Download International Trained-PharmD (ITPD

International Trained-PharmD (ITPD)
Foundational Examinations Study Guide
All applicants for the ITPD program are required to pass two foundational pharmacy sciences competency
exams (one on biomedical sciences and one on pharmaceutical sciences) prior to admission into the ITPD
program. These foundational competencies exams will cover the following learning objectives.
BASIC BIOMEDICAL SCIENCES
Anatomy & Physiology
structure and function of Minor body systems: integumentary, muscular skeletal, cardiovascular, lymphatic,
respiratory, digestive, nervous, endocrine, urinary, reproductive, and body fluid and electrolytes
molecular aspects of cell biology
cell physiology and cellular structure and organization
Pathology/pathophysiology
basic principles and mechanisms of disease including: inflammation & repair, degeneration, disturbances on
hemodynamics, developmental defects, neoplasia
pathophysiology of disease states amenable to pharmacist intervention
Microbiology
pathogenic micro-organisms of man
Immunology
human immunity and immune response
principles of antigen-antibody relationships
molecular biology of immune response
genetic basis for antibody synthesis, development, function, and immunopathology
Biochemistry/biotechnology
chemistry of biomacromolecules (proteins, lipids, carbohydrates, and DNA)
enzymology and co-enzymes and kinetics
metabolic pathways to energy utilization
nucleic acid metabolism, including DNA replication and repair, RNA, and protein synthesis
recombinant DNA technology
Molecular biology/genetics
cell structure and components
ion channels and receptor physiology
mitosis and meiosis
chromosomes and DNA
gene transcription and translation processes
recombinant DNA technology
Biostatistics
understanding of commonly-used statistical tests and their basis
management of data sets
evaluation of statistical results
understanding of statistical versus clinical significance
PHARMACEUTICAL SCIENCES
Medicinal chemistry
physico-chemical properties of drug molecules in relation to drug absorption, distribution, metabolism, & excretion
chemical basis of pharmacology and therapeutics
fundamental pharmacophores for drugs used to treat disease
structure activity relationships in relation to drug-target interactions
chemical pathways of drug metabolism
application to making drug therapy decisions
Pharmacology
mechanism of action of drugs in various categories
role of pharmacology in drug choice and the treatment of disease
pharmacodynamics of drug action and absorption, distribution, metabolism, and elimination
adverse effects and side effects of drugs
drug-target interactions
drug-drug, drug-food, drug-lab test interactions
drug discovery and development
Pharmacognosy & alternative & complemetary med.
concepts of crude drugs, semi-purified, and purified natural products
variability of occurrence of pharmacologically active substances in plants & impact on regulatory aspects of herbal
products
Toxicology
mechanism of toxicity and toxicokinetics
acute and chronic toxic effect of xenobiotics on the body, including drug or chemical overdose and toxic signs of
drugs of abuse
antidotes and approaches to toxic exposures
Pharmaceutics/biopharmaceutics
physical-chemical principles of dosage forms
biological principles of dosage forms
principles of drug delivery via dosage forms (e.g., liquid, solid, semi-solid, controlled release, patches, & implants)
principles of dosage form stability and drug degradation in dosage forms
materials and methods used in preparation and use of dosage forms
Pharmacokinetics/clinical pharmacokinetics
basic principles of in vivo drug kinetics (linear and nonlinear)
principles of bioavailability/bioequivalence
physiologic determinates of drug onset and duration
drug, disease, and dietary influences on absorption, distribution, metabolism, and excretion
clinical pharmacokinetics of commonly used and low-therapeutic-index drugs
the pharmacokinetic-pharmacodynamic interface
Extemporaneous compounding/parenteral/enteral
United States Pharmacopeia guidance on compounding and FDA Compliance Policy Guidelines
techniques and principles used to prepare and dispense individual extemporaneous prescriptions, including dating of
compounded dosage forms
liquid (parenteral, enteral), solid, semi-solid, and topical preparations
dosage form preparation calculations
sterile admixture techniques: United States Pharmacopeia (USP) Chapter 797, stability and sterility testing and dating,
clean room requirements, infusion devices and catheters
Suggested Study References:
BASIC BIOMEDICAL SCIENCES
• Molecular Biology of the Cell, 4th edition; Bruce Alberts, Alexander Johnson, Julian
Lewis, Martin Raff, Keith Roberts, and Peter Walter. New York: Garland Science; 2002.
