Module A Flashcards
(106 cards)
1
Q
Heparin is largely confined to the plasma compartment because of its __________
A
high molecular weight
2
Q
Maintenance doses are designed to maintain a steady state of plasma concentration and for convenience are often administered in intervals equal to _________
A
the drug’s half life
this will lead to a mximum two-fold fluctuation in the drug’s plasma concentration which is seen as acceptable in most cases
3
Q
By definition, drugs delivered by the IV route have ____% bioavailability
A
100%
4
Q
Drug clearance (Cl) is defined as:
A
The volume of body fluid from which the drug is removed per unit time.
5
Q
an antagonist that binds to a receptor irreversibly through covalent bonding is said to be _________
A
non-competitive
6
Q
In the dose-response relationships shown here, drug B would act as a ___________ in the presence of drug C
A
antagonist
Drug B is an incomplete agonist and will act as a competitive inhibitor in the presence of a drug with higher efficacy
7
Q
In general, acidic drugs bind to plasma _________
A
albumin - A for Acid and Albumin
8
Q
npo means:
A
nothing by mouth
“nil per os”
9
Q
ED50 is used to measure _________ (potency / efficacy) and is defined as:
A
ED50 (median effective dose) measures drug potency and is the dose that produces 50% of the maximal effect of the drug
10
Q
qh means
A
every hour
“quaque hora”
11
Q
Drugs that are eliminated by Zero-order kinetics have a _______ (constant / variable) half-life and a ________ (constant / variable clearance) relative to plasma concentration of the drug.
A
variable half-life and variable clearance. The half-life is proportional to plasma concentration while the clearance is inversely proportional
12
Q
desensitization/tachypylaxis is a ________-term adaptation to exposure to a drug, while down-regulation is _________-term reaction
A
desensitization is short term, down-regulation is long term
13
Q
Aqueous diffusion of a drug is limited by __________
A
Molecular weight (only small molecules can diffuse through aqueous pores)
14
Q
A drug that has affinity for a receptor and only incomplete efficacy is a(n) _________
A
partial agonist
15
Q
pc means
A
after meals
“post cibum”
16
Q
Weakly acidic drugs absorb best in the (stomach / intestine)
A
intestine - there is a greater surface area available for diffusion, which is more important than acid/base ionization effects
17
Q
ex aq means:
A
in water
18
Q
bid means
A
twice per day
“bis in die”
19
Q
The organs most involved in excretion are the _____
A
Kidneys
20
Q
Phosphorylation of receptors in response to repeated exposure to ligand is an underlying mechanism of
____________
A
desensitization
phosphorylation may reduce the affinity of ligand for receptor or may mark the receptor for cellular internalization, reducing receptor density on the cell surface
21
Q
Define enterohepatic cycling
A
The phenomenon whereby drugs excreted through the biliary pathway are metabolized by gut flora and reabsorbed into the circulation
22
Q
The main purposes of biotransformation are:
A
reduce the toxicity of drugs and make them more soluble to facilitate excretion
23
Q
Describe what a prodrug is and why it may be given
A
a prodrug is inactive until metabolized by the body. It may be given because the prodrug molecule is better absorbed than the active molecule (ex: elanapril).
24
Q
The time indicated by E in this drug plasma concentration curve is called ______ and represents _____
A
Onset represents the time after drug administration until the MEC is reached, i.e. the time until a measurable therapeutic effect is observed
25
compare and contrast the **therapeutic index (TI)** and **certain safety factor (CSF)** of a drug
Both are measures of a drugs safety in relation to its potency
## Footnote
**Therapeutic index (TI)** is the ratio between LD50 and ED50
**Certain safety factor (CSF)** is the ratio between LD1 and ED99 of a drug. It is a more restrictive and perhaps more practical measure of the safety of a drug.
