptors to decrease the rate of SA nodal diastolic depolarization.
C. increase HR due to the synaptic release of NE onto the SA node where it
stimulates beta-adrenergic receptors to increase the rate of SA nodal diastolic
depolarization.
D. increase HR due to the synaptic release of epinephrine onto the SA node where it
stimulates beta-adrenergic receptors to increase the rate of SA nodal diastolic
depolarization.
E. decrease HR due to the synaptic release of ACh onto the SA node where it stimulates
nicotinic receptors to increase the rate of SA nodal diastolic depolarization.

8. Arrhythmias can be broadly differentiated on the basis of the cell type involved those
involving FAST versus SLOW tissue. Please choose the following pairs which correctly
describe conditions which are most likely to cause an arrhythmia in FAST and SLOW
tissue, respectively.
A. reduced inactivation of Na+ channels in ventricular muscle, reduced activation of
delayed-rectifier K+ channels in AV node.
B. enhanced inactivation of Na+ channels in SA node, enhanced activation of delayedrectifier K+ channels in AV node.
C. reduced inactivation of Na+ channels in ventricular muscle, enhanced activation of
delayed-rectifier K+ channels in HIS/Purkinjie fibers.
D. enhanced inactivation of Na+ channels in ventricular muscle, reduced activation of
delayed-rectifier K+ channels in atrial muscle.
E. reduced inactivation of Na+ channels in ventricular muscle, reduced activation of
delayed-rectifier K+ channels in ventricular muscle.
9. Which of the following lists the answers in the correct order?
The heart rate is calculated from the _____; the time required to complete ventricular
activation is derived from the _______ whereas the _____ indicates the entire time of
hemodynamic systole; and the time required for a normal SA heart beat to reach the
ventricles from its point of initiation is due mainly to the time indicated by the ______.
A. PP interval, QRS interval, QT interval, PR interval
B. PR interval, PP interval, QRS interval, QT interval
C. PR interval, QRS interval, QT interval, PP interval
D. PP interval, QT interval, QRS interval, PR interval
E. PP interval, PR interval, QRS interval, QT interval

10

Pharmaceutical Biochemistry (PHR341C)

Dr. Whitmans Lecture Objectives:
At the end of each of lecture (and after doing the assigned reading and problems), you should
know or have an understanding of the following concepts and the ability to do the following
objectives. The content of each lecture is approximate.
Lecture #1
Define Biochemistry and its relationship to Pharmacy.
Know (recall) your functional groups, structure and properties of water, and covalent/noncovalent interactions (types and relative strengths).
Know and/or understand the definitions and meaning of acid/base, strong vs weak acid,
conjugate acid/base (examples and recognize/identify them when you see them!) pH, pKa,
the Henderson/Hasselbalch equation, calculations using the Henderson/Hasselbalch
equation, determination of the pKa, titration curves and interpretation; buffers and buffer
capacity, and the carbon dioxide/bicarbonate buffering system as well as acidosis and
alkalosis (respiratory and metabolic) and interpretation.
Lecture #2
The general structure and properties of an amino acid and the 20 common amino acids, three
letter codes, and identification of the various acid/conjugate base pairs for the 20
common amino acids. Know the important structural features, as indicated in class
Lecture #3
(continuing from above) the approximate pKa values, titration curves and interpretation,
whether they are charged or not charged at different pH values and how the charges
and/or properties of the side chains are important to the structure of a protein/enzyme, the
pI (and implications), modified amino acids (with examples).
The peptide bond, characteristics and examples (aspartame, glutathione) and relevance
Lecture #4
(continuing from above) more examples (enkephalins, Cyclosporin A, oxytocin,
vasopressin, insulin) and relevance.
Lectures #4-6
Definition of protein, importance and relevance, four levels of protein structure, and
denatured vs native structure (and relevance). Characterization of the levels of structure,
and recognition of structural elements, interactions and properties, globular/fibrous
proteins and collagen triple helix (with an emphasis on the relationship between
structure/function), interactions and properties, folding, and ribbon diagrams. Examples
(botox and EPO) and relevance and more on insulin (implications of pI).

11

Lectures #6-7
The structure and properties of myoglobin and hemoglobin, heme chemistry, behavior of
iron with oxygen, oxygen binding to myoglobin and hemoglobin, interpretation of
oxygen binding curves, implications of curves and properties of myoglobin and
hemoglobin for oxygen transport, cooperativity, and structural basis for cooperativity (T
and R states). Definition, role, and effects of allosteric regulators, (e.g., 2,3-bisphosphoD-glycerate, protons, carbon dioxide), on adult and fetal hemoglobin and structural basis
for the effects. Understand the Bohr effect, the molecular basis for it, and the
implications. Understand what Sickle Cell Anemia is, the molecular basis, and the
implications.
Lecture #8
Know what an enzyme is and the importance of enzymes to Pharmacy and drugs. Know
the basics of enzymatic catalysis, general concepts, terminology, and properties of
enzymes, specificity, and how enzymes work (in general).
Lecture #9-10
Know/understand the basics of enzyme kinetics, the Michaelis-Menten equation, terms,
implications, general observations (on the plot), and the importance, relevance, and
interpretation of the equation and terminology, the definition of the kinetic parameters
(Km, kcat, kcat/Km) and their importance.
Definition of an enzyme inhibitor, its role and importance, definition and difference between
reversible and irreversible inhibitors, competitive and non-competitive inhibition, the
meaning and relevance of Ki, Lineweaver-Burke plots and interpretations, and examples
of the different types of inhibitors. Know the mechanism of penicillin.
Lectures #10-12
Know the definition of a protease and the importance of proteases to pharmacy, the
characteristics/properties and mechanisms (arrow pushing) of serine proteases and
hydrolases (acetylcholinesterase and b-lactamases), cysteine proteases, metalloproteases
(angiotensin converting enzyme), and aspartic proteases (HIV protease). Know the
structural basis of specificity for proteases and the mechanism of inhibition of DIPF,
nerve gases, augmentin, captopril/ACE inhibitors, and HIV protease inhibitors. For all,
know the relevance and importance to pharmacy.
Lecture #13
Know the importance/significance of regulatory strategies and key strategies
(phosphorylation, zymogen activation) and examples (digestive enzymes and blood
clotting). Know the role of protease inhibitors (also a regulatory strategy) and examples
(a-antitrypsin and emphysema).
Lectures #13-14
Know the distinction between the two classes of vitamins (water-soluble vs lipid soluble)
and the distinguishing properties.

12

For the water-soluble vitamins know the vitamin, coenzyme (if relevant), potential
disease (if deficient and relevant), biochemical role and mechanism of action for this role
(if relevant). At a minimum, thiamine, riboflavin, niacin, pantothenic acid, and
pyridoxine will be covered. The other water-soluble vitamins may not be covered.
Know the important structural features, as indicated in class.

For the lipid-soluble vitamins know the vitamin, coenzyme (if relevant), potential disease
(if deficient and relevant), biochemical role and mechanism of action for this role (if
relevant). The lipid-soluble vitamins may not be covered. Know the important structural
features, as indicated in class.

Lecture #14-15
The classification, nomenclature, and chemistry of mono-, di-, and polysaccharides
including reducing sugars and the reaction of glucose with proteins (Amadori
rearrangement and advanced glycation products). Know the distinction between reducing
and non-reducing end of a sugar. Know the glycosidic bond and the basis for lactose
intolerance, and structure of sucralose (Splenda). For all, know the important structural
features, as indicated in class.
Lectures #16-17
Know the structures of ATP and other phosphorylated compounds (if covered) and the
electron carriers, NAD+ and FAD, as indicated in class. Understand the structural basis
for the hydrolysis of ATP and importance of ATP and phosphorylated compounds.
Know the 10 reactions of glycolysis (and location), the key features of each reaction and of
each of the three stages, and understand the overall logic and relevance to various
conditions/diseases. Know the mechanism of aldolase and the mechanism and
importance of the glyceraldehyde 3-phosphate dehydrogenase reaction, fates of pyruvate,
and the energy yield (aerobic vs anaerobic) and the implications of the yield for various
diseases/conditions and drug design. Know the important structural features of the
glycolytic intermediates, as indicated in class.
Know/understand how glycolysis is regulated at the enzyme and hormone levels, the roles of
Insulin vs Glucagon, and the effects of low carbohydrate diets and diabetes on regulation.
Lecture #18-19
Know the location and significance of the Pyruvate Dehydrogenase reaction and the eight
reactions of the Citric Acid (Krebs) Cycle, the mechanism and importance of citrate
synthase, aconitase, and isocitrate dehydrogenase, and the regulation of the cycle. Know
the importance of the cycle in terms of energy production and the production of
biosynthetic precursors. Know how the cycle fits into the overall scheme of metabolism
(including oxidative phosphorylation).

13

Dr. Dalbys Lecture Objectives:

At the end of Dr. Dalbys lectures and after reviewing the reading and review material you
should be able to do the following:
1. Introduction
Describe metabolism and how it relates to drug discovery and the practice of pharmacy
2. Electron Transport and Oxidative Phosphorylation
Describe the role of electron transport in metabolism
Describe the importance of mitochondrial structure in ATP production
Describe the organization of the electron transport complexes
Describe what reactions take place in the respiratory complexes
Describe how electron transport and ATP synthesis are linked
Describe what the coupling factor in oxidative phosphorylation is
Describe how respiratory inhibitors can be used to study the electron transport chain
Describe the importance of the shuttles and how their mechanisms differ from one
another
Describe some mitochondrial diseases
3. Structures of Lipids and Membranes
Describe the characteristic properties of phospholipids
Describe the properties of lipid bilayers and membranes
Describe the essential features of glycerophospholipids, cardiolipin, and plasmalogens
Describe respiratory distress syndrome
Describe what distinguishes platelet-activating factor from other lipids
Describe the role and specificity of the phospholipases
Describe the essential features of sphingophospholipids
Describe the metabolism of sphingomyelin and the molecular basis for Niemann-Pick
disease
Describe the essential features of glycolipids (glycosphingolipids)
Describe the basis for the group of diseases called sphingolipodoses
4. Prostaglandins, leukotrienes and related Compounds
Describe the essential features of the prostaglandins (PG)
Describe the essential features of the thromboxanes (TX)
Describe the isozymes COX-1 and COX-2
Describe approaches towards inhibiting prostaglandin synthesis
Describe the essential features of the leukotrienes
Describe the role of aspirin in platelet homeostasis
5. Lipid Digestion
Describe the process of digestion of dietary lipids
Describe the function of Lingual and gastric lipases
Describe how cholesterol esters (CE), phospholipids (PL) and TAGs containing LCFAs
are degraded in the small intestine by enzymes secreted by the pancreas.
Describe how dietary lipids are absorbed by the intestine.

