PT Exam II Fall 2013 Flashcards

Question

EGF

Answer 1

for cell growth and tissue repair

Answer 2

for blood vessel growth in healthy and cancerous tissues

Answer 3

one way for body to reduce BP

Answer 4

- each inactive receptor binds an agonist molecule - ligand binding forms stable active receptor homodimer & turns on enzymatic domain - cross-phosphorylate tyrosine residues in each other's cytoplasmic domain--> prolonging receptor activation & causes conformational change exposing binding sites for polypeptide substrates (signaling proteins) - Phosphorylation activates/inactivates these proteins affection cell functn

Answer 5

regulates many processes - cell division - membrn protein internalization - protein down regulation

Answer 6

polypeptides consisting of: - extracellular hormone-binding domain - cytoplasmic domain - hydrophobic polypeptide segment that connects the 2 domains across the cell mrbn - separate mobile tyrosine kinase molecules, called janus kinase molecules (JAK)

Answer 7

- growth hormone - erythropoietin - interferon - other regulators of growth and differentiation

Answer 8

- Ligand binding induces receptor subunits to bind to one another - Tyrosine residues in cytoplasmic domain are P by JAK - Phosphotyrosines on the receptor attract STAT proteins - Activated JAK phosphorylates STAT (signal transducers and activators of transcription) - STAT molecules dimerize and travel to nucleus to start transcription of specific genes whose protein products alter cellular function

Answer 9

-intracellular receptors for lipid-soluble agents | 3 common functional domains: hormone binding domain, DNA binding domain, transcription activating domain

Answer 10

1. binding of hormone stimulates release of chaperone protein (hsp 90) 2. receptor folds into functionally active conformation 3. receptor forms homo/heterodimer w other nuclear receptor 4. activated receptor binds to specific DNA segments called hormone response elements and regulates transcription of target genes

Answer 11

100 kcal/mole irreversible at body temperature long duration of action (not always good)

Answer 12

5 kcal/mole

Answer 13

2-5 kcal/mole, reversible but stable | -plays a significant role in establishing the selectivity and specificity of drug-receptor interaction

Answer 14

bond energy = 0.5 kcal/mole -plays a significant role in determining drug-receptor specificity better the fit = more van der waals

Answer 15

area of solution or fluid surrounding the receptor -drug move around randomly within -

Answer 16

drug molecules are initially attracted to receptors via

Answer 17

will lead to continuous association and dissociation between drug and molecule

Answer 18

must be present in order for drug molecule to form chemical bonds and bind w receptor

Answer 19

Kd, measurement of how readily a molecule will bind to a receptor, conc. of the drug required to bind 1/2 the receptors, usually 1-100nM -the higher the KD of the drug the lower its affinity for the receptor

Answer 20

the max biological response attainable for an agonist activating a receptor (conc is increased until response plateaus)

Answer 21

the ability of a single ligand-receptor complex to generate a biological response

Answer 22

ability of a dose to generate a biological response | it depends on affinity and intrinsic efficacy

Answer 23

a substance that produces even at highest conc and full receptor occupation, less that the max response - have affinity and varying degrees of efficacy - may act as inhibitors in presence of full agonist

Answer 24

full agonist and inverse agonist combination

Answer 25

involves a direct chemical interaction btwn the agonist and antagonist that renders the agonist pharmacologically inactive

Answer 26

represents the interaction of two agonists thaat act independently of each other but cause opposite effects i.e Acetylcholine and epinephrine

Answer 27

a substance that inhibits a biological response by acting at a site beyond the response

Answer 28

- most common in clinical setting - agonist and antagonist compete for the same receptor - have affinity but no efficacy

Answer 29

1. Equilibrium-Competitive antagonist (Reversible antagonist) 2. Nonequilibrium-Competitive (Irreversibly Antagonist)

Answer 30

- binds reversibly to the receptor - antagonism increases as conc. of antagonist increases - overcome by increasing the conc of agonist at the receptor

Answer 31

- binds irreversibly via a covalent bond - antagonism increases as antagonist conc increases - cannot be overcome by increasing agonist

Answer 32

developed the concept of a receptor

Answer 33

the response of a drug was some UNKNOWN POSITIVE FUNCTION of receptor occupancy

Answer 34

receptors spontaneously switch between inactive and active conformation - agonists have a high affinity for R* (active) - inverse agonists have a high affinity for R (inactive) - antagonists do not alter the equilibrium of R & R*, but prevent other substances from altering the equilibrium

Answer 35

- first described by Sutherland (1952) when liver cells w epinephrine showed elevated levels of cAMP - operates in a variety of cells and tissues w specific different functions - initiated by G-protein-coupled receptors that are activated by first messengers

Answer 36

1. B-adrenergic receptors 2. glucagon 3. prostaglandin I2 - kidney & GI secretion 4. parathyroid hormone 5. FSH (follicle stimulating hormone)

Answer 37

-GTP binding to the alpha subunit causes it to dissociate away from the BY-subunits of the heterotrimer to begin the next step in the signal transduction process

Answer 38

- 2 transmembrane regions - 2 catalytic domains - length of activation is dependent on the rate of GTP hydrolysis by the alpha-a isoform

Answer 39

Adenosine TriPhophate --> (adenylyl cyclase) cyclic adenosine monophosphate --> (Phosphodiesterase) 5-adenosine monophosphate

