NR565 Advanced Pharmacology Fundamentals Week 1 questions and solutions

NR565 Advanced Pharmacology Fundamentals Week 1
questions and solutions

Drug Development Process - answersPre-clincial Stage (Animal testing) of R&D
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INDClinical (Safety and effectiveness) ak ak ak




R&DFinal Product Development ak ak




Post-marketing
Variations in drug development process ak ak ak ak




Preclinical stage of R&D - answers1. Drug discovery ak ak ak ak ak ak ak




2. Biological characterization (drug action/ fate)
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3. Pre-formulation studies
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4. Initial formulations
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5. Manufacturing and controls
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6. Package label and design
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Clinical Stage - answersPhase 1: Biological effects, safe dosage
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Phase 2: New drug treats small amount of patients
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Phase 3: Larger size, must be as good as or better than others.
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Drug Discovery - answers1. target identification and validation
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2. hit identification and screening
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3. lead identification and optimization
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4. candidate preclinical and clinical drug development
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Graded dose response - answersDrug response is continuous and gradual. The concentration increases, the magnitud
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of the effect increases
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Types of Drug Response - answers-Graded - responses that can be measured (BP, HR, Diuresis, Bronchodilation, Pai
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scale, Coma Score)
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-Quantal Effects- may or may not occur (convulsions, pregnancy, rash, sleep, death)
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Receptors exist in what two states? - answers1) Inactive (R)2) Active (R*)Equilibrium favors inactive state (R)
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Four major receptor families- receptors are proteins that transduce extracellular signals to intracellular responses -
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answers1) Ligand-gated ion channel
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2) G protein-coupled receptors
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3) Enzyme-linked receptors
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4) Intracellular receptors regulating gene expression
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Ion Channel Receptors / Gated ion channels - answers- Rapid onset and short duration (muscle contraction)
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Transmit signals across the cell membrane by increasing the flow of ions and altering the electrical potential or separatio
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of charged ions across the membrane
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Gated Ion Channel Receptors: ak ak ak




Open or close channels to allow certain ions to pass through cell membrane.
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,ak A gated channel for a specific ion. The opening or closing of such channels may alter a cell's membrane potential.
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G protein-coupled receptors (Guanine nucleotide regulatory proteins) - answers-Found in cell membrane
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-Made up of 3 major subunits (alpha α, beta β, gamma γ) and can have isotopes (variations)
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Generate intracellular second messengers that trigger a change in cell function ak ak ak ak ak ak ak ak ak ak




Transmembrane receptors - answers-Extracellular hormone-binding domain ak ak ak ak ak




-Intracellular enzyme domain ak ak




-combinations cause 2 receptors to bind to each other. ak ak ak ak ak ak ak ak




(Insulin, and platelet) ak ak




Have its ligand-binding domain on the cell's surface.Key feature: down-regulation of receptors (decrease in number of
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receptors available for response)
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Intracellular receptors - answerslipid soluble drugs attach to intracellular receptors and initiate direct changes in the celak ak ak ak ak ak ak ak ak ak ak ak ak ak ak ak




by affecting DNA transcription
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Intracellular receptors are different receptors in what way? - answersEntirely intracellular so ligand must diffuse into cel ak ak ak ak ak ak ak ak ak ak ak ak ak ak ak ak




interact with receptor. Must be lipid soluble to be transported attached to plasma protein such as albumin. DNA, RNA
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transcription into proteins. (i.e. Antineoplastic agents)
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Eg: Corticosteroids, mineralocorticoids, sex steroids, vitamin D, and thyroid hormones...producing more sustained
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responses.
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Enzymes - answersBiological molecules that encourage specific chemical reactions. ak ak ak ak ak ak ak ak




Six ways gene expression can be regulated between DNA + protein - answers1. Transcription --> when/how often
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2. Controlling mRNA splicing or processing
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3. Selecting which mRNA are exported to cytosol
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4. Selectively degrading some mRNAs
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5. Selecting which mRNAs are translated by the ribosomes
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6. Selectively activating or inactivating proteins once made.
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Drug action at receptors - answers-agonists
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-antagonists
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agonists - answersAgonists, or full agonists, are drugs that produce receptor stimulation and a conformational change
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every time they bind. Full agonists do not need all of the available receptors to produce a maximum response. --
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-Less than 10% needed for maximum response. ak ak ak ak ak ak




Antagonists - answers-Antagonists are drugs that occupy receptors without stimulating them. Antagonists occupy a ak ak ak ak ak ak ak ak ak ak ak ak ak




receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response. -
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-Antagonists produce no direct response. The response we see following administration of antagonists results from the ak ak ak ak ak ak ak ak ak ak ak ak ak ak ak




inhibiting receptor stimulation by agonists. For example, beta blockers such as propranolol and atenolol act as
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antagonists at the beta-adrenoceptor.
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partial agonists - answersPartial agonists are drugs that have properties in between those of full agonists and
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antagonists. Partial agonists bind to receptors but when they occupy the receptor sites, they stimulate only some of the
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receptors. This is sometimes called intrinsic activity. So they can act as part agonist and part antagonist. Partial agonist
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would require all of the available receptors to produce their full response, and the maximum response for a partial agoni
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is less than that for a full agonist.The beta blockers acebutolol, penbutolol, and pindolol are partial agonists.
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