14

Describe the mechanism of Orlisat

Describe the synthesis, fate and properties of chylomicrons.
Describe Type I and type III hyperlipoproteinemia
Describe the synthesis, fate and properties of very-low-density lipoproteins (VLDL)
Describe the synthesis, fate and properties of low-density lipoproteins (LDL)
Describe the synthesis, fate and properties of high-density lipoproteins (HDL)
Describe the structures of lipoproteins
Describe the role of lipoproteins in the role in cholesterol homeostasis
Describe hyperchylomicronemia

6. Fatty acid synthesis

Describe the properties of fatty acids
Describe the synthesis of fatty acids from acetyl CoA
Describe elongation and desaturation
Describe the essential fatty acids
Describe the synthesis and fate of VLDLs
7. Fatty acid oxidation
Describe the release of fatty acids from TAGs
Describe the essential elements of fatty acid degradation:
Describe the essential elements of the carnitine shuttle
Describe the causes and effect of carnitine deficiency
Describe the effect of medium chain fatty acyl CoA dehydrogenase deficiency
Describe how fatty acids with odd numbers of carbons are oxidized
8. Gluconeogenesis
Describe the pathway for gluconeogenesis
Describe when gluconeogenesis is important
9. Ketone Bodies
Describe the synthesis of ketone bodies from Acetyl CoA
Describe the importance of ketone bodies to peripheral tissues
Describe what ketoacidosis is
10. Cholesterol
Describe the properties of cholesterol
Describe essential elements of cholesterol synthesis
Describe essential elements of cholesterol regulation
Describe the mode of action of the statins
Describe the essential elements of the synthesis of bile salts and their physical properties
Describe the enterohepatic circulation
Describe the essential elements of hypercholesteroemia
Describe the essential elements of cholelithiasis
11. Steroids
Provide a brief overview of steroid synthesis mechanism and metabolism.

15

Pharmaceutical Biochemistry (341C) Sample Milestone Questions

1. Histidine is used as a buffer in your experiment. The side chain of histidine has a pKa value
of 6.0. Which of the following statement(s) is/are TRUE about this buffer?
A.

The effective buffering range due to histidines side chain is about 7 to 9.

B.

At pH 7.0, the ratio of conjugate base to acid is 10 (ignoring functional groups

other than the side chain).

C.

In the histidine buffer solution at pH 6.5, the side chain is mostly charged.

D.

The percentage of conjugate base for histidine (ignoring functional groups other
than the side chain) at pH 5 is about 90.9%.

2. Absorption of food in the stomach and intestine depends on the ability of molecules to
penetrate the cell membranes and pass into the bloodstream. Because hydrophobic
molecules are more likely to be absorbed than hydrophilic or charged molecules, the
absorption of orally administered drugs may depend on their pKa values and the pH in
the digestive organs. Using a pKa of 3.5 for the ionizable carboxyl group of aspirin
which of the following statements is/are TRUE?

A.

At pH 5.0 (intestine), aspirin is mostly ionized and charged.

B.

At pH 2.0 (stomach), ~96.9% of the aspirin will be absorbed through the

membrane.

C.

At pH 5.0 (intestine), ~3.1% of the aspirin will be absorbed through the

membrane

D.

All of the above

3. A pharmacy student becomes extremely anxious the night before a Biochemistry

examination and begins to hyperventilate uncontrollably. What are the effects of the
hyperventilation?

16

A.

The blood levels of CO2 increase and the blood pH decreases

B.

There is no effect on the blood levels of CO2 or the blood pH

C.

The blood levels of CO2 decrease and the blood pH increases

D.

None of the above

4. In the Cori cycle

A.

glucose is converted to lactate in the muscles and this lactate returns to the liver
where it is converted to glucose.

B.

pyruvate is converted to glucose by the glycolytic enzymes, but in the reverse

direction.

C.

glucose is converted to pyruvate in the muscles and this pyruvate returns to the
liver where it is converted to glucose.

D.

pyruvate dehydrogenase plays a major role.

5. Pyruvate
A.

is converted to ethanol in yeast under anaerobic conditions in the presence of

pyruvate decarboxylase, alcohol dehydrogenase, and the appropriate coenzymes.

B.

can be converted to lactate under anaerobic conditions. At the same time, NAD is
converted to NADH (+ H+), which is a critical requirement for the glyceraldehyde3-phosphate dehydrogenase reaction

C.

can be converted to acetyl CoA. In the process, NAD is produced.

D.

All of the above

6. A patient has a Vitamin B12 deficiency. Assuming the patient is taking adequate amounts of
all other vitamins, the Vitamin B12 deficiency is likely to lead to

A.

increased levels of THF and decreased levels of 5-CH3-THF.

B.

increased levels of methylmalonyl CoA

C.

increased levels of methionine.

D.

increased levels of deoxyribose uridine monophospahte (dUMP).

17

7. You discover a mutant yeast where the glyceraldehyde 3-phosphate dehydrogenase+reaction

NADH + H
NAD
is replaced
CHO by the following reaction. All the other steps remain the same.

CHOH
CH2

CHOH

O
O

P
O

CH2

A.

Under anerobic conditions, the production of ATP is not significantly affected.

B.

Under anerobic conditions, the production of NAD+ is significantly affected.

C.

Under aerobic conditions, there is only a minimal effect on ATP production.

D.

Under aerobic conditions, the mutant is not able to process pyruvate.

8. Fetal hemoglobin is able to bind oxygen well because

A.

fetal red blood cells have high levels of 2,3-phosphoglycerate (2,3-BPG).

B.

fetal hemoglobin (HbF) binds 2,3-BPG tightly.

C.

2,3-BPG binds less tightly HbF, compared with HbA

D.

the oxygen partial pressure levels of the placenta are high.

9. Plasmodium falciparum, the parasite that causes malaria, slightly decreases the pH of the
blood cells it infects. Why does this decrease in pH cause these blood cells to sickle in
patients with the sickle cell mutation of hemoglobin (HbS)?

CO2

A.

The lower pH stimulates the production of 2,3-phosphoglycerate (2,3-BPG).

B.

The lower pH favors the deoxy form, which causes HbS polymerization and
subsequent sickling.

C.

The lower pH facilitates the release of oxygen from HbS. The increased oxygen
pressure causes HbS polymerization and subsequent sickling.

D.

The lower pH increases the CO2 levels in the blood, which causes HbS
polymerization and subsequent sickling.
18

10. As blood glucose rises after a meal, the rate of glucose uptake by liver cells increases
proportionately, whereas the rate of uptake by muscle cells levels off. Why?
A.

Glucokinase is inhibited by glucose-6-phosphate.

B.

Hexokinase is not inhibited by glucose-6-phosphate.

C.

Glucokinase has a high Km and is not readily saturated by glucose.

D. The chemical properties of glucose make it more difficult to get into muscle cells.
11. Inhibitors of acetylcholinesterase, such as edrophonium (below), can be used to treat
Alzheimers disease. The substrate for acetylcholinesterase, acetylcholine, is also shown
below. Which of the following statement(s) is/are true about these compounds?
A.

Edrophonium is most likely an irreversible inhibitor of acetylcholinesterase,

forming a covalent bond to the active site serine.

B.

The inhibition of acetylcholinesterase by edrophonium can be overcome in vitro

by saturating concentrations of substrate.

C.

The Lineweaver-Burk plots for the reactions of acetylcholinesterase in the

presence of substrate and in the presence of substrate plus edrophonium would
exhibit the same slopes.

D.

The Lineweaver-Burk plots for the reactions of acetylcholinesterase in the

presence of substrate and in the presence of substrate plus edrophonium would
exhibit different y-intercepts but the same x-intercepts.

12. An enzyme recognizes only the a-anomer of glucose as a substrate and converts it to
product. If the enzyme is added to a mixture of the a- and b-anomers, why are all the
sugar molecules eventually converted to product?
A. The a- and b-anomers are in equilibrium. Depletion of the a-anomer will cause
more of the b-anomer to convert to the a-anomer.

B.

The enzyme changes the equilibrium constant for the a- and b-anomers. Depletion
of the a-anomer will cause more of the b-anomer to convert to the a-anomer.

C.

The enzyme increases the energy of activation for the b-anomer so that the
enzyme can now recognize the b-anomer.

D.

The enzyme decreases the energy of activation for the b-anomer so that the
enzyme can now recognize the b-anomer.

19

Biopharmaceutics (PHR 252C)

Core Concepts
1. Concepts of Drug Development
History of Drug Regulation in The United States
o Federal Food, Drug, and Cosmetic Act (1938). Safety
o Kefauver-Harris Amendments (1962). Efficacy
o Drug Price Competition & Patent Restoration Act
o Waxman-Hatch Act, 1983
o Treatment Use of Investigational New Drugs (1987)
o Prescription Drug User Fee Act, 1987
Human Participant Protection Education Ethics of Clinical Testing
2. How Drugs are developed
Technical development of new drugs
Patent Considerations
New Drug Development process
o Preclinical Studies
o Investigational New drug Application
o IND Study Protocol
o Phase I Clinical Studies
o Phase II Clinical Studies
o Phase III Clinical Studies
o Phase IV Drug Development Studies.
Essential in Planning a Phase II Trial
Institutional Review Boards
Fast Track Approval
Treatment IND
Supplemental NDA ( sNDA)
Abbreviated NDA (ANDA)
3. FDA Organization
FDA Review Process
Changes at the FDA
4. Radioisotopes in The Biological Sciences- Clinical Applications
Particles and Nomenclature
Nuclear Reactions
o Fusion
o Fission
Units of Radioactivity
Types of Radiation
o Alpha
o Beta
o Gamma

20

 Rate of Radioactive Decay

o Mathematical development
o Specific Activity
Sources of Errors on Tracer Studies
o Chemical effects
o Radiochemical Purity
o Radiation Effects
o Isotope Effects
o Exchange Reactions
Instrumentation
o Positron Emission Tomography
o Gamma Camera-Scintillation Camera
o Single Photon Emission Tomography
o Clinical Applications
Brain Scans
Blood and Heart Scans
Bone Scan
Brachytherapy
o Interstitial Therapy
o Intracavitary Therapy
o Lung Scans
o Thyroid Scans
o Boron Therapy
Dosimetry Calculations
o Radiation Absorbed Dose ( RAD)
o Radiosensitive Tumors
o Radioresistant Tumors
o Side Effects
5. Kinetics of Drug Action
Potency
Efficacy
Therapeutic Index
Margin of safety
Dose Optimization Based on Pharmacokinetic-Pharmacodynamic Modeling
o Fixed Effect Model
o Linear Model
o Log-Linear Model
o Emax Model
o Sigmoidal Emax Model
Hysterisis Loops
o Equilibration Delays and Links to Other Compartments
Direct Link PK-PD
Indirect Links
Sources of Variability
o Metabolism

21

o Genetics
o Environmental
o Drug-Drug Interaction
6. Transport of Drugs Across Biological Membranes
Membrane Structure and Composition
o Davson-Danieli Model
o Singer-Nicolson Model
o Intrinsic, Extrinsic Proteins, Cholesterol, Glycolipids, and oigosacharides
o Fusogenic Peptides
Transport Mechanisms
o Ficks Law and Passive Diffusion
o Facilitated Diffusion
o Active Transport
o Vesicular Transport
Pinocytosis
Phagocytosis
Exocytosis
o Solvent Drag
o Pore Filtration
o Ion-Pair Formation
Role of Intestinal Transporters in Drug Absorption
o Absorption and Exsorption
Apical Transporters Organic Anions and Cations
The ABC (ATP- binding cassette proteins), Pgp (for lipophilic
compounds), MRP2 (for drug Conjugates), BCRP
7. Physiological Variables In The GI Tract Relevant to Drug Absorption
pH
Complexation
Transit time
Bile Components
Luminal and Brush Border Enzymes
Absorbing Capacity of the Epithelia
8. Hormonal and Anatomical Variables in The GI Tract Relevant To Drug Absorption
Basal Secretion
Prandial Secretion
Cephalic Phase
Gastric Phase
Chemical Agents
Stomach Emptying
Functional Types Of Movements In the GI Tract
o Mixing Movements
o Propulsive Movements

