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Chapter 1

Psychopharmacology Chapter 1 textbook notes

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PSY 214
Tara M Burke

Chapter 1: Principles of Psychopharmacology ­ Pharmacology: The scientific study of the actions of drugs and their effects on a living organism ­ Neuropharmacology: Concerned with drug-induced changes in the functioning of cells in the nervous system ­ Psychopharmacology: Emphasizes drug-induced changes in mood, thinking and behaviour ­ Neuropsychopharmacology: Identifies chemical substances that act on the nervous system to alter behaviour that is disturbed from injury, disease or environment ­ DrugAction: Molecular changes produced by a drug when it binds to a particular target site or receptor ­ Drug Effects: Alterations in physiological or psychological functions associated with a specific drug o The site of a drug action may be VERY different than the site of a drug effect. (i.e. taking morphine through the mouth, to help with leg pain) o Therapeutic Effects: Drug-receptor interaction creates a desired physical or behavioural change o Side Effect: All other effects (unwanted) o Specific Drug effects: Those based on physical and biochemical interactions of a drug with a target site in living tissue o Non-specific drug effect: Those that are not based on the chemical activity of a drug-recptor interaction, but on certain unique characteristics of the individual (i.e. present mood, expectations of drug effect etc) ­ Placebo effects and double blind experiments o Double Blind Experiment: Neither the patient nor the observer knows what treatment the patient has received Pharmacokinetic Factors Determining DrugAction 1. Routes of administration: How/ where drug is administered determines how quickly/ completely it is absorbed 2. Absorption and distribution: Because a drug rarely acts where it initially contacts the body, it must pass through a variety of cell membranes and enter the blood plasma, which transports the drug to virtually all cells of the body 3. Binding: Once in the blood plasma, some molecules move to tissue to bind to active target sites (receptors). While in the blood, a drug may also bind (depot binding) to plasma proteins or may be stored temporarily in bone or fat, where it is inactive 4. Inactivation: aka biotransformation, occurs as a result of metabolic processes in the liver. The amount of drug in the body at any time depends on the balance b/w absorption and inactivation. Thereore, inactivation influences the intensity and duration of the drug 5. Excretion: The liver metabolites are eliminated from the body with the urine or feces. Some drugs are excreted in an unaltered form by the kidneys Methods of DugAdministration influence the onset of drug action ­ Enteral: Use the Gastrointestinal tract, slow in onset, produce highly variable blood levels of drug (i.e. rectal and oral) ­ Parenteral: Do not use injection and topical administration ­ First-pass metabolism: Once the drug is swallowed, it is absorbed from the stomach and intestine into the blood and goes directly to the liver through general circulation. This can be beneficial because the liver can chemically alter by enzymes before entering to the heart, thus if there are any harmful chemicals/ toxins they may be removed/ altered by the liver ­ Metabolism: Of drugs will reduce the amount of available drugs before it reaches the general circulation ROUTE ADVANTAGES DISADVANTAGES Oral Convenient, relatively safe, Slow and highly variable and economical. absorption; subject to first- pass metabolism; less predictable blood levels Intravenus (IV) Suitable for suspensions and Overdose danger; cannot be oily vehicles.Absorption is readily reversed; requires rapid from solutions and is sterile needles and medical slow and sustained from technique suspensions. Intramuscular (IM) Slow and even absorption Localized irritation at site of injection; needs sterile equipment Subcutaneous (SC) Slow/ prolongued absorption Variable absorption depending on blood flow Inhalation Large absorption surface; very Irritation of nasal passages; rapid onset; no injection small particles inhaled may equipment needed damage lungs Topical Localized action and effects; May be absorbed into general easy to self-administer circulation Transdermal Controlled and prolonged Local irritation; useful only absorption for lipid soluble drugs Epidural Bypasses blood-brain barrier; Not reversible; needs trained very rapid effect on CNS anesthesiologist; possible nerve damage Special Injection Methods must be used for some drugs that act on nerve cells, because the blood-brain barrier prevents/ slows the passage of these drugs … ­ I.e. Epidural: Injected directly into the cerebral spinal fluid ­ Infusion Pump: implanted under the skin of the scalp, programmed to deliver a constant does of antibiotics into the cerebral ventricles; permits treatment of brain infection ­ Gene Therapy: Application of DNAto a particular site. Can be used to increase or block the expression of a gene (one difficulty is creating an appropriate gene delivery system ­ Psychoactive