TY

Behavioral Neuroscience -  Neuropharmacology

  • Neuropharmacology
    • the study of how substances affect our nervous system and behavior
    • one of the main areas of neuroscience research today
    • usually starts with animal research, once safety is established moves to human clinical studies
    • often (but not always) involves comparing active substances to a placebo (saline solution)
    • may use “active” placebo and may use double-blind research design
  • Basic terms
    • Agonist --- increases NT activity
    • Antagonist --- decreases NT activity
    • Placebo --- an inert substance that is given to an organism instead of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug
    • sometimes creates same effect as the drug

Research terms

  • Half-life --- time it takes 1/2 of the drug to leave the body
    • used as a safety and maintenance factor
    • must examine drug “metabolites” as well as active ingredients
    • Drug metabolism: the process by which the body breaks down and converts medication into altered chemical substances
    • can be active or inactive
    • may not cause desired effect but affect other things; active = produce effect, inactive don’t
    • Elimination of a drug characterized by more than one half-lif every time half is eliminated = half-life
    • Time required for a drug concentration to reach steady state is determined by half-life
    • in most clinical situations, the attainment of steady state can be assumed after 3-5 half-lives
    • When the drug concentration is around 5% it is said to be negligible, therefore around 4 or 5 half-lives must elapse until the drug is eliminated
    • Time for drug “negligibility” = half-live * 5
  • Dose-response curve
    • a graph of the relationship between drug doses and the effects
    • attempts to find effective and safe dose of drug
    • can be used to plot the results of many kinds of experiments; X-axis usually drug/hormone concentration, Y-axis plots response (can be almost anything) \n * have to do a different curve for each of the effects of drug including side-effects
    • the specific measurement (DV) will be defined b/c pharmacological agents can have multiple effects
    • plots increasing drug dose (usually on a logarithmic scale) against increasing strength of the response being studied
    • the dose at which the drug shows half of its maximal effect is termed the effective dose 50% (ED50) ED50 = the dose at which 50% of the population sees an effect
    • Therapeutic window--- many drugs only work at specific doses; high and low often have little effect
    • Nonmonotonic DRC --- a DRC that is normal up to a point but then reverses and the measured response begins to decrease with larger doses
  • Dose-response functions
    • Minimum effective dose (ED50) --- lowest dose to produce desired effect in 50 % of clinical subjects
    • Median Toxic dose (TD50) --- dose which produces the first signs of toxicity in 50% population
    • high build-up in blood
    • Threshold dose --- smallest dose to produce detectable change
    • change must be defined by therapeutic effect
    • We can assess the relative potency of two drugs by comparing their ED50 values
    • Maximum response (max dose) --- the greatest degree of response that can be achieved with a specific drug
    • usually there is a plateau effect past which further dose do not increase effect
    • sometimes higher doses decrease effect (like amphetamines) because other effects begin to interfere with desired effect
    • We can compare drug efficacies by evaluating maximal responses, rather than doses
    • Partial agonist/antagonist - a drug of only moderate efficacy
    • Therapeutic index (TI) --- the separation between the effective dose and a toxic one
    • Safe index - ratio between TD50/ED50
    • TI = 100x safe (over-the-counter), TI =10x hazardous
    • becomes an issue with uncontrolled recreational use---tolerance to recreational effect occurs very quickly
  • Clinical efficacy---refers to the degree to which a drug is able to induce a given effect
    • related to maximal response
    • DRC can allow the comparison of difference drugs
  • Potency-- the amount of a drug needed to produce a desired effect
    • lower the needed dose, more potent

Drug interactions

  • Affinity - capacity of a compound (drug) to maintain contact or be bound to a receptor
  • binding affinity = the degree of chemical attraction between a ligand and a receptor
    • a drug with a high affinity for its receptor will be effective at very low doses
    • when two substances are being taken, one with the most affinity will have greater effect
    • penicillin and alcohol

Tolerance/Dependency

  • Tolerance - when there’s a decreased susceptibility or increase in amount of drug being taken needed
    • represented by a rightward shift in the dose response curve
    • has a physiological and psychological component
  • Factors
    • Metabolic tolerance --- organ systems become more effective at eliminating the drug
    • Elevation in Hepatic Microsomal Enzyme (HME) - reduces drug to metabolites so they become ineffective and easier to eliminate
    • ‘hepatic’ = liver
    • creates inactive and easier-to-eliminate metabolites
    • with repeated use of the brain creates more HMEs
    • associated with cross-tolerance to related substances
      • tolerance to once drug gives pre-existing tolerance to another (ex. surgical, analgesics, and narcotics)
    • creates dangerous interactions between drugs that share the same HMEs---sedatives and alcohol
      • biotransformation produces active metabolites that may produce side effects
    • Functional tolerance: target tissue may show altered sensitivity to the drug
    • up and down-regulation of receptors
    • with repeated drug use nervous sys can respond by altering the density of post-synaptic receptors
    • increase density = up-regulation, antagonist
    • lower density= down regulation; agonist
  • Drug dependent
  • Physical dependency: when