22

9. Effect of Food on drug Absorption

Triglycerides
Amino Acids
Carbohydrates
Acids
Alkali
Other Factors
o Viscosity
o Body Position
o Particle Geometry
o Enterohepatic Cycling
10. Lymphatic Absorption
Lymph Formation
Chylomicrons
11. Routes of Drug Administration. Bioavailability, Advantages and Disadvantages
Enteral
o Oral Cavity
o Sublingual
Bucal
o Oral
o Rectal
Parenteral
o Intravenous and Intra-arterial
o Intramsucular
o Subutaneous
o Intraperitoneal
o Nasal
o Topical
o Inhalation
o Intratechal
o Ophthalmic
12. Biopharmaceutic Considerations In drug Product Design
Rate Limiting Steps in Drug Absorption
o Pharmacodynamic Considerations
Therapeutic Objective
Toxic Effects
Adverse Reactions
o Drug Considerations
Chemical and Physical Properties
o Drug Product Considerations
Pharmacokinetics of Drug
Bioavailability of Drug
Route of Administration

23

Desired Dosage Form

Desired Dose of Drug
o Patient Considerations
Compliance and acceptability of Product
Cost
o Manufacturing Considerations
Cost
Availability of raw materials
Stability
Quality Control
In Vitro Disintegration
In Vitro Dissolution
o Noyes Whitney Equation
Compendial Methods of Dissolution
Basket Method
Paddle Method
o In Vitro-In Vivo Correlations
12.4 Bioavailability
o Relative
o Absolute
o Assessment of Bioavailability
From Plasma Levels after single dose or at steady state
o Area calculation
o From Urine Levels after a single dose or at steady state
o From Pharmacological Response
Bioequivalence
o Sources of Variability of Bioequivalence Studies
Inescapable Variation
Controllable Variation
Statistical Considerations
Design, reference Standard, and Data
Evaluation
o Estimation of 90% Confidence Intervals
o Therapeutic Equivalence
o Generic substitution
o Federal and State Regulations

24

Medicinal Chemistry (PHR143M)

Dr. Daviss Drug Metabolism Section Learning Objectives:
1. Importance of Studying Drug Metabolism

Describe the basic reasons why the study of metabolism is important from the
pharmaceutical perspective.
Describe the major possible consequences of metabolism related to therapeutic activity
(bioinactivation, bioactivation, detoxification, and toxification) and give an example of
each.
Describe the role of metabolism in prodrug design.
Describe the metabolic basis of potential drug-drug interactions and give two specific
examples.
Describe the importance of sterochemistry in metabolism (both in terms of substrate and
product stereoselectivity).
Describe (in general terms) how medicinal chemists systematically modify drug structure
to control metabolism.

2. Phase 1 and Phase 2 Metabolism

Differentiate phase-1 and phase-2 metabolism from the standpoint of functional group
involvement and the polarity consequences.
Describe the location and involvement of the major organs involved in drug metabolism.
Differentiate the importance of the liver relative to the other organs (quantitatively and
qualitatively).

3. Phase 1 Reactions

Describe the catalytic role of cytochrome P-450 in xenobiotic metabolism.

Describe the importance of multiple forms of P-450 in broad-based metabolism.
For each oxidative and reductive pathway specified, be able to show the specific
introduction of a functional group or interconversion of existing functional groups.
For each mechanism discussed, be able to use that mechanism to predict whether a
related drug molecule will undergo the specified reaction.
Be able to examine a drug molecule you have not seen before and predict five logical
phase-1 metabolites that would result from the action of P-450, reductases, oxidases, and
hydrolases.

4. Phase 2 Reactions

Describe the mechanism of glucuronidation and the functional groups potentially

involved.

25

Describe the mechanism of arly sulfate formation, and the functional groups potentially
involved.
Describe the mechanism by which glutathione inactivates biologically-derived
electrophiles. Describe this role in terms of detoxification, and the implications of
glutathione depletion.

5. Factors Affecting Drug Metabolism

Describe the major factors that affect drug metabolism positively or negatively.
Using model therapeutic agents, be able to describe whether each of these factors would
be expected to increase or decrease drug metabolism, and what the therapeutic &
toxicological consequences would be in each case.
Based on your understanding of P-450 isoforms, clearly distinguish between an isoform
and an isozyme.
Based on your understanding of P-450 isoform biology, predict instances in which one
drug (or nutrient) would impact (positively or negatively) the metabolism of another
drug.
Define pharmacogenomics. Explain why genetic differences in drug metabolism (in
particular), drug transport, and drug receptor formation influence drug action.

6. Putting it All Together: The Liver Game, A Problem-Solving Class Exercise

Understand the dynamics of drug metabolism involving multiple enzyme systems on a

given substrate.
Understand the interplay between phase-1 and phase-2 metabolism in generating excreted
metabolites.
Understand why logically predicted metabolites sometimes to do not appear at
quantifiable levels.

Overall: Can you do the following:

1.
2.
3.

Based on the chemical structure of a drug molecule (i.e., the functional groups
present), predict logical pathways for metabolism of that drug?
Explain how changes in metabolic pathways (e.g., induction, inhibition) can impact
the therapeutic activity, toxicity, and/or drug interactions.
Explain how genetic differences in drug metabolism result in predictable differences
in drug response.

26

Dr. Kerwins Learning Objectives:

1. Introduction
What is medicinal chemistry and how does it relate to drug discovery/development and
the practice of pharmacy?
What are physicochemical properties and how do they impact ADME and SAR?
2. Functional Group Review
For each of the following drug skeletons and common functional groups, know and be
able to rationalize the chemical and metabolic stability, contribution to water solubility,
effect on LogPo (i.e., approximate Hansch p value), intermolecular interactions with
proteins and the amino acid side-chains that are commonly involved in these
intermolecular interactions. Also, be able to address the specific concepts introduced
under individual functional groups below.
o Aliphatic carbons
o Alkene carbons
How does conjugation of alkenes with electron donating or withdrawing
groups affect their chemical properties.
o Phenyl rings
Be able to identify two common motifs for p-p.
Be able to identify aromatic versus non-aromatic carbo- and heterocyclic
ring systems.
Be able to identify the following common heterocycles: pyridine, purine,
pyrimidine, pyrrole, furan, thiophene, imidazole, benzofuran,
benzimidazole, indole, and 1,4-benzodiazepine.
o Halogens
What is the origin and effect of bond dipoles on physicochemical
properties of molecules?
Be able to identify the sign of the Hammett sigma values for halogens
(and other common substituents).
o Alcohols
Know the effect of chain homologation on LogP and be able to predict the
relative LogP of a series of homologous drugs.
o Phenols
Know the structures of the products of oxidation of phenols.
Know and be able to use the Henderson-Hasselbalch equation to calculate
ionization state of phenols (and other drugs).
Be able to show and describe the effect of resonance stabilization on the
pKa of phenols.
Know the effect of intramolecular hydrogen bonding on physicochemical
properties such as water solubility and LogP.
o Thiols

27

Be able to describe the significance of disulfide bonds in proteins and

between drugs/proteins.
Ethers and Thioethers
Amines
Be able to predict and rationalize the approximate pKa of pyridines and
imidazoles
Anilines
Ketones and Aldehydes
Be able to identify important tautomeric forms of carbonyl compounds.
Be able to draw and rationalize the equilibrium ratio of hydrated
carbonyl forms for different ketones/aldehydes.
Carboxylic acids
Be able to explain the relative acidity of simple carboxylic acids based
on inductive effects.
Esters and Amides/Lactones and Lactams
Be able to explain the utility of produgs employing ester groups in
modifying the physiochemical properties of drugs.

o
o
o
o

o
o

3. Fundamental Concepts in Medicinal Chemistry

Be able to convert between equilibrium binding constants and thermodynamic binding
energies and vice-versa. For a given change in binding energy (or equilibrium binding
constant), be able to calculate the corresponding change in equilibrium binding constant
(or binding energy).
Know approximate favorable binding energy ranges for the following intermolecular
interactions: ionic, reinforced ionic, ion-dipole, dipole-dipole (H-bonding), and van der
Waals.
Be able to explain the role of water in drug-receptor interactions and the origin of the
hydrophobic effect.
Know the definition of a pharmacophore and be able to describe two ways to identify the
pharmacophore of a given class of drugs.
Be able to define isosterism and identify common isosteres for selected functional
groups.
Be able to identify and employ a Craig plot to dissect electronic and
lipophillic/hydrophilic contributions of substituents to biological activity.
Be able to identify constitution, connectivity, constitutional isomers, configuration,
configurational isomers, diastereomers, and enantiomers.
Be able to describe the effect of stereochemistry and conformation on the biological
activity of drugs.
Be able to define eutomer, distomer, and eudismic ratio. Be able to describe two types of
trends observed between eudismic ratio and potency of series of chiral drugs and the
origins of these trends.
Be familiar with the concept of QSAR.

28

Medicinal Chemistry (PHR143M) Sample Questions

Dr. Kerwins Sample Questions
Learning Objective:
For .drug skeletons and common functional groups, know and be able to
rationalize the chemical and metabolic stability, contribution to water solubility,
effect on LogPo (i.e., Hanschp value), intermolecular interactions with proteins and
the amino acid side-chains that are commonly involved in these intermolecular
interactions.
Question: The induction period for volatile anesthetics such as halothane and diethylether is
proportional to their solubility in blood: the more soluble the longer the induction period.
Predict the LogPo for diethylether (CH3CH2OCH2CH3) [Use Hanschp values]. Using
your predicted LogPo for Halothane from question #16 above and what you know
concerning the relationship between logPo and water solubility, what can you predict
concerning the relative properties of these two drugs?
A. Halothane has the higher LogPo, which indicates that it has a higher solubility in blood and
a longer induction period than diethylether.
B. Diethylether has the higher LogPo, which indicates that it has a higher solubility in blood
and a longer induction period than halothane.
C. Halothane has the higher LogPo, which indicates that it has a lower solubility in blood and a
shorter induction period than diethylether.
D. Diethylether has the higher LogPo, which indicates that it has a lower solubility in blood and
a shorter induction period than halothane.
E. Halothane and diethylether have approximately the same LogPo (within 0.5 units), which
indicates they have similar solubility in blood and similar induction periods.
Learning Objective:
Be able to explain the utility of produgs employing ester groups in modifying the
physiochemical properties of drugs.
Question: The drug whose structure is shown below was found to inhibit a certain kinase
involved in cell proliferation and is being considered as a new anti-cancer drug.
However, in order to be administered IV, the drug must have appreciable (> 0.1 mg/mL)
solubility in water. Which of the following derivatives of this drug might have improved
water solubility, but undergo rapid conversion to the drug in plasma?

29

A.

D.

B.

E.

None of the above

C.

