Deja Ch 1 Pharmacokinetics Flashcards
1
Q
Define Pharmacokinetics
A
Field of study that deals with time required for drug absorption, distribution in the body, metabolism, and method of excretion. In short, it is the body’s effect on the drug.
2
Q
Define Volume of distribution (Vd)
A
The apparent volume in the body available to contain the drug. Formula: Vd = Dose/Plasma Drug Concentration
3
Q
Is Vd a physiologic value?
A
No
4
Q
Is Vd an absolute value for any given drug?
A
No
5
Q
Define Clearance (CI)
A
Volume of blood cleared of the drug per unit time; Cl = Rate of elimination of drug/plasma drug concentration; Total Body Cl = Clhepatic + Clrenal + Clpulmonary + Clother
6
Q
Define Half-life (t1/2)
A
Half-life (t1/2) Time required for plasma concentration of drug to decrease by one-half after absorption and distribution are complete; t1/2 = (0.693 x Vd)/(Cl)
7
Q
Define Bioavailability (F)
A
The fraction of (active) drug that reaches the systemic circulation/site of action after administration by any route; F = (AUCpo)/(AUCiv), where AUCpo and AUCiv are the extravascular and intravenous areas under the plasma concentration versus time curves, respectively
8
Q
Define Steady state (Css)
A
Steady state is reached when the rate of drug influx into the body = the rate of drug elimination out of the body; Css = plasma concentration of drug at steady state
9
Q
How much drug is left after two half-lives?
A
25%
10
Q
How much drug is left after three half-lives?
A
12.50%
11
Q
During constant infusion, what percent of steady state is reached after one half-life?
A
50%
12
Q
During constant infusion, what percent of steady state is reached after two half-lives?
A
75%
13
Q
During constant infusion, what percent of steady state is reached after three half-lives?
A
87.50%
14
Q
During constant infusion, what percent of steady state is reached after four half-lives?
A
94%
15
Q
Give the equation Clearance (Cl)
A
Cl = K x Vd, where K is the elimination constant
16
Q
Give the equation Volume of distribution (Vd)
A
Vd = (LD)/(CSS)
17
Q
Give the equation Half-life (t1/2)
A
tl/2 = (0.693)/(K) or (0.693 x Vd)/(Cl)
18
Q
What happens to the steady state concentration of a drug if the infusion rate is doubled?
A
Steady state concentration is also doubled; remember that dose and concentration are directly proportional (linear kinetics); Css x k0/Cl
19
Q
If there is no active secretion or reabsorption, then renal clearance (Clrenal) is equal to what?
A
Glomerular filtration rate (GFR)
20
Q
If a drug is protein bound, then Clrenal is equal to what?
A
GFR _ free fraction (of drug)
21
Q
What happens to the LD in patients with impaired renal or hepatic function?
A
Stays the same
22
Q
What happens to the MD in patients with impaired renal or hepatic function?
A
Decreases
23
Q
For each of the following statements, state whether it refers to zero-order elimination or first-order elimination?Rate of elimination is constant, regardless of concentration
A
Zero-order elimination
24
Q
For each of the following statements, state whether it refers to zero-order elimination or first-order elimination? Plasma concentration decreases exponentially with time
A
First-order elimination
25
For each of the following statements, state whether it refers to zero-order elimination or first-order elimination? Rate of elimination is proportional to the drug concentration
First-order elimination
26
For each of the following statements, state whether it refers to zero-order elimination or first-order elimination? Plasma concentration decreases linearly with time
Zero-order elimination
27
For each of the following statements, state whether it refers to zero-order elimination or first-order elimination? Rate of elimination is independent of concentration
Zero-order elimination
28
For each of the following statements, state whether it refers to zero-order elimination or first-order elimination? Rate of elimination is dependent on concentration
First-order elimination
29
What are some examples of drugs/substances that undergo zero-order elimination?
Acetylsalicylic acid (Aspirin, ASA) at high/toxic concentrations; phenytoin; ethanol
30
Describe the following types of metabolism: Phase I metabolism
Metabolism that generally yields more polar, water-soluble metabolites (may still be active); enzyme activity decreases with patient's age
31
Describe the following types of metabolism: Phase II metabolism
Metabolism that generally yields very polar, inactive metabolites (renally excreted); enzyme activity does not decrease with patient's age
32
Phase I (microsomal) metabolism involves what types of reactions?
Oxidation; reduction; hydrolysis (carried out by cytochrome P-450 enzymes)
33
Phase II (nonmicrosomal) metabolism involves what types of reactions?