• The Cell, 2nd edition; A Molecular Approach; Geoffrey M Cooper. Boston University
Sunderland (MA): Sinauer Associates; 2000.
• Immunobiology, 5th edition; The Immune System in Health and Disease; Charles A
Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik. New York: Garland
Science; 2001.
• The Biology of Cancer, 7th Edition; Robert A. Weinberg. New York: Garland Science;
2007.
• Lehninger Principles of Biochemistry, by David L. Nelson and Michael M. Cox, Fifth
Edition.
• Biochemistry by Jeremy M. Berg, John L. Tymoczko, and Lubert Stryer, Sixth Edition.
•
Foye’s Principles of Medicinal Chemistry 7th edition. Thomas L. Lemke. Lippincott Williams &
Wilkins; 2012
PHARMACEUTICAL SCIENCES
• Bauer, Larry A. Applied Clinical Pharmacokinetics. McGraw-Hill. 2001.
• Handbook of Basic Pharmacokinetics, Including Clinical Applications, 7e (Wolfgang
Ritschel, Gregory Kearns)
• Basic Physical Pharmacy. 1st edition. Joseph K.H. Ma and Boka W. Hadzija. 2013
• Foye’s Principles of Medicinal Chemistry 7th edition. Thomas L. Lemke. Lippincott
Williams & Wilkins; 2012
• Brunton L L, Blumenthal D K, Murri N, Dandan R H, Knollmann B C. Goodman & Gilman's
The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill, 2011
Learning Objectives : Intro to Immunolgy
Please note: The objectives in this unit are intended to familiarize you with learning
objectives as we use them in this course. Try to answer them now as well as you can, but
don't panic if you think your answers are inadequate; all the material in Unit 1 will be
covered again later in the course. Rest assured that by mid-term time these somewhat
difficult-looking objectives will be easy as pie.
1. Please define: antigen
antigenic determinant
toll-like receptor
pattern-recognition receptor
pathogen-associated molecular pattern
cytokine
chemokine
2.
Discuss the role of the innate immune system.
3.
Describe how innate immunity can lead to adaptive
immunity, and name the cell that bridges the two systems.
4.
Give an example each of how the immune system can be
helpful or harmful to its host.
5.
Describe the recognition and effector functions of the
immune system. Distinguish recognizing and effector cells.
6.
Discuss the similarities and differences between T cellmediated and antibody-mediated immunity.
7.
Describe at least 2 functions of T cells.
8.
Describe at least two functions of the complement
system.
9. Define the concept of immunopathology, and give two
examples
Learning Objectives:
Anatomy and Physiology of the Immune System
1.
Define:
leukocytes
mononuclear cells
polymorphonuclear cells
granulocytes
mast cells
plasma and serum
2.
Sketch schematically a neutrophil; eosinophil; basophil; small
lymphocyte; lymphoblast; plasma cell; monocyte. Indicate the
characteristic features which distinguish each cell type.
6.
Define antigen, and compare it to immunogen. Discuss a
potential uses if any antigen could be made into a tolerogen.
7. Discuss lymphocyte activation by antigen with respect to:
receptor binding, proliferation, differentiation.
Antibody Structure
1. Define:
H chain
L chain
kappa and lambda chains
hinge region
Fab, F(ab')2, Fc
complementarity-determining region
variable (V) and constant (C) regions
VL and CL
2. Name the 5 antibody classes, and their characteristic heavy
chains.
3. Draw a diagram of the structure of typical molecules of each
class. Label the heavy and light chains; Fc and Fab parts; J chains;
antibody combining sites; main interchain disulfide bonds; secretory
component.
