Principles Of Psychopharmacology PDF Lecture Notes

10/17/24 Principles of Psychopharmacology Outline: Pharmacokinetics: what effect has the body on the drug The process by which drugs are Absorbed, Distributed within the body, Metab...

10/17/24 Principles of Psychopharmacology Outline: Pharmacokinetics: what effect has the body on the drug The process by which drugs are Absorbed, Distributed within the body, Metabolized, and Excreted (ADME).. Pharmacodynamics: what effect has the drug on the body Drug action at the Synapse Agonists and Antagonists Copyright © 2011 Pearson Education, Inc. All rights reserved. 1 1 Pharmacokinetics Several factors determine the rate at which a drug in the bloodstream reaches sites of action within the brain. The most important is lipid solubility. The blood–brain barrier is a barrier only for water-soluble molecules. Molecules that are soluble in lipids pass through the cells that line the capillaries in the central nervous system, and they rapidly distribute themselves throughout the brain. 2 2 1  10/17/24 The blood–brain barrier (BBB) is a separation of circulating blood from the brain cerebrospinal fluid (CSF) Kolb & Whish aw, An Introdu http://www.youtube.com/watch?v=_e60_4ZV0zs ction to Brain and Behavi 3 or, Third Edition - Chapte r8 Principles for passing the Blood brain barrier (BBB) Small, uncharged molecules are fat soluble and can freely cross the BBB Larger, charged molecules (e.g., glucose, amino acids) must be actively transported across the BBB Difficulty developing drugs for the brain: they must be small and uncharged or they must be structurally similar to a substance that already has an active transporter that allows it to pass the BBB Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 4 2  10/17/24 Dose-response curve: Plots the magnitude of the effect of a drug as a function of the amount of the drug administered. 5 5 Therapeutic index The ratio between the dose that produces the desired effect in 50% of the animals and the dose that produces toxic effects in 50% of the animals. 6 6 3  10/17/24 Drugs vary widely in their effectiveness The effects of a small dose of a relatively effective drug can equal or exceed the effects of larger amounts of a relatively ineffective drug. The best way to measure the effectiveness of a drug is to plot a dose-response curve. 7 7 The method administration affects the time-course (Pharmacokinetics) of drug action 8 8 4  10/17/24 Methods of drug administration – Intravenous (IV) injection Injection of a substance directly into a vein. – Intramuscular (IM) injection Injection of a substance into a muscle. – Oral administration Administration of a substance into the mouth, so it is swallowed. 9 9 Methods of drug administration –Subcutaneous (SC) injection Injection of a substance into the space beneath the skin. –Oral administration Administration of a substance into the mouth, so it is swallowed. 10 10 5  10/17/24 Methods of drug administration – Inhalation Administration of a vaporous substance into the lungs. – Topical administration Administration of a substance absorbed through the skin. 11 11 Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 12 6  10/17/24 Possible Effects of Repeated Administration – Tolerance A decrease in the effectiveness of a drug that is administered repeatedly. – Sensitization An increase in the effectiveness of a drug that is administered repeatedly. – 13 13 Tolerance: decrease in response to a drug with the repeated use – Pharmacodynamic (Metabolic) tolerance Increase in number of enzymes used to break down substance – Pharmacodynamic (cellular, synaptic) tolerance Activities of brain cells adjust to minimize effects of the substance – Behavioral (learned) tolerance People learn to cope with being intoxicated 14 7  10/17/24 15 Withdrawal symptom: the appearance of symptoms opposite to those produced by a drug when the drug is administered repeatedly and then suddenly no longer taken. 16 8  10/17/24 Addiction and Dependence Withdrawal Symptoms Physical and psychological behaviors displayed by an addict when drug use ends Examples: muscle aches and cramps, anxiety attacks, sweating, nausea, convulsions, death – Time-course Withdrawal symptoms from alcohol and morphine start within several hours of last dose and intensify over several days before subsiding https://www.yalemedicine.org/news/how-an-addicted-brain-works https://my.clevelandclinic.org/health/diseases/16652-drug-addiction-substance-use-disorder-sud 17 Principles of Psychopharmacology – Placebo Effects Behavioral effects of drugs in humans induced by expectation – Placebo An inert substance given to an organism in lieu of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug. – https://www.youtube.com/watch?v=yfRVCaA5o18 18 18 9  10/17/24 Principles of Psychopharmacology Outline: Pharmacokinetics: what effect has the body on the drug The process by which drugs are Absorbed, Distributed within the body, Metabolized, and Excreted (ADME).. Pharmacodynamics: what effect has the drug on the body Drug action at the Synapse Agonists and Antagonists Copyright © 2011 Pearson Education, Inc. All rights reserved. 