Learning Objective:
Be able to identify and employ a Craig plot to dissect electronic and
lipophillic/hydrophilic contributions of substituents to biological activity.
Question: The following series of compounds were tested for their ability inhibit thrombin,
and the results, reported as the concentration required for one-half maximal inhibition
(IC50) appear in the table below. Based upon this data, what can you conclude about the
role of the R substituent on thrombin inhibition. You may want to refer to the Craig Plot
shown at the end of this question to answer this question.

R=
Cl

IC50
1 M

30

H
Me
tBu
OMe
A.
B.
C.
D.
E.

10 M
1 M
0.05 M
10 M

The role of the R substituent is primarily electronic the more electron withdrawing the
R substituent, the tighter the receptor binding.
The role of the R substituent is primarily electronic the more electron donating the R
substitutent, the tighter the receptor binding.
The role of the R substituent is primarily lipophilic the more lipophilic the R
substituent, the tighter the receptor binding.
The role of the R substituent is primarily hydrophilic the more hydrophilic the R
substituent, the tighter the receptor binding.
The role of the R substituent is neither electronic nor lipophilic/hydrophilic.

31

Dr. Daviss Sample Questions

Learning Objective:
Explain how changes in metabolic pathways (e.g., induction, inhibition) can impact
the therapeutic activity, toxicity, and/or drug interactions.
Question: The immunosuppressive cyclosporin is metabolized by CYP3A4 to inactive
products. A patient on cyclosporin to prevent liver transplant rejection, unfortunately
develops depression because of his illness, and decides to self-treat with herbal product,
St. Johns Wort. However, you alert the transplant team that St. Johns Wort is a strong
CYP3A4 inducer based on the presence of the natural product hyperforin. The team says,
and so what does that mean? How do you respond (i.e., what is your primary
concern)?
A.
B.
C.
D.
E.

The use of St. Johns Wort in this patient without adjusting any doses may result in much
more profound immunosuppression (with resultant bone marrow destruction).
Enhanced metabolism of hyperforin (in St. Johns Wort) may result in inadequate
treatment of his depression.
The use of St. Johns Wort in this patient without adjusting any doses may result in liver
rejection.
Decreased metabolism of hyperforin (in St. Johns Wort) may result in hyperforin
toxicity.
There really isnt a problem here since other P450 isoforms will probably metabolize
cyclosporin.

Learning Objective:
Based on the chemical structure of a drug molecule (i.e., the functional groups
present), predict logical pathways for metabolism of that drug.
Question: For the pathways shown below, all of the following are acceptable (possible)
except:

32

A.
B.
C.
D.
E.

Pathway I
Pathway II.
Pathway VII.
Pathway VIII.
All four pathways listed above (I, II, VII, VIII) are possible.

Learning Objective:
Explain how genetic differences in drug metabolism result in predictable differences
in drug response.
Question: S-Mephenytoin (shown below) is an anticonvulsant that shows sedation as a
potential side effect. This drug is metabolized primarily by CYP2C19 to inactive
products.

There are significant polymorphisms associated with CYP2C19. For example, ~20% of
subjects of Southeast Asian descent are poor metabolizers based on their inability to
produce active enzyme in sufficient quantities.
Mrs. Nguyen (an immigrant from Viet Nam) is your patient; she is currently stabilized on a
standard dosing regimen (standard dose and time) with mephenytoin in the treatment of
her epilepsy. She is now going to start taking the fluoxetine to treat her depression.
Fluoxetine is a potent inhibitor of CYP2C19. What are your concerns?
A.

B.
C.
D.
E.

No problem. Although she is considered a poor metabolizer because of her genetic

polymorphism (resulting in increased levels of mephenytoin), inhibition of CYP2C19
would be expected to bring her mephenytoin levels to therapeutic values. Thus, the two
effects counteract each other, and she will be just fine.
Excess sedation due to accumulation of mephenytoin. She is already considered a poor
metabolizer because of her genetic polymorphism, and the inhibition of CYP2C19 will
further enhance her blood levels of mephenytoin.
Excess sedation due to accumulation of mephenytoin. Although there is no indication
that she is a poor metabolizer based on CYPP2C19 genetic polymorphisms, the inhibition
of CYP2C19 will increase her blood levels of mephenytoin.
Epileptic seizures due to loss of control of her epilepsy. She is already considered a
poor metabolizer because of her genetic polymorphism, and the inhibition of CYP2C19
will further decrease her blood levels of mephenytoin.
Epileptic seizures due to loss of control of her epilepsy. Although there is no indication
that she is a poor metabolizer based on CYPP2C19 genetic polymorphisms, inhibition of
CYP2C19 based metabolism by fluoxetine would be expected to decrease her blood
levels of mephenytoin, possibly below therapeutic levels

33

Learning Objective:
Be able to show the flow of electrons (push arrows) for common chemical reactions
in medicinal chemistry, including: ester/amide hydrolysis, the NIH-shift,
aldol/retro-aldol reactions, biotin-dependent enzymes, and PLP-dependent enzymes.
Question: Which of the following best represents the flow of electrons (arrow pushing) for the
N-formylation reaction shown?
A.

B.

34

C.

D.

Learning Objective:
Be able to apply the CIP nomenclature system to describe the stereochemistry of
drug molecules.
Question: Describe the correct stereochemical descriptors to the hydrogens labeled A and
B in the structure of valacycloriv below?

A.

A is the pro-R hydrogen, B is the pro-S hydrogen. Substitution of A with

deuterium would produce the enantiomer of the product of substitution of B with
deuterium.
35

B.

A is the pro-S hydrogen, B is the pro-R hydrogen. Substitution of A with

deuterium would produce the enantiomer of the product of substitution of B with
deuterium.
C. A is the pro-R hydrogen, B is the pro-S hydrogen. Substitution of A with
deuterium would produce the diastereomer (not enantiomer) of the product of substitution
of B with deuterium.
D. A is the pro-S hydrogen, B is the pro-R hydrogen. Substitution of A with
deuterium would produce the diastereomer (not enantiomer) of the product of substitution
of B with deuterium.
E. A is the S-hydrogen, B is the R-hydrogen.
Learning Objective
For each common functional group, know and be able to rationalize the
contribution to water solubility, [and] effect on LogPo (i.e., Hansch p value)...
Question: Chloral hydrate, the active ingredient in the notorious Mickie Finn is rapidly
metabolized to trichloroethanol. Ethchlovynol is also a sedative-hypnotic. Assuming
that the onset of action of these drugs is a function of their LogPo (the higher the LogPo,
the more rapid the onset), predict which of these two alcohols has the fast onset of action.

A.
B.
C.
D.
E.

Trichlrorethanol has the higher LogPo based on Hansch p values, and therefore the faster
onset of action.
Ethchlorvynol has the higher LogPo based on Hansch p values, and therefore the faster
onset of action.
Both trichloroethanol and ethchlorvynol have similar LogPo based on Hansch p values
(within 0.5 units), and therefore similar onset of action.
Both trichloroethanol and ethchlorvynol have similar LogPo based on Hansch p values
(within 0.5 units), but ethchlorvynol, being branched, is predicted to be less lipophillic
and have slower onset of action.
Both trichloroethanol and ethchlorvynol have similar LogPo based on Hansch p values
(within 0.5 units), but ethchlorvynol, being branched, is predicted be more lipophillic and
have a faster onset of action.

Learning Objective
Be able to explain the utility of produgs employing ester groups in modifying the
physiochemical properties of drugs.
Question: Valacyclovir is the L-valine ester of acyclovir (see structures below), an antiviral
agent effective against herpes viruses. Both oral acyclovir (200 mg, 5 times a day for 710 days) and oral valacyclovir (1 g, twice a day for 7-10 days) are recommended for the
treatment of initial episodes of genital herpes simplex virus (HSV-2) infection in
immunocompetent adults and adolescents. Which of the following statements best

36

describe the factors that you would consider in making a choice of oral acyclovir versus
oral valacyclovir in treating a patient suffering from genital HSV-2 infection?

A.
B.
C.
D.
E.

The different sensitivity of this particular strain of HSV-2 to these two drugs.
The different potential for the emergence of resistance to these two drugs.
The difference in the potential for patient compliance with the dosing schedule between
these two drugs
Both A and C
All of the above (A, B, and C)

Learning Objective:
Know the definitions of LogPo and LogPapp. Be able to estimate LogPo for drugs
containing the functional groups reviewed in class. Be able to explain the
significance of LogPapp in ADME.
Question: The induction period for sodium salts of barbiturates is attributed to the rapid
partitioning of the predominant solution form of these drugs in the blood, across the
blood/brain barrier and into the sites of action in the brain. This rapid partitioning is a
function of the LogPapp of these drugs: the higher the LogPapp, the more rapid the
partitioning into the brain. By predicting the LogPapp for the two barbiturates below,
predict which one will have the more rapid onset of action.
HINT1: The pKas for these two drugs are identical
HINT 2: Assume the Hansch p value for sp carbons is the same as that for sp2 carbons.

A. Methohexital has a higher LogPo than butabarbital, but a lower LogPapp, which indicates
that butabarbital has a more rapid partitioning to the brain and a shorter induction period
than methohexital.
B. Methohexital has a higher LogPo than butabarbital, and a higher LogPapp, which indicates
that methohexital has a more rapid partitioning to the brain and a shorter induction period
than butabarbital.
C. Butabarbital has the higher LogPo, but a lower LogPapp, which indicates that methohexital
has a more rapid partitioning to the brain and a shorter induction period than butabarbital.

37

D. Butabarbital has the higher LogPo, and a higher LogPapp, which indicates that butabarbital
has a more rapid partitioning to the brain and a shorter induction period than
methohexital.
E. Methohexital and butabarbital have approximately the same LogPo (within 0.5 units), and
approximately the same LogPapp, which indicates they have similar partitioning to the
brain and similar induction periods.

38

Physical and Chemical Principles of Drugs (PHR 342C)

Learning Objectives
1. Introduction
What is Physical Pharmacy?
o Role of Physical Pharmacy in Daily Pharmaceutical Practice
Examples of Drug Stability
Examples of Drug Reliability
Examples of Drug Safety
2. Thermodynamics
Basic definitions
State Functions
Equilibrium and relation to State Functions
Effect of temperature on equilibrium
o the vant Hoff equation
3. Intermolecular Interactions
Modes of Interaction
Intermolecular Interactions and drug formulation and drug action
Interactions in pure compounds
o boiling point
o melting point
Relationship between melting and boiling point
o methods for prediction of melting and boiling point
Interactions in Solution
o solubility
o partition coefficient
o Raoults Law
o colligative properties
o adjusting tonicity
4. Equilibria Important to the Pharmaceutical Sciences
Chemical Reactions
Complexation
drug, receptor
drug, protein
drug, drug
complexation and drug stability
Vapor Pressure
o aerosols and Raoults Law
Solubility

39

o electrolytes
o nonelectrolytes
PartitioningofNonElectrolytes

5.Acid/BaseEquilibria
Basicdefinitions
SolvingpHandbufferproblems
o pHandbufferproblemsinphysiology
EffectofpHonsolubilityofdrugs
EffectofpHondrugpartitioningandabsorption

6.ChemicalKinetics
Basicconcepts
Zeroorderprocesses
Firstorderprocesses
Pseudoorderprocesses
Effectoftemperatureonrateofaprocess
EffectofpHonrateofaprocess

40

Introduction to Pharmacy Practice (PHR 242DA/B)

Course Objectives
Define the concept of assisted-living, and identify services provided residents at assistedliving facilities, and by whom these services are provided.
Discuss demographics of the population residing in assisted-living facilities.
Identify the possible barriers to communicating with the elderly (physical, mental, social,
generational, economic) and identify strategies to overcome these barriers.
Identify the most common medical conditions that affect the elderly
Define the Beers Critria. Learn about medications that should be used with caution in
persons age 65 years and older (Beers Criteria).

