Physical Pharmacology 2023

Ruben Abagyan. January - March, 2023.

The UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences

Objectives

Understand the underlying quantitative laws and principles governing the behavior of therapeutic agents
Understand the relationship between chemical structure of an active ingredient and active metabolites and their pharmacology and adverse effects.
Equation Sheet
Equation Sheet as a pdf
Supplementary Information
Lab publications

News, Message Board

The SPPS 222 final

Everyone passed! Congratulations!

Figure: Imatinib (Gleevec) inhibiting human ABL kinase constitutively active in the Ph-positive chronic myelogenous leukemia

Schedule

Date	Time	Unit	Lecture materials	Lab and practice materials
w1. Thu, Jan 5	8-8:50	u1. Drug matter, molecules, sizes and energies	Lecture Problems. Practice	Video: Math review, Significant figures or this one or Video: Accuracy and Precision Video: Types of Matter (Mr. Causey) Video: Physical and Chemical changes: Mr. Causey
w1. Thu, Jan 6	9-9:50	u2. Gases. Breathing, Temperature, Inhaled Drugs	Lecture Problems. Practice W1 Quiz Results	List of medical inhalants (wiki) Video: Mole, Avogadro, Molar Masses. Mr. Causey Video: Moles and number of atoms: practice. Mr.Darell Causey Video: SI, Gas Law (practice): Mr.Causey
w2. Thu, Jan 12	8-8:50	u3. Thermodynamics. Drug binding basics. 1st law. Enthalpy and Heat	Lecture Practice	Video: Thermodynamics: Energy, Work, Enthalpy. Mr.Darell Causey Video: 1st Law of Thermo Video: Hank's crash course #17. Energy, Work, Heat Video: Hank's crash course #18. Enthalpy, Hess's law Video: Hank's crash course #19. Calorimetry, Heat Capacity
w2. Thu, Jan 12	9–9:50	u4. Heat. Enthaplies of drug transitions. Cold/Hot Packs	Lecture Practice W2 Quiz Results	Video: Nitroglycerin, Sobrero and Nobel Video: Enthalpy of Hydration Video: Enthalpy of Formation Example (methane) Video: Enothalpy of Reaction
w3. Thu, Jan 19	8-8:50	u5. Entropy and Free Energy. Drug-Target Interactions Balance. Inhalers	Lecture Seminar (part 1)	Video: Entropy of Transition Video: Hank's crash course #20. Entropy, Free Energy
w3. Thu, Jan 19	9-9:50	u6. Boiling. Phase transitions. Drug crystals	Lecture Seminar (part 2) W3 Quiz Results	Video: K.A. boiling Inhalers with propellant Inhalers without propellants Video: Clapeyron-Clausius Equation. Practice Video: Hank on Chemical Equilibria
w4. Thu, Jan 26	8–8:50	u7. Mixtures and Reactions. Drug Binding	Lecture Practice (part 1)	Video: Chemical potential Video: Chemical potential in muxtures Video: Chemical potential and related equations
w4. Thu, Jan 26	9–9:50	u8. Edema,Rault, Henry. Fluid compartments in human body, Interstitium, Blood pressure	Lecture Drug partitions. Practice, part 2 W4 Quiz Results	Video: Hank on Dalton's law and partial pressures Video: Na-K pump Video: Osmoregulation Video: Edema 1 Video: Edema 2 Video: Nephron (physiology) Video: Gibbs-Donnan Equilibrium: ion/protein balance