4. Discuss the significance of the fact that in any one antibody
molecule, both H and both L chains are identical.
6. Describe the structure of antibody combining sites.
7. Explain why complementarity-determining regions are also called
hypervariable regions.
8. Give an example of a subclass, an allotpe, an idiotype.
11. Define Fc receptors. Name the inflammatory cells which have
them.
Learning Objectives: Antibody Specificity, Diversity, Genes:
1. Define: toxoid; DNA recombination; RNA splicing; somatic
hypermutation.
2. Define cross-reactivity. Give an example of a non-self antigen
which cross-reacts with a self antigen. Explain, in terms of
lymphocyte activation, how a self antigen might not itself elicit
antibody, but might react with antibody elicited by a cross-reacting
antigen.
3. Discuss the Clonal Selection Theory.
4. Define allotypic exclusion. Demonstrate your knowledge of the
concept by first stating the number of chromosomes in a cell which
bear H or L genes, and then the number that actually contribute to
a particular B cell's antibody product.
5. Draw a diagram of the heavy and light chain gene regions of
human DNA. Indicate V, D, J and C subregions. Show how a heavy or
light chain gene is assembled out of these subregions during the
differentiation of a B cell.
6. Describe the somatic recombination model which explains how
antibodies of the same specificity (idiotype) can be found in two or
more different classes ("class switching").
8. Define somatic mutation, and describe the essential difference
between the somatic mutation and germ line hypotheses of
immunological diversity.
9. Describe the mechanisms by which more diversity is created by
nucleotide insertion and removal during V(D)J recombination,
Learning Objectives: Antibody Function and Complement:
1. Define: valence, affinity, precipitation, agglutination
2. Distinguish the five classes of immunoglobulins in terms of:
a. passage across the placenta
b. ability to activate complement by the classical pathway
c. ability to activate complement by the alternative pathway
d. involvement in allergic diseases
e. “first line of defense”
f. most resistant to enzymatic digestion
6. Compare and contrast precipitation and agglutination in terms of
the nature of the antigens involved, and sensitivity of the tests.
7. Discuss how complement plays roles in both innate and adaptive
immunity.
8. List the components of complement in the order in which they
become activated in the classical pathway. Name those that are also
activated in the alternative pathway.
9. Discuss the lectin-mediated pathway of complement activation.
10. Discuss the different ways in which complement is activated by:
IgG; IgM; IgA; polysaccharides.
11. Identify the complement components which are: opsonizing; lytic;
anaphylatoxic; and chemotactic.
Learning Objectives: Ontogeny, T and B Cells:
1. Define: stem cell; B cell; T cell; pre-B cell; pre-T cell; selftolerance.
4. Describe the sequence of appearance of cytoplasmic and surface
immunoglobulins in developing B cells. Using these data, derive a
model that could explain self-tolerance at the B cell level ("clonal
abortion").
5. Draw a graph showing the antibody response to a typical antigen
in a primary and in a secondary response. Show both IgM and IgG
antibody levels.
6. Draw a graph which shows relative IgG and IgM levels in a normal
infant from conception to one year of age. Distinguish maternal
from infant's antibodies.
7. Given a newborn's antibody titer, interpret its significance if the
antibody is IgG, or IgM. If IgG, calculate what the titer will be at 4
months of age, and state the assumptions you made when you did
the calculation.
Learning Objectives: T Cells 1 and 2:
1. List the four main types of T cells, and define their functions.
2. Describe the surface markers that can be used to distinguish
between T and B cells in humans.
3. Describe markers that Th1, Th2, and killer T cell (CTL)
subpopulations in humans have on their surfaces.
4. Define lymphokine and cytokine, and give an example of each.
5. Describe an activity of interferon-gamma (IFNã).
6. Define mitogen, and name two T cell mitogens. Name a mitogen
that stimulates both B and T cells in humans.
7. Distinguish between the effects of a mitogen and an antigen when
added to normal blood lymphocytes.