41

Pharmacy Administration I (PHR 224C)

Dr. Wilsons and Mr. Salzmans Course Objectives
Section on Pharmacy Personnel Management
History of Management Theory and Pharmacist as a Knowledge Worker
Define the term management.
Explain why management is both an art and a science.
Describe why management can be called a profession.
Compare the three levels of managers and their use of conceptual, human and technical
skills.
Discuss the different management theories that have been utilized over the last 100 years
and what effect society has had on these theories.
Discuss a knowledge worker.
Management Functions and Authority in Management
List and describe the five management functions.
Describe and give examples of the differences between authority and responsibility.
When would an increase in political behavior be expected within an organization.
Describe the positive and negative use of power and influence.
Given a situation describing political behavior decide if inducement, persuasion,
coercion, or obligation can best define that form of manipulation.
Describe how a manager can reduce uncertainty and competition within an organization.
Know Yourself
Select the strengths and limitations of each personality type described in the SELF
profile.
2. Explain how you would manage each personality type described in the SELF
profile.
3. Describe techniques you would use in working with each personality type
described in the Self profile.
Theory X vs. Theory Y
Explain how you might apply McGregor's Theory of X and Y to different classes or
groups of workers.

42

 Describe how a manager's assumptions about the nature of people will change their
management style.
How does Theory X and Y differ.
Apply McGregor's Theory X and Y to a management problem in a pharmacy setting.
Discuss Theory Z, Six Sigma and Balanced Scorecards and how they are applied in
pharmacy.
Motivation Theories: Maslow & Herzberg
Describe Maslow's hierarchy theory.
Given a description of an employee explain where that person would fit into Maslow's
hierarchy.
Apply Maslow's theory to a pharmacy setting.
Explain the Hawthorne studies.
Describe Herzberg's hygiene theory and apply it to a pharmacy setting.
Compare and contrast Maslow's and Herzberg's theories.
Leadership Differences Based Upon Sex-Role Orientation
Define leadership.
Define and compare the five theories of leadership.
Describe the elements of the leadership style characterized as "Androgynous Leadership."
Discuss the advantages for men and women to become androgynous leaders.
Customer Service
Explain the purpose, importance and basic facts relating to quality customer service.
Discuss the importance of quality customer service to the success of any organization.
Define quality customer service and discuss the four basic guidelines for providing it to
customers.
Explain and distinguish between external and internal customers.
Employee Performance and Evaluation
Discuss the importance to the individual employee of objective performance appraisals.
Discuss the importance and value of an objective performance appraisal system to
organizational success.
Describe the basic components, procedures and techniques utilized in conducting
performance appraisals.
Explain the three basic functions of performance appraisals.

43

 Describe and explain the three "secrets" of the "One Minute Manager."
Time Management
List and explain the "Top Ten Time Eaters."
Compare and explain efficiency and effectiveness.
Explain and demonstrate the theory and application of Pareto's Principle (80/20 rule).
Identify and explain the three essential steps to planning your day.
Briefly discuss task management, a planning tool for project management.
Managing Generations
(new unit underdevelopment)

44

Dr. Browns Course Objectives:

Section on Social and Behavioral Pharmacy
The Drug Use Process
Describe and understand the medical care process.
Understand the pervasiveness of medication use in American society.
Describe the eight steps in the drug use process.
Identify and discuss the factors that influence the drug use process.
Describe factors that contribute to suboptimal drug use.
Health, Illness And Sick Role Behaviors
Understand and describe how sociodemographic factors influence access to and use of
health care services.
Briefly describe the Health Belief Model and Suchmans Stages of Illness and understand
how they may apply to health and illness behavior.
Recognize examples of Suchmans Stages of Illness in The Doctor.
Describe Parsonss sick role model and understand its limitations.
Compare and contrast Parsonss sick role model and the new sick role model.
Pharmaceutical Care
Define and describe pharmaceutical care and the importance of this paradigm shift in
pharmacy.
Identify the eight drug-related problems and recognize an example of each.
Define the Pharmacists Workup of Drug Therapy and identify each of the seven steps.
Describe the Behavioral Pharmaceutical Care Scale and its applications.
List barriers and benefits of pharmaceutical care and understand how they impact the
practice of pharmaceutical care.
Understand the current level of pharmaceutical care activities among practicing
pharmacists.
Medication Adherence
Describe the scope of nonadherence and its consequences.
Understand issues related to adherence and nonadherence and effective strategies for
combating nonadherence.
Identify reliable measures of adherence and the best ways to ask patients questions about
adherence.

45

Special Populations: The Elderly

Describe the changing U.S. demographics regarding the elderly.
Understand issues related to health among elderly persons and how these issues impact
their use of medications.
Self-Care
Understand the history of self-care and reasons why self-care practices have been
increasing.
Identify types of self-care practices and the benefits and barriers to self-care.
Describe the role of the pharmacist in self-care.

46

Pharmacy Administration I (PHR 244C) Sample Questions

Section on Social and Behavioral Pharmacy
Objective: List barriers and benefits of pharmaceutical care and understand how they
impact the practice of pharmaceutical care.
You have just started a new job at a chain pharmacy in a traditionally underserved community.
You plan to provide pharmaceutical care services to patients, but you recognize that this
small community has no prior experience with this level of pharmacy service. When
providing this new service, you want to avoid as many problems as possible. What are
some key issues you must consider before implementation?
1.
2.
3.
4.
5.

Cooperation of local medical providers

Access to patient clinical data
Resource and environmental needs
All of the above
A only

Objective: Understand issues related to adherence and nonadherence and effective

strategies for combating nonadherence.
At her 6-month visit, your patient with diabetes indicated that she started off taking her
medications very well but just got tired of doing this day after day. She indicated that she
is especially prone to miss doses since she sees no difference if she takes her medications
or not. Which are likely medication adherence issue(s) that you need to address with this
patient?
1.
2.
3.
4.
5.

Poor medication adherence in chronic, asymptomatic illness

Depression
Regimen complexity
Side effects
All of the above

47

Professional Development Convocation (PHR 152H)

Course Objectives
By the completion of this course, students should be able to:
Demonstrate self-directed learning abilities through the use of techniques such as
reflection and critical thinking.
Apply introductory skills related to career decision-making.
Relate their personalized understanding of professional development expectations (e.g.,
professional and ethical behavior, leadership) to a real-life example of a professional in
pharmacy. )
Interpret the impact of federal, state, and professional regulations on first year
pharmacy students.
Identify the impact of specific contemporary issues on pharmacy practice and health
care.
Understand how University and College regulations and policies affect first year
students.

48

Pharmaceutics I (PHR 356C - PHR156P)

Course Objectives Spring 2010
To know the functionality as well as the physical and chemical properties of drugs and
pharmaceutical excipients in pharmaceutical dosage forms.
To learn the art, science, and the correct procedures in order to extemporaneously
compound a prescription product and then put this knowledge into practice in the
laboratory class, PHR 156C.
To understand the principles and factors controlling drug stability and bioavailability.
From the composition list of a product and other technical information from the
manufacturer, the student will be able to comprehend the mechanism of drug release
and whether a tablet dosage form is a rapid release or modified release product.
To have a complete understanding of all stages of drug product development from
conception though the phases of preclinical testing and clinical testing of the drug
product.
The student will also be familiar with patents and regulatory issues of drug
development, as well as the documentation, i.e. IND, NDA and ANDAs, that must be
submitted to the FDA for approval of prescription drug product, before such product
can be dispensed by the pharmacist.
The student will also learn the generic and brand names as well as the therapeutic use
and manufacturer of the 200 most prescribed pharmaceutical products. List is attached.
The student will learn the principles of physical pharmacy, powder technology and
polymer science, pertaining to the design and development of conventional and novel
drug delivery systems.
To understand the principles of formulation technology, processing and manufacturing
of pharmaceutical products on both a small and large scale.
To be able to review the list of ingredients in a commercial pharmaceutical product and
understand the functionality of each ingredient and be able to compound a similar
product when a patient is allergic to one of the inert ingredients in the commercial
product.

49

Course Outline
INTRODUCTION Chapters 1-5
multidisciplinary development of a drug candidate
routes of drug administration
the variety of dosage forms
therapeutic considerations in dosage form design
biopharmaceutic considerations
o bioavailability and bioequivalence
current cGMP and cGCP
patents
POWDERS AND GRANULES Chapter 6
advantages - disadvantages
particle size reduction
comminution, mixing of powders
packaging
o bulk, divided powders
official powders and granules
effervescent products
CAPSULES Chapter 7
advantages disadvantages
materials
o gelatin, plasticizers, colorants, preservatives
hard gelatin capsules
o sizes and shapes
o sealing and self-locking closures
soft gelatin capsules
preparation of capsules
formulation
filling operation
o solid, semisolid, and liquid formulations
special capsules
packaging and storage
TABLETS Chapter 8 Dr. McGinity
types and classes of tablets
advantages - disadvantages
drug release from tablets in gastrointestinal tract
properties of good tablets
tablet excipients
o fillers, binders, disintegrants, glidants, lubricants, etc.
manufacturing
o single-rotary punch tablet press
o wet granulation -direct compression

50

o recompression
evaluation of tablets
o dissolution and disintegration testing
o hardness, friability
o weight and drug content uniformity
special tablets
o layered tablets
o buccal and sublingual tablets
o lozenges
o chewable tablets
o effervescent tablets
SOLUTION THEORY Chapters 5, 13
definition of a solution, solvent, solute, mole fraction, solubility and dissolution rate
dissolution - energetics
hydrogen bonding and solvation
dielectric constant
cosolvents
Factors Influencing Solubility
o salt forms of drugs and pH
o intermolecular hydrogen binding
o crystal lattice energy
o ionic strength
o polymorphism
PHARMACEUTICAL LIQUIDS Chapter 13 Dr. Williams
alcohols in water
volatile oils in water
water USP - definition of 5 grades
aromatic water
syrups, their preparation and use
miscellaneous liquid preparations
isotonic solutions
nonaqueous solutions
alcohols and ethers
spirits and elixirs
tinctures and fluid extracts
the extraction process
examples of the above
DISPERSE OF POLYPHASIC SYSTEMS Chapter 14 Dr. Williams
definitions
types of polyphasic systems: colloids, suspensions, emulsions and creams
Colloids
o distinction between a colloid and a true solution

