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Transcript
Lecture 4 Outline – Administration, Absorption, and Fate of Drugs PSY432 Spring, 2006 I. Three factors, other than chemical structure, affecting the action of drugs A. Rate of accumulation B. Concentration of the drug at the site of action C. Duration of the drugs contact at the site of action II. Psychokinetics – movement of drugs within a biological system A. Routes of Administration of drugs – getting the drug into the body 1. Enteral routes – oral or anal a. Swallowing pills, capsules, etc. drug absorbed by blood vessels in the stomach and small intestines b. Suppositories drug absorbed vessels of the large intestines c. Absorption slower than other routes d. Great variability stomach contents can influence rate of absorption e. Hostile acid environment influences absorption rate f. Some people can’t take pills or won’t take pills 2. Parenteral Routes a. Intravenous (IV) injection – injection directly into a blood vein 1) Advantage: fastest way to get drug into blood stream 2) Advantage: most accurate dosage – all the drug gets into blood stream 3) Disadvantage: chance of infection if conditions not sterile 4) Disadvantage: no way to retrieve drug in the case of allergic or toxic reaction b. Intramuscular injection - injection into muscle mass 1) Advantage: fast, but not as fast as IV 2) Advantage: safer than IV; more time to react to bad reactions 3) Disadvantage: possible infection ; slower than IV c. Subcutaneous injection – injection or implant placed under skin for slow dispersal d. Injection directly into the nervous system – mostly for control of pain 1) CNS –block signals in the spinal cord - very quick 2) PNS – local anesthesia (e.g. novacaine) e. Pulmonary route – inhalation into lungs d. Topical route – placing drug on surface of body 1) Sublingual – under the tongue 2) Intranasal – absorption through the mucous membrane of the nose 3) Skin – rubbed on skin use of skin patches B. Absorption of Drugs – getting the drug into the bloodstream (except IV) 1. Concentration gradient – chemicals flow from areas of high concentration to areas of low concentration 2. Drug needs to be absorbed into the bloodstream and exit the bloodstream a. capillaries of bloodstream semi-permeable b. cells of capillaries in the brain tightly packed – drug has to move through the cells to exit c. Blood-brain barrier made up of glial cells (astrocytes) seal capillary walls 3. Drug has to be absorbed into neurons a. drug has to absorbed by glial cells b. pass from glial cells into neurons 4. Blood-brain barrier protects the brain from infection and our own immune system 5. Movement across semi-permeable membranes II. III. a. intracellular fluid, extracellular fluid, blood fluid b. fluids move back and forth across cell membranes c. some drugs can move across membranes – concentration gradient d. solubility – water or lipid C. Distribution of Drugs 1. Drugs evenly distributed throughout bloodstream 2. Importance of drug concentration 3. Result of a drugs affinity for body tissues and other molecules 4. Effects of Binding to large proteins 5. Increasing speed of slow acting drugs a. increase dosage b. administer 2nd drug with greater affinity for large proteins, etc. 6. Unintentional drug interactions 7. Therapeutic window 8. Where in the body can drugs be stored? 9. Initial effect of a drug and secondary effect of a drug 10. High solubility versus low solubility – effects of Pentathal and Pentobarbital Fate of Drugs - Removing drugs from the body A. Heavy metals very difficult to remove B. Elimination by exhaled breath 1. Drugs in the bloodstream into lungs because of chemical gradient 2. Breath analyzer tests for alcohol C. Drugs also eliminated by perspiration, saliva and feces Most elimination of drugs and other substances done by liver and kidney A. Liver 1. Largest organ in body after the skin 2. Modofies toxins into less harmful substances 3. Two blood supplies a. From digestive system – first-pass metabolism b. Directly from the heart 4. Metabolism of lipid soluble substances a. Oxidation –enzymes use O2 to modify molecules 1) Interaction of drugs modified by same enzyme 2). Enzymes and side effects b. Conjugation – enzymes add molecule to drug inactivating it c. Step 1 – oxidation, step 2 – conjugation 5. Factors that alter drug metabolism a. Giving a second drug that competes for the same enzyme b. Past experience c. Age – humans of different ages respond differently d. Species differences B. Kidneys 1. Primary function is to filter out chemicals metabolized by liver and water soluble drugs 2. all substances except blood cells and large proteins absorbed by kidneys 3. fluids, lipid soluble substances, and needed substances (glucose) reabsorbed in to blood 4. Rest excreted through urine 5. Water the first substance to be reabsorbed a. alcohol inhibits antidiuretic hormone I increasing urination b. resulting dehydration causes more fluid to be retained by kidneys – including alcohol 6. Reabsorption and ph gradient 7. Absorption, elimination and the therapeutic window