8. Compare and contrast the antigen receptors of T and B cells.
9. Discuss the structures recognized by T cell receptors.
Distinguish between what is recognized by helper and cytotoxic T
cells.
10. Discuss what is meant by "MHC-restriction". Name the classes
of MHC molecules by which CTL, Th1 and Th2 are restricted.
11. Describe the role of T cells in ridding the body of a viral
infection.
12. Describe the characteristics of T-independent antigens.
14. Discuss the mechanism by which T cells help B cells.
LEARNING OBJECTIVES: Immunity and Vaccines
1. Compare the roles of cell-mediated and humoral immunity in virus
infections with regard to: preventing the infection; controlling
spread of viruses in the body; which is responsible for recovery
from disease; how each can cause immunopathology.
2. Discuss the possible roles of Th1 and CTL in recovery from virus
infection.
3. Define "local immunity" and give an example.
4. Identify those organisms against which cell-mediated immunity is
most effective.
5. Identify those organisms against which humoral immunity is most
effective.
6. Identify the types of organisms against which IgE immunity may
play an important role; discuss possible mechanisms.
7. Describe the mechanism by which trypanosomes in sleeping
sickness evade the host's humoral immune response.
8. Give an example of a human and an animal antitoxin; a toxoid; a
killed virus vaccine; and a live virus vaccine. Identify the one which
produces the longest-lasting immunity. Discuss possible hazards of
each type of preparation.
9. State the appropriate times for immunization of children against
diphtheria, pertussis (whooping cough), tetanus, polio, and measles.
Discuss why live viral vaccines tend to be ineffective in the very
young.
10. Discuss the use of IgG and IgM antibody titers in the diagnosis
of intrauterine and neonatal infections.
11. Identify the oral and parenteral polio vaccines by the names of
their developers. Discuss their relative advantages and
disadvantages, and note which is currently used in the USA.
12. Discuss the pros and cons and advances in pertussis (whooping
cough) immunization.
LEARNING OBJECTIVES: Immunohematology
1. For persons of the A, B, AB and O blood groups, give the following
data: most and least common groups; red cell antigens; specificities
of the ABO antibodies in their plasma; safe donors to that type;
safe recipients of blood from that type; possible genotypes.
2. Name the class of most ABO isohemagglutinins.
9. Define heterophile antibody, and identify a common disease in
which one type is increased enough to be useful diagnostically.
10. In Hemolytic Disease of the Newborn, explain:
a. The consequences of severe hemolysis in the newborn.
b. The way in which the mother becomes sensitized.
c. The class of antibody to Rh(D) the mother makes.
d. The consequences of sensitization to subsequent fetuses.
e. The role of Rh-immune globulin.
11. Explain the situation in which ABO hemolytic disease of the
newborn can occur.
Learning Objectives for Type I Immunopathology
1. Define the following: atopic; immediate hypersensitivity;
allergy, allergen; anaphylaxis; asthma; urticaria, hives, wheal-andflare reaction
2. State the approximate incidence of atopic diseases in
the general population, and in individuals with allergic parents.
3. Describe the mechanism of IgE-mediated hypersensitivity in
terms of: IgE attachment to basophils or mast cells; reaction with
allergens; mediator release; effects of mediators on target tissues
and cells.
4. Discuss the features that the various atopic diseases have in
common which justify lumping them together.
5. State the principles of the RAST and basophil degranulation
tests. Compare these tests to intradermal skin tests with
reference to safety and specificity.
6. Discuss specific hyposensitization therapy of allergic disease,
considering duration of effect, risk of anaphylaxis, percent of
patients obtaining significant relief.
7. Describe the immediate allergic reaction and the late-phase
reaction in terms of:
a. time course of the reaction
b. mediators involved
c. histology
8. Discuss the similarities and differences between anaphylactic
and anaphylactoid reactions.
Type II Immunopathology: Learning Objectives:
1. Describe the molecular and cellular details of the immunologic
mechanism by which tissue damage occurs in a Type II
("cytotoxic antibody") reaction.
