NR565 Advanced Pharmacology
Fundamentals Week 1
Drug Development Process - ANSWER...-Pre-clincial Stage (Animal testing) of R&D
INDClinical (Safety and effectiveness)
R&DFinal Product Development
Post-marketing
Variations in drug development process
Preclinical stage of R&D - ANSWER...-1. Drug discovery
2. Biological characterization (drug action/ fate)
3. Pre-formulation studies
4. Initial formulations
5. Manufacturing and controls
6. Package label and design
Clinical Stage - ANSWER...-Phase 1: Biological effects, safe dosage
Phase 2: New drug treats small amount of patients
Phase 3: Larger size, must be as good as or better than others.
Drug Discovery - ANSWER...-1. target identification and validation
2. hit identification and screening
3. lead identification and optimization
4. candidate preclinical and clinical drug development
Graded dose response - ANSWER...-Drug response is continuous and gradual. The
concentration increases, the magnitude of the effect increases
Types of Drug Response - ANSWER...--Graded - responses that can be measured (BP,
HR, Diuresis, Bronchodilation, Pain scale, Coma Score)
-Quantal Effects- may or may not occur (convulsions, pregnancy, rash, sleep, death)
Receptors exist in what two states? - ANSWER...-1) Inactive (R)2) Active
(R*)Equilibrium favors inactive state (R)
Four major receptor families- receptors are proteins that transduce extracellular signals
to intracellular responses - ANSWER...-1) Ligand-gated ion channel
2) G protein-coupled receptors
, 3) Enzyme-linked receptors
4) Intracellular receptors regulating gene expression
Ion Channel Receptors / Gated ion channels - ANSWER...-- Rapid onset and short
duration (muscle contraction)
Transmit signals across the cell membrane by increasing the flow of ions and altering
the electrical potential or separation of charged ions across the membrane
Gated Ion Channel Receptors:
Open or close channels to allow certain ions to pass through cell membrane.
A gated channel for a specific ion. The opening or closing of such channels may alter a
cell's membrane potential.
G protein-coupled receptors (Guanine nucleotide regulatory proteins) - ANSWER...--
Found in cell membrane
-Made up of 3 major subunits (alpha α, beta β, gamma γ) and can have isotopes
(variations)
Generate intracellular second messengers that trigger a change in cell function
Transmembrane receptors - ANSWER...--Extracellular hormone-binding domain
-Intracellular enzyme domain
-combinations cause 2 receptors to bind to each other.
(Insulin, and platelet)
Have its ligand-binding domain on the cell's surface.Key feature: down-regulation of
receptors (decrease in number of receptors available for response)
Intracellular receptors - ANSWER...-lipid soluble drugs attach to intracellular receptors
and initiate direct changes in the cell by affecting DNA transcription
Intracellular receptors are different receptors in what way? - ANSWER...-Entirely
intracellular so ligand must diffuse into cell to interact with receptor. Must be lipid
soluble to be transported attached to plasma protein such as albumin. DNA, RNA
transcription into proteins. (i.e. Antineoplastic agents)
Eg: Corticosteroids, mineralocorticoids, sex steroids, vitamin D, and thyroid
hormones...producing more sustained responses.
Enzymes - ANSWER...-Biological molecules that encourage specific chemical
reactions.
Six ways gene expression can be regulated between DNA + protein - ANSWER...-1.
Transcription --> when/how often
2. Controlling mRNA splicing or processing
3. Selecting which mRNA are exported to cytosol
4. Selectively degrading some mRNAs
5. Selecting which mRNAs are translated by the ribosomes
Fundamentals Week 1
Drug Development Process - ANSWER...-Pre-clincial Stage (Animal testing) of R&D
INDClinical (Safety and effectiveness)
R&DFinal Product Development
Post-marketing
Variations in drug development process
Preclinical stage of R&D - ANSWER...-1. Drug discovery
2. Biological characterization (drug action/ fate)
3. Pre-formulation studies
4. Initial formulations
5. Manufacturing and controls
6. Package label and design
Clinical Stage - ANSWER...-Phase 1: Biological effects, safe dosage
Phase 2: New drug treats small amount of patients
Phase 3: Larger size, must be as good as or better than others.
Drug Discovery - ANSWER...-1. target identification and validation
2. hit identification and screening
3. lead identification and optimization
4. candidate preclinical and clinical drug development
Graded dose response - ANSWER...-Drug response is continuous and gradual. The
concentration increases, the magnitude of the effect increases
Types of Drug Response - ANSWER...--Graded - responses that can be measured (BP,
HR, Diuresis, Bronchodilation, Pain scale, Coma Score)
-Quantal Effects- may or may not occur (convulsions, pregnancy, rash, sleep, death)
Receptors exist in what two states? - ANSWER...-1) Inactive (R)2) Active
(R*)Equilibrium favors inactive state (R)
Four major receptor families- receptors are proteins that transduce extracellular signals
to intracellular responses - ANSWER...-1) Ligand-gated ion channel
2) G protein-coupled receptors
, 3) Enzyme-linked receptors
4) Intracellular receptors regulating gene expression
Ion Channel Receptors / Gated ion channels - ANSWER...-- Rapid onset and short
duration (muscle contraction)
Transmit signals across the cell membrane by increasing the flow of ions and altering
the electrical potential or separation of charged ions across the membrane
Gated Ion Channel Receptors:
Open or close channels to allow certain ions to pass through cell membrane.
A gated channel for a specific ion. The opening or closing of such channels may alter a
cell's membrane potential.
G protein-coupled receptors (Guanine nucleotide regulatory proteins) - ANSWER...--
Found in cell membrane
-Made up of 3 major subunits (alpha α, beta β, gamma γ) and can have isotopes
(variations)
Generate intracellular second messengers that trigger a change in cell function
Transmembrane receptors - ANSWER...--Extracellular hormone-binding domain
-Intracellular enzyme domain
-combinations cause 2 receptors to bind to each other.
(Insulin, and platelet)
Have its ligand-binding domain on the cell's surface.Key feature: down-regulation of
receptors (decrease in number of receptors available for response)
Intracellular receptors - ANSWER...-lipid soluble drugs attach to intracellular receptors
and initiate direct changes in the cell by affecting DNA transcription
Intracellular receptors are different receptors in what way? - ANSWER...-Entirely
intracellular so ligand must diffuse into cell to interact with receptor. Must be lipid
soluble to be transported attached to plasma protein such as albumin. DNA, RNA
transcription into proteins. (i.e. Antineoplastic agents)
Eg: Corticosteroids, mineralocorticoids, sex steroids, vitamin D, and thyroid
hormones...producing more sustained responses.
Enzymes - ANSWER...-Biological molecules that encourage specific chemical
reactions.
Six ways gene expression can be regulated between DNA + protein - ANSWER...-1.
Transcription --> when/how often
2. Controlling mRNA splicing or processing
3. Selecting which mRNA are exported to cytosol
4. Selectively degrading some mRNAs
5. Selecting which mRNAs are translated by the ribosomes
