Chapter 5 Psychopharmacology And New Drug Development


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Chapter 5 Psychopharmacology And New Drug Development

  1. 1. Psychopharmacology and New Drug Development Chapter 5
  2. 2. Characteristics of the User <ul><li>In this chapter we focus on how biological and psychological characteristics of the drug user and social and environmental factors influence the drug experience. Biological characteristics include: </li></ul><ul><li>Initial Sensitivity – The effect of a drug on a first-time user. Differences in sensitivity are thought to be determined genetically </li></ul><ul><li>Gender – The same dose of a drug administered to a man and a woman will generally have greater effects on the woman due to the higher percentage of body fat and therefore less body water in women. Thus the drug is more concentrated. Also, since some drugs bind to body fat, they are eliminated more slowly and remain active in the body longer </li></ul>
  3. 3. <ul><li>Weight – A heavier person has more blood and other fluids and thus, as stated above, there is less concentration of the drug with less drug effect </li></ul><ul><li>Age – Children and elderly can be more sensitive due to enzyme systems that metabolize drugs not fully developed in children or impaired in the elderly. As a result, there is an increased duration of drug action in both </li></ul><ul><li>Psychological characteristics include: </li></ul><ul><li>Sensation seeking – The need for varied, novel, and complex sensations and experiences and the willingness to take physical and social risks for the sake of such experience </li></ul><ul><li>Types of sensation seeking are: thrill and adventure seeking, experience seeking, disinhibition, and boredom susceptibility </li></ul>
  4. 4. <ul><li>Some studies have shown that the more sensation seeking a person is, the more he or she tends to use alcohol and drugs and to use more kinds of drugs </li></ul><ul><li>Stress Response Dampening (SRD) Model – Stress-prone people are more likely to use drugs such as alcohol and the benzodiazepines that have anxiety-reducing effects to cope with unwanted stress </li></ul><ul><li>Addictive Personality – The hypothesis of a personality structure common to all people with substance-use disorders. It implies that people with a particular personality make-up experience a unique reaction to alcohol and drugs, or they find them especially valuable in coping with life’s stressors </li></ul><ul><li>Though a common belief, research does not support the addictive personality hypothesis </li></ul>
  5. 5. <ul><li>Drug Expectancy – A person’s anticipation of or belief about what he or she will experience upon taking a drug. In some cases this can be more influential than the drug’s pharmacological action! </li></ul><ul><li>Expectancies are based on a person’s previous experience with a substance either directly (own use) or indirectly (instruction, friend’s use, media, etc.) </li></ul><ul><li>Studies have shown that the effects of alcohol, marijuana, tobacco, and alcohol and caffeine in combination can all be greatly influenced by drug expectancy </li></ul>
  6. 6. Social and Environmental Factors <ul><li>Environment – A broad term ranging from government laws about alcohol and drug availability, to the people and places that define the immediate drug use setting </li></ul><ul><li>Setting has a particularly important influence on the effects of alcohol, marijuana, and hallucinogenic drugs </li></ul><ul><li>With alcohol, studies showed that the number of people you drink with affects how you interpret the physiological changes that alcohol induces </li></ul><ul><li>This was also true for marijuana, though more so with lower doses of the drug </li></ul>
  7. 7. Tolerance <ul><li>Tolerance - Repeated administration of a given dose of a drug often results in reduced response to the drug. Types of tolerance include: </li></ul><ul><li>Dispositional Tolerance – An increase in the rate of metabolizing a drug as a result of its regular use. The user must consume greater quantities of the drug in order to maintain a certain level of it in his or her body </li></ul><ul><li>Functional Tolerance – The brain and other parts of the CNS become less sensitive to a drug’s effects, therefore the person experiences decreased behavioral effects of the drug as a result of its regular use </li></ul>