w5. Thu, Feb 2	8-8:50	u9. Drug binding. Bound fractions	Lecture.Ligand-target binding Practice, part 1
w5. Thu, Feb 2	9-9:50	Nuclear Medicine	Lecture Practice (part 2) W5 Quiz Results	Video: Technetium 99m Video: Positron Emission Tomography Video: Becquerel, gray and sievert Video: Fluorescence explained Video: Fluorescence explained by John Eliott (+ parts 2,3)
w6. Thu, Feb 9	8-8:50	u11. Molecular interactions. Electrostatics. Formal charges in drugs	Lecture Practice	Video: Coulomb's law (Paul Andersen) Video: Electrostatic interactions (basics)
w6. Thu, Feb 9	9-9:50	u12. Electrostatic Interactions. Permeability. Practice.	Lecture Practice Quiz: text Enter results	Video: Lewis, Hybridization Video: Formal Charge 1. (KA) Video: Formal Charge 2. (KA) Video: Resonance structures and FC 1. (KA) Video: Resonance structures and FC 2. (KA) Video: Resonance structures, amide, peptide bonds. (KA) Video: Van Der Waals Forces (KA) Video: Intermolecular FF, van der Waals (PA,Bz)
w7. Thu, Feb 16	8-8:50	u13. Drug-target interactions: hydrogen bonding, hydrophobicity	Lecture	Hydrogen bonds and hydrophobicity in drug complexes Video: The Hydrophobic Effect (Thermo) (Michael Evans) Video: Hydration Shell Dynamics of a Hydrophobic Particle
w7. Thu, Feb 16	9-9:50	u14. Drug Ionization, Solubility and Permeability, Henderson–Hasselbalch equation	Lecture	Video: Acids, Bases and pH (PA,Bz) Video: Buffers and Henderson-Hasselbalch (KA)
w8. Thu, Feb 23	8-8:50	u15. Drug Salts, LogD, Crystals	Lecture Practice
w8. Thu, Feb 23	9-9:50	u16. Prodrugs. Metabolism.	Lecture	Chemistry: Prodrugs example: Ethyl Esters and the Anti-Viral Pro-Drug Tamiflu (by Ron Davis, chemsurvival)" Video: Duchenne Muscular Dystrophy and Dystrophin (see the 7th minute). Defective genes, gene therapy
w9. Thu, Mar 2	8-8:50	u17. Kinetics. Drug diffusion	Lecture Kinetics: Practice	Video: Duchenne Muscular Dystrophy and a PMO drug Video: Spinal Muscular Atrophy (SMA) and how to fix defective SMN1 protein
w9. Thu, Mar 2	9-9:50	u18. Drug Kinetics, Diffusion, Rate constants	Lecture Quiz text Enter Answers	Video: Introduction to Kinetics. Crash Course Chemistry Video: Introduction to Kinetics (KA) Video: Kinetics of drug metaboism: 1st and 0th order (Areo S)
w10. Thu, Mar 9	8-8:50	u19. Methods and Data in Pharmacology. Review	Lecture Review Equation Sheet	Quizzes recompiled as practice tests (anonymous but with answers after you submit): week1 week2 week3 week4 week5 week6 week7 week8
w10. Thu, Mar 9	9-9:50	CNS drugs and Blood Brain Barrier (Dr. Paul F Jackson)	u20. BBB: Lecture (Dr. Paul F Jackson, JNJ
w11. Fri, Mar 17	10–12	Final exam, HSEC	Links to two documents you need to start the quiz. You may use lecture notes too, as well as calculators. Please do not use other materials. Congratulations! Everyone passed! (all > 57% correct). No one failed More information later

