Principles of Pharmacology Flashcards
(110 cards)
1
Q
What is a drug
A
a chemical substance of known structure other than a nutrient or essential dietary ingredient, which, when given to a living organism produces a biological effect
2
Q
What is the most common target for drugs
A
proteins
3
Q
What are the 4 different protein targets
A
transmembrane receptors
enzymes
carriers (transporters)
ion channels
4
Q
What effect does an agonist have on a receptor
A
it activates a receptor
5
Q
what effect does an antagonist have on a receptor
A
it blocks activation of a receptor
6
Q
Selectivity
A
the higher the selectivity the more precise it is in the receptor it bonds to. very selectively bonds
7
Q
What is affinity
A
the strength with which the drug binds to the receptor
8
Q
what is efficacy
A
how well the drug activates the receptor
9
Q
what is the affinity/efficacy of a good agonist
A
it should have high affinity and high efficacy
10
Q
what is a full agonist
A
a drug that completely activates the receptor (100% efficacy) takes the receptor to emax
11
Q
What is Emax
A
100% efficacy, or the maximum response a drug can get out of a receptor
12
Q
what is a partial agonist
A
a drug that activates the receptor but doesn’t get a full response (doesn’t ever reach emax no matter the concentration)
13
Q
What is the affinity/efficacy an antagonist
A
high affinity and low efficacy
14
Q
What does the DRC show
A
the DRC is the dose response curve and it shows us the receptors response (Y axis) to a drug with increasing concentration (X-axis, log scale)
15
Q
What is intrinsic activity
A
the efficacy (how well the drug activates the receptor)
16
Q
What is the EC50
A
the concentration of a drug required to get 50% of its own maximum efficacy
17
Q
what is the EC50 used for
A
to show “effective concentrations” of the drug
18
Q
What is potency
A
the amount of drug required to produce a given effect (EC50 is often the desired effect measured)
19
Q
something that has high potency…
A
requires low concentrations to get your desired effect
20
Q
What is a competitive antagonist
A
an agonist the competes for the same binding site as the agonist
21
Q
What is a reversible antagonist
A
same thing as a competitive antagonist
22
Q
What happens to the dose response curve in the presence of a competitive antagonist
A
it shifts to the right (this means that in the presence of the competitive antagonist higher concentrations are required to get the same effect as lower concentrations not in the presence of the competitive antagonist)
23
Q
What is a non-competitive antagonist
A
an antagonist that can’t be overcome by the agonist, no matter the agonist concentration
24
Q
what is an irreversible antagonist
A
the same thing as the non-competitive antagonist
25
what happens to the dose response curve in the presence of a non-competitive antagonist
the curve shifts down (this is because the non-competitive antagonist completely inactivates the receptors so that no matter the dose of agonist it can't get back to emax in the presence of the non-competitive antagonist
26
what is allosteric modulation
when a drug acts on a different site than the normal ligand, but causes a change in the receptor which alters the response (can be negative and positive)
27
What is the Quantal dose response curve
dose on the X axis
| percentage of population exhibiting therapuetic effect on the Y axis (as opposed to % of receptor activation)
28
what is ED 50
the dose of drug at which 50% of the population receives the desired effect
29
what is LD 50
the dose of drug at which 50% of the population dies from toxicity
30
what does the therapeutic index of a drug tell us
how safe the drug is.