19 19 One can classify a drug by its most pronounced behavioral or psychoactive effect 1. Antianxiety Agents and Sedative Hypnotics 2. Antipsychotic Agents 3. Antidepressants 4. Mood Stabilizers 5. Opioid Analgesics (pain relieve) 6. Psychomotor Stimulants 7. Psychedelic and Hallucinogen Stimulants 20 10  10/17/24 Most psychoactive drugs exert their effects by influencing chemical reactions at synapses Agonist – Substance that INCREASES the effectiveness of a neurotransmitter Antagonist – Substance that DECREASES the effectiveness of a neurotransmitter Kolb & Whish aw, An Introdu ction to Brain and Behavi 21 or, Third Edition - Chapte r8 Drug Actions at the Synapse Neurotransmitter Production – Manipulating the synthesis of a neurotransmitter will affect the amount available for release Neurotransmitter Storage – Interfering with the storage of a neurotransmitters in vesicles within a neuron Neurotransmitter Release – Drugs can modify the release of a neurotransmitter in response to the arrival of an action potential 22 11  10/17/24 Drugs can alter chemical processes at any of seven major stages of synaptic transmission 1. Synthesis 2. Storage 3. Release 4. Receptor Interaction 5. Inactivation 6. Reuptake 7. Degradation Kolb & Whish aw, An Introdu ction to Brain and Behavi 23 or, Third Edition - Chapte r8 Class I: Antianxiety Agents and Sedative Hypnotics Barbituates – Produce sedation and sleep (e.g., alcohol) – Can also produce general anesthesia, coma, and death Benzodiazepines – Minor tranquilizers – Antianxiety agents Drugs that reduce anxiety (e.g., Valium) Often used for temporary purposes (e.g., coping with stress due to a death in family) Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 24 12  10/17/24 Alcohol, benzodiazepines, and barbiturates act as sedatives by potentiating the effects of GABA at the GABAA receptor. 25 Class I: Antianxiety Agents and Sedative Hypnotics The GABAA Receptor – Excitation produces an influx of chloride (Cl-) ions, which hyperpolarizes the neuron The GABAA Receptor Has Two Sites: – Sedative-Hypnotic Site: Alcohol and barbituates Directly influences Cl- influx – Antianxiety Site: Benzodiazepines Enhances binding effects of GABA Effect is dependent upon amount of GABA present 26 13  10/17/24 Class II: Antipsychotic Agents Psychosis: characterized by hallucinations (false sensory perceptions) or delusions (false beliefs). Major Tranquilizer (Neuroleptic) – Drug that blocks the D2 dopamine receptor – Used mainly for treating schizophrenia – Mechanism of therapeutic action is still not understood Immediate effect of reducing motor activity After short period of use, there is a reduction in the symptoms of schizophrenia Negative side effect: Dyskinesia (impaired control of movement) Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 27 Figure 8.8 Trends in resident care Kolb/Whishaw: Brain and Behavior, Third Edition Copyright © 2011 by Worth Publishers 28 14  10/17/24 Drug Interactions at the Dopaminergic Synapse 29 Dopamine is active in many brain regions Dopaminergic pathways: Nigrostriatal system: Movement control Mesolimbic system: Emotion, Memory, ‘Reward’ system Mesocortical system: Planning, Decision making http://www.youtube.com/watch?v=k9gtcuZL YTI&feature=channel 30 15  10/17/24 Class III: Antidepressants Three Classes of Antidepressants: 1. Monoamine Oxidase (MAO) Inhibitors – Block the enzyme MAO from degrading neurotransmitters such as dopamine, noradrenaline, and serotonin 2. First-generation antidepressants that block serotonin reuptake transporter proteins 3. Second-Generation Antidepressants – Action is similar to first-generation antidepressants, but is more selective. – Selective Serotonin Reuptake Inhibitors (SSRIs): block the reuptake of serotonin into the presynaptic terminal Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 31 Class III: Antidepressants Major Depression – Mood disorder characterized by Prolonged feelings of worthlessness and guilt Disruption of normal eating habits Sleep disturbances General slowing of behavior Frequent thoughts of suicide – Common: ~6% of adult population – Twice as common in women as in men Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 32 16  10/17/24 Drug Interactions at the Serotonergic Synapse 33 Drug Interactions at the Serotonergic Synapse 34 17  10/17/24 Serotonin (5-HT): thought to play a role in the regulation of mood, the control of eating, sleep, dreaming, and arousal 35 Class III: Antidepressants Although antidepressants affect synapses very quickly, their antidepressive actions take weeks to develop Prozac, an SSRI, enhances neurogenesis in the hippocampus – Part of therapeutic effect? ~20% of patients with depression fail to respond to antidepressants, suggesting that depression can likely have many causes Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 36 18  10/17/24 Class IV: Mood Stabilizers Used to treat bipolar disorder (manic-depressive illness) Mutes the intensity of one pole of the disorder, thus making the other pole less likely to recur Mechanism is not well understood – Lithium may increase serotonin release – Valproate may stimulate GABA activity Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 37 