51

o types of colloidal systems

o lyophilic and lyophobic colloids
o association colloids
o preparation of colloids
o properties of colloids
o the Zeta potential and colloidal stability
o protective colloids
o how charge arises on colloids
o examples
Gels
o definitions, how formed
o synersis and thixotrophy
o types of gels - inorganic and organic
o examples
Suspensions
o definition and properties
o the need for suspensions
o sedimentation - causes and remedies
o suspending agents
o methods of stabilizing suspensions
o colloid theory in relation to suspensions
o crystal growth and caking
o examples of suspensions in dosage forms
SURFACE TENSION AND SURFACTANTS Chapter 14 Dr. Williams
definition of surface and interfacial tension
how surface tension arises
modification of surface tension by surfactants
micelle formation
solubilization, detergents and emulsification
classification of surfactants
Hydrophilic - Lipophilic Balance (H.L.B.)
uses of surfactants
examples
SUPPOSITORIES AND COLONIC DRUG DELIVERY SYSTEMS Chapter 12
description and use
types of suppositories
advantages and disadvantages
local vs. systemic function
manufacture
ingredients
polymorphism of cocoa butter
lipoidal bases and water soluble bases
EMULSIONS AND EMULSION TECHNOLOGY Chapter 14

52

definition of terms
internal and external emulsions
preparation of emulsions
emulsifying agents
HLB and emulsification
preservation of emulsions
examples

TOPICAL DOSAGE FORMS Chapter 10

introduction to skin structure and function
the skin as a barrier to drug passage
ways of enhancing skin penetration by drugs
the aims of topical therapy
percutaneous absorption of drugs
classification of topical formulations
typical components of topicals
formulation and manufacture
Ointments
o classification
o preparation by fusion and direct incorporation
o hydrous and anhydrous absorption bases
o water washable bases examples
Creams
o types of creams
o water washable and vanishing
o emulsifiers in creams
o preparation of creams
o preservatives
o examples
Miscellaneous Topicals
o pastes
o gels
o lotions
PULMONARY AND NASAL DRUG DELIVERY SYSTEMS Chapters 5, 6, 14, 17
inhalation therapy
factors influencing deposition
drug targeting
METERED-DOSE INHALER TECHNOLOGY Chapter 14
definition
aerosol technology
devices
principles of aerosol generation
examples

53

DRY POWDER INHALER TECHNOLOGY Chapter 17

definition
classification of devices
examples
BUCCAL DRUG DELIVERY SYSTEMS Chapter 17
Definition
Principles of buccal drug delivery
Examples
PHARMACEUTICAL COMPOUNDING Chapters 3, 4, 14, 15
methodology
order of mixing
properties of additives
suspensions, gels, liquids, topicals, suppositories
MOFIFIED-RELEASE DOSAGE FORMS AND DRUG DELIVERY SYSTEMS
Chapters 9, 11, 20
terminology
advantages and disadvantages
biological factors
o half-life, absorption, metabolism, margin of safety
physiochemical factors
o dose, pka, solubility, partition coefficient, stability
reservoir-and matrix systems
o release mechanism
biodegradable drug delivery systems
o biodegradability, biocompatibility
o biodegradable polymers -implants
swelling controlled drug delivery systems
osmotically controlled systems - OROS system
ion exchange systems
bioadhesive drug delivery systems
pulsatile drug delivery systems
transdermal drug delivery systems
nasal drug delivery systems
o physiology
ocular drug delivery systems
o physiology
o importance of residence time
o bioadhesive microparticles
o inserts
intravaginal and intrauterine
targeted drug delivery systems
o biophysical aspects
o passive and active targeting

54

o
o
o
o
o
o

liposomes
nanoparticles
prodrugs
cellular drug carriers
storage and sterility
toxicity

PARENTERALS Chapter 15 Dr. McGinity

definition of sterility
methods of sterilization
classification of parenterals
USP classifications of injections
aseptic technique
small and large volume parenteral formulations
biotechnology products
PREFORMULATION Chapters 2, 4
timing and goals of preformulation
organoleptic properties
purity
characterization of particle size, shape and surface area
solubility, partition coefficient
dissolution of drug substance
crystallinity, polymorphism
stability
o in solid state, in solution
o testing
compatibility tests
COATING OF SOLID DOSAGE FORMS Chapter 8
rationale
equipment
o pan coating
o fluidized bed coating
sugar coating
film coating
o polymer properties and technology
o aqueous film coating
o organic film coating
o colloidal polymer dispersions
o enteric polymers
compression coated tablets
coating of small particles and beads

55

RADIOPHARMACEUTICALS Chapter 18
definitions
physical half-life
radioisotopes
application
diagnostic and therapeutic
production using cyclotron and a nuclear reactor
corporation, vehicle and biodistribution moiety

56

Pharmacology Principles (PHR 153M)

Dr. Gonzales Course Objectives:
Section 1: 1/21 - 3/21
Drug targets, drug receptors, binding sites, sites of action
Drug actions on receptors (e.g., agonists, antagonists, etc)
Understand, distinguish and generate dose-response curves
Modes of drug-receptor bonds (e.g., covalent, hydrogen, etc)
Principles of drug affinity, efficacy, Kd, Bmax

Differentiating pharmacological versus clinical efficacy

Generating, graphing and interpreting equilibrium binding equation
Receptor properties, receptor density, Scatchard analysis
Methods to determine, plot and interpret ligand binding (e.g., nonspecific, total, specific)
Receptor occupation theory, EC50, modified receptor theory
Classification and issues regarding drug agonism, antagonism, therapeutic significance,
agonist/antagonist interactions
Dose response curves: Synonyms, types of responses (e.g., isolated, intact, adverse),
response characteristics (e.g., min, max, max), slope,
Logistic function, therapeutic index: LD50, ED50
Interpreting graphic representations of various antagonist/agonist binding scenarios (e.g.,
reversible non-competitive antagonist + agonist)

Dr. Duvauchelles Course Objectives:

Section 2: 3/25 - 5/6
Autonomic Nervous System: Classification and Divisions, biological significance of
physiological responses, neurotransmission, biosynthesis and degradation of
neurotransmitters, ANS receptors, 2nd messenger systems, principles of autoreceptors
and heteroreceptors
Drugs acting on parasympathetic nervous system
o Cholinomimetics: specific drugs and classifications, receptors, mechanisms of
drug action to treat glaucoma, GI motility, myasthenia gravis, Alzheimers,
Sjogrens, drug side effects, toxicity
o Parasympatholytics: natural, synthetic, tissue sensitivity curve, mechanisms of
action, clinical action as poison antidote (e.g., insecticide, nerve gas, mushroom),
vertigo treatment, ocular exam, decreased GI motility, airway dilation (e.g.,
COPD patients), decreased acid secretion, relevance for Parkinsons and
Alzheimers disease.
Drugs acting on the sympathetic nervous system
o Sympathomimetics: topical vs systemic effects, mechanism of drug actions
affecting superficial bleeding, drug diffusion, decongestant effects, glaucoma,
attention deficit disorder, hypo/hypertension, shock, allergic reaction, smooth

57

muscle relaxation, drug classifications, sympathetic actions, receptor subtypes,

side effects, toxicity
o Sympatholytics: specific drugs and drug types (e.g., direct, indirect; synthesis
inhibitors, receptor blockers, etc), mechanism of action, clinical actions for
pheochromocytoma, hypertension, Parkinsons Disease, hypertension, benign
prostatic hyperplasia, sexual dysfunction, side effects, toxicity

58

Pharmocology Principles (PHR 153M) Sample Questions

Objective # 1: Familiarity of drug actions on the parasympathetic nervous system
1. The mechanism of action common to all cholinesterase inhibitors include
_________________.
a. interactions with the acetylcholinesterase enzyme that ultimately interfere with its
activity
b. direct activation of nicotinic and muscarinic receptors
c. rapid hydrolysis of acetylcholine
d. blockade of memory-inhibiting sympathomimetic effects
2. Atropine actions on the parasympathetic nervous system can be described as
_________________.
a. enhancement of the acetylcholinesterase enzyme to increase the rate of acetylcholine
metabolism
b. competitive antagonism: competing with acetylcholine for a binding site on the
muscarinic receptor and can be displaced by higher concentrations of acetylcholine
c. direct activation of pre-ganglionic muscarinic receptors
d. sympathomimetic effects on pre-ganglionic nicotinic receptors and parasympathetic
activation on post-ganglionic muscarinic receptors.
Objective #2: Familiarity of actions on the sympathetic nervous system
3. Indirect-acting sympathomimetics, such as d-amphetamine and cocaine exert major effects
through _________________.
a. inhibiting the breakdown and/or metabolism of epinephrine and norepinephrine
b. blocking neuronal re-uptake and/or facilitating the release of norepinephrine
c. mimicking the effects of the sympathetic nervous system by combining directly with
postsynaptic adrenergic receptors
d. activation of presynaptic 2 receptors on the brainstem
4. Sympatholytic drugs, such as prazosin [Minipress], nadolol [Corgard] or timolol [Timoptic]
exert their effects via _________________.
a. inhibiting the synthesis and storage of norepinephrine
b. interfering with the release of norepinephrine or epinephrine
c. blocking the activity of the adrenergic receptors
d. neuronal degeneration of sympathetic pathways

59

RESPONSE (% of maximal)

100

60

Figure 6

40
20
0
-16 -14 -12 -10 -8 -6 -4 -2 0
LOG DRUG CONCENTRATION (M)

1.

In figure 6 above, curve A represents an agonist dose-response curve, and curve B

represents the dose response curve for the same agonist in the presence of a neutral
antagonist. What would you do to determine the whether the antagonist is orthosteric or
allosteric?

a.

Repeat the dose-response curve with the same agonist and a lower concentration of
antagonist.
Repeat the agonist dose-response curve with the same agonist and a single concentration
of a known orthosteric antagonist.
Do the experiment over with a known high efficacy full agonist.
Determine the dose response curve with a known partial agonist in the presence and
absence of the same concentration of the antagonist.
There is no need to do any more experiments because it can be concluded that the
antagonist is orthosteric because it shifted the agonist dose response curve to the right in
a parallel manner.

b.
c.
d.
e.

80

60

2. The following two curves represent equilibrium binding data for two drugs obtained using
the same preparation of receptors. If the two drugs bind to the same receptor, which of
the following is true?
a.
b.
c.
d.
e.

The Bmax of the two drugs is different.

Both the Bmax and the Kd of the two drugs are different.
The Kd of the two drugs is similar.
The Bmax for both is approximately equal, but the Kd for one drug is about 10 fold
lower than the other.
These curves do not represent a realistic picture given the assumptions.