31
how do you calculate the therapeutic index
LD50/ED50
32
what does a high therapeutic index tell you
that the drug is safe (it takes a lot of the drug to kill 50% of the population in comparison to what it takes for 50% of the population to get its benefits)
33
What is toxicity
an adverse drug reaction that occurs when the dose is too high (acts on similar mechanism to the therapeutic effect)
34
what is a side effect
an adverse drug reaction that occurs within the therapeutic dose range
35
what is a drug allergy
an adverse immune reaction to the drug
36
what is an idosyncratic reaction
an adverse reaction to a drug that is due to the genetics of the patient (not immune based)
37
What is a pharmacokinetic interaction
a drug-drug interaction in which one drug affects the metabolism, excretion, or absorption of the other
38
what happens in a pharmacokinetic interaction when drug A increases the metabolism of drug B
concentration of Drug B decreases as well as its effect
39
what happens in a pharmacokinetic interaction when drug A decreases the excretion of drug B
concentration of drug b increases as well as its effect
40
what happens in a pharmacokinetic interaction when drug A decreases the absorption of drug B
concentration of Drug B decreases as well as its effect
41
What is a target drug-drug interaction
when drugs bind to the same receptor (can be same site or not)
42
what are the potential consequences of a target drug-drug interaction
1. they can both increase the same effect which leads to excessive action of the drugs
2. one can block the action of the other which leads to inadequate action of the blocked drug
43
What is synergism
when a drug causes a greater effect than normal in the presence of another drug
44
What affect did the 1906 Wiley act have
it prohibited the manufacturing and shipment of adulterated and misbranded foods and drugs
45
what affect did the 1914 Harrison Narcotic act have
regulated opiates and cocaine
46
what affect did the 1938 food, drug and cosmetic act have
mandated the FDAs role in regulating the safety of drugs
47
what affect did the 1952 Durham-Humphrey act have
called for certain drugs to be prescription only
48
what affect did the 1983 orphan drug amendment have
it provided incentives for developping drugs for rare diseases
49
what affect did the 1997 FDA modernization act have
allowed manufacturers to discuss off label uses for drugs and streamlined approval for drugs treating life threatening conditions
50
what affect did the 2005 combat methamphetamine epidemic act have
new regulations for sale of ephedrine, psuedoephedrine, and phenylpropanolamine
51
what affect did the 2016 21st century cures act have
$6.8 billion for treating opiod abuse, cancer research, and for expanding mental health care
52
What are the two things the FDA requires drug manufacturers to prove about their drugs
that they are safe and effective
53
what are the steps of clinical drug tests
1. drug discovery
2. preclinical development
3. phase 1 - testing in healhty individuals
4. phase 2- small scale testing in patients
5. phase 3 - large scale controlled trials
6. regulatory approval
7. postmarketing surveilling
54
What is the regulation system for drugs to be used during pregnancy
used to be categorized from A - D and X (based on how safe they are)
now uses narrative structure to convey potential risks
55
What are the four things that happen to a drug in the body
```
ADME
Absorption
Distribution
Metabolism
Excretion
```
56
how do we think of the body in terms of distribution of drugs
like a series of well stirred compartment (well stirred meaning the concentration in a compartment is uniform throughout the entire compartment)
57
What are the 3 barriers drugs must cross to move from compartment to compartment
1. cell membranes (ICF vs. ECF)
2. epithelial barriers (GI mucosa, renal tubules)
3. vascular endothelium (plasma and interstitial water)
58
how does the permeability of vascular endothelium change in different locations in the body
low permeability - tight junctions - BBB
| high permeability - fenestrated junctions - kidneys
59
what are the four ways drugs can cross cell membranes
1. diffusion through lipid bilayer
2. diffusion through aqueous channels
3. via carriers (ATP-ases)
4. pinocytosis (insulin)
60
What is the main determinate of a drugs ability to diffuse through lipid bylayer
solubility in the membrane
| - lipophilic, uncharged, small
61
drugs are often weak acids or bases that exist in ionized and unionized forms what determines whether they are ionized or not
the pKa of the drug and the ph of the fluid they are in.
62
which is going to pass through the lipid membrane better, the ionized or unionized form of the drug
the unionized form (no charge = more lipophilic)
63
what is ion trapping
when there is a large pH difference between adjacent compartments. in one compartment the pH is such that the drug exists as the unionized form so it is more able to permeate the membrane. in the other compartment the pH is such that the drug exists in the ionized form and thus can't permeate cell membranes.
64
What happens to a weak acid drug in a acidic environment
the weak acid drug is mostly unionized and thus can permeate
65
how do we think of acids and bases in the simple way
acids try to give away H
| bases try to steal H
66
what happens to a weak acid drug in a basic environment
the weak acid drug becomes mostly ionized and becomes ion trapped
67
what happens to a weak base drug in a basic environment
the weak base drug is mostly unionized and thus can permeate
68
what happens to a weak base drug in an acidic environment
the weak base becomes mostly ionized and becomes trapped
69
What determines how much of a drug will go to adipose tissue
hydrophilic drugs won't go to fat very much
| highly lipophilic drugs will be come concentrated in fat
70
what is a complication in highly lipophilic drugs
they become concentrated in fat so they are less predictable and often less effective (especially in patients with lots of fat)
71
what is absorption of a drug
a drugs movement into the plasma
72
What are enteral routes of drug administration
routes through the GI tract
- oral
- sublingual
- rectal
73
what is the benefit of sublingual drug administration
it bypasses the hepatic portal system (avoids first pass metabolism)
74
what are parenteral routes of drug administration
routes not through the GI tract
- topical
- inhalation
- injection
75
how long does it take for an orally taken drug to be 75% absorbed
1-3 hours
76
what is bioavailabilty
the fraction of an orally administered drug that reaches systemic circulation
77
what affects the bioavailabilty of a drug
intestinal and hepatic enzymes that metabolize the drug before it can be absorbed
(drug preparation and genetics of the individual affect how much of the drug is metabolized)
78
What is a bioequivalent drug
a generic drug that reaches similar plasma concentrations in a similar amount of time and for a similar duration.
