NR 565 Advanced Pharmacology Fundamentals Week 1-4
& Midterm Exam Study Guide
drug Development Process
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
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
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
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
Drug response is continuous and gradual. The concentration increases, the magnitude of the effect
increases
Types of Drug Response
-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?
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
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
- 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)
-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
-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
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?
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
& Midterm Exam Study Guide
drug Development Process
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
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
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
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
Drug response is continuous and gradual. The concentration increases, the magnitude of the effect
increases
Types of Drug Response
-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?
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
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
- 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)
-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
-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
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?
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
