Test #1 Neurophramacology PDF

Chapter 1 Study Questions: What are the principal pharmacokinetic factors, and how do they determine bioavailability? Compare and contrast different drug administration methods, their advantages, and disadvantages. Explain how lipid solubility and ionization affect drug absorption....

Chapter 1 Study Questions: What are the principal pharmacokinetic factors, and how do they determine bioavailability? Compare and contrast different drug administration methods, their advantages, and disadvantages. Explain how lipid solubility and ionization affect drug absorption. What is the blood-brain barrier, and why is it important for psychopharmacology? Define depot binding and its impact on drug action duration and intensity. Explain the difference between synthetic and non-synthetic drug metabolism. Describe factors that influence drug metabolism and elimination. Define agonist, antagonist, partial agonist, and inverse agonist in drug-receptor interactions. What is a dose-response curve? How does it illustrate ED50 and maximum response? How do potency and efficacy differ, and how are they shown graphically? Explain the importance of the therapeutic index in drug safety evaluation. How does a competitive antagonist affect drug potency and efficacy? Define drug tolerance and describe the three major types of tolerance. What is pharmacogenetics, and how does it contribute to personalized medicine? Provide an example. Chapter 3 Review Questions: Describe the structure of a typical axodendritic synapse, including both presynaptic and post- synaptic elements. How do axosomatic synapses, axoaxonic synapses, and neuromuscular junctions differ from axodendritic synapses? List the criteria required for a substance to be verified as a neurotransmitter. Of these, which might be considered most important? Neurotransmitters can be classified based on the chemical category to which they belong. Name these categories and give at least one example of a member of each category. Describe how the synthesis of neuropeptides differs from that of other types of neurotransmitters. What is the difference between a neurotransmitter and a neuromodulator? How are neuromodulators related to the concept of volume transmission? What is exocytosis and what is its role in neurotransmitter release? Describe the process of vesicle recycling and the various models that have been proposed to explain the recycling process. How do these models differ with respect to factors such as speed of recycling, area of the nerve terminal where vesicle membrane retrieval occurs, and the involvement of the protein clathrin and of endosomes? Discuss the concept of a retrograde messenger and how this concept applies to lipid and gaseous transmitters. What is the difference between somatodendritic and terminal autoreceptors? How do these receptors control the rate of neurotransmitter release? Discuss the mechanisms by which neurotransmitters are inactivated. Chapter 5&6 Review Questions: Catecholamines 1. Which neurotransmitters make up the category called catecholamines? What are the distinguishing chemical features of this category? 2. Describe the steps involved in the biosynthesis of dopamine and norepinephrine. Name the enzyme that catalyzes each biochemical reaction, and indicate which reaction is the rate- limiting step in catecholamine synthesis. 3. Discuss the factors that regulate the rate of catecholamine synthesis. 4. List the names of the proteins that transport catecholamines in synaptic vesicles. Which of these proteins is expressed in the brain, and which is expressed in the adrenal medulla? 5. What is meant by single-spiking versus burst firing mode as applied to the firing patterns of midbrain dopaminergic neurons? How do these different firing patterns influence dopamine release at the nerve terminal? 6. Describe how catecholamine release is regulated by autoreceptors, including differences in the location and mechanism of action of terminal versus somatodendritic autoreceptors. What  adrenergic subtypes function as noradrenergic autoreceptors? Name an adrenergic autoreceptor agonist and an antagonist and indicate what effects these drugs have on nor- adrenergic cell firing. 7. What are the two basic mechanisms by which catecholamine transmission is terminated? 8. Name the major metabolites of DA and NE. 9.. Name and discuss the clinical uses of drugs that alter either catecholamine reuptake or catecholamine metabolism. 10. Describe the two major dopaminergic path-ways that originate in the midbrain and project to forebrain structures. Include in your answer the derivation of each pathway’s name. 11.. The midbrain dopaminergic cell groups have been shown to play important roles in motor function, motivation, and cognition. Much of this information has been obtained using either neurotoxins to damage/kill the cells or genetic engineering methods to produce a biochemical DA deficiency (i.e., DD mice). Compare and contrast these methodological approaches, and then discuss the behavioral characteristics of laboratory animals that have been generated using one or the other technique. 12. Describe (a) the behavioral functions of the mesolimbic versus the mesocortical dopaminergic pathways, and (b) the involvement of different subsets of VTA dopaminergic neurons in responding to rewarding versus aversive stimuli. 13. How many different subtypes of DA receptors exist? How are these subtypes grouped into families? Discuss the differences between D1 and D2 receptors with respect to signaling mechanisms and affinity for DA. 14. What is behavioral supersensitivity? In the case of D2 receptor supersensitivity, how is this phenomenon produced pharmacologically, and what is the hypothesized mechanism? 15. Discuss the major sources of NE in the forebrain and in the peripheral nervous system. What is the “fight-or-flight” response, and how do EPI and NE mediate this response? 16. Describe the adrenergic receptor subtypes and their signaling mechanisms. 