79
what does bioequivalence imply
that the generic drug can be substituted for brand name drugs and the outcomes will be similar
80
what compartments is the body water divided into, and what are the ratios of the total water
intracellular fluid = 2/3 of the total body water
extracellular fluid = 1/3 of total body fluid
- plasma = 8%
- interstitial fluid = 25%
81
What is the total body water in an average person
42 L
- 28 L = ICF
- 14 L = ECF
- 9.5 L = interstitial fluid
- 3.5 L = plasma
82
What is the volume of distribution
the total amount of drug in the body/ divided by the plasma concentration
Vd = Q/Cp
83
what does the volume of distribution represent
the volume of fluid that would be needed to contain all of the drug given, at the same concentration as measured in the plasma
84
What does a high volume of distribution mean
that the drug is highly distributed into the tissues
85
What is a prodrug
a drug that starts as an inactive precursor, that upon metabolism becomes activated
86
what are the two processes by which drug elimination occur
metabolism
| excretion
87
What are the two phases of drug metabolism
phase 1 - catabolism
| phase 2 - anabolism
88
what are the different routes of elimination from the body
kidneys
hepatobiliary system
lungs
fecal
89
what is the product of phase 1 of metabolism usually like
usually has a free hydroxyl group and the product can be more active than the original substrate
90
what is the product of phase 2 of metabolism usually like
usually inactivated, and more easily excreted (except when the original compound is a prodrug)
91
what is first pass metabolism and why is it important
the hepatic portal system takes absorbed comopounds from the gut to the liver where it undergoes some metabolism.
its important because some drugs are highly metabolized and their bioavailability becomes low
92
What is enterohepatic circulation
when the liver transfers some compounds into bile. this acts a reservoir for the drug and prolongs it action
93
what drugs are prone to enterohepatic circulation
glucuronides
94
what are the 3 processes in renal excretion
glomerular filtration
active tubular secretion
passive diffusion across tubular epithelium
95
what is the main determinant of whether a not a drug will undergo glomerular filtration
size of the particle (most drugs are small enough unless bound to proteins)
96
what drugs undergo reabsorption from kidney tubules via passive diffusion
lipid soluble drugs (means they stay in circulation longer)
97
how does the ph of urine affect secretion
it causes ion trapping in urine.
low ph means weak bases will be ionized, trapped, and excreted
high ph means weak acids will be ionized, trapped, and excreted
98
what is TDM?
therapeutic drug monitoring, is when plasma drug concentration is constantly monitored.
99
what is CLtot
clearance, the sum of all of the routes of drug clearance in the body
100
how do you find the rate of drug elimination
Cp x CLtot
101
What does it mean if you have first order kinetics of drug elimination
that the drug concentration is falling exponentially. that is that a certain percentage of the drugs is eliminated per unit of time
102
what is the half time of a drug
the amount of time it takes for half of the drug to be eliminated from the body
103
what is the elimination rate constant (Kel) of a drug
the fraction of a drug eliminated per unit of time
104
what does Kel of .2/h mean
20 % of the drug is eliminated per hour
105
how are half life and the elimination constant related
```
t1/2 = .693/Kel
Kel = .693/t1/2
```
106
how does a single compartment model of elimination differ from a two compartment model of elimination
single compartment model takes only plasma concentration into account
two compartment model takes plasma and tissues into account
107
what are the two exponentials used to model a two compartment model of elimination
```
fast = drug from plasma into tissue
slow = drug elimination from body
```
108
what causes some drugs to be eliminated linearly as opposed to exponentially
saturation of enzymes (when enzymes are completely saturated they can only eliminate at a linear rate
109
what is zero order elimination
AKA saturation kinetics, when enzymes are saturated and drugs are eliminated at a linear rate
110
Why do we need to be conscious of drugs that have zero order kinetics
because it is hard to predict the steady state plasma concentration of the drug and thus hard to know when you are nearing overdose levels