2. Give an example of a Type II mechanism disease of muscle,
kidney, heart, red cells, platelets, lung, thyroid, pancreatic
islets.
3. Describe the fluorescent antibody tests which would allow you
to make the diagnosis of Goodpasture's Syndrome, given:
patient's kidney biopsy; normal kidney biopsy; patient's serum;
and fluoresceinated goat antisera to human IgG and
complement.
4. Distinguish between the "lumpy-bumpy" and linear
immunofluorescent patterns in terms of the most probable
immunopathologies they represent.
5. Describe how autoimmune disease could result from:
A. The innocent bystander phenomenon
B. Cross-reaction of a foreign antigen with self
C. Coupling self antigen with a foreign antigenic "carrier"
D. Physicochemical alteration of self
E. Emergence of a forbidden clone
F. Exposure of a sequestered antigen
G. Failure of suppressor T cells
6. Identify "Rheumatoid Factor" and describe its molecular
nature.
7. Give an example of a condition in which antibody stimulates
rather than inhibits or harms its target cell.
Learning Objectives Immunodeficiency:
1. Characterize the infections you would expect in a pure B cell
deficiency; in a pure T cell deficiency.
2. Describe the clinical features which, although not immunological,
are associated with Di George syndrome.
3. Name the enzyme which is absent in some cases of SCID. Discuss
possible approaches to replacing this enzyme.
4. Discuss transplantation therapy in immunodeficiency diseases.
Include a consideration of side effects.
5. Given a child with recurrent infections, describe in principle tests
which could be done to determine if there is a T, B or combined
immunodeficiency, or a PMN, macrophage or complement problem.
6. Describe the contents of commercial gamma globulin and indicate
the conditions in which it can be useful replacement therapy.
Compare and contrast intramuscular and intravenous therapy.
7. Name two viruses which are immunosuppressive in humans.
Discuss a possible mechanism for the immunosuppression caused by
one of these viruses.
8. Describe the immunological problem of the Nude mouse, and name
which immunodeficiency condition it resembles.
9. Name the enzyme which is absent in some cases of SCID. Discuss
possible approaches to replacing this enzyme.
Learning Objectives Type III Immunopathology:
1. Arthus reaction and serum sickness are local and general
manifestations of immune complex disease; describe the mechanism
of tissue damage. Discuss why this is sometimes called "innocent
bystander injury".
2. Indicate the critical size at which immune complexes get stuck in
basement membranes.
3. Describe "one-shot" serum sickness.
4. Discuss the, types of tissues in which damage is most likely to
occur from deposition of immune complexes.
5. Discuss the immunological mechanism of a typical Type III
disease involving exogenous antigen.
6. Discuss how urticaria could result from interaction of antigen
with either IgE or IgG antibody.
Learning Objectives Type IV Immunopathology
1. Describe the sensitization (immunization) process in cell-mediated
immunity (CMI), in terms of: antigen association with macrophages;
sites of T cell proliferation; time involved.
3. Describe the mechanism of contact hypersensitivity; give
examples of common sensitizers.
4. Distinguish between resting and "angry" (activated) macrophages.
5. Describe how delayed hypersensitivity can be passively
transferred to another individual. Discuss how this maneuver can be
used to show that delayed hypersensitivity is a T cell-mediated
reaction. Discuss problems in the transfer of delayed
hypersensitivity in humans.
6. Describe an in vitro test by which one can determine if a patient
has cell-mediated immunity (delayed hypersensitivity) to a
particular antigen.
7. Distinguish between specific and generalized anergy.
8. Describe the differences between first-set, second-set and
hyperacute allograft rejection. Outline the mechanisms involved in
each case.
10. Describe immune deviation in cellular and cytokine terms.
Immunodiagnosis
Learning Objectives:
1.
Describe the procedure used in serum protein electrophoresis, and the
underlying principles.
2.
Discuss the serum protein electrophoretic pattern which would be
expected if a patient:
a.
b.
c.
d.
e.
was normal
had selective IgA deficiency
had multiple myeloma
had severe pyogenic (high-grade bacterial) infections
was hypogammaglobulinemic
3. Discuss single radial immunodiffusion, with regard to the types of
antigens that can be quantitated with it, and the way that quantitation
is done
4.
