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PSYCHOLOGY 335 SECTION 001 - 011224 ZACH WALSH PH.D. Basic Pharmacology  What is a Drug?  A substance that alters the physiology of the body but is not a food or nutrient.  We will focus on psychoactive drugs  cross the blood-brain barrier  act upon the central nervous system  affect brain fun...

PSYCHOLOGY 335 SECTION 001 - 011224 ZACH WALSH PH.D. Basic Pharmacology  What is a Drug?  A substance that alters the physiology of the body but is not a food or nutrient.  We will focus on psychoactive drugs  cross the blood-brain barrier  act upon the central nervous system  affect brain function  change perception, mood consciousness, cognition, behavior  used recreationally, entheogenically, medically Basic Pharmacology  Names of Drugs     Chemical Name Generic Name Trade Name Street Name Drug Names  A drug’s chemical name reveals its chemical composition and molecular structure  Pharmaceutical companies also may patent brand names, or trade names, for their product  Generic drugs   contain same active ingredients as the original brand name drug must be pharmacologically equivalent. Drug Names Drug Names  Excipients Drug Names  Excipients  Carrier medium  USA - selling 100 doses of pure LSD = minimum sentence < 1yr  100 doses on paper = Min sentence two years, three months  100 doses on sugar cubes = Min sentence > 15 years  “..an almost unfathomable level of ignorance about drugs on the part of the policy maker…These are men and women who know nothing about drugs” Eric Sterling president of the Criminal Justice Policy Foundation and a former assistant counsel to the House Subcommittee on Crime. Drug Names  Excipients Drug Names  Excipients Drug Names  Prozac Drug Names  Sarafem Drug Names  Sarafem Marketed by its manufacturer, Eli Lilly, for PMDD treatment after it acquired another patent--Prozac's patent was due to expire. Lilly spent more than $30 million promoting the drug Pharmacodynamics  What a drug does to the body  Describing Doses   Milligrams: 1/1000 of a gram Doses given in accordance to body weight Pharmacodynamics Dose Response Relationships  To determine the effect of a drug, we have to study several doses and measure the change in some response.  Relationship between dose and response is called the dose-response curve (DRC). Pharmacodynamics Pharmacodynamics  Important characteristic of DRC is slope.  Refers to the mostly linear central part of the curve; how sharply the effect changes with each change in dose.  If a small change in dose produces a large change in effect, the slope is steep.  If large changes in dose produces small changes in effect, the slope is shallow. Pharmacodynamics Describing Doses  ED50  The Median effective dose  The dose that is effective in 50% of the subjects tested.  LD50  Median  The lethal dose dose that was lethal in 50% of the subjects tested. Pharmacodynamics ED50 and LD50 One curve shows the percentage of animals in each group that lost consciousness (ED); the other curve shows the percentage that died at each dose (LD). Pharmacodynamics Therapeutic index (TI)  TI = LD 50 / ED50   The greater the TI, the safer the drug; the difference between the desired effect and the undesired or lethal effect is larger. To be safer, the TI can be calculated by using the LD1 / ED99  The lower the TI, the lower the safety.  THC - >1000, Morphine - 70, Cocaine - 15, Alcohol 10, Heroin - 6  Pharmacodynamics 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).  Complicated by absorption / excretion curves Pharmacodynamics  Potency and Effectiveness   The extent of the drugs effect Potency  Differences  in the ED50 Effectiveness  Differences in the maximum effect that drugs will produce at any dose Pharmacodynamics  Effectiveness: The maximum effect obtainable, with additional doses producing no effect.  Some drugs may be potent, but they might never be able to produce a peak response no matter how much is given  A drug that is more effective can produce a greater peak, or maximum, effect than a drug that is less effective. Pharmacodynamics Heroin and morphine are equally effective, with heroin more potent. Aspirin is less effective Pharmacodynamics  Primary and Side Effects  Primary/main effect  Intended  result in treatment Side effect  Unintended;    i.e. may be harmful Addiction? Bupropion - Wellbutrin - Zyban Pharmacodynamics  Drug Interactions  Drug Antagonism  One drug diminishes the effect of the other  Additive Effect  Shifts  the DRC to the left Superadditive Effect/Potentiation/ Agonism  Combining   drugs increases the effect Physiological  Alcohol & sedatives Behavioral  Alcohol & stimulants Pharmacodynamics  Drug Interactions 1979-2008 According to the Chief Medical Examiner of New York, Heath Ledger "died as the result of acute intoxication by the combined effects of oxycodone (Percocet), hydrocodone (Vicodin), diazepam (Valium), alprazolam (Xanax), temazepam (Restoril), and doxylamine (Unisom)." diazepam & oxycodone 1996-2017 Fentanyl & Xanax (Alprzolam) Pharmacodynamics Drug Interactions After an extensive review of the latest scientific evidence, the U.S. Food and Drug Administration announced today that it is requiring class-wide changes to drug labeling, including