Pharmacodynamics Flashcards
1
Q
1906 Pure Food and Drug Act
A
Products must be accurately labeled
2
Q
1938 Food, Drugs, and Cosmetic Act
A
Demo of safety before release into market
3
Q
1951 Humphrey-Durham Amendment
A
Established Prescriptions for certain drugs (pot harmful, complicated instructions)
4
Q
1962 Drug Amendments
A
Safety and required demo of efficacy (thalidomide)
5
Q
Clinical Testing Phases
A
I (safe, kinetics), II (does it work in pts.), III (double blind)
6
Q
Quantal dose-response curves
A
How many people (all or none?)
7
Q
What do Quantal dose-response curves predict?
A
Population frequency
8
Q
Graded dose-response curve
A
How much effect?
9
Q
What does a graded dose response curve predict?
A
Population response magnitude
10
Q
ED50
A
dose producing a defined effect in 50% pop (quantal dose-response)
11
Q
EC50
A
Concentration producing 50% of the maximal effect (graded dose-response curve)
12
Q
LD50
A
dose of a drug that will produce a lethal (not actually lethal, highly toxic) effect in half pop
13
Q
TD50
A
dose of a drug that will produce a toxic effect in half the population
14
Q
TI
A
ratio of LD50 to ED50
15
Q
Drugs with large TIs are ____
A
very safe
16
Q
TI =
A
LD50/ED50
17
Q
vitamins/supplements/”natural products” can cause____
A
liver injury
18
Q
What are the concerns of regulating dietary supplements?
A
effectiveness, contain whats listed, contaminated, contain prescription drugs but not reported
19
Q
1994 Dietary Supplement Health and Education ACt
A
accurately labeled
20
Q
2006 Dietary Supplement and NonPresciption Drug Consumer Protection Act
A
must report serious adverse effects post marketing, burden of proof is with FDA
21
Q
Whats an example of drug regulation for supplements?
A
DMAA - amphetamine derivative marketed as dietary supplement (adverse effects: arrhythmia and heart attacks)
22
Q
What makes a drug unsafe?
A
Receptors -which bind, action, where located
Interactions
Who is taking (kids, preg, elderly, genetics)
23
Q
safer drugs often have greater _____
A
organ and receptor selectivity
24
Q
Drugs interaction with ___
A
other drugs, dietary constituents, herbal remedies
25
What does a narrow therapeutic window mean?
Small changes in amount can lead to toxicity
26
What do things that result in drug interactions commonly effect?
PK of drug: CYPs and drug metabolism
27
If a drug demonstrates receptor selectivity, it means ____
at rel low drug conc, it primarily acts at one receptor/receptor subgroup; but increasing the drug conc will result in reduced selectivity
28
Factors influencing receptor selectivity
drug solubility , drug and receptor structure, and chemical forces influencing drug-receptor interaction
29
Beta-2 Adrenergic Binding Pocket is a _____
dynamic interaction, dynamic conformation change
30
What is the importance of a covalent bond in receptor phamacology?
The ligand - receptor complex is essentially permanent
31
most receptors have ____ bonds
ionic (reversible interactions)
32
What are types of drug targets?
Receptors, Ion channels (anti-epileptics), enzymes (ACE inhibitors), transporters (SSRIs)
33
What are different types of receptors?
Ligand-gated ion channels, G-protein coupled receptors, kinase-linked receptors, nuclear receptors
34
Target 1 (a subunit examples)
adenylyl cyclase (Gs, Gi), Phospolipase C (Gq)
35
Target 2 (bg subunit) examples
K+ channel, Ca++ channel, PI3 K
36
Gs action?
activates adenylyl cyclase
37
what inhibits cAMP
phosphodiesterases
38
Gi action?
inhibits adenylyl cyclase
39
Gq action?
activates phospholipase C
40
What does the G-protein Beta/Gamma Subunits target?
K channel, calcium channel, PI3 Kinase
41
What are some other drug targets?
Chemical & physiochemical mechanisms, DNA/RNA and the ribosome, Biopharmaceuticals, gene therapy
42
Desensitization
diminished response after continuous application to repeated exposure to an agonist
43
What can desensitization be observed as?
decrease in potency (right shift in curve), decrease in efficacy
at any single conc, see reduced response
44
What does desensitization look like at the receptor level?
Reduction in receptor responsiveness
45
Tolerance
reduction in response to repetitive use of same drug can be overcome by increasing dose
46
Drug resistance:
reduced effectiveness of drug usually in reference to microorganisms or population of cancer cells
47
what are diminishing drug effects due to
altered metabolism of drugs, exhaustion of mediators, phys adaptations, active etrusion from cells, change in receptors, down-regulation and loss of receptors
48
with continued activation of the receptor, the system responds by:
decreasing responsiveness
49
What does increased receptor responsiveness result from
chronic reduction of receptor stimulation, tissue response to pathological conditions
50
with continued block of the receptor, the system responds by
increasing responsiveness
51
when withdrawing pt from a drug, what should you do?