Answer 40

i. e. Cialis - drugs that inhibit, increase bronchiodilation - terminates signal from cAMP

Answer 41

- directly opposes the actions of Gs on adenylyl cyclase | - effects of Gi on adenylyl cyclase primarily observed in the presence of stimulated adenylyl cyclase

Answer 42

-activated PKA initiates a biochemical cascade by P and activating phosphorylase kinase which in turn P phosphorylase b to a which is involved in the degradation of stored glycogen into glucose-1-P

Answer 43

activated PKA in certain cell types will P inactive lipase to the active form which then catabolizes stored triglycerides into free fatty acids

Answer 44

relationship of the quantity of a substance (drug or ligand) to the graded effect that the substance has on a biological system - allows for a general curve-->increases the reliability of the data - more closely models the true dose-effect from a limited data set

Answer 45

- different based on how data is generated - D-R generated w increasing, individual drug-doses - C-R curves generated w increasing conc. of drug

Answer 46

1. independent variable (controlled) 2. drug and dose rangers - usually plotted in log scaled to get S curve (linear portion allows for more precise curve to curve comparison of drugs) - significant increases in agonist-induced response usually occur over large dose range (5+) 3. Graded response- multiple increasing doses of drug

Answer 47

1. dependent variable (measured) 2. represents the magnitude of the biological response 3. Normalizatn of data - eliminates biological variablility - e.g. % of max response / response:tissue

Answer 48

- the change in response decreases as the drug reaches its max response - may be difficult to measure in vivo - "the dose of a drug needed to produce maximum response usually has serious side effects or toxicities"

Answer 49

- a response that changes proportionately w each single dose of drug given - data on the x-axis is made up of multiple doses of the drug agonist - each single dose produces a single tissue response - multiple responses generated separately by individual doses of a drug - no time component on the x-axis

Answer 50

- populatn response (different from graded) - represent the all of nothing therapeutic end point of a drug e. g. headache, seizures, sleep - x-axis is made up of multiple doses of drug - each single dose of agonist produces a chosen therapeutic endpoint in a certain percentage of test subjects - % of subjects that demonstrate desired therapeutic endpoint is plotted for each increasing drug dose

Answer 51

compares the relative effectiveness of drugs acting by similar mechanisms - comparisons of ED50 values or common points can be used - no direct relationship between potency and affinity - more potent does not mean that the drug is better - more potent if to the left

Answer 52

- ratio of a drug's max biological activity at a receptor to that of a full agonist - measure 0-1 - full agonist = 1 - antagonists=0

Answer 53

-graphically represented as a rightward shift while still being able to achieve a max response

Answer 54

-the more antagonist that is added the more receptors that you bind the less of a max response that you can achieve

Answer 55

- antagonist that inhibits the generation of a biological response by acting at downstream from the receptor (w. components of its signal transductn cascade) - can bind reversibly/irreversibly - lower max response on graph

Answer 56

- stephenson, furchgott, nickerson - S. proposed that not all receptors have to be occupied/activated to achieve max response - F and N proved this theory by demonstrating the concept using irreversible anatagonists

Answer 57

larger the number the safer the drug

Answer 58

- used to determine a drugs clinical merit - Components: ED50 and TD50 (toxic dose) - TD50/ED50 i. e. Phenobarbital 1. Phenobarbital=3 sedation/seizure protection

Answer 59

the process of converting extracellular signals or impulses to a physiological response

Answer 60

are molecules or peptides secreted by cells that initiate chemical signaling cascades in nearby/distal cells i.e. epinephrine dopamine insulin GH

Answer 61

- molecules/proteins that are activated w/in a cell upon stimulation of the cell by 1st messengers i. e. cAMP

Answer 62

-simple -prevalent in brain and skeletal muscle regulation i.e. nicotinic, acetylcholine receptor (Na+ channel) GABAa Cl Channel glutamate Ca++ Channel -Ach binds to alpha subunits then channel opens & Na+ moves thru the pore into the cell -Curare (plant) and a-bungarotoxin (cobra) bind the same a-subunit

Answer 63

1. Serpentine Receptor:adrenergic, muscarinic, histaminic, serotonergic 2. G protein 3. Intracellular Effectors

Answer 64

each has its own effect - adenylyl cyclase, guanylyl cyclase, phospholipase C, ion channels - proteins affected by a 2nd messenger

Answer 65

developed the concept of the receptor for occupancy theory

Answer 66

- 1st person to quantitatively describe interactn betwn a drug and a receptor & the produced biological response - magnitude of the response is directly proportional to # of receptors occupied by the drug, max response only when all receptors occupied - primarily described affinity

Answer 67

drug action depends on 2 factors: fixation (drug binding to the receptor) & ability to produce action after fixation - described quantitatively the interactn of a ligand and receptor molecule - one molecule of a drug interacting w only one receptor - amt of drug/neurotransmitter in receptor biophase is greater than the # of receptors avaible for activatn

Answer 68

- hypothesized that the biological response of a drug is dependent on 1. affinity-the strength of the interactn betwn drug & receptor (Clark) 2. intrinsic activity - property of a drug to induce effect after binding (proposed max effect of drug used as a measurement of intrinsic activity)

Answer 69

- max effect could be produced by an agonist occupying only a small proportn of receptors - response of a drug is some unknown positive functn of receptor occupancy - unknown = efficacy

Answer 70

- provided direct scientific evidence for Stephenson | - proved Clark & Ariens wrong