patient information, to help inform health care providers and patients of the serious risks associated with the combined use of certain opioid medications and a class of central nervous system (CNS) depressant drugs called benzodiazepines. Among the changes, the FDA is requiring boxed warnings – the FDA’s strongest warning – and patient-focused Medication Guides for prescription opioid analgesics, opioid-containing cough products, and benzodiazepines – nearly 400 products in total – with information about the serious risks associated with using these medications at the same time. Risks include extreme sleepiness, respiratory depression, coma and death. Today’s actions are one of a number of steps the Pharmacodynamics Drug Interactions Pharmacokinetics Pharmacokinetics: “what the body does to a drug”  Administration  How  Absorption  How  a drug gets into the blood Distribution  How  a drug gets into the body it travels Binding at Sites of Action  Where  the drug needs to go Inactivation and Excretion  How the drug leaves Pharmacokinetics Pharmacokinetics Administration Routes – Parenteral – Under the skin  Vehicle is needed  Liquid  Subcutaneous  Injected  Intramuscular IM  Needle  inserted into the muscle Intravenous IV  Injected  to form a bolus just under the skin (skin popping) into the vein (mainlining) Other Parenteral Routes  Intraperitoneal (gut), Intraventricular (brain), Intrathecal (spine) Pharmacokinetics Administration  Absorption from Parenteral Sites  Reliant on blood flow  IV  is direct Enters blood stream via capillaries  Tiny vessels from with pores (porous)  # capillaries in an area influences speed of absorption  Diffusion  Substances  moves from are of high to low concentration until equal Depot Injections  Slowly dissolves into the body over a long period of time Pharmacokinetics Administration  Inhalation of Gases  The Lungs  Efficient gas exchange system  Oxygen  Carbon Dioxide  Artery from heart to brain without the liver Pharmacokinetics Administration  Inhalation of Smoke and Solids  Burning of dried plant material  i.e. tobacco  Vapor & tiny particles of ash  Not exhaled like gasses  Popular among humans but under-studied  Difficult with animals Pharmacokinetics Administration  Inhalation of Smoke and Solids  Vaporization – Reduced Carbon monoxide/ hydrocarbons Pharmacokinetics Administration  Sniffing of drugs  Intranasal administration  i.e.  Oral Administration   Peroral (p.o.) Buccal membranes  i.e.  cocaine chewing tobacco Suppository   Unconscious Vomiting Pharmacokinetics  The Digestive System  Drugs absorbed in intestines  Faster on empty stomach  To reach capillaries must pass intestinal membranes   made of lipid bilayer Lipid Solubility  Olive  How much in water/oil  Ions   oil partition coefficient are not lipid soluble Level of ionization determines degree of absorption Can take place in the gut via metabolism - onset of effects Pharmacokinetics Administration  Transdermal Administration  Absorbed through the skin  Epidermis  Outer layer of the skin  Keratin   Lipid soluble (but waterproof!) i.e. nicotine patch Pharmacokinetics Administration Pharmacokinetics- Excretion/Metabolism  Excretion and Metabolism  The Liver  Enzymes     Catalysts - change molecular structure i.e. Alcohol Dehydrogenase Restructuring molecules aka Metabolism Metabolites  > useful / < toxic  > ionized = easily excreted  Detoxification  The metabolic process Pharmacokinetics- Excretion/Metabolism  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  Excretion  Half-life most efficient at higher blood levels PharmacokineticsExcretion/Metabolism 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. Pharmacokinetics- Excretion/Metabolism  Excretion and Metabolism  The Kidneys  Filter everything from blood and reabsorb what is needed    Lipid soluble passed back to blood  Unless actively transported out Ionized / non lipid-soluble substances passed to bladder  Unless actively reabsorbed Ph influences – blood basic/ urine acid = bases excreted Pharmacokinetics- Excretion/Metabolism   Factors That Alter Drug Metabolism Important determinant of individual differences in effects  Stimulation of Enzyme Systems  Enzyme induction  Responsible for development of metabolic tolerance  >Alcohol Dehydrogenase  > metabolism Pharmacokinetics- Excretion/Metabolism  Factors That Alter Drug Metabolism  Depression of Enzyme Systems  Metabolism of Alcohol  Disulfiram (Antabuse)  Used to prevent drinking Pharmacokinetics- Excretion/Metabolism  Factors That Alter Drug Metabolism  Age  Young not able to metabolize the dose of an adult   Incomplete enzyme development Infant with drugs in system at birth  Elderly  – less efficient liver & kidneys Species  Alcohol  dehydrogenase rats (60%) vs. guinea pig (160%) vs. humans Pharmacokinetics Combining Absorption and Excretion Functions Time Course    absorption curve, assuming no excretion excretion curve, assuming instantaneous absorption and distribution the resultant of these two theoretical processes. The resultant curve is typical of the time course for blood level of most drugs Pharmacodynamics 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).  Complicated by absorption / excretion curves Pharmacokinetics