TAPER the dose
52
long term stimulation of the receptor is likely to cause
desensitization and/or down-regulation
53
long term blockage of the receptor is likely to cause
up regulation and/or sensitization
54
placebo
dosage form devoid of active ingredient
55
written prescriptions are required for
Schedule II drugs
56
Agonist drug
active site of similar shape to the endogenous ligand so binds to the receptor and produces the same effect
57
Antagonist drug
close enough in shape to bind to the receptor but not close enough to produce an effect; takes up receptor space and prevent endogenous ligand from binding
58
Where is the most accurate part of a Dose response curve
middle of curve - EC50
59
dose
amount of drug administered to person (in vivo)
60
concentration
amount of drug per unit volume
61
Occupation of a drug is governed by
affinity
62
Activation of a drug is governed by
efficacy
63
efficacy
ability of ligand-receptor complex to produce an effect
64
affinity
interaction of a ligand and a receptor
65
agonist
ligand which binds to a receptor and produces no effect one its own by will reduce the effect of an agonist
66
an agonist has ___ and an antagonist has ___
efficacy, no efficacy
67
affinity is ____ upon activation of the receptor
independent
68
the stronger a drug is bound to a receptor (higher affinity), the ____ the Kd
smaller
69
A high affinity means ____
you need less drug to occupy 50% of receptors
70
the higher the affinity, the smaller the ____
Kd
71
potency
how much of a drug is needed to generate a response
72
How can a low potency drug still be effective?
need more of it
73
efficacy
how much a response is generated
74
low ____ drugs cannot reach maximal response
efficacy
75
the response is maximal when ____
all receptor sites have been occupied
76
orthosteric
ligand binds at the same site as endogenous ligand
77
allosteric
ligand binds at a site distinct from endogenous ligand binding site
78
positive allosteric modulator
has no effect by itself but enhances orthosteric ligand affinity or efficacy
79
a positive allosteric modulator/enhancer ____ the effect of an antagonist
potentiates
80
allosteric agonist
mediates receptor activation on its own at site distinct from orthosteric site
81
neutral allosteric ligand
binds allosteric site without affecting orthosteric site but blocks action of other allosteric modulator (blocks ability of anything else to bind)
82
Allosteric antagonist (negative allosteric modulator)
reduces orthosteric ligand affinity or efficacy
83
Examples of positive allosteric modulators
barbiturates, benzodiazepines, alcohol (enhance effect of GABA)
84
example of neutral allosteric ligand
flumazenil (doesnt impact GABA, inhibits binding of other allosteric modulators)
85
example of allosteric antagonist
picrotoxin
86
synergism
effect two drugs are greater than in ind. effects add together
87
drug potentiation
a drug without an effect of its own increases the effect of a second drug
88
additive effects
1+1=2
89
agonist effect blocked in a _____ manner by antagonist
dose-dependent
90
types of noncompetitive allosteric sties
reversible and irreversible
91
what are nonreceptor antagonists
chemical, pharmacokinetic, physiological antagonists
92
competitive (reversible) antagonism
a ligand that reduces the action of another ligand by blocking access to its binding
93
competitive (reversible) antagonism binds at
the same site or overlapping site as the endogenous ligand
94
how can an agonist bind with competitive antagonists
increase dose (antagonist reversibly binds)
95
competitive (reversible) antagonist cause ____ change in efficacy but ___ change in potency
no, reduction
96
how does a competitive (R) antagonist shift the agonist log concentration-effect curve
shifts to the right without changing slope or maximum
97
competitive irreversible antagonist
a ligand which binds to agonist binding site and dissociates very slowly or not at all thus decreasing the action of the agonist
98
what does a competitive irreversible antagonist do the action of the agonist
decreases it
99
allosteric antagonism
ligand which binds a site on the receptor distinct from the orthosteric ligand binding site and reduces the agonist effect
100
how does allosteric antagonism prevent reduces agonist effect
preventing the receptor from full conformational change
101
a competitive antagonist will cause ____ potency and ____ efficacy
reduced, not change
102
a noncompetitive/I competitive antagonist will _____ potency and ____ efficacy
reduce/not change/ reduce
103
partial agonist as antagonist
effect of adding a partial agonist when the receptor is occupied by a full gonist
104
what does a partial agonist do
decrease max effect of agonist (not get full effect)
105
what is a partial antagonist good for (example)
withdrawal (opiods)
106
chemical antagonism
combines with agonist in solution so that the agonist is no longer able to interact with receptor (antiacids, chelating agents, and neutralizing bodies)
107
pharmacokinetic antagonism
reduces concentration of the agonist
108
how does pharmacokinetic antagonism reduce the concentration of the agonist
by decreasing rate of absorption, increasing metabolic degradation, increasing rate of renal excretion, ion trapping
109
medication administered for allergic reaction
epinephrine
110
what are the effects of epinephrine
vasoconstricts and bronchodilates
111
effects of histamine
vasodilates and bronchoconstricts
112
The swallowing center is located where?
Medulla of brain stem
113
Dehydration has what effect on salivary flow?
inhibits
114
What “glands” in small intestine secrete alkaline mucus?
brunners
115
Most water and electrolyte recovery occurs in what GI section?
LI
