NROSCI 1030Exam # 1 Study Guide Lectures: 1 - 7Lecture 1 (1/7): IntroductionHistory of Psychiatric Disorders- The number of people suffering from psychiatric disorders is even more than reported due to a social stigma- Common psychiatric disorders in the world population: 1% schizophrenia, 1.5% bipolar disorder, 15% depression- 1900-1950s: number of people with reported mental disorders increased from 150,000 to 500,000; treatment were rare during this time period- Experiments of John Cade with ureic acid in 1949 on the behavior of wild pigs – 1949; led to the discovery of lithium as a treatment for bipolar disorder- Laborit (1952): utilized chlorinated promazine as a hypothermic sedating agent for his surgeries; characterized it as a neuroleptic agent- Deloy + Denicker: used chlorpromazine (neurostabilizer) to successfully treat hallucinations in their patientsCharacteristics of Resistance to Drug Treatment- Biological or psychological: it is important to differentiate a disease based on this classification for effective drug treatment- Psychotherapy or drug treatment- Patient rights: if a psychiatric patient refuses to drug treatment, he/she is not given the drug- Side effects; ex. tardive dyskinesia (uncontrolled movements) results when Parkinson’s patients are given dopamine blocking anti-psychoticsLecture 2 (1/9): Pharmacology – Dose/Response, Receptors- Pharmacology is the study of drug actions and its effects on living organismsDynamics of Drug AdministrationRoutes of Drug Administration- Intravenous (IV): into the vein; fast acting; can be titrated; ex. anesthetics- Intramuscular (IM): into the muscle; ex. vaccines, epipen for allergic reactions- Subcutaneous (SC): slow absorption/diffusion over time- Oral – most difficult yet most desirable route; difficulty with absorption – has to be able to sustain acidic stomach environment; easy to overdose – long period oftime before pills act, long time for them to exit, takes longer to de-drug- Partition coefficient: determines drug solubility (hydrophobic vs hydrophilic) and consequently how long a drug remains active in the body- Hydrophobic (ex. phenobarbital): dissolves in fat, not water; it has a slow onset of action, very long duration; good drug behavior for anxiety or epilepsy to control the disorder over a long time- Hydrophilic (ex. pentobarbital): very soluble in water, not fat; given for oral surgery; very fast onset of action, very fast offset of action; as it is rapid, it is also the one that has the highest abuse potential- Elimination of drugs from the body has to do with charge; a charged drug is retained in the body while an uncharged drug is excreted in urine- Acetylation: process used to metabolize/remove compounds from the body; degree of acetylation varies by ethnicityDrug-Receptor InteractionsBasic Terminology- Receptors: concept derived by Langley in 1905; he stated that “drugs act in a verypotent way and very specifically such that the drugs must have a specific way of being recognized by the body”; he presumed receptors were on the outside of the cell’s membrane and were combined with an effector inside the cell to cause changes inside the cell- Ligand: drug binding to a receptor- Agonist: drug that binds to a receptor and mimics the action of the transmitter that usually binds to that receptors- Antagonist: drug that binds to a receptor but does not produce an action; prevents transmitter from binding to the receptor- Non-competitive antagonist: binds to the receptor and forms a covalent bond; never leaves the receptor; it does not interfere with agonist binding of unbound receptors; when introduced the Kd does not change as the ability to bind free receptors has not changed- Competitive antagonist: binds to the receptor; leaves the receptor after a certain amount of time depending on the affinity of the agonist for the receptor- Partial agonist: binds to the receptor but doesn’t activate it completely; also prevents transmitter from binding and having a full action: dose response curve for partial agonist is at a lower maximal level than the dose response curve for the agonistDose-Response Curves- Dose-response curves are graphs of a physiological response vs log[x] of the doseof a drug- The classic curve is of a sigmoidal shape - The maximal rate of change, which is where there is 50% of the maximum response is called ED50, which stands for the Effective Dose when the response level is 50%- The more potent the drug, the lower the ED50 - The lower the maximal response, the lower the efficacy of the drug5 Assumptions of Binding- It is saturable – the system has a finite number of receptors- Specific – the receptor is stereospecific; it responds only to a ligand binding in a specific orientation- It is reversible – the ligand can be un-bound from the receptor- Distribution of binding should be related to its actions; ex. binding of receptors inthe hippocampus should lead to changes in functions associated with that structure- Binding affinity should be related to potency – the stronger a drug binds to the receptor, the stronger the effect should beDrug-Receptor Interactions Ligand --- [X] Receptor --- [R] Ligand-Receptor Complex --- [XR]- Drug receptor interactions are all based on kinetics; the probability of a drug finding a receptor is based on the relative concentration of the drug and receptor; affinity is a kinetic term – it describes how long a drug stays on the receptor- [X] + [R] --- [XR] (the formation of the complex is based solely on how long it takes the two to find each other); [X][R]K1 = rate of association- [XR] ---- [X] + [R]; the more stable the complex, the slower the rate of dissociation; [XR]K2 = rate of dissociation- At equilibrium, the rate of association equals the rate of dissociation; [X][R]K1=[XR]K2; (K2/K1) = ([X][R])/([XR]); Kd=(K2/K1); the higher the Kd, the less the affinity of a drug; the less the affinity of the drug, the more of the drug you need to deliver a greater physiological effect- [XR]/[RT] = [X]/([Kd + [X]); [XR]/[RT] = % bound (which is approximately the response); R – number of bound receptors; RT – number of total receptorsLecture 3 (1/14): Pharmacology – Agonists/Antagonists, Second MessengersBinding Curves- Graph of [XR]/[RT] vs log[X] is a binding curve - When there is 50% binding on the y-axis, you find Kd on the x-axis-