Class V: Opioid Analgesics Opioid Analgesic – Drugs with sleep-inducing (narcotic) and pain-relieving (analgesic) properties – Opiates: Many of these drugs are derived from opium, an extract of the seeds of the opium poppy – Substances derived from the poppy plant Codeine: ingredient of cough medicines and pain relievers Morphine: powerful pain reliever Heroin Opiates are addictive 38 19  10/17/24 Class V: Opioid Analgesics Nalorphine and Naxolone – Opiate antagonists that block the effects of morphine Heroin – An opiate drug synthesized from morphine – More fat soluble and penetrates the BBB faster than morphine, therefore it produces very rapid pain relief Opiates are potentially addictive Endorphin – Peptide hormone that acts as a neurotransmitter and may be associated with analgesia and well being. – Mimicked by opiate drugs such as morphine, heroin, opium, and codeine – Runners ‘high’ an evolutionary trait of hunters? Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 39 Class VI: Psychomotor Stimulants General Stimulants Drugs that cause a general increase in the metabolic activity of cells Caffeine – Increase in cAMP leads to an increase in glucose production within cells, which makes more energy available and allows for higher rates of cellular activity Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 40 20  10/17/24 Class VI: Psychomotor Stimulants Behavioral Stimulants Increase motor behavior and elevate a person’s mood and level of alertness – Cocaine – Obtained from the leaves of the coca plant – Addictive – Blocks dopamine reuptake – Derivates such as Novocaine are used as local anesthetics – Risks: Symptoms of acute psychosis are very similar to those of the acute phase of schizophrenia 41 Class VI: Psychomotor Stimulants Amphetamine – Dopamine agonist: releases dopamine into the synapse and blocks the reuptake of dopamine, as well – Some Uses: Initially an asthma treatment Study aid Improvement of alertness and productivity Weight-loss aid Risks: Symptoms of acute psychosis are very similar to those of the acute phase of schizophrenia Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 42 21  10/17/24 Class VII: Psychedelic and Hallucinogenic Stimulants Psychedelic Drugs Alter sensory perception and cognitive processes and can produce hallucinations Four main types – Acetylcholine psychedelics – Norepinephrine psychedelics (e.g., mescaline) – Serotonin psychedelics (e.g., LSD, psilocybin) – Tetrahydrocannabinol (THC): active ingredient in marijuana Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 43 Factors Influencing Individual Responses to Drugs Addiction and Dependence Substance Abuse – Use of a drug for the psychological and behavioral changes that it produces aside from its therapeutic effects Addiction (a.k.a. substance dependence) – Desire for a drug manifested by frequent use of the drug, leading to the development of physical dependence in addition to abuse – Often associated with tolerance and unpleasant, sometimes dangerous, withdrawal symptoms upon cessation of drug use Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 44 22  10/17/24 Factors Influencing Individual Responses to Drugs Sex Differences in Addiction Females twice as sensitive to drugs on average – Smaller body size, hormonal differences Females only slightly less likely to become addicted to some drugs Females more likely to abuse certain drugs – Nicotine, cocaine, amphetamine, opioids, cannabinoids, caffeine, PCP Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 45 Hormones Hierarchical Control of Hormones Hormones affect almost every neuron in the brain Hormones Neurons Genes Proteins Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 46 23  10/17/24 Classes and Functions of Hormones Classifying Hormones by Structure Steroid Hormones – Fat-soluble chemical messenger synthesized from cholesterol – Examples: gonadal (sex) hormones, thyroid Peptide Hormones – Chemical messenger synthesized by cellular DNA that acts to affect the target cell’s physiology – Examples: insulin, growth hormone Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 47 Classes and Functions of Hormones Classifying Hormones by Function Homeostatic hormones – Maintain a state of internal metabolic balance and regulation of physiological systems Gonadal (sex) hormones – Control reproductive functions; sexual development and behavior Glucocorticoids – Secreted in times of stress; important in protein and carbohydrate metabolism Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 48 24  10/17/24 Stress Response: The physiological and behavioral arousal and any attempt to reduce the stress Kolb & Whishaw, An https://www.youtube.com/watch?v=BIfK0L8xDP0 Introduction to Brain and Behavior, Third Edition - Chapter 8 49 Ending a Stress Response Normally, stress responses are brief Stress responses are turned on and off in the brain Sapolsky (2005) – Hippocampus is involved in turning off the stress response – Too much cortisol will damage neurons in the hippocampus – Vicious cycle involving prolonged stress, cortisol levels, and hippocampal functioning Kolb & Whishaw, An Introduction to Brain and Behavior, Third Edition - Chapter 8 50 25