61

Anatomy and Physiology (PHR 253C)

Dr. Van Den Bergs Course Objectives:
Respiration & respiratory mechanics, Gas exchange, control of respiration (Ch. 13)
Identify and describe the anatomy of the respiratory airways and explain the basic
functions of each anatomical part in respiration.
Discuss respiratory control including the various neural and peripheral responses.
Discuss the target sites and mechanisms thereof for respiratory stimulants and
depressants important for tissue homeostasis during rest and exercise.
Explain respiratory mechanics i.e. how is air moved into and out of the lungs and the
importance of gas partial pressure gradients.
Explain how gas partial pressure gradients dictate gas transfer from the alveoli to blood
and blood to tissue under various physiologic conditions.
Describe the role of hemoglobin (Hgb) in oxygen, carbon dioxide, an
d H+ carrying capacity in both the tissue and lungs. Know how CO interferes with
oxygen carrying capacity of Hgb.
Provide the definitions of various measurements obtained from pulmonary function
tests (PFTs).
Understand how PFTs are used for disease diagnosis.
Explain the effect of bicarbonate on the chloride shift in red blood cells.
Acid-base balance (Ch. 15)
Understand the importance of Na+ and K+ in ICF and ECF fluid osmolarity.
Describe the influence of hyper- and hypo-tonicity on fluid shifts from ICF and/or ECF.
Explain how vasopressin and the renin/angiotensin/ aldosterone system respond to
hypotonicity or fluid balance.
Discuss the importance of the four buffer systems in acid/base balance.
Given a specific disease and/or HCO-3/CO2 values, categorize the acid/base disorder
and describe the mechanism(s) for respiratory or renal mediated acid/base correction.
Understand acid-base reactions in the kidney

62

Dr. Wrights Course Objectives:

Renal System (Ch. 14)
Understand and be able to define the anatomy, function and basic processes of the
kidney
Integrate the following into an understanding of glomerular filtration: Blood Pressure /
Starling forces; Influence of Regulatory Mechanisms; Net Filtration Pressure and Kf
Know and understand the reabsorptive process: Mechanism of Transepithelial
Transport / Na+ is key; Influence of Regulatory Mechanisms / Hormonal control;
Important for Understanding Diuretic Pharmacology; Concept of Tm
Incorporate what you have learned regarding filtration and reabsorption into
understanding: Tubular Secretion Basically reabsorption in reverse; H+, K+ and
organic ions most important substances secreted; Organic Ion Secretory Systems;
Plasma Clearance; Mechanism of Countercurrent Multiplication
Thorough knowledge of the concept of countercurrent multiplication will allow
understanding of: Establishment of vertical osmotic gradient; How anatomy of vasa
recta maintains; Role of vertical osmotic gradient in controlling [urine]; Action of
Vasopressin
Blood (Chapter 11)
Understand and be able to define:
Blood constituents and their function; Hematopoiesis and Erythropoiesis; Role of HIF1; Anemia
Incorporate your understanding of the blood constituents and how they function to:
Provide Immunity; Control clot formation; Drive the inflammatory process
Immune System (Chapter 12)
Understand these important aspects of the immune system: The cellular mediators;
Innate vs. Adaptive Immunity; The inflammatory process NF-kB; Components of
innate immunity
Integrate your understanding of the immune system components into the function of:
Components of innate immunity; Adaptive Immunity: B-cells; Adaptive Immunity: Tcells; Tolerance and autoimmunity

63

 Know and understand these immune processes: Antigen Presentation to activate Tcells; Immune tolerance and autoimmune disease; Immune surveillance and immune
disease; External defenses

Dr. Gore/Dr. Yins Course Objectives:

Unit 1: General endocrinology-Chapters 4, 18
Learn about the principles of endocrinology.
Understand general and molecular properties of hormones.
Be able to compare and contrast hormones and neurotransmitters, and differentiate
endocrine vs. nervous system communication.
Understand the molecular mechanisms of action by which hormones signal.
Learn about physiological control of processes by endocrine systems.
Learn the principles of negative feedback.
Gain an introductory understanding of the concept of endocrine dysfunctions.
Unit 2: Hypothalamus and pituitary Chapter 18
The basic neuroanatomy and function of the hypothalamus and pituitary the central
endocrine organs.
The definition of neuroendocrinology.
The hypothalamic-pituitary anatomical & functional links.
Understand posterior pituitary hormones and their functions.
Know all of the hypothalamic releasing/inhibiting hormones, their corresponding
pituitary hormones, and corresponding target hormones by abbreviation and by full
name(s)!
Learn more about negative feedback.
Learn about biological rhythms controlled by hypothalamus and pineal hormones.
Unit 3: Energy balance and temperature regulation Chapter 17
Learn the principles of energy balance.
Understand the role of the hypothalamus in energy balance and feeding behavior.
Know the hypothalamic and peripheral neuropeptides/hormones that control energy
balance.

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 Know the hypothalamic neural circuit involved in these processes.

Learn about temperature homeostasis.
Understand the hypothalamic control of temperature.
Understand how fever happens and is controlled.
Unit 4: Growth & Bone Chapter 18
Understand the hypothalamic-pituitary-liver control of growth.
Learn about the respective hormones and receptors at each of these biological levels.
Understand the mechanisms for bone growth.
Introduction to pathophysiology.
Unit 5: Fuel metabolism and pancreatic hormones Chapter 19
Intermediary metabolism
Introduction to pancreatic hormones
Insulin glucoregulation; pathophysiology, including diabetes mellitus
Glucagon
Insulin-glucagon balance
Other metabolic hormones involved in fuel metabolism
Unit 6: Calcium metabolism and bone Chapter 19
Plasma Ca++ regulation homeostasis & balance
Parathyroid hormone and its role in Ca++ regulation
Bone remodeling
Pathophysiology osteoporosis
Calcitonin and Ca++ metabolism
Vitamin D and Ca++ regulation
Pathophysiology
Unit 7: Thyroid Chapter 19
Anatomy of the thyroid gland
Thyroid hormone biosynthesis

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 Thyroid hormone physiological roles

Hypothalamic-pituitary-thyroid axis and hormones
Feedback regulation
Pathophysiology hyperthyroidism, hypothyroidism, goiter
Unit 8: Adrenal/stress Chapter 19
Anatomy of the adrenal medulla & cortex
Adrenocortical hormones (mineralocorticoid, glucocorticoid, sex hormones)
Stress response
Hypothalamic-pituitary-adrenal axis & hormones
Pathophysiology of adrenal cortex
Adrenal medullary hormones - catecholamines
Unit 9, Reproduction Chapter 20
Introduction to reproduction and the Hypothalamic-pituitary-gonadal axis
Sexual determination and differentiation
Male reproductive physiology
Female reproductive physiology
Fertilization
Pregnancy
Parturition
Lactation

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Anatomy and Physiology (PHR 253C) Sample Questions

Objective: Pulmonary Section of A/P
WM is a 33yr woman from Austin TX (altitude 550 ft) who is vacationing in Leadville CO
(altitude 10,152 ft) for a week. This morning WM went out for her usual 4 mile run on
the mountain trails near her hotel. During her run she experienced shortness of breath,
hyperventilation and muscle fatigue. The HCO-3/CO2 in WMs blood is 14/1. WMs
symptoms most likely result from:
a.
b.
c.
d.

A lower pO2 gradient between the alveoli and capillary blood resulting in lower
Hgb affinity for O2 in the lungs.
Respiratory acidosis
A lower pO2 gradient between the alveoli and capillary blood resulting in
lower Hgb saturation and O2 delivery to the tissues.
Metabolic alkalosis

Objective: Integrate your understanding of the immune system components into how
tolerance prevents autoimmunity.
A patient is visiting with you about an allergy attack they are having against oak pollen. They
are curious as to why they are experiencing allergies to oak pollen when they have never
had them before. What do you tell them?
(a) They are experiencing a delayed hypersensitivity response that is mediated by B cells
secreting antibodies against a harmless antigen.
(b) They are experiencing a delayed hypersensitivity response that is a T cell-mediated
immunity against a harmless antigen.
(c) They are experiencing an immediate hypersensitivity response that is a T cellmediated immunity against a harmless antigen.
(d) They are experiencing an immediate hypersensitivity response that is mediated
by B cells secreting antibodies against a harmless antigen.

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Pathology (PHR 253D)

CELL ADAPTATION, INJURY AND DEATH
Text References: pp. 1-22
Learning Objectives:
To know understand how changes in the environment can induce various adaptations in
cells (atrophy, hypertrophy, hyperplasia, Metaplasia and dysplasia) that may be
reversible if environmental normalcy is restored.
To understand the etiologies and mechanisms underlying development of reversible cell
injury or may lead to irreversible cell injury and death by the process of cell necrosis.
To understand the etiologies and mechanisms underlying the development of cell death
by the process of apoptosis (programmed cell death). To understand why and how on
the one hand the process of apoptosis normally is highly beneficial to the host but on
the other hand may be involved in the development of various disease processes.
MEDIATORS OF INFLAMMATION
Text References: pp. 44-53
Learning Objectives:
To understand how and why various preformed and newly synthesized inflammatory
mediators orchestrate acute and chronic inflammation.
To understand the mechanisms of action of the currently available non-steroidal and
steroidal anti-inflammatory drugs and to appreciate the rationale for the development of
new anti-inflammatory modalities.
INFLAMMATORY TISSUE DYSFUNCTION/INJURY
Text References: pp. 40-44; 57-58
Learning Objective:
To understand why and how, under certain circumstances and settings, innate and/or
acquired immunity can effect the development of severe (sometimes life threatening)
acute and/or chronic inflammatory tissue dysfunction and/or injury.
HEMOSTASIS, THROMBOSIS & INFARCTION
References: pp. 86-98; 468-475
Learning Objectives:
To understand the mechanisms regulating normal hemostasis, both thrombosis and
fibrinolysis.

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 To understand the mechanisms underlying development of abnormal hemostasis and

their pathologic consequences including bleeding diatheses, arterial and venous
thrombosis and thromboembolism, and disseminated intravascular coagulation (DIC).
THE HEALING OF TISSUE(REGENERATION & REPAIR)
Text References: pp. 59-63; 68-79
Learning Objective:
To know and understand why and how, under certain circumstances and settings after
irreversible cell injury (necrosis, apoptosis), tissue may undergo the healing by the
process of tissue regeneration and/or tissue repair.
IMMUNOPATHOLOGY
Learning Objective:
To compare, contrast and understand the beneficial and detrimental aspects of innate
and acquired immunities.
MOLECULAR PATHOLOGY
Text references: Robbins Basic pathology, 8th Ed., pgs 165-237, 248-251, 257-262.
Learning Objectives:
Describe different types of genetic lesions and their detection
Explain why genetic damage may lead to cancer
Name specific pharmacologic applications of molecular biology in inherited diseases,
cancer, and coagulation.
NEOPLASIA
Text references: Robbins Basic pathology, 8th Ed., pp 173-223
Learning objectives:

To understand the features that distinguish benign from malignant neoplasms

To understand the system of naming (nomenclature) benign and malignant neoplasms
To understand the patterns and consequences of metastatic cell growth
To understand the prognostic implications of tumor staging and grading
To review the normal cell cycle and apoptosis
To understand the role of multiple genetic mutations in carcinogenesis, i.e., the
molecular basis of cancer
To know the four classes of normal regulatory genes and their roles in carcinogenesis
To define the role of infectious agents, genetics, and environmental factors in
carcinogenesis
To identify methods of cancer prevention, including screening for common cancers.