26
A drug that has both affinity and efficacy with a receptor is a(n) \_\_\_\_\_\_\_\_\_
agonist
27
List the 4 types of drug receptors
1. G-Protein coupled (GPCRs)
2. Ligand-gated ion channels
3. Membrane-bound enzymes
4. Intracellular (nuclear)
28
qd means:
every day
29
In the dose-response relationships shown here, ED50 of drug B is \_\_\_\_\_\_
1 mg/kg
30
Compare and contrast G-Protein signal transduction for Gαs, Gαi, and Gαq containing G-proteins
All pathways are activated by a ligand binding to a GCRP which causes G-protein activation by GTP-binding and GDP release. They differ in the effector system and second messengers used.
## Footnote
Gαs and Gαi either stimulate or inactivate **adenylyl cyclase**, leading to up or down-regulation of **cAMP** production
Gαq activates **phospholipase C** which produces **IP3** and **diacylglyerol (DAG)**. These two cause an elevation of intracellular Ca2+
31
upregulation in CYPs that metabolize opioids in response to chronic opioid exposure is an example of __________ (pharmacokinetic / pharmacodynamic) tolerance
pharmacokinetic
## Footnote
*changes in number of enzymes for metabolism is a pharmacokinetic change. Changes in number of receptors is a pharmacodynamic change with regards to tolerance.*
32
To facilitate excretion of a weak base drug, the clinician should target a _____ (acidic/basic) tubular pH
acidic. drugs can not be passively reabsorbed in their ionized form, so the ionized weak base will be excreted more readily.
33
non rep means:
do not repeat
34
List three ways that drug receptors are classified:
1. Drug specificity
2. Tissue location
3. Primary amino acid sequence
35
glucuronosyltransferases, acetyltrasnferases, and sulfotransferases are associated with phase _____ (i/ii) biotransformation
phase ii. phase ii reactions are conjugation reactions and thus all involve a "transferase" enzyme
36
The time indicated by B in this drug plasma concentration curve is called ______ and represents \_\_\_\_\_
Tmax represents the time until the maximum plasma concentration (Cmax) of the drug is reached
37
The organ that is most involved in biotransformation is the \_\_\_\_\_
Liver
38
compare an allosteric to orthosteric drug-binding site
allosteric = a different binding site than the endogenous ligand
orthosteric = same binding site as the endogenous ligand
39
\_\_\_\_\_\_\_ is the ability of a drug to bind with its receptor or target
affinity
40
When GDP is bound to a g-protein, it is _______ (activated / inactivated)
inactivated
## Footnote
*g-protein alpha-subunit activation is marked by GTP-binding*
41
Clearance is defined as \_\_\_\_\_\_\_\_\_\_\_\_\_
the rate of elimination divided by the plasma concentration
42
in the presence of a complete agonist, a partial agonist may act as a \_\_\_\_\_\_
antagonist through competitive inhibition
43
An advantage of the inhalational route is it has a _____ (high/low) local effect and a _____ (high/low) systemic effect
high, low
44
bioavailability of a PO drug is calculated by:
dividing the AUC of the PO drug by the AUC of the same dose of the drug given IV
45
Drugs that have a high fraction bound to plasma proteins will have a ______ (high/low) glomerular filtration rate
low
46
Explain the difference between phase I, II, and III clinical trials
**Phase I:** drug administered to healhty individuals to study pharmacokinetics and pharmacodynamics
**Phase II**: Drug administered to individuals with condition of study to establish dosing, efficacy, safe use, etc.
**Phase III:** large-scale trials to study drug therapeutic benefit
47
ADME stands for:
Absorption, Distribution, Metabolism, Excretion
48
a.c. means
before meals
"ante cibum"
49
Describe differences between the one-compartment and two-compartment models of pharmacokinetics
the two component model treats blood plasma and tissues/organs as two separate compartments and describes a third rate constant for determining movement of drugs between these two.