drugs: Have an affect on thinking, mood and behaviour ­ Phospholipids: complex lipid (fat) molecules which have a negatively charged region at one end and two uncharged lipid tails. What cell membranes are primarily made out of. ­ Passive Diffusion: how drugs with high lipid solubility move through cell membranes. They leave the water in the blood or stomach juices and the lipid layers of membranes. movement across the membranes is always in a direction from higher to lower concentration o Concentration Gradient: Larger the concentration difference on each side of the membrane, the more rapid the diffusion o Partition Coefficient: Away to predict the relative rate of movement of a drug through cell membranes is to estimate its lipid solubility using this coefficient. The ratio of the amount of drug dissolved in oil divided by its concentration in water is the oil/ water partition coefficient ­ Ionization: depends on 2 factors: the acidity/ pH of the solution and the pKa (weak acids ionize less readily in acidic environments) o Drugs that are highly charged in both acidic and basic environments are very poorly absorbed from the gastrointestinal tract and cannot be administered orally Drug Distribution is limited by selective barriers… ­ High concentrations of drugs will be found in the heart, brain, kidneys and liver ­ Blood-brain barrier: o Many substances found in the blood fluctuate significantly and would have disruptive effects on brain cell activity if materials were transferred freely b/w blood and the brain o Seperation b/w the brain capillaries and the brain/ CSF is called the Blood-Brain Barrier ­ Cerebrospinal fluid: clear liquid that fills space surrounding the brain and spinal cord o Manufactured by the cells of the choroid plexus (line the cerebral ventricles) ­ The job of blood vessels: deliver nutrients to cells & remove waste, the walls are made of endothelial cells with small gaps & large openings o Intercellular clefts: small gaps o Fenestrations: large openings o Pinocytotic vesicles: Type of vesicles that transport large molecules across the capillary wall o Tight Junctions: Connections b/w cells characterized by a fusing of adjoining cell membranes o Astrocytes: star-shaped cells of the nerve tissue that have numerous extensions and that modulate the chemical environment around neurons and metabolically assist neurons o Area Postrema: the "vommiting" center. Causes vomiting when toxic substances are detected in the blood o Median eminence: of the hypothalamus where capillary fenestrations in this region allow neurohormones manufactured by the hypothalamus to move into the blood travelling to the pituitary gland- which regulate hormone secretion Limited permeability of the blood-brian barrier is important in psychopharm because we need to know which drugs remain non-ionized at plasma pH and readily enter the CNS, and which drugs only circulate throughout the rest of the body. Placental Barrier ­ Asecond barrier found b/w the blood circulation of a pregnant mother and her unborn fetus; nutrients obtained from digestion of food, drugs, air etc are exchanged o Potentially damaging fetus effects: acute toxicity & teratogentic effects o Acute Toxicity: after exposure to high drug-blood level in mother (child can exibit symptoms of withdrawal afterwards) o Teratogens: drugs, exposure to Xrays, maternal infections are dependant on the timing of the exposure & can have neg effects Depot binding alters the magnitude & duration of drug action… ­ Drug Depots: Inactive sites where drugs accumulate. There is no biological effect from drugs binding at these sites, nor can they be metabolized ­ Depot binding: Type of drug interaction involving binding to an inactive site to bone or fat. It alter the magnitude and duration of drug action 1. reduces concentration of drug at its sites of action because only freely circulating drugs can pass across membranes 2. Because binding to fat & muscle is nonselective, many drugs w/ similar physiochemical characteristics compete with each other for these sites 3. Bound drug molecules can’t be altered by liver enzymes because the drug is not free to leave the blood to enter liver cells for metabolism o Depot binding often prolongs the time that the drug remains in the body 4. Depots may be responsible for terminating the action of a drug (i.e. rapid-acting CNS depressant thiopental) Biotransformation and elimination of drugs contribute to bioavailability… ­ Drugs are eliminated from the body through biotransformation (metabolism) and excretion of metabolites ­ Drug Clearance o First order kinetics: a constant fraction (50%) of the free drug in the blood is removed in each time interval o Half Life: the amount of time required for removal of 50% of the drug in blood. o Steady state plasma level: desired blood concentration of drug achieved when the absorption/ distribution phase is equal to the metabolism/ excretion phase o Zero-order Kinetics: drug molecules are cleared at a constant rate regardless of drug concentration; graphically represented as a straight line Biotra
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