  8. 8. <ul><li>Acute Tolerance – A type of functional tolerance that occurs within a course of action of a single drug dose or first few doses of a drug. Acute tolerance is common for alcohol. For example, when the alcohol level is rising in the blood, there are greater drug effects than when the blood level is falling. Acute tolerance also develops rapidly with cocaine, resulting in decreased pleasurable effects with a second administration even when the same amount is taken </li></ul><ul><li>Protracted Tolerance – A type of functional tolerance that occurs over the course of two or more drug administrations but is most noticeable with regular or chronic drug administration, i.e., a person who once became intoxicated on 6 beers now requires 24 and heroin addicts who must use more of the drug now just to prevent withdrawal symptoms </li></ul>
  9. 9. <ul><li>Behavioral Tolerance – Adjustment of behavior through experience using a drug to compensate for its intoxicating effects, i.e., a person learns to compensate for the effects of alcohol on motor coordination by walking slowly or with a lower center of gravity to keep from falling – even if he or she is quite drunk </li></ul><ul><li>Cross-tolerance – Tolerance to a drug or drugs never taken that results from protracted tolerance to another drug or drugs. This can be a problem for anesthesiologists as people with high tolerances for alcohol or barbiturates may show such a tolerance to anesthetics </li></ul>
  10. 10. <ul><li>Tolerance may develop to some effects of a drug but not to others </li></ul><ul><li>Tolerance develops quickly to the sleep-inducing and euphoria effects of barbiturates, but not to the effects of impaired motor coordination and slowed reaction time. How might this be a problem? </li></ul><ul><li>Tolerance develops rapidly to the appetite-suppressant and euphoric effects of amphetamines, but not to the psychosis -like effects. Tolerances do not develop to the paradoxical attention-focusing and calming effects of Ritalin, an amphetamine used to treat Attention Deficit/Hyperactivity Disorder </li></ul>
  11. 11. <ul><li>Psychosis – A sever mental disorder whose symptoms include disorganized thinking and bizarre behavior </li></ul><ul><li>Attention Deficit / Hyperactivity Disorder – A disorder with features such as a greater than normal amount of activity, restlessness, difficulty concentrating or sustaining attention, and impulsivity </li></ul><ul><li>Paradoxical – Contrary to what is expected. A paradoxical drug effect is opposite in direction to what is expected based on the drug’s chemical structure </li></ul><ul><li>Reverse Tolerance (Sensitization) – Increased sensitivity to a drug with repeated use of it. Less research on this area than drug tolerance, though it has been reported for marijuana and cocaine </li></ul>
  12. 12. Explanations of Tolerance <ul><li>Cell Adaptation Theory – Also called the Adaptation-homeostasis Hypothesis, assumes that a drug acts on certain cells in the CNS causing them to “adapt” to the presence of the drug with repeated exposure to it. The adaptation allows the cells to maintain normal functioning, or homeostasis , and thus more of the drug is required to disrupt cell functioning </li></ul><ul><li>Homeostasis – A state of equilibrium or balance. Systems at homeostasis are stable; when homeostasis is disrupted, the system operates to restore it </li></ul>
  13. 13. <ul><li>Drug Compensatory Reactions and Learning involves the following: </li></ul><ul><li>When a drug is taken that disrupts the body’s homeostasis, the body counteracts with a reflex-like response opposite to the drug effect </li></ul><ul><li>With repeated use of a given drug dose, compensatory reactions become stronger (tolerance) </li></ul><ul><li>Learning through classical conditioning occurs as cues associated with drug taking (conditioned stimuli) become associated with drug actions and compensatory reactions </li></ul><ul><li>Over repeated pairings of drug taking and drug taking cues, just presenting the drug taking cues, may elicit a compensatory reaction </li></ul>
  14. 14. <ul><li>For example, presenting drug taking paraphernalia such as a syringe to IV heroin users may elicit strong urges to use caused from the biological reaction (compensation response) associated with drug deprivation (opposite to the drug effect) </li></ul><ul><li>Drug compensatory reactions seem to grow stronger with their repeated pairings with the same environment. Thus, the “sum” of the drug effect and counter effect depends on how often the same drug-taking conditions have occurred in the past </li></ul><ul><li>Extinction – When people are exposed to conditioned stimuli many times without the drug, compensatory effects such as discomfort and craving begin to dissipate. </li></ul>
