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PSYB21H3 (18)
Chapter 7

Chapter 7 Neuropsychology.docx

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University of Toronto Scarborough
Steve Joordens

Chapter 7 - Psychopharmacology is the study of how drugs affect the nervous system and behavior - A drug is a chemical compound that is administered to bring a desired change in the body - Psychoactive drugs are substances that act to alter mood, thought, or behavior and are used to manage neuropsychological illness (substance abuse) - To be effective, psychoactive drug has to reach target in nervous system. The way a drug passes through body to reach target is the route of administration - Not all drugs can penetrate digestive tract or withstand gastric secretions. Fewer barriers between a drug and its target if drug is inhaled rather than swallowed - Fewest obstacles faced if it is injected into brain - To reach bloodstream, drug must be absorbed through lining of stomach or small intestine - Drug: weak acid absorbed across stomach lining; weak base cannot be absorbed until it passes intestine (digestive juices could have it destroyed) - Blood has high water concentration so drug must be hydrophilic to mix with blood. - Hydrophobic substance will be blocked from entering bloodstream and is diluted if makes way into circulatory system - To reach neurological target, drug must travel from blood into extracellular fluid. Must be small enough and can still be further diluted and destroyed by metabolic processes in the cell. - Drugs metabolized especially in kidneys, liver and bile - There is a single later of endothelial cells that compose brain capilliaries - They are surrounded by the end feet of astrocyte glial cells. Glial’s main function is to provide a route for the exchange of food and waste between capillaries and the brain’s extracellular fluid and from there to other cells. - Astrocytes may also play a role in maintaining tight junctions between endothelial cells and in making capillaries dilate to increase blood flow to brain (in places neurons are more active). These substances can pass through the endothelial cells’ junctions in the body but not in the brain - The building blocks of proteins (oxygen, glucose and amino acids) travel from the blood to brain cells . Two ways in which substances cross the blood brain barrier: 1. Small molecules such as oxygen and carbon dioxide which are not ionized and so are fat soluble can pass through capillary wall 2. Molecules of glucose, amino acids and other nutrients can be carried across the capillary by active transport systems which are pumps. - Pituitary gland secretes many hormones, and their release is triggered by other hormones carried to the pituitary gland by the blood. The absence of blood brain barrier at the area postrema of the lower brainstem allows toxic substances in the blood to trigger a vomiting response. - The pineal gland also lacks barrier and is therefore open to the hormones that modulate the day night cycles Drug Routes and Dosage - The most effective drugs must consist of small molecules, weakly acidic, water or fat soluble, potent in small amounts and not easily degraded. - Inhaling or injecting psychoactive drug is quickest, avoids obstacle of the stomach Drug Actions in Synapses Steps in Synaptic Transmission - Seven major events that contribute to synaptic neurotransmission: 1. Synthesis of the neurotransmitter can take place in the cell body, axon, or terminal. The neurotransmitter may then be 2. Stored in storage granules or in vesicles until it is 3. Released from the terminal’s presynaptic membrane to 4. Act on a receptor embedded in the postsynaptic membrane. 5. Deactivation of excess or 6. Reuptake 7. Degradation/reuse and remove unneeded byproducts - Drugs that increase the effectiveness of neurotransmission are called agonists, those that decrease its effectiveness are called antagonists. Examples of Drug Action: An Ach Synapse - Black widow spider venom is an agonist. - Botulinum toxin is an antagonist and blocks release of ach. - Nicotine acts as an agonist, fits into ach receptors binding sites. Stimulates receptors - Curare acts as antagonist, blocking receptors. - Physostigmine and organophosphates block inactivation. Small doses of physostigmine are used to treat myasthenia gravis, in which muscle receptors are less than normally responsive to Ach. Organophospates bind irreversibly to Ach. Classification of Psychoactive Drugs - Class 1. Sedative Hypnotics and Antianxiety agents: at low doses they reduce anxiety, medium doses they tranquilize and at high doses they induce coma and kill. Alchol, barbiturates and benzodiazepines. All sedative hypnotic drugs may act by influencing a receptor, GABA which controls chloride channels and excitation of the receptor produces influx of Cl- ions. This increases negative charges inside the cell, hyperpolarizing the membrane and making it less likely to propagate action potential. - GABA produces inhibitory effect by decreasing a neuron’s firing rate. - The sedative hypnotic site is the site where alcohol and barbiturates works and it increases Cl ions and produces same effect as GABA. - Anti anxiety site enhances the binding of GABA to its receptors, but GABA concentrations are never excessive because it is very quickly reabsorbed. - Class 2. Antipsychotic Agents: major Tranquilizers or neuroleptics are used to treat psychosis. One effect that all have in common is an immediate reduction of motor activitiy which helps to alleviate the excessive agitation of some patients. - They block the D2 receptor. - Amphetamine might cause schiz by blocking the reuptake of dopamine. - Class 3. Antidepressants: three different types of drugs have antidepressant effects, monoamine oxidase inhibitors, tricyclic antidepressants and second generation antidepressants (atypical). - Antidepressants are thought to act by improving chemical transmission in serotonin, noradrenaline, histamine, and acetylcholine synapses and perhaps dopamine too. - Monoamine oxidase is an enzyme thought to break down serotonin within the axon terminal. - The second generation antidepressants are thought to be especially selective in blocking serotonin reuptake. - Brains of suicide victims had smaller orbital frontal cortex and amygdale. These brain regions contribute to decisions. - Class 4. Mood Stabilizers: Lithium may increase the synaptic release of serotonin, and valproate may stimulate GABA activity. - Mood stabilizers mute the intensity of one pole of the disorder thus making the other pole less likely to reoccur. - Class 5. Narcotic Analgesics: These drugs have both sleep inducing and pain relieving properties. Many are derived from opium (codeine and morphine). - Heroin is synthesized from morphine. It is more fa
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