b(t)

advertisement
Hormones, Drugs, and
Pregnancy
Marsha Timmerman, LaSalle University
Tracy Schatteman, Lincoln Land Community College
Gretchen A. Koch, Goucher College
Anton Weisstein, Truman State University
Goals
• Create a problem based learning module
to teach students about hormones
• Three venues
– Human A&P course: Reproductive system
– Cell biology course: Cell signaling
– Pharmacology course: Pharmacokinetics
Learning Objectives:
Anatomy and Physiology
• Role of hormones in modulating female
reproductive cycle
• Complexity of negative feedback
mechanisms at the organismal level
• Pharmacology – intake, half-life, and
excretion of medications
• Understand the public health implications
of pregnancy and birth control
Learning Objectives:
Cell Biology
• Structure and form of steroid molecules
• Role/function of steroid hormones on
cellular level
• Specificity of cells – what makes a cell a
target cell
• Cell signaling receptors
• Specificity of receptors – triggers and
outcomes
• Applications to cancer on the cellular level
Problem Based Learning
Concept Map
The Hook: Initial case history of woman
who gets pregnant on birth control pills
Inquiry phase: students discuss and research into
reproductive system, hormones and birth control pills.
Students present what they have learned to the class.
Case history part 2: Provides more information
Investigative phase: students use tools such as Excel
modules and AgentSheets to delve deeper into the
subject. In this phase, each venue can move in the
direction appropriate for the intent of their class.
Anatomy and Physiology Module
Initial Case
Bill walks into the student lounge and sees Amy sitting
in a corner looking very dejected. Bill approaches
Amy.
Bill: “Hi Amy. You look upset. Is anything wrong?”
Amy: “I guess. This morning I took a home pregnancy
test, and it came up positive. I’m really shocked that
I’m pregnant. I need to think about it for a while.”
Bill: “Congratulations! I know that you and Ron have
been talking about having a family. I did not realize
that you had stopped using birth control.”
Amy: “That’s the problem. I am still taking birth
control pills; I think the one I am on is called
Aygestin. Ron and I were thinking about a family
but were not quite ready to take the plunge. I guess
we don’t need to make the decision any longer.”
Anatomy and Physiology Module
Step 2
• Anticipated inquiries from initial student
discussions
– Can someone taking birth control get
pregnant?
– How does the reproductive system work?
– How does birth control work?
– What are hormones?
– What is Aygestin?
• Students should work on their own to
obtain answers to the above questions.
• Students need to present what they have
learned to their group.
Anatomy and Physiology Module
Step 3
More of the case…
Amy goes to her doctor for a prenatal checkup.
Amy: “I was taking my birth control pills as prescribed.
The only time I missed one was a couple of weeks
ago when I was up very late studying for an exam.
After exams, Ron and I went away for a weekend
get away to enjoy ourselves before the summer
semester started.”
Doctor: “Aygestin is a progesterone birth control pill.
A woman’s reproductive system is controlled by a
number of hormones that continually cycle.”
Female Reproductive Cycle
Feedback Mechanisms:
Female Reproductive Hormones
http://www.vrp.com/graphics
/fem_repro_homeo.jpg
Reproductive Hormone ESTEEM
Module
Assumptions of the
Reproductive Hormone Model
• Average 28 day
menstrual cycle
• Does not include: GnRH,
LH, estrogen
• Birth control pills:
– Progesterone only
(mini-pill)
– Taken on days 1-21
– Placebo days 22-28
• Progesterone
– Suppresses FSH
levels
– Small release in
follicular phase
– Large release in luteal
phase
– Day 26: levels decline
sharply
• Pregnancy blocks
progesterone decline.
Pharmacokinetics
• Study of how drugs move through the
body (1)
• Enter via ingestion, injection,
absorption (1)
• Exit via excretion, metabolism (1)
• Possible Lesson: Birth control and
hormones
– How many doses can one skip before you
get pregnant?
– Must it correspond to the hormonal cycle?
A little mathematics…
Ingestion
GI Tract
f (t )
•
•
•
•
g (t )
Decay in GI
tract and
absorption
into blood
b
Metabolism
Blood
b( t )
f(t): the dosage function (2)
Half-life rates: α and b
g(t): concentration of drug in GI tract
b(t): concentration of drug in bloodstream

Mathematical Equations
dg
 f (t )  b g (t )
dt
db
 b g ( t )   b( t )
dt



Rate of change = Rate In – Rate Out
The rate of change in the concentration of the drug in the GI tract is
equal to the amount being ingested minus the concentration that is
decaying.
The rate of change in the concentration of the drug in the blood is equal
to the concentration that is decaying from the GI tract minus the
concentration decaying in the blood.
One Compartment Model
Ingestion
Metabolism
Blood
f (t )
b( t )

• f(t): the dosage function (2)
• Half-life rate: α
• b(t): concentration of drug in bloodstream
Mathematical Equations
db
 f (t)   b(t)
dt


Rate of change = Rate In – Rate Out
The rate of change in the concentration of the drug in the blood is
equal to the amount being ingested minus the concentration that is
being metabolized.
Model description
and assumptions
Dosing Function
Sliders to
change
dosage function
dynamically.
Drug Concentrations
Versus time
Blood concentration
versus GI concentration
Time is still independent variable.
Comparisons of Steroids
Cholesterol
Estrogen
Progesterone
Testosterone
Future directions
• Elaborate and improve Hormone Module
• Public health applications
– GapMinder, CDC Website
• Pharmacokinetics Modules
– Documentation, Case Study, Sample Labs
• Model for cell signaling mechanisms
– AgentSheets
Acknowledgements
Tony Weisstein
John Jungck
Raina Robeva
Michael Garman, Sean Lonsdale, David
Ludgin, Kelley Moran, and Katrina
Ramirez-Meyer
Previous BioQUEST Participants
References
1.
2.
3.
Aygestin® Product Insert, Duramed Pharm., Inc., Pomona, NY, July 2007
Drugs@FDA, http://www.accessdata.fda.gov/scripts/cder/drugsatfda/
Conneely, O. and B. Jericevic. Progesterone Regulation of Reproductive Function
Through Functionally Distinct Progesterone Receptor Isoforms. Rev. in Endocrine &
Metabolic Disorders 3:201, 2002
4. Menstrual cycle hormone animation, IAMSE
http://www.healcentral.org/content/collections/McGill/MENSESANIMFINAL800x600.s
wf
5. Physician Information for Depo-Provera Pharmacia & Upjohn Company,
Kalamazoo, MI, Feb. 2004
6. Shughrue, P., D. Lubahn, A. Negro-Vilar, K. Korach, and I. Merchenthaler.
Responses in the brain of estrogen receptor a-disrupted mice. PNAS, 94:11008,
1997
7. Spitznagel, E. (Fall 1992) Two-Compartment Pharmacokinetic Models C-ODE-E.
Harvey Mudd College, Claremont, CA.
8. Wierman, M. Sex steroid effects at target tissues: mechanisms of action, Advan.
Physiol. Edu. 31: 26-33, 2007
9. Wierman, M. http://www.theaps.org/education/refresher/Wierman%20talk/player.html
10. Yeargers, E.K., Shonkwiler, R.W., and Herod, J.V. (1996) An Introduction to the
Mathematics of Biology. Birkhäuser.
Download