  15. 15. Final Notes on Tolerance <ul><li>Once tolerance to a drug effect has developed, it is not irreversible . A period of abstinence from a drug increases the user’s sensitivity to drug effects that he or she may have become highly tolerant to in the past. If the user does not take into account the loss of tolerance, it could result in death by overdose if they try to use the same amount </li></ul><ul><li>Acute tolerance reverses in a short time, whereas protracted tolerance requires more extended abstinence to reverse. For example, a cocaine user may again experience the pleasurable effects of the drug for a given dose when taking the drug several days later, however, an alcoholic with protracted tolerance may have to abstain for years before his/her tolerance begins to reverse </li></ul>
  16. 16. Behavioral Pharmacology <ul><li>Behavioral Pharmacology – The specialty area of psychopharmacology that concentrates on drug use as a learned behavior. The premise is that drug use is learned behavior governed by the same principles as any other learned behavior. Drug us is “operant” or voluntary behavior </li></ul><ul><li>The basic principle of operant learning is that behavior is controlled by its consequences: reinforcement and punishment </li></ul><ul><li>Reinforcer – A consequence of a behavior that increases its future likelihood. Most effective when presented immediately following a behavior </li></ul>
  17. 17. <ul><li>Positive Reinforcement – Receipt of something results in an increase in behavior. Pleasant or desired drug effects is an obvious example </li></ul><ul><li>Negative Reinforcement – Behavior increases if it results in avoidance or escape from something, i.e., to escape withdrawal symptoms in drug addicted users or escape from anxiety or depression in early alcohol users. </li></ul><ul><li>Punisher – A consequence of a behavior that suppresses or decreases its future likelihood. Like reinforcement, most effective when it is immediate </li></ul>
  18. 18. <ul><li>Why do people continue to use drugs in the face of punishing consequences ? </li></ul><ul><ul><li>People use drugs for many reasons. One survey showed almost 50 reasons cited for just using alcohol ! </li></ul></ul><ul><ul><li>Drug use effects are immediate, especially when the drug is smoked or injected </li></ul></ul><ul><ul><li>Some negative consequences such as social, family, and health problems occur some time after drug use </li></ul></ul><ul><ul><li>Drug effects are usually certain, where as many consequences, i.e., arrest, health problems, are not </li></ul></ul>
  19. 19. Drug Research <ul><li>Self-administration Study – Involves testing whether research participants will “give themselves” a drug to assess drugs as reinforcers by using drug access as a consequence of behavior. Animals are trained to perform a behavior such as pressing a lever by following the lever press with access to drugs </li></ul><ul><li>Drug Discrimination Study – Research procedure that primarily concerns the differentiation of drug effects. By incorporating placebos into the study design, animals can learn to discriminate between drug and nondrug states, and discriminate between different doses of a drug and among different drugs. Such techniques make it possible to classify experimental drugs according to their “subjective” effects even before they have been administered to humans </li></ul>
  20. 20. <ul><li>Conflict Paradigm – A research procedure that concerns the effects of a drug on a behavior that has a history of both reinforcement and punishment. An animal may be trained to press a lever to get food as a reinforcer and after this is learned, an electric shock as punisher is added. This arrangement of consequences typically suppresses the behavior in question except with the class of antianxiety drugs called the benzodiazepines. The assumption is that such drugs reduce the perception of anxiety that would normally produce a conflict </li></ul>
  21. 21. Animal Models and Human Drug Use <ul><li>Relevance of findings about drugs based on nonhuman animals has remarkably good generalizability to humans </li></ul><ul><li>Generalizable – Applicability of a research finding from one setting or group of research participants to others </li></ul><ul><li>Animal studies have increased our knowledge without risk to humans </li></ul><ul><li>Some causal relationships between drugs and functioning in parts of the human body such as the brain could not have been established without animal studies </li></ul>
  22. 22. <ul><li>Causal Relationship – A relationship between variables in which changes in a second variable are due directly to changes in a first variable </li></ul><ul><li>Because some animal rights activists argue that researchers are unnecessarily cruel to animals, animal research has become tightly regulated. Organizations such as the Institutional Animal Care and Use Committee (IACUC) make unannounced site visits to laboratories to ensure the research conforms to ethical standards and steps are taken to minimize animal discomfort. If regulations are not being followed, research projects can be shut down. </li></ul>