17. Discuss the involvement of the central noradrenergic system in arousal and cognition. Include in your answer information derived from pharmacological manipulations of this system and the role of specific adrenergic receptor subtypes. 18. What is the evidence that peripheral EPI plays a role in the consolidation of emotional memories? What are the hypothesized mechanisms underlying this effect of EPI? 19. Describe the uses of specific medications that work by either stimulating or blocking peripheral adrenergic receptors. Serotonin 1. List the steps involved in 5-HT synthesis, including the name of the enzyme catalyzing each step. Which is the rate-limiting step in the synthetic pathway? 2. Describe the pharmacological and dietary methods used either to increase or to decrease brain 5-HT levels. 3. Discuss the effects of increasing or decreasing brain 5-HT on mood and cognition in humans. 4. Describe the processes involved in 5-HT storage, release, and inactivation. Name the drugs mentioned in the text that influence these processes, including the effect of each drug on serotonergic transmission. 5. What is the name given to the group of cells that synthesize 5-HT in the brain? Name the two specific cell groups that are responsible for most of the serotonergic projections to the forebrain and list the major forebrain areas that receive these projections. 6. Discuss how the firing of dorsal raphe serotonergic neurons varies with behavioral state and in response to rewards and punishments. 7. List the names of all the serotonergic receptor subtypes. Which of these receptors are metabotropic, and which are ionotropic? 8. Describe the signaling mechanisms of the 5-HT1A and 5-HT2A receptor subtypes. 9. Some of the important functions mediated by brain 5-HT have been studied using Tph2- knockout mice along with mice that have developed without central serotonergic neurons. Discuss the various ways in which these mice differ from normal mice behaviorally and physiologically. 10. Several medications used clinically to treat anxiety disorders exert their primary actions on the serotonergic system. Which serotonergic receptor subtypes have been implicated in the control of anxiety and anxiety-related behaviors? Provide relevant experimental findings to support your answer. 11. Discuss the involvement of 5-HT in pain regulation and the use of serotonergic medications to treat pain-related disorders. 12. 5-HT1A, 5-HT4, and 5-HT6 receptors have all been implicated in processes of learning and memory. Describe the experimental findings obtained from laboratory animals that implicate each receptor subtype, including the brain area(s) of receptor expression thought to be important for each subtype. 13. What are the sources of 5-HT in the GI tract, and why are pharmacologists interested in 5-HT from these sources? Include in your answer a discussion of the clinical relevance of gut 5-HT, including serotonergic medications that have been developed to treat GI disorders. Chapter 7 Review Questions: 1. What are the chemical reactions involved in ACh synthesis and breakdown? Include the names of the enzymes catalyzing each reaction. Which of these enzymes is used as a bio- chemical marker for cholinergic neurons? 2. Briefly discuss the factors that regulate the rate of ACh synthesis. Are there any current therapeutic interventions targeting the process of ACh synthesis? 3. By what mechanism is ACh taken up and stored in synaptic vesicles? Name a drug that interferes with vesicular ACh uptake and describe the effects of this drug on cholinergic transmission. 4. List and discuss the effects of toxins that either stimulate or inhibit ACh release. Include in your answer the therapeutic applications of toxins that inhibit the release of this neurotransmitter. 5. Unlike the monoamine transmitters discussed in previous chapters, there is no reuptake system for ACh itself. Describe the alternative mechanism that has evolved to help cholinergic neurons recycle/reutilize the transmitter. How do we know that this recycling process plays an important role in normal functioning of the nervous system? 6. List and discuss the various drugs that function as AChE inhibitors. In general, what is the effect of these drugs on cholinergic transmission? Include in your answer a consideration of the different consequences of peripheral versus central AChE inhibition and also the different consequences of reversible versus irreversible inhibition of the enzyme. 7. Describe the localization and functions of ACh in the peripheral nervous system. 8. Name and indicate the location of the principle cholinergic cell groups in the brain. Discuss the role of the BFCS in cognitive function, including relevant experimental findings. 9. Describe the molecular structure and signaling mechanism of nicotinic cholinergic receptors. 10. A nicotinic receptor complex can be in one of three different states: open, closed, and desensitized. Describe the properties of each state, including whether agonist is bound or not as well as the state of the receptor channel. 11. Discuss the molecular structure, signaling mechanisms, and localization of muscarinic cholinergic receptors in the brain. 12. Discuss the role of M5 muscarinic receptors in the control of dopaminergic cell firing and the rewarding and reinforcing effects of abused drugs. Include relevant experimental findings in your answer. 13. Describe the locations and functional roles of muscarinic receptors expressed by peripheral organs and glands. Include in your answer a discussion of the so-called dry mouth effect. 14. Discuss the role of pancreatic M3 muscarinic receptors in the control of insulin secretion and the involvement of this receptor subtype in the development of insulin resistance that accompanies the administration of certain anti-psychotic drugs. 15. What is meant by the terms parasympathomimetic and parasympatholytic agents? List examples of drugs belonging to these categories along with their physiological effects and medical or other uses.