Additional Information

Suggested Reading: Florence and Attwood. “Physicochemical Principles of Pharmacy ” In most cases the information in handouts will be sufficient.
SSPPS Course Policies:General SSPPS Policies and Information
General Guidelines: This syllabus could change at any time. You may expect additional PhysPharm time within the schedule during the quarter.
Lab: Fridays 10 a.m. - noon. The lab time will be mostly used for seminars and problem solving, it may be used for lectures. The second hour is devoted to group learning and weekly quizzes.
Website, course materials: ruben.ucsd.edu The course notes are copyrighted .
PDFs and Handouts: PDF-files will be available for download in advance. Please print them out yourself as needed.
Course Director and Instructor:Ruben Abagyan (ruben@ucsd.edu) Office Phone: (858) 822 3404, Office: SSPPS 3226. (most likely I will not be in the office, office hours by Zoom every Friday at 3pm. zoom link
Lecturer: Dr. Paul Jackson (Email: PJackso3@its.jnj.com).
Lecturer and Instructor: Tigran Makunts, PharmD (tmakunts@health.ucsd.edu)
Homework policy:No specific lecture-related and exam-related homework will be assigned. Some students may need to review certain chapters of math, physics or chemistry.
Exams and Grading:
The SPPS-222 total grade will consist of the following contributions:
1. Weekly quizzes combined: 35 %
2. Final exam: 60 %
3. Attendance: 5%
Criteria for pass/fail and honors grades
Pass/Fail:
- The students are required to complete all four activities listed above.
- To pass a quiz or exam one needs to have at least 50% correct answers with respect to the highest scoring student (typically 100%) for that exam. It is also required that the minimum cumulative percentage for the whole course exceeds 70%. Links to SSPPS policies on Progression and Rescheduling of Exams are provided above.
The honors grade
Up to 35% of the high combined scoring students according to weights listed above are eligible for the honors grade. From these students those are selected with the fraction of the correct answers above 90% for the quizzes and the final exams. The Y grade
It is also possible to receive an intermediate grade, Y, to signify work in progress. The Y grade is not included in calculating the grade point average. Each Y grade is replaced by the earned letter grade when the sequence has been completed.
Exam and Graded-Quiz Rules
- Calculators are allowed at exams and tests.
- Printed Equation sheets will be distributed along with the test.
- Access to the lecture notes and equation sheets is allowed during the weekly quizzes. Access to the equation sheets, lecture notes, and calculators is allowed during the final exams. Please do not forget to take calculators and laptops with you. The submitted result is final and will not be modified after submission.
- Students need their laptops to access lecture notes and/or to enter the test results at the end at the following web-address: http://ruben.ucsd.edu . Laptops may not be used for any other purpose
- The laptops, ipads, and other mobile devices can only be used during the final exam for accessing calculator, lecture notes, and the entering of the results to the computer system at the end.
- The paper exam (with student name and ID) needs to be returned. The computer-entered results are final and supercede the paper answers.
Software:We will be using the free ICM browser for laboratories. The browser can be downloaded at any time from www.molsoft.com .
Exam dates:Exam dates are listed above but may be subject to change, though unlikely. Sufficient prior notice will be given in case the dates change.
Office hours: The preferred office hours this quarter are going to be every Friday at 3pm by Zoom at the same Zoom link as the course ( https://uchealth.zoom.us/j/86998750601 ). Personal meetings with R.A., or P.J. at the SSPPS 3th fl., room 3226 (RA) may be arranged by appointment.
Acknowledgments: I (R.A.) am thankful to the following people for help with the course: Dr. Andy McCammon and Dr. Irina Kufareva. I thank Eugene Raush and Chris Edwards for their help with website and exam software.
Diversity Statement
Further reading:
- Physical Chemistry, Peter Atkins and Julio de Paula, 7th Edition.;
- Physical Pharmacy by Alfred N. Martin Pub. Date: October 1993. Public sources: www.wikipedia.org
Course and Faculty Evaluations for Required and Elective Courses:Course and faculty evaluations provide important feedback to instructors to improve course content and teaching methodology. Teaching evaluations are also an important factor in faculty advancement, merit and promotion. The School and the University require this information. As such, completion of course and instructor evaluations is a requirement for successful completion of the course. This is also part of developing professional conduct and behavior. To facilitate ease of completion of evaluations an electronic format has been implemented. Students who have academically passed a course but who have not completed 1) the evaluation of the course, 2) the evaluation of the course chair(s) and 3) evaluations of at least 90% of guest lecturers will receive a grade of “I” (incomplete) for the course. If an “I” has been assigned due to incomplete evaluations, changing the “I” grade will require completion of the evaluations prior to the start of the next academic quarter. A grade of “I” must be changed to an “H” (Honors) or “P” (Pass) by the end of the next academic quarter in which the student is enrolled or the grade is automatically changed by the Registrar’s Office to an “F” (Fail). A petition is required to change the “I” grade.