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PSYC 2920: Drugs and Behaviour

Lecture 2. PSYC 2920: Drugs and Behaviour. Some Basic Pharmacology. Inhalation of Gases The Lungs Extremely efficient gas exchange system Oxygen Carbon Dioxide Isoflurane vs. Halothane Lower blood and lipid solubility Lower rate of metabolic breakdown.

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PSYC 2920: Drugs and Behaviour

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  1. Lecture 2 PSYC 2920: Drugs and Behaviour

  2. Some Basic Pharmacology • Inhalation of Gases • The Lungs • Extremely efficient gas exchange system • Oxygen • Carbon Dioxide • Isoflurane vs. Halothane • Lower blood and lipid solubility • Lower rate of metabolic breakdown

  3. Percentage of inhaled dose that is metabolized

  4. Some Basic Pharmacology Inhalation of Gases • The circulatory system. The heart circulates blood returning from the body via the veins and the lungs and then sends it out via arteries to the body and the brain.

  5. Some Basic Pharmacology • Inhalation of Smoke and Solids • Burning of dried plant material • i.e. tobacco • Sniffing of drugs • Intranasal administration • i.e. cocaine

  6. Some Basic Pharmacology • Oral Administration • Peroral (p.o.) • Buccal membranes • Convenient route of administration for over the counter drugs

  7. Some Basic Pharmacology • The Digestive System

  8. Some Basic Pharmacology • The Digestive System • Lipid Bilayer • A cross-section of a typical membrane • The Digestive System • - Lipid Solubility • - Olive oil partition coefficient • - Ions are not lipid soluble. • - pKa and the acidic or basic nature of the drug determines degree of ionization

  9. Some Basic Pharmacology • Transdermal Administration • Absorbed through the skin • Epidermis • Outer layer of the skin • Keratin • E.g. Nicotine patch • Not practical in furry small rodents but pharmacokinetics can be simulated to some extent with the use of osmotic minipumps

  10. Some Basic Pharmacology • Distribution of Drugs • Lipid Solubility • Distribution to the Central Nervous System • Blood-Brain Barrier • Active and Passive Transport Across Membranes (particularly important for non-lipid soluble drugs) • Passive Transport Mechanism • Active Transport Mechanism • Protein Binding • The Placental Barrier • Intermediary organ between the fetus and the wall of the uterus • Does very little filtering (i.e. allows 75-80% of substances through from mother’s blood)

  11. Some Basic Pharmacology • Excretion and Metabolism • The Kidneys • Maintain balance between water and salt in the body • The Nephron • Long tube • Bowman’s Capsule • Cuplike structure • Are not effective in eliminating lipid soluble drugs that are readily reabsorbed back into the flood stream through passive diffusion

  12. Some Basic Pharmacology The Kidneys

  13. Some Basic Pharmacology Excretion and Metabolism The Liver Enzymes catalyst e.g. Alcohol Dehydrogenase Metabolism Restructuring molecules Metabolites Vary in terms of physiological effects Detoxification The metabolic process

  14. Some Basic Pharmacology First-Pass Metabolism Any drug absorbed from the digestive system will pass through the liver before going anywhere else in the body. Subjected to liver enzymes Rate of excretion Half-life

  15. Some Basic Pharmacology First-Pass Metabolism Rate of Excretion (Half Life) • The top panel shows a typical excretion curve for a drug like nicotine, which has a half-life of about 30 minutes. The bottom panel shows the excretion function for alcohol, which is excreted at a constant rate (about 15 mg/100 ml of blood per hour). Because the excretion function for alcohol is a straight line, the concept of half-life does not apply.

  16. Some Basic Pharmacology Factors That Alter Drug Metabolism Stimulation of Enzyme Systems Metabolism of Alcohol Acetaldehyde Alcohol Dehydrogenase Aldehyde Dehydrogenase Enzyme induction Responsible for development of metabolic tolerance

  17. Some Basic Pharmacology • Steps in the Metabolism of Alcohol

  18. Some Basic Pharmacology Factors That Alter Drug Metabolism Depression of Enzyme Systems Metabolism of Alcohol Disulfiram (Antabuse) Sometimes used to prevent drinking Cytochrome P4503A4 Grapefruit juice Busparone, lovastatin, simvastatin, slidenafil

  19. Some Basic Pharmacology Factors That Alter Drug Metabolism Age Young not able to metabolize the dose of an adult Theophylline Species rats vs. humans Rat liver contains lower proportion of alcohol dehydrogenase per unit weight vs. human liver BUT the rat liver is substantially larger relative to body size

  20. Effect of age and route of administration on BALs in Wistar rats

  21. Some Basic Pharmacology Combining Absorption and Excretion Functions Time Course • A theoretical absorption curve, assuming no excretion; a theoretical excretion curve, assuming instantaneous absorption and distribution; and a third line showing the resultant of these two theoretical processes. The resultant curve is typical of the time course for blood level of most drugs.

  22. Some Basic Pharmacology Combining Absorption and Excretion Functions Time Course • The time courses for blood levels of a drug given by different routes of administration.

  23. Some Basic Pharmacology • Therapeutic Window • The therapeutic window is a range of blood concentrations of a medicine above a level that is ineffective (therapeutic level) and a level that has toxic side effects (toxic level).

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