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RED & WHITE BLOOD CELL DISORDERS

Text references: Robbins Basic Pathology, 8th Ed. pgs 421-468
Learning Objectives:
To understand blood composition and hematopoiesis. To understand common
causes of anemia and other blood cell deficiencies. To understand reactive and
neoplastic white cell disorders.
HEMOSTASIS AND COAGULATION
Text references: Robbins Basic Pathology, 8th Ed. pgs 81-105 and 468-476
Learning Objectives:
To gain an understanding of hemostasis and coagulation. To understand the
coagulation cascade and how pathological conditions lead to thrombosis, embolus
formation and infarction. To understand inherited and acquired platelet disorders
and hemophilia
INFECTIOUS DISEASES BACTERIA, FUNGI, etc.
Text references: Robbins Basic pathology, 7th Ed., pgs 307-322.
Learning Objectives:
Describe features of bacterial and fungal structure, classification, and habitat
Understand types of bacterial and fungal infections, and factors that influence
their presentation and severity
Understand mechanism of action of the major classes of antimicrobial agents and
methods of resistance
Name and describe examples of significant bacterial and fungal pathogens
INFECTIOUS DISEASES - VIRAL INFECTIONS
Text references: Robbins Basic pathology, 8th Ed., pgs 319-338, 605-609; also of interest,
pgs 508-528, 843-844.
Learning Objectives
After this lecture, students should be able to explain how different characteristics
of viral infections affect clinical manifestations, describe methods for the
diagnosis viral infections, and list several viruses for which specific antiviral
therapy is available.
CAUSES & PREVENTION OF DISEASE I: ANTIBIOTIC RESISTANCE
Text references: Robbins Basic pathology, 8th Ed., pgs 319-338.
Learning Objectives:
Explain how antimicrobial resistance emerges and how it is transferred
List the four mechanisms of antibiotic resistance
Describe the common causes of antibiotic resistance

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 List several examples of important resistant organisms and their mechanisms of

resistance, including MRSA and VRE
Topic Objectives Not included (please refer to your lecture handouts):

Cardiovascular I & II
Pulmonary Pathology
Renal Pathology
Metabolic Diseases
Diseases of Aging
Geriatric Clinical Pharmacology

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Pharmaceutical Biochemistry II (PHR 251C)

Dr. Dalbys Course Objectives:
1. Cholesterol Metabolism
Describe the properties of cholesterol
Describe the essential elements of cholesterol synthesis
Describe the essential elements of cholesterol regulation
Describe the mode of action of the statins
Describe the essential elements of the synthesis of bile salts and their physical
properties Describe the enterohepatic circulation
Describe the essential elements of hypercholesteroemia
Describe the essential elements of cholelithiasis
2. Steroids
Provide a brief overview of steroid synthesis mechanism and metabolism
3. Plasma Lipoproteins
Describe the physical properties, composition and structures of the plasma lipoproteins
Describe the function of key apolipoproteins
Outline the metabolism of Chylomicrons
Outline the metabolism of Very Low Density Lipoproteins
Outline the production of LDL from VLDL
Outline the metabolism of Low-density Lipoproteins
Describe the role of endocytosed cholesterol on cellular cholesterol homeostasis
Describe the metabolism of HDLs and their role in cholesterol homeostasis
Define hyperchylomicronemia
4. Amino Acids as a Nitrogen Source
List the essential and nonessential amino acids
Describe how body and dietary proteins are utilized to assimilate amino acids
List the proteolytic enzymes involved in protein digestion
Explain the specificity and mechanism of activation of the proteolytic enzymes
Correlate some clinical problems with abnormal protein digestion and amino acid
absorption Define nitrogen Balance
Describe Hartnup Disorder, Cystinuria, Cystic Fibrosis and Kwashiorkor
5. Ammonia
Describe the properties of ammonia
Describe the biosynthesis of ammonia
Describe how ammonia is converted into amino acids
Describe the roles of glutamate dehydrogenase and glutamine synthase
Describe transamination reactions
Define the mechanism of pyridoxal phosphate (PLP) in transamination reactions

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 Describe the role of glutamate in urea production

Describe the conversion of ammonia from glutamate and glutamine List sources of
ammonia Describe hyperammonemia
Describe the pathophysiology of hyperammonemia and the neurotoxicity associated
with ammonia
6. Urea cycle
Describe the Urea Cycle
Describe mechanisms of short-term regulation of the Urea Cycle
Describe the role of carbamoyl phosphate synthetase I (CPSI)
Describe mechanisms of long-term regulation of the Urea Cycle
Describe Urea Cycle defects (UCDs)
7. Metabolism, biosynthesis and uses of amino acids
Provide a metabolic classification of amino acids
Outline how amino acids are metabolized
Describe the glucose/alanine cycle in muscle
Discuss Lysine
Describe Phenylketonuria, Alcaptonuria, Histidemia and Maple Syrup Syndrome
Outline the biosynthesis of nonessential amino acids
Describe the diagnostic value of transaminases
Describe a treatment for Leukemia
Describe the synthesis of Histamine, Serotonin, Catecholamines, Acetylcholine, GABA
and Thyroxine (T4)

Dr. Lees Course Objectives:

1. Nucleotide Metabolism
Describe biological roles of nucleotides
Discuss defects in nucleotide metabolism (PRPP, HGPRT, ADA, PNP)
List and describe nucleotide metabolism-related diseases (Lesch-Nyhan syndrome,
SCID, gout)
List and describe the mechanisms of action of drugs that target nucleotide metabolism
(Sulfa drugs, 5-FU, methoxtretate, trimethoprim, mycophenolic acid, allopurinol,
immucillin H)
Outline de novo biosynthetic pathways for purines and pyrimdines
(PRPP, IMP, GMP, OMP, UMP, CTP, dTMP etc.)
Discuss origin of the ring atoms of purines and pyrimidines
Describe function of PRPP
Discuss the ammonia channeling in PRA formation
Explain why some enzymatic reactions in purine and pyrimidine biosyntheses require
ATP
Outline conversion of IMP to AMP and GMP
Describe regulation of de novo purine synthesis
Explain why sulfa drugs are bacteria selective
Discuss roles of N10-formyl THF and N5,N10-THF

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 Describe functions and/or reaction mechanisms of enzymes involved in nucleotide

metabolism (amidophosphoribosyl transferase, dihydrofolate reductase, IMP
dehydrogenase, ribonucleotide reductase, thymidylate synthase, HGPRT, PNP, ADA,
xanthine oxidase)
Describe synthesis of 2-deoxy nucleotides (A,G,C,U vs. T)
Discuss drugs that block dTMP synthesis
Outline catabolism of purines and pyrimidines
List and describe anticancer antimetabolite drugs
2. Nucleic Acid Structure
Discuss structural features of DNA
Describe sugar pucker, helix sense, and nucleotide conformations in B, A, and Z DNA
Explain Watson-Crick vs. Hoogsteen H-bondings
List examples where Hoogsteen face is used to form H-bondings
Describe the features of DNA-binding motifs that uses -helix for DNA recognition
(HTH, homeodomains, bHLH, leucine zippers, zinc fingers)
Outline basic structure of nucleosome
Describe interactions between histones and DNA
Outline structural features of RNA
List structural differences between DNA and RNA
3. Biosynthesis of DNA
Describe DNA replication fork
Outline differences between eukaryotic and prokaryotic DNA
Discuss differences between eukaryotic and prokaryotic DNA replication
Discuss general features of DNA replication
Discuss mechanism of DNA elongation
Discuss features of leading and lagging strands in replication fork
Explain functions of enzymes involved in DNA replication
Discuss substrate recognition and catalysis by DNA polymerase
(DNA polymerase III and I, DNA topoisomerase, DNA telomerase)
Discuss roles of AZT and topotechan
Explain size and end problems in eukaryotic DNA replication
Compare DNA topoisomerases (type IA, IB, and II)
List factors that contribute to the fidelity of DNA replication
List epigenetic DNA modifications
4. DNA Damage
After studying this, you should be able to:
List types of DNA damages
Explain differences between transition and transversion mutations
Discuss the fates of 5-methylcytosine deamination and spontaneous
depurination/depyrimidination (U and T formation)

List and discuss reactive oxygen species (H2O2, HO, O2-)

Discuss why 8-oxoguanine is mutagenic (GC to TA)
Discuss DNA damages by direct and indirect effects of ionizing radiation

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Describe products of UV DNA damage (CPD, T-T dimer)

Describe DNA crosslinking by bisalkylating agents (Mustard)
Explain mutagenicity of O6-methylguanine (GC to AT)
Differentiate between alkylators and metabolically activated alkylators (Aflatoxin B1,
benzopyrene, acrylamide)
Outline roles of temozolomide, mitomycin C, calicheamicin, and cisplatin
5. DNA Repair
List types of DNA repair
Describe repair of pyrimidine dimers in prokaryotes and eukaryotes
Explain base-flipping mechanism
Explain functions of DNA repair proteins (Photolyase, Ada, MGMT, AlkB, UDG,
AAG, hOGG1, MutY, and PARP1)
List substrates for DNA repair proteins
Discuss why PARP1 is a promising target for cancer therapy
Discuss NER defects

Dr. Kerwins Course Objectives:

1. Transcription and Its Regulation
How do transcription and DNA synthesis differ?
How are they the same?
What descriptors are used to refer to the DNA strand that is copied in transcription?
The other DNA strand?
How are transcribed regions of DNA recognized in prokaryotes?In eukaryotes?
What is the function of the sigma factor in prokaryote RNA polymerase?
What carries out the corresponding function in eukaryotes?
What distinguishes constitutive and regulated gene expression?
What is an operon? Be able to sketch out the lac operon and describe how it functions.
What are transcriptional repressors and activators?
How many RNA polymerases are there in eukaryotes? What are their roles?
How does Transcription terminate in prokaryotes? In eukaryotes?
What structural features allow regulatory proteins to recognize DNA? To recognize
each other?
How does the organization of eukaryotic DNA affect the way it is transcribed?
How do DNA and histone modifications regulate transcription?
2. Posttranscriptional RNA Modifications
What is an intron and how is it removed from mature mRNA?
What are the features that distinguish eukaryotic mRNA from mRNA in prokaryotes?
What function(s) do these features serve? How does rRNA get processed in bacteria? In
eukaryotes? How does tRNA get processed in bacteria? In eukaryotes?
3. Translation
What do we mean when we say the genetic code is: unambiguous, degenerate, comma

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less, non-overlapping?
Where in the cell does protein synthesis occur?
How are amino acids activated for incorporation into proteins?
What are the structural features of tRNA and amino-acylated tRNA?
How is the fidelity of the genetic code maintained during amino-acyl tRNA synthesis?
What portion of ribosome is involved peptide bond formation catalysis.
How does protein synthesis initiate?
What features of the mRNA are recognized inbprokaryotes? In eukaryotes?
What is required for protein synthesis elongation? What is required for translation
termination?
How does puromycin work, and how can it be used to make RNA-protein chimeras?
How do antibiotic aminoglycosides and macrocyclic lactones work?
How does ricin work?
How does diptheria toxin work?

4. Co- and Post-translational Modifications

How do proteins fold?
What other proteins are required?
What are some common co- posttranslational modifications?
How are proteins phophorylated?
Which amino acids get phosphorylated?
What determines the phosphorylation status of a given protein?
How are proteins tagged for degradation? How are they degraded?
How is this involved in the regulation of protein function?
How does post-translational modification function in the regulation of genes?
5. Biotechnology
How can DNA be isolated and analyzed?
What are restriction endonucleases? Exonucleases? Ligases?
How can these be used to stitch together DNA?
What is the difference between a cloning vector and an expression vector?
How is recombinant human insulin produced?
What is PRC and how does it work? What are some limitations?
What are protein and DNA microarrays and how can they be used?
How can proteins containing non-cannonical amino acids be produced?
How can the methylation status of DNA be determined?
What are the implications of DNA hyper- or hypo-methylation?

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