50
A pharmacodynamic drug interaction where the effect of two drugs given together is greater than the sum of their individual effects is called
a synergistic effect
51
po means
by mouth
"per os"
52
List 5 methods of excretion that are not renal:
bile, sweat, saliva, tears, feces, breast milk, exhaled air
53
\_\_\_\_\_\_\_\_\_\_\_ tolerance is caused by a change in number/density of receptors, whereas __________ tolerance is caused by a change in the number of enzymes responsible for drug elimination
**_pharmacodynamic**_ tolerance is caused by a change in number/density of receptors, whereas _**pharmacokinetic_** tolerance is caused by a change in the number of enzymes responsible for drug elimination
54
hs means:
at bedtime
"hora somni"
55
Adenylyl cyclase is stimulated by the G-protein _______ and catalyzes production of \_\_\_\_\_\_\_
Gαs and catalyzes production of cAMP
56
What is the importance of AUC in pharmacokinetics?
AUC (area under curve) represents the total amount of drug made available to the systemic circulation for therapeutic effect
57
To facilitate excretion of a weak acid drug, the clinician should target a _____ (acidic/basic) tubular pH
basic. drugs can not be passively reabsorbed in their ionized form, so the ionized weak acid will be excreted more readily.
58
qid means
4 times a day
"quater in die"
59
Drugs that are weak acids have best absorption in ______ (acidic / basic) environments
acidic
60
In the dose-response relationships shown here, the drug with the highest **potency** is \_\_\_\_\_\_
drug A as it has the lowest ED50
61
alt hor means:
every other hour
"alternis horis"
62
prn means
as needed
"pro re nata"
63
A synergistic drug interaction is:
A pharmacodynamic drug interaction where the effect of two drugs given together is greater than the sum of their individual effects
64
describe the distribution and elimination phases of pharmacokinetics
after administration of a drug, there is a rapid decrease in plasma concentration (ditribution phase) as the drug is ditributed in body fluids. After that, the plasma concentration decreases more slowly as the drug is metabolized and excreted
65
The primary determinant of drug efficacy is \_\_\_\_\_\_
receptor affinity
66
Phase i biotransformation involves the processes \_\_\_\_\_, \_\_\_\_\_, and \_\_\_\_\_
reduction, oxidation, and hydrolysis
67
Biliary excretion tends to only include drugs with a _____ (high / low) molecular weight
high
68
The time interval indicated by D in this drug plasma concentration curve is called ______ and represents \_\_\_\_\_
Duration represents the amount of time that the drug will have a measurable therapeutic effect
69
List the 4 steps of renal excretion and an important factor in determining the rate of each one
1. glomerular filtration - depends on level of drug-albumin binding
2. active tubular secretion - depends on competitive inhibition by other drugs/metabolites
3. passive tubular reabsorption - Depends on tubular pH (ionized forms will not reabsorb)
4. excretion - depends on urine flow rate
70
An antagonist that binds to the receptor reversibly is said to be \_\_\_\_\_\_\_\_\_\_
competitive
71
Bioavailability is defined as:
the fraction of the administered dose of a drug that reaches the systemic circulation in an active form
72
Define elimination
Elimination = metabolism + excretion
73
all adrenergic receptors belong to the class \_\_\_\_\_\_
G-Protein coupled receptors (GPCRs)
74
CYP isozymes are primarily associated with phase _____ (i/ii) biotransformation
phase i
75
Define Volume of distribution (Vd)
The volume of fluid a certain dose of drug would need to be dissolved in to achieve the same concentration as it has in plasma
76
The concentration indicated by C in this drug plasma concentration curve is called ______ and represents \_\_\_\_\_
Minimum Effective Concentration (MEC) represents the minimum plasma concentration required to have a measurable therapeutic effect
77
In general, basic drugs bind to plasma \_\_\_\_\_\_\_\_\_
glycoproteins and Beta-globulins - B for Base and Beta-Globulin
78
Organs receiving the highest proportion of cardiac output, like ___________ (list 4) will receive drugs at the highest rate.
