PSYCH 265 1st Edition Lecture 10Outline of Last Lecture I. Pharmacokinetics vs. pharmacodynamics II. Pharmacokinetics a. Administration b. Absorptionc. Distributiond. Metabolism e. Excretion III. Plasma protein binding IV. Blood brain barrierV. First pass effectVI. Enzyme induction/inhibition a. Inductionb. Inhibition VII. Drug excretion VIII. Routes of drug excretionOutline of Current LectureI. Pharmacodynamics II. Proteins These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.a. Structural b. Transporterc. Enzymesd. Ion channelse. Receptors III. What do drugs do?IV. NeurotransmitterV. Receptor agonists VI. Receptor antagonists VII. Releasing agentsVIII. Reuptake inhibitors IX. Presynaptic regulation Current Lecture-Pharmacodynamics oMajority of drugs interact with target molecules, usually a protein-Enzymes-Ion channels-Transporters-Receptors-ProteinsoReceptors are macro molec that are made up of amino acid building blocksoProteins are found in all body tissues and serve a number of roles-Structural -Transporter-Enzymes-Ion channels-Receptors-Enzyme proteins as drug targetso3D proteins consisting of amino acids that catalyze biochemical reactionsoEnzymes can be either induced or inhibited by different drugsoDrug disulfiram (antabuse), used to alcoholism, inhibits the enzyme acetaldehyde dehydrogenase-Ion channels as drug targetsoIon channel proteins regulate the ionic environment inside and outside the neuron and play a role in transmembrane signalingoAlcohol targets GABA-and glutamate-gated ion channels to produce its behavioral effects-Transporter proteins as drug targetsoSome substances are transported across cell membranes by binding to specific carrier proteinsoNeuronal reuptake utilizes neurotransmitter-specific transporter proteinsoCocaine is a drug of abuse that works through inhibition of transporter proteins-Receptors as drug targetsoMacromolecules that serve to recognize ligands and initiate a response to receptor activation oCan respond to endogenous ligands (hormones, neurotransmitters) or exogenous ligands(drugs)oFound on the surface of the neuronal cell membrane or target cell membrane oOther receptors located inside the cell and are called nuclear receptors or transcription factors oMetabotripic receptors usually 7-transmembrane-spanning G-protein coupled receptors oAlso ionotropic receptors (see ion channel receptors)oDrugs of abuse such as LSD, morphine or marijuana produce their central effects by acting at serotonin 5HT opiate and cannabinoid receptors respectively -What do drugs do?oChange rate of physiological processoDon’t make the body do anything that it doesn’t normally do oInfluence physiological function by altering neurotransmissionoAltered neurotransmission means that the level of post-synaptic or post-junction receptor activation is either increased or decreased-NeurotransmitteroActivates receptors on the target cell to produce a response-Norepinephrine activates 3 subtypes of adrenergic receptors to produce sympathetic effects-Receptor agonistsoDirectly activate receptors and augment the stimulatory effects of the transmitteroCan be full or partial-Dobutamine is B1 adrenergic receptor agonist and can direction activate B1 receptors in the heart to increase cardiac activity -Receptor antagonistsoBlock receptors & prevent their activation by the transmitter-Propranolol is a B blocker and reduces cardiac activity while prazosin is a alpha blocker and reduces blood pressure-Releasing agentsoCause neuronal release of neurotransmitter to activate receptors -Amphetamine causes release of norepinephrine and increases heart rate and blood pressure-Reuptake inhibitors oPrevent reuptake of transmitter, leaving transmitter to activate receptors -Cocaine prevents reuptake of NE, and the increased levels of NE increases heart rate and blood pressure-Enzyme inhibitors oPrevent transmitter breakdown increasing levels of transmitter to activate receptors -MAO-inhibitors prevent breakdown of norepinephrine and tyramine, potentially causing a dramatic increase in heart rate and blood pressure-Presynaptic regulation oAutoreceptors can inhibit neuronal release of neurotransmitter-Agonist drugs like clonidine can activate these receptors to inhibit neuronal release of transmitter and reduce sympathetic