126A F2011 1st Midterm Name_________________________________________ 10/16/11 (100 points total) Perm #________________________________________

Do not open exam until instructed to do so

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Answer questions 1-11 on your Scantron form (3 points for each correct answer) 1. An aromatic amino acid decarboxylase inhibitor would have an effect on heart rate similar to a. a β1 adrenergic agonist b. an Uptake 1 inhibitor c. a M2-specific muscarinic agonist d. a muscarinic antagonist e. an α1 adrenergic agonist 2. What can you conclude if you find that the slope of a Schild plot is equal to 1? a. The antagonist behaves as a noncompetitive inhibitor b. The antagonist behaves as a competitive inhibitor c. The antagonist shows cooperative binding to the receptor d. The antagonist binds to the receptor at an allosteric site e. Your KB/KI value is invalid 3. Each of the following is characteristic of the sympathetic nervous system except for a. A common side effect of overstimulation of this system is constipation b. The sympathetic nervous system is not essential for survival c. The sympathetic nervous system involved in the regulation of lipid metabolism d. Systemic stimulation of the sympathetic nervous system may produce bronchoconstriction e. The sympathetic nervous system uses acetylcholine as a neurotransmitter 4. Which of the following is known to be a mechanism for drug desensitization? a. decreased rate of drug metabolism b. increased rate of receptor gene expression c. receptor endocytosis d. a change in the conformation of the receptor e. both c and d 5. Which of the following is characteristic of muscarinic cholinergic receptors? a. linked to voltage-gated ion channels b. G-protein coupled receptors c. found at pre-ganglionic junctions in both the sympathetic and parasympathetic NS d. are ionotropic receptors e. both b and d 6. Which of the following is true only when V = Vmax? a. V = Kd/2 b. [D] = Kd/2 c. [DR] = Kd/2 d. V = [Rtotal]- [DR] e. [DR]/[Rtotal] = 1 7. Which of the following is used to determine the relationship between the Kd and Kd apparent? a. The structure activity relationship b. The occupancy assumptions c. The Scatchard plot d. The Schild equation e. The therapeutic index

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8. Which of the following would not be an expected side effect of systemic administration of an acetylcholinesterase inhibitor? a. Hypertension b.Bronchoconstriction c. Dilation of the iris (eye) d. Diarrhea e. Both a and c 9. Shown below is a plot of the hydrolysis of acetylcholine by acetylcholinesterase where Δ is the fraction of the maximal hydrolysis rate and [A] is the concentration of acetylcholine (think of enzyme activity as a measure of biological activity). Y represents the enzyme activity of AChE alone and X represents the activity of AChE in the presence of an antagonist. Which of the following is true? a. The Kd apparent is unchanged by the antagonist but the maximum response is reduced b. The Kd apparent is increased by the antagonist but the maximum response is unchanged c. The Kd apparent is decreased by the antagonist but the maximum response is unchanged d. The Kd apparent is increased by the antagonist and the maximum response is reduced e. The Kd apparent is unchanged by the antagonist but the maximum response is increased

10. Which type of inhibition is depicted in question 11? a. competitive b. noncompetitive 11. Compounds other than acetylcholine and its agonists are also degraded by cholinesterases. Which of the drugs whose structures are shown below could be degraded by this class of enzymes?

A B

a. Compound A b. Compound B c. Both A and B d. Neither A or B 12. (4 points) A compound that increases the proportion of inactive receptors is known as a/an ______________________________________________ agonist

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13. (5 points) You carry out a drug binding study and use your data to produce a plot of fractional receptor occupancy vs log drug concentration. You obtain a Kd of 25 µM. You repeat the binding experiments the next day but this time you obtain a Kd of 3 µM. The only difference between the two experiments was that you incubated drug with receptor for a longer time on the 2nd day. Use your knowledge of pharmacodynamics to explain why the two experimental results differed. 14. (7 points) The Scatchard plot below reveals two binding sites on the same receptor.

a. How would you determine the Kd values of the two sites?

b. Which of these sites, A or B, has the highest binding affinity for the drug?

15. (5 points) Give a one sentence definition of Dale’s Principle. 16. (6 points) Briefly describe the two primary mechanisms by which neurotransmission via the sympathetic nervous system is terminated. 4

17. (12 points) (a) Name the plot shown below. log(x-1) (b) What is the pA2 of this antagonist? (c) What is the KB/KI of the antagonist? 18. (5 points) Given two compounds with pA2 values of 1 and 4. Which would have the most potent antagonistic activity on the biological response generated by an agonist that binds to the same receptor? 19. (4 points) The mechanism by which a neurotransmitter regulates its own release is known as ______________________________________________ regulation. 20, (6 points) What are the features of Van der Waals forces that explain the significant role these

interactions have on the specificity of binding of drugs to their receptors?

0 0.5

1 1.5

2 2.5

3 3.5

4

6 7 8 9 10 -0.5

- log [Antagonist] M

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21. (9 points) Recently a physician wrote a prescription for Salagen (a trade name for pilocarpine). The prescription was relayed over the phone to a pharmacist who thought the nurse who called in the prescription had said “selegiline”. Selegiline is a monoamine oxidase inhibitor used to treat Parkinson’s disease. The pharmacist realized her error when the technician who gave the prescription to the patient remarked how that individual didn’t show even the slightest symptoms of Parkinson’s. The pharmacist immediately rushed out the door to try and catch the patient before he drove away. a. What medical condition is pilocarpine used to treat?

b. Why was the pharmacist so concerned that this patient was given selegiline? 22. (4 points) In comparison to a full agonist, a partial agonist has a lower degree of ________________________________________ in its interaction with its receptor.

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