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Department
Psychology
Course
PSYC62H3
Professor
Suzanne Erb
Semester
Winter

Description
CHAPTER 2 Basic Principles Drugs and Receptors - Drug is a chemical that affects one or more biological processes, however not all chemicals can be considered drugs. For example, vitamins and minerals are not drugs, but in some doses, if the vitamin or mineral is isolated and taken in particular doses it can be a drug. o A nonfood chemical that alters one or more normal biological processes in living organisms. With several potential exceptions. - 1994 Dietary Supplement Health and Education Act allows for untested dietary supplements to be put on the market o Most popular is St Johns Wort successful as a herbal anti-depressant. o Supreme Court eventually ruled against the FDA having control and regulation over tobacco products. o Alcohol (ethanol) should be considered a drug in that it disrupts the normal biological function/activities of the human body. - Endogenous substances chemicals originating or produced within an organism that are used to carry out the normal biological functions in the body are not usually considered drugs. - Exogenous substances drugs o But there have been endogenous substances that have been isolated, extracted and synthesized, and administered in its pure form to reverse neurological deficits. L-dopa is one of these substances, normally needed in regulatory brain functioning, is used to treat Parkinsons. - Prostaglandins class of chemicals found throughout the body that play a vital role in almost every life process, including respiration, reproduction, and circulation. Concentration of drug at its site(s) of action + Rate of accumulation at site(s) of action depend on both: - Drug dose the quantitiy of drug administered at one time. o Usually calculated by unit of drug per unit of body weight of the organism. (mg/kg) - Drug dosage refers to administration of the drug per unit of time. (10 mg/kg four times a day for three days) Pharmacodynamics refers to the biochemical and physiological effects of drugs and their mechanisms of action. - Receptors fairly large molecules (usually protein) which comprise the sites where biologically active chemicals of the body, often called ligands, induce their effects - Ligands most are hormones, insulin, testosterone, estrogen and adrenaline, as well as neurotransmitters. - Bound when a chemical occupies a receptor - Activated the receptor then starts some biological activity. - Dissociate when chemical leaves receptor. - Affinity refers to the relative capacity of a compound to maintain contact with or be bound to a receptor. - Efficacy refers to the degree of biological activity or relative capability of a compound to activate the receptor after being bound to it. o They are independent of each other, but without receptor affinity a compound is unlikely to exhibit efficacy. - Agonists are compounds with both an affinity for and a capability of activating a receptor (has efficacy). Endogenous (called a ligand). Exogenous (called a drug) o Indirect agonist drug does not combine directly to a receptor, but enhances the amount of the endogenous ligands available for the receptor. o Partial agonist drug that displays intermediate efficacy in receptor activation between the efficacy of a full agonist and an antagonist. it can reduce the full agonists accessibility to its receptors. Ex schizophrenia is due to excessive DA receptors, (Abilify) but one recent drug, is a partial agonist at dopamine, therefore eliminates the excessive stimulation. o Inverse agonist defined as a drug that appears to act through the same receptor as an agonist but produces effects opposite to those of the agonist. www.notesolution.com o Mixed agonist-antagonist evidenced when a drug acts as an agonist by itself , but blocks the activity of another agonist in the same system. - Cooper et al view of the receptor as having one elemental binding site and another elemental effector site - Receptors exist in an active and an inactive configuration, each of which is capable of combining with a drug molecule. Therefore, the ratio of the drugs affinity for the two configurations determines whether the drug will be an agonist or antagonist. - Agonist with high efficacy causes maximal response by activating proportionally fewer receptors, whereas with low efficacy, the agonist may fail to elicit a maximal response compared with compounds with higher efficacy. - Antagonists drugs that exert their effects by blocking the action of agonists. o Competitive antagonists ligands that bind to these sites but do not change the complex configuration. o Physiological antagonism form of drug interaction in which two drugs act at two different kinds of receptors that is receptors whose biological actions oppose each other. Receptors: - Ionotropic receptors produce very rapid changes in neuronal activity o Comprised of 5 subunits (greek symbols alpha beta theta, tri) comprised of a string of amino acids. The subunits form an internal pore of ion channel through which specific types of ions can flow through to alter the excitability of the neuron. o Various binding sites, x, y, z. for ligands on subunits which when occupied may change the conformation of the receptor to increase (or decrease) the passage of ions through the channel. o Allosteric modulators - May possess binding sites for ligands that DO NOT directly alter ion flow, but which modulate the influence of agonists binding to other sites on the complex. Ex benzodiazepines, like Valium, used for sedation and reduction of anxiety related symptoms is a indirect agonist and works like this. - Metabotropic Receptors - Produce relatively slow-developing and long-lasting effects on neurons. o Comprised of a long string of amino acids that's loops back and forth through the neuronal membrane. o Coupled with a G-Protein, specialized and embedded in the inside membrane, which is in turn connected to a effector unit. o 1 type of receptor - G-protein is linked to an ion channel. Therefore when the receptor is activated a subunit of the g-protein breaks off and binds with the ion channel and opens it. o Secondary Messengers - Effector is an anzyme that is activated when a subunit of the g-protein breaks off and bind to the enzyme. This enzyme then triggers the forumation of a bunch of molecules inside the neurons axon which eventually lead to biochemical alterations within the neuron. - Key- and-lock analogy - Sedvall &Farde 1990s identified approximately 300 receptor types. Parmacogenetics attempt to discover differential effects of a drug in different patients, depending on the presence of inherited variated in genes, with the goal of providing more patient-disease-specific health care. Pharmacogenomics attempt to discover differential effects of compounds, either in vivo or in vitro, on gene expression among all genes that are expressed in humans, with the goal of finding the best drug candidate from a given series of compounds under evaluation. Dose-Response Relationships The usual way of discussing a drugs effects in terms of dose-response function expresses the relationship between the dose administered and the response observed. - Determined by taking groups of individuals, administering each group a different amount of the drug in question, and then waiting for sufficient time as to assess the degree of effect or the number of individuals displaying a specified effect of the drug. - Placebo one group is administered a substance without any physiological effects instead of the drug itself. o Saline is most often used in animals because it is a combination of water and sodium chloride that is normally found within the human body. Therefore no change occurs based on drug. www.notesolution.com o Active placebo mimics some of the noticeable physiological characteristics of the drug being evaluated but without the effects on the brain that the researcher is interested in. o Double-blind procedure whereby neither the subject not the person administering the preparation knows whether it is a drug or placebo. - Biphasic function increase up to a point, plateau - Curvilinear function increase relatively, but high high dose causes less activity than no dose at all. - Therapeutic window levels below and above the window are associated with poorer dose-response drug manifestations. - Plasma half-lives drugs with a therapeutic threshold or range of effeictive drug levels the time it takes to eliminate half the drug from the bloodstream. o This can help
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