Outline the principles involved in nephelometry. Compare to single
radial immunodiffusion for cost and speed.
5.
Describe a test that is used for determining if a patient has antibody
to a soluble or particulate antigen.
6.
Describe in principle the ELISA and RIA tests. Discuss the types of
antigens that can be measured in these tests. Diagram the reactants
involved when the ELISA is used to measure antibody, and to measure
antigen.
7.
Describe a test which can be used to evaluate T cell
immunocompetence in a clinic or on the ward.
8.
Describe tests to evaluate T cell numbers and function in the lab.
LEARNING OBJECTIVES: HIV AIDS
1.
Explain the difference between "HIV-seropositive" and "AIDS".
2. Name the virus that causes AIDS, and its classification.
3. Discuss the origin of the AIDS virus and the origins of the
current epidemic.
4. Identify the approximate number of cases in the U.S. and in the
world, and discuss the rate of change in incidence.
5. Discuss the pathogenesis of AIDS, including target cell types,
mode of entry of the virus into a cell mode of exit, latency versus
productive infection.
6. Distinguish between the roles of Th1 and Th2 in the progression
of HIV infections.
7. Discuss the types of infections seen in AIDS patients, and
provide an immunological basis for this spectrum.
8. Discuss possible reasons for which the total number of CD4 cells
in AIDS patients decline.
9. Discuss reasons for which antibody seems to be ineffective in
HIV infection.
10. Describe the laboratory diagnosis of AIDS.
11. Discuss risk groups and risky behavior in AIDS.
12. Discuss the prospects and problems of AIDS vaccine
development.
Learning Objectives Tumor Immunology:
State the concept of the Immune Surveillance theory. Show
how data from immunosuppressed and immunodeficient patients
support the theory. In light of this theory, discuss the failure of
nude mice to spontaneously develop cancer.
1.
2.
Describe the difference between virally-induced and
chemically- induced tumors in terms of antigenic cross-reactivity.
3.
Compare and contrast:
Tumor-associated antigens (TAA)
Tumor-specific transplantation antigens (TSTA)
4. Define carcinoembryonic antigen (CEA) and discuss its
usefulness in screening for, diagnosis and follow-up of bowel cancer.
5. Describe these mechanisms by which the body may kill tumor
cells:
a.
b.
c.
d.
e.
f.
g.
Antibody / complement-mediated lysis
Antibody/ opsonization
ADCC
Killer T cells (CTL)
Th1 and angry macrophages
Lymphotoxin
Natural killer (NK) cells
6. In the context of the above list of mechanisms, discuss the low
incidence of spontaneous tumors in nude mice and Di George
syndrome patients.
8. Define tumor immunotherapy.
9. Describe two mechanisms by which BCG treatment may cause
tumor regression.
10. Discuss prospects and problems concerning the use of
monoclonal antibodies in the diagnosis or treatment of cancer (see
also Unit 20).
11. List actions of interferons that might be important in the
response to tumors.
12. Describe the nature and use of lymphokine-activated killer cells.
LEARNING OBJECTIVES: Immune malignancies/New Directions
1. Identify a malignant condition in which the cells involved
resemble:
A. null cells
B. activated T cells
C. resting B cells
D. activated B cells
E. activated B cells secreting IgM
2. Discuss the events thought to be necessary for the development
of Burkitt's lymphoma, including: the virus involved, the nature of
the chromosomal translocation, the role of malarial infection.
3. Describe an experiment that shows that immune responses might
be "conditioned" in a Pavlovian sense.
4. Describe in principle the procedure for making a monoclonal
antibody. Discuss advantages and disadvantages compared to a
conventional antiserum.
5. Describe in principle the way in which a person could be induced
to make an auto-anti-idiotypic response. Suggest a use for such a
procedure.
6. Define superantigens, and show diagrammatically how they work
to stimulate T cells.