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Lecture 2

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University of Toronto Scarborough
Suzanne Erb

Lecture 2: Principles of Pharmacology 1. Drug-Receptor Interactions - Important basic concepts:  Receptors: large protein molecules that drugs and naturally occurring chemicals of the body act on to exert their effects. -Receptors: drugs in central nervous system synapse with the terminal adjacent to the postsynaptic neuron. Receptor molecules are embedded in the postsynaptic neuron where neurotransmitter that are released will bind  Ligands: Biologically active chemicals in the body (e.g., hormones, neurotransmitters, neurohormones, etc). - Ligands: the chemicals themselves are also attracted to bind to the neurotransmitter  Affinity: The ability of a compound to bind to or maintain contact with a receptor. -Does the ligand fit the receptor? This is known as Affinity – (eg: key and lock) - Affinity: the drug will attach to receptor and have the effect, then disassociate  Intrinsic activity: The relative capability of a compound to activate a receptor after binding with it. -Intrinsic Activity: Does the drug/ligand activate the drug after binding (eg: wrong key in lock has no intrinsic activity) -there isn’t a direct relationship between intrinsic activity and affinity -->as affinity increase intrinsic activity can increase or decrease Drugs act at receptors as either agonists or antagonists -Agonist: produce some sort of biological activity (both affinity + intrinsic activity) -Antagonist: fit the “lock” (receptor) but no activation (affinity but no intrinsic activity) Indirect agonist: a drug that does not interact directly with a receptor but enhances the amount of endogenous ligand available for the receptor. -by increasing the natural ability or amount available for the receptor -example: dopamine and cocaine the amount of dopamine increases in the synapse Partial agonist: a drug that is not as effective as a full agonist but is more effective than an antagonist. -not as effective as a full agonist but more effective than an antagonist -the full agonist, when competing with the partial agonist would then have an antagonist effect it decreases the effect because not all the receptors are activated with full agonist Inverse agonist: a drug that acts at the same receptor as an agonist but that decreases basal activity at the receptor and, thereby, produces effects opposite those of the agonist. agonist because it produces a change in the body however it is inverse because it has the opposite effect of the full agonist Graph of all of the Agonists Competitive antagonist: an antagonist that is capable of dissociating from the receptor, allowing for ‘competition’ between the agonist and antagonist for the receptor. - eventually, given an appropriate number of agonist and antagonist, the agonist can eventually win over the antagonist (which disassociates and allows the agonist to bind). Non-competitive antagonist: an antagonist that is not capable of dissociating from the receptor. -the non-competitive antagonist cannot be overcome by increasing the number of agonists added -does not disassociate from receptor. Mixed agonist-antagonist: a drug that acts as an agonist itself but blocks the activity of another agonist in the same system. -acts as agonist at some receptors and antagonist at other receptors -eg: opium –acts as an antagonist at mu opioid receptors and the same drug at kappa and delta opioid receptors acts as partial agonist 2. Dose-response functions Definition: The relationship between the dose of a drug administered in particular group of individuals and the degree of response or number of individuals exhibiting the response. • Dose-response functions are typically obtained by administering one group a placebo or vehicle, and two or more groups different doses of the drug of interest. • Dose-response functions are dose, response, and species/age/gender dependent. -Species some species are more sensitive to some drugs some species would be affected when others might not be infants and the elderly are more effective -they are more sensitive to certain drugs females versus males may respond differently to different drugs Graph Fig 2-1: -Dose is always plotted on the X axis and behavioral effects are always plotted on the y axis. Active Placebo not just saline, an actual effect occurs just not the actual effect of the drug being studied. -dose response are dependent on concentration of drug and dose -dose = quantity of drug -increased body = more drug needed -Response- all depends on the response looking you are looking at to depend what the graph will look like -a dose response function is almost never completely linear. Usually is sigmoidal. - (red line) There's a minimum threshold dose that needs to be reached before the drug has any effect. Once the drug reaches threshold on the effect increases until it
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