  23. 23. Human Behavioral Pharmacology <ul><li>Nuremberg Code – Set of ethical guidelines to govern scientific research </li></ul><ul><li>Control Group – The reference or comparison group in an experiment. The control group does not receive the experimental manipulation or intervention whose effect is being tested </li></ul><ul><li>Placebo Control – A type of control originating in drug research. Placebo subjects have the same makeup and are treated exactly like a group of subjects who receive a drug, except that placebo subjects receive a chemically inactive substance </li></ul>
  24. 24. <ul><li>“ Double Blind” Method – Neither the experimenter nor the subject knows which experimental condition the subject is in </li></ul><ul><li>Group Design – A type of experimental design in which groups (as compared to individual cases) of subjects are compared to establish experimental findings </li></ul>
  25. 25. New Drug Development <ul><li>Though your text is concerned mostly with nonmedical drug use, an understanding of how legal drugs are developed is important because: </li></ul><ul><li>Many legal drugs are used in a way not prescribed by a physician </li></ul><ul><li>Medical drug use is more prevalent among adults than is nonmedical use </li></ul><ul><li>Legal drug development and distribution make up a major economic force in the United States </li></ul>
  26. 26. <ul><li>The “discovery” of new drugs generally occurs in one of three ways: </li></ul><ul><li>Rediscovery of folk usages of naturally occurring products </li></ul><ul><li>Accidental observation of an unexpected drug effect </li></ul><ul><li>Synthesizing of known or novel compounds </li></ul><ul><li>However, the procedure for testing and marketing a drug is fairly standard </li></ul>
  27. 27. Stages in the Testing and Marketing of a Drug (Table 5.1) <ul><li>Belief that a particular compound has clinical value </li></ul><ul><li>Animal studies </li></ul><ul><li>Experimental studies with healthy volunteers </li></ul><ul><li>Experimental studies with clinical patients, rigorously conducted </li></ul><ul><li>Broader clinical trials </li></ul><ul><li>Licensing and marketing approval </li></ul><ul><li>After marketing evaluation of clinical use, particularly short-term and long-term effects </li></ul>
  28. 28. Steps in the Development of a New Drug (Table 5.2) <ul><li>Initial synthesis and preclinical studies 1-3 years </li></ul><ul><li>Phase 1 clinical trials: to establish safety, 2-10 years </li></ul><ul><li>up to 50 normal volunteers </li></ul><ul><li>Phase 2 clinical trials: controlled studies in </li></ul><ul><li>patients with a target disease, 50-200 patients </li></ul><ul><li>Phase 3 clinical trials: controlled and open studies </li></ul><ul><li>of 1,000 or more patients monitored for drug effectiveness </li></ul><ul><li>and for adverse reactions; data used for determining </li></ul><ul><li>doses and labeling requirements </li></ul><ul><li>FDA review/approval 1-2 years </li></ul><ul><li>Post-marketing testing 1-2 years </li></ul>
  29. 29. <ul><li>In 2003, the U.S. Pharmaceutical industry spent $25.3 billion on developing new drugs </li></ul><ul><li>For every drug that makes it to market approval, 5,000-10,000 drugs have been screened, 250 enter clinical testing, and 5 enter clinical trials </li></ul><ul><li>Concorde study – Conducted in 1993 in response to the FDA’s decision to shorten the drug approval process for AZT. Found that AZT may show benefits in slowing the progression of AIDS during the first several months but not in the longer term. Suggests the clinical trials process will continue to take a substantial period </li></ul><ul><li>Chemical Name – The name given to a drug that represents its chemical structure </li></ul>
  30. 30. <ul><li>Brand Name – The commercial name given to a drug by its manufacturer </li></ul><ul><li>Generic Name – The general name given to a drug that is shorter (and easier for most people to say) than its chemical name </li></ul><ul><li>Generic Drugs – Drugs deemed equivalent in effect to their brand name counterparts by the FDA (not chemical copies) usually sold at a lower price and thus account for 50% of prescription drugs dispensed. </li></ul><ul><li>When a drug is approved, the drug company that developed it is granted sole rights to market it for 17 years. Generics can only be sold by competing companies after that time </li></ul><ul><li>Consumers save $8 billion to $10 billion at pharmacies using generics each year </li></ul>
  31. 31. <ul><li>OH NO ! IT’S TEST TIME ! </li></ul>