Heart, brain, liver, kidneys
79
In the dose-response relationships shown here, the drug with the highest **efficacy** is \_\_\_\_\_\_
drug C as it has the highest effect
80
Pulmonary drug kinetics are not well reflected by plasma concentration curves, so instead a _________ curve is used
time-clinical effects curve
81
Compare a potentiative effect to a synergistic effect
both are cases where two drugs combined have a greater effect than the sum of their individual effects. A potentiative drug interaction follows the formula (0 + 1 = 3) i.e. one of the drugs activates the other. A synergistic effect follows the formula (1 + 1 = 3)
82
The site of most drug metabolism is \_\_\_\_\_\_\_\_\_\_
the liver
83
Drug metabolites tend to be __________ (more / less) water-soluble than the parent molecule
more
84
Explain why it would be favorable for drugs delivered by the inhalational route to have a high first pass metabolism
We generally want these drugs to have a large local and small systemic effect. Some of these drugs will invariably be ingested enterally. We want there to be a high first-pass effect on the ingested fraction to avoid systemic effects
85
Lipid diffusion is facilitated by a drug having high \_\_\_\_\_\_\_\_\_\_\_\_\_\_
Lipid solubility
86
Describe Fick’s law
The rate of diffusion of a substance is proportional to the concentration gradient and surface area of diffusion
87
Drugs that are weak __________ (acids / bases) absorb best in the stomach
acids
88
An additive or summative effect is:
A pharmacodynamic drug interaction where the effect of two drugs given together is equal to the sum of their individual effects
89
Metabolism is also called \_\_\_\_\_\_\_\_\_\_
Biotransformation
90
The attachment of polar groups to drugs to hasten excretion and inactivate the drug is called \_\_\_\_\_\_\_\_\_\_
conjugation
91
Phase ii biotransformation reactions involve adding a polar group, known as \_\_\_\_\_\_
conjugation
92
competitive inhibition may slow the excretion of drugs that are excreted through the process of \_\_\_\_\_\_\_
active tubular secretion. In this case active transporters are occupied by competing molecules.
93
conjugation
The attachment of polar groups to drugs to hasten excretion and inactivate the drug
94
A pharmacodynamic drug interaction where the effect of two drugs given together is equal to the sum of their individual effects is called:
An additive effect
95
cap means
community aquired pneumonia
96
compare and contrast **potency** and **efficacy** of drugs
both measure the effect of a drug on the body
## Footnote
**potency** measures the effect of a drug relative to the dose given. Drugs with high potency have their maximum effects at relatively low doses (this does not mean that they have a large effect!)
**efficacy** measures the effect of a drug relative to the maximum possible effect at a given receptor. A drug with high efficacy will have the highest possible effect for a given receptor type
97
ad lib means
as desired
"ad libitum"
98
chronic exposure to antagonists may cause ___________ of receptors as a compensatory mechanism
up-regulation
99
Define loading dose and explain how it is calculated
loading dose is a relatively large initial dose of a drug given to achieve a desired plasama concentration. It is calculated as:
Loading Dose = Vd X C
*where Vd is the volume of distribution and C is the desired plasma concentration*
100
Drugs administered by the sublingual or rectal route have __________ (more / less) first pass metabolization than those administered by the oral route
less
101
Zero-order elimination kinetics, as seen in ethanol, occur when \_\_\_\_\_\_\_\_\_\_
there is saturation of the enzymes responsible for elimination.
102
The concentration indicated by A in this drug plasma concentration curve is called ______ and represents \_\_\_\_\_
Cmax represents the maximum plasma concentration of the drug
103
Drugs that are eliminated by First order kinetics have a _______ (constant / variable) half-life and a ________ (cosntant / variable clearance) relative to plasma concentration of the drug.
constant half-life and constant clearance.
## Footnote
*the rate of elimination changes with palsma concentration, but half-life and clearance remain cosntant*
104
A drug that has affinity for, but no efficacy with a receptor is a(n) \_\_\_\_\_\_\_\_\_
antagonist
105
tid means:
three times daily
106
Describe the role of ABC transporters like Pgp in drug distribution
ABC transporters line the luminal side of endothelial cells in the GI tract, brain capillaries, and other tissues. They pump drugs into the luminal space, effectively reducing the tissue concentrations of drug. Pgp is inhibited by drugs like amiodarone and propranolol, which may increase potency of other drugs
