Principles of Drug Action
Principles of Drug Action 81.0
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BIOL 1000 - 001
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This 4 page Class Notes was uploaded by Arielle Reiner on Thursday September 3, 2015. The Class Notes belongs to 81.0 at University of Pittsburgh taught by Fanselow,Erika in Fall 2015. Since its upload, it has received 97 views. For similar materials see DRUGS AND BEHAVIOR in Neuroscience at University of Pittsburgh.
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Date Created: 09/03/15
Principles of drug action 09022015 Drugs must travel from the site of entry into the body to the brain via circulatory system Pharmacokinetics effect of body on drug Pharmacodynamics effect of drug on body Amount concentration depends on 0 Dose administered 0 Rate of accumulation 0 Rate of removal from the site of action Drug or neurotransmitter contacts with receptor brie y and causes intracellular effects 0 Receptor Protein located on the surface of or inside of a cell that is the site of action for a drug or other molecule 0 Ligand Molecule that binds to a receptor Receptors recognize a speci c molecular shape 0 Ligand binding alters the shape of the receptor conformational change 0 Binding to a receptor is temporary Receptor subtypes are not xed 0 Number and sensitivity can change 0 Receptors can have similar subtypes 0 Drug molecules oating around in cerebral spinal uid and connect to transmitters and come off multiple times to create an effect 0 Eg Norepinephrine acts differently in the heart than in the brain because of the different receptor subtypes found in the 2 locations 0 Brain can adjust to environment and move receptors around or create moreless Ugands o Agonist o Binds to receptor agonist receptor interaction to create a drug effectaction o Antagonist o Binds to receptor in a way that blocks drug effectaction antagonist receptor interaction Dose Quantity of drug administered Usually reported as amount of drug by body weight eg mgkg Important determinant of a drug s effects A drug s actions depend on the amount of drug available at the site of action which in turn is dependent upon the dose of the drug given Relationship between the dose administered and the behavioral response observed is called the 0 Dose response functioncurve Dosage Number of administrations per unit time eg mgkg 4 times a day for 3 days How calculated Groups of individuals are administered different amounts of a drug and their response to the drug is measures A dose response curve is determined by making a graph indicating the size of the response to the drug for a given amount of drug administered 0 X axis dose of drug 0 Y axis effect of drug Can have different shapes 0 Increased dose is associated with increased effect response with a plateau at the maximum effect 0 Increased dose is associated with increased effect but beyond a certain point the effect decreased U shaped function 1 drug can have different dose response curves depending of the effect being measured 0 Eg What responseeffect is being measured Seizure prevalence Mood symptoms Threshold dose minimally effective dose 0 Can be determined from a dose response curve Maximal response greatest degree of a given response that can be achieved with a speci c drug 0 Max out receptor binding cannot reach any more effect 0 Can be determined from a dose response curve 0 Therapeutic window Doses for which a given therapeutic response occurs 0 Too high side effects 0 Too low no effects 0 Effective and lethal doses ED50 Effective dose for 50 dose at which half of the maximal effect is achieved OR effective dose for half of the subjects tested 0 Therapeutic index A measure of a drug s relative safety for use computed as the ratio of LD50 to ED50 0 Therapeutic index LD50ED50 o The greater the ratio the safer the drug optimally more than 100 0 Less than 10 is considered very unsafe o TD50 Toxic dose used in human drug studies LD50 Lethal dose used in animal studies 0 If using TD50 therapeutic indexTD50ED50 Clinical trials 0 Pre clinical 0 Phase 1 check for safety 1St state of testing in humans 0 Phase 2 checking for ef cacy How well does the drug work 0 Phase 3 con rm results Drug must be safe Comparison with current quotgold standardquot treatment 0 FDA reviewphase 4 trials Real patients Efficacy How well a drug can produce a given effect 0 Not all drugs in a given class produce the same maximal effect Potency How much of a drug is needed to produce a given effect 0 Not all drugs produce the maximal effect at the same doses 0 The less of a drug required to produce an effect the greater the drug s potency 0 Drugs differ in their ef cacy and their potency 0 Ef cacy morphineheroin gt aspirin Drug interactions 0 The potency andor ef cacy of a drug can be altered by the presence of another drug or substance 0 Antagonism potency or ef cacy of a drug is reduced in the presence of another drug 0 Synergism 2 drugs together are more potent andor effective than either drug given alone
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