Glucuronidation; acetylation; sulfation; amidation; glutathione conjugation
34
Give examples of drugs that undergo phase II metabolism:
Isoniazid (INH), morphine, 6-mercaptopurine, acetaminophen
35
What are the potential consequences of phase I oxidation reactions with regard to drug activity and elimination?
Drug activity may or may not change (no rule, ie, potentially dangerous outcome). Drug elimination is usually increased due to greater water solubility.
36
What are the potential consequences of phase II reactions with regard to drug activity and elimination?
Drug products of phase II reactions are usually inactive and their renal elimination is enhanced.
37
Where are cytochrome P-450 enzymes found?
Smooth endoplasmic reticulum of cells in mainly the liver, but also found in the gastrointestinal (GI) tract, kidney, and lungs
38
Explain what each type of the following clinical phases in drug development is trying to accomplish? Phase I
Safety in healthy individuals; drug pharmacokinetics
39
Explain what each type of the following clinical phases in drug development is trying to accomplish? Phase II
Efficacy in diseased individuals (small scale trials, single- double-blind)
40
Explain what each type of the following clinical phases in drug development is trying to accomplish? Phase III
Efficacy in diseased individuals (small scale trials, single- or double-blind)
41
Explain what each type of the following clinical phases in drug development is trying to accomplish? Phase IV
Postmarketing surveillance (monitored release)
42
At what point during drug development is an investigational new drug (IND) application filed?
Before phase I
43
At what point during drug development is a new drug application (NDA) filed?
After phase III (and before phase IV)
44
What does the term bioequivalence mean?
When comparing two formulations of the same compound, they are said to be bioequivalent to each other if they have the same bioavailability and the same rate of absorption.
45
What is the first-pass effect?
After oral administration, many drugs are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism, therefore usually decreasing the bioavailability of certain oral medications.
46
How many liters are in each of the following compartments of an average adult human? Blood
5L
47
How many liters are in each of the following compartments of an average adult human? Plasma
3L
48
How many liters are in each of the following compartments of an average adult human? Total body water (TBW)
42 L (avg. 70 kg man _ 60%. For women 50% of mass [body weight] in kg is body water due to lower lean muscle mass and higher fat content [adipose tissue]).
49
What is the most common plasma protein that drugs bind to?
Albumin
50
Displacing a drug that is bound to plasma protein(s), for example, albumin, will increase its what?
Its free fraction (therefore may possibly increase the risk of toxicity because the plasma concentration of active drug has been increased, yet depending on the drug, an increase in free fraction may actually increase its metabolism because more drug is available to metabolizing enzymes)
51
For each of the following mechanisms of membrane transport, state if energy is required, if a carrier is required, and if the system is saturable? Passive diffusion
No energy required; no carrier; not saturable (proportional to concentration gradient)
52
For each of the following mechanisms of membrane transport, state if energy is required, if a carrier is required, and if the system is saturable? Facilitated diffusion
No energy required; carrier required; saturable
53
For each of the following mechanisms of membrane transport, state if energy is required, if a carrier is required, and if the system is saturable? Active transport
Against concentration/electrical gradient, therefore energy required; carrier required; saturable
54
The permeation of drugs across cellular membranes is dependent on what drug properties and (local) circumstances?
Drug solubility; drug concentration gradient; drug ionization; surface area; vascularity
55
Acidification of urine will increase renal elimination of what types of drugs?
Weak bases (ionized form of drug, BH+) will be trapped in the renal tubules and thus excreted in the urine.
56
Acidification of urine will decrease renal elimination of what types of drugs?
Weak acids (nonionized, HA, form of a drug) can cross membranes.
57
Alkalinization of urine will increase renal elimination of what types of drugs?
Weak acids (ionized, A_, form of a drug) will be trapped in the renal tubules and thus excreted in the urine.
58
Alkalinization of urine will decrease renal elimination of what types of drugs?
Weak bases (nonionized, B, form of a drug) can cross membranes.
59
What agents are used to acidify urine?
NH4Cl; high dose of vitamin C
60
What agents are used to alkalinize urine?
NaHCO3; acetazolamide
61
Give an example of a weakly acidic drug:
Acetylsalicylic acid (ASA); barbiturates
62
Give an example of a weakly basic drug:
Amphetamines
63
Give examples of drugs metabolized by each of the following cytochrome P-450 enzymes metabolizes: CYP 1A2
Caffeine; ciprofloxacin; theophylline; R-warfarin
64
Give examples of drugs metabolized by each of the following cytochrome P-450 enzymes metabolizes: CYP 2C9
Ibuprofen; naproxen; phenytoin; S-warfarin
65
Give examples of drugs metabolized by each of the following cytochrome P-450 enzymