Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacotherapy - Vanwert Module I Sept 2013 > PT Exam II Fall 2013 > Flashcards

PT Exam II Fall 2013 Flashcards

1
Q

Pharmacology

A

the study of the interaction of chemicals w biological systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Toxicology

A

the study of adverse effect of chemicals on biological systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Pharmacodynamics

A

study of the biochemical and physiological effects of drugs and their MECHANISM OF ACTION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Objectives of Pharmacodynamics

A
  1. To delineate the chemical or physical interactions btwn a drug and a target cell
  2. to characterize the full sequence and scope of actions of each drug
  3. to provide the basis for both the rational therapeutic use of a drug and the design of new and superior therapeutic agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Drug

A

chemical substance that alters physiologic function of cells and tissues through a chemical reaction.

  1. alter perceptional and/or psychological states and cause habituation or addiction
  2. used as tools to study cell/tissue function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Chemical Classification

A

drugs that are grouped alike due to similar molecular structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Pharmacological classification

A

Drugs that are grouped alike based on physiological activity or MOA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Therapeutic classification

A

drugs that are organized according to their indication or use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Biochemical Response

A

can be measured at the level of cell, tissue, organ, or whole organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Drug Size

A

Most drugs have a MW btwn 100-1000 g/mol
~sufficient size gives a cpd a unique structure facilitating selective receptor binding
~smaller cpds and ions do not selectively bind to receptors
~large drug molecules may not be readily absorbed into the GI tract and may only be administered parenterally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Stereoisomerism

A

Normally only one optical isomer of a drug is pharmacologically active. It affects drug side effects and drug metabolism (enzymes and receptors are stereo-specific)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Receptor Location

A
  • Plasma Membrane
  • Cytoplasm (floating free or w an organelle)
  • Nucleus
  • Circulating free in the blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Normal Function of a Receptor

A
  1. Regulate a physiological function
  2. Regulate the flux of ions
  3. Regulate a biochemical function (glucose metabolism)
  4. Regulate the expression of mRNA
  5. Regulate blood clotting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Receptor Activation

A

By neurotransmitters, peptides, and hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Physical characteristics of the receptor

A

Protein based, purely nucleic acids, quaternary structure (multiple subunits)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Common features of Receptors

A
  1. Protein component
  2. Lipid and Carb components
  3. Receptors can move laterally in mbrn and interact freely with other mbrn proteins
  4. Molecular weight 45-200 kdaltons
  5. Can be composed of a single protein or multiple separate protein subunits
  6. can have multiple subtypes i.e. adrenergic receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

7-TMS G-Protein Coupled Receptor structure

A

~also called Metabotropic Receptors

  1. 7, nonpolar transmbrn regions
  2. 3 extracellular loops
  3. 3 intracellular loops
  4. extracellular amino terminal tail
  5. intracellular carboxy terminal tail
  6. coupled to G proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Examples of Endogenous Activators (7-TMS)

A
  1. Norepinephrine
  2. serotonin
  3. acetylcholine
  4. histamine
    - these activators are mimicked, stabilized, or inhibited by drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Examples of Receptors

A
  1. adrenergic receptors ( alpha and beta)
  2. sertonergic (5-HT receptors)
  3. muscarinic cholinergic receptors (M1-M5)
  4. histamine (h1 and h2)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Ligand-Gated Ion Channels (Ionotropic)

A

-composed of multiple protein subunits
-these subunits constitute a pore in the cell mbrn thru which + or - ions can flow
-ion flow can be regulated by various ligands
produce biological responses by altering cell mbrn potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Endogenous Activators (Ionotropic)

A
  1. acetylcholine
  2. GABA
  3. activation may require binding of multiple agonist molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Examples of Ionotropic Receptors

A 
Nicotinic Cholinergic Receptors
GABAergic receptor (A subtype)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Tyrosine Kinase Receptors Structurally

A

polypeptides consisting of:

  • extracellular hormone binding domain
  • cytoplasmic enzyme domain (tyrosine kinase, serine kinase, or guanylate cyclase)
  • hydrophobic polypeptide segment that connects the two domains across cell mbrn
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Endogenous Activators of Tyrosine Kinase

A
  1. insulin: for glucose utilization
  2. epidermal growth factor (EGF)
  3. Vascular Endothelial Growth Factor (VEGF)
  4. Platelet-derived growth factor (PDGF)
  5. Atrial natriuretic factor (ANF)
    - most are mimicked or inhibited by drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

EGF

A

for cell growth and tissue repair

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

VEGF

A

for blood vessel growth in healthy and cancerous tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

ANF

A

one way for body to reduce BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Tyrosine Kinase Receptor Activation

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Tyrosine Receptor Regulation

A

regulates many processes

  • cell division
  • membrn protein internalization
  • protein down regulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Cytokine Receptors: Janus-Kinase Linked Structural Characteristics

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Endogenous Activators of Cytokine Receptors : JAK

A
  • growth hormone
  • erythropoietin
  • interferon
  • other regulators of growth and differentiation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Cytokine Receptors JAK Activation

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Nuclear Receptors Structural

A

-intracellular receptors for lipid-soluble agents

3 common functional domains: hormone binding domain, DNA binding domain, transcription activating domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Nuclear Receptor Activation

A
  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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Covalent Bond Energy

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Ionic Bond energy

A

5 kcal/mole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

H Bond Energy

A

2-5 kcal/mole, reversible but stable

-plays a significant role in establishing the selectivity and specificity of drug-receptor interaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

van der Waals

A

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

39
Q

Biophase

A

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

40
Q

ionic forces

A

drug molecules are initially attracted to receptors via

41
Q

noncovalent bond

A

will lead to continuous association and dissociation between drug and molecule

42
Q

amino acids

A

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

43
Q

Binding Affinity

A

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

44
Q

efficacy

A

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

45
Q

intrinsic efficacy

A

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

46
Q

potency

A

ability of a dose to generate a biological response

it depends on affinity and intrinsic efficacy

47
Q

partial agonist

A

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
48
Q

intermediate effect

A

full agonist and inverse agonist combination

49
Q

chemical antagonism

A

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

50
Q

physiological antagonism

A

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

51
Q

indirect antagonism

A

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

52
Q

Competitive Antagonist

A
  • most common in clinical setting
  • agonist and antagonist compete for the same receptor
  • have affinity but no efficacy
53
Q

types of competitive antagonists

A
  1. Equilibrium-Competitive antagonist (Reversible antagonist)
  2. Nonequilibrium-Competitive (Irreversibly Antagonist)
54
Q

Equilibrium Competitive Antagonist

A
  • binds reversibly to the receptor
  • antagonism increases as conc. of antagonist increases
  • overcome by increasing the conc of agonist at the receptor
55
Q

Non-Equilibrium-Competitive Antagonist

A
  • binds irreversibly via a covalent bond
  • antagonism increases as antagonist conc increases
  • cannot be overcome by increasing agonist
56
Q

Langley and Ehrlich

A

developed the concept of a receptor

57
Q

Stephenson efficacy

A

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

58
Q

Two State Theory

A

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
59
Q

cAMP-PKA system

A
  • 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
60
Q

Receptor Systems that use Gs-adenylyl cyclase-cAMP to produce physiological response

A
  1. B-adrenergic receptors
  2. glucagon
  3. prostaglandin I2 - kidney & GI secretion
  4. parathyroid hormone
  5. FSH (follicle stimulating hormone)
61
Q

activation of the G-proteins

A

-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

62
Q

Adenylyl Cyclase Function

A
  • 2 transmembrane regions
  • 2 catalytic domains
  • length of activation is dependent on the rate of GTP hydrolysis by the alpha-a isoform
63
Q

Metabolism of ATP to cAMP

A

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

64
Q

Phosphodiesterase

A

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

65
Q

Effects of Gi-coupled receptors on adenylyl cyclase

A
  • directly opposes the actions of Gs on adenylyl cyclase

- effects of Gi on adenylyl cyclase primarily observed in the presence of stimulated adenylyl cyclase

66
Q

Regulation of glycogen metabolism in liver, heart

A

-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

67
Q

Regulation of lipid metabolism in adipocytes

A

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

68
Q

Dose-Response Curve

A

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
69
Q

Conc. Response Curve

A
  • different based on how data is generated
  • D-R generated w increasing, individual drug-doses
  • C-R curves generated w increasing conc. of drug
70
Q

x-axis of D-R curve

A
  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
71
Q

y-axis

A
  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
72
Q

Maximum response

A
  • 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”
73
Q

Graded Response

A
  • 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
74
Q

Quantal Dose Response Curve

A
  • 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
75
Q

Potency

A

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
76
Q

Intrinsic Activity

A
  • 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
77
Q

Equilibrium-Competitive/Reversible Antagonism

A

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

78
Q

Nonequilibrium-Competitive/Irreversible Antagonism

A

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

79
Q

Indirect Antagonism

A
  • 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
80
Q

Spare receptors

A
  • 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
81
Q

Therapeutic Index

A

larger the number the safer the drug

82
Q

Protective Index

A
  • used to determine a drugs clinical merit
  • Components: ED50 and TD50 (toxic dose)
  • TD50/ED50
    i. e. Phenobarbital 1. Phenobarbital=3 sedation/seizure protection
83
Q

Signal transduction

A

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

84
Q

1st messengers

A

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

85
Q

2nd messengers

A
  • molecules/proteins that are activated w/in a cell upon stimulation of the cell by 1st messengers
    i. e. cAMP
86
Q

Signal Transduction of Ligand-Gated Ion Channels

A

-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

87
Q

7-TMS G protein Couple Receptor System

A
  1. Serpentine Receptor:adrenergic, muscarinic, histaminic, serotonergic
  2. G protein
  3. Intracellular Effectors
88
Q

Intracellular Effectors

A

each has its own effect

  • adenylyl cyclase, guanylyl cyclase, phospholipase C, ion channels
  • proteins affected by a 2nd messenger
89
Q

Langley (1878) & Ehrlich (1913)

A

developed the concept of the receptor for occupancy theory

90
Q

A. J. Clark (1926)

A
  • 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
91
Q

A.J. Clark (1937)

A

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
92
Q

Ariens (1954)

A
  • 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)
93
Q

Stephenson (1956)

A
  • 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
94
Q

Furchgott (1955) & Nickerson (1956)

A
  • provided direct scientific evidence for Stephenson

- proved Clark & Ariens wrong

Pharmacotherapy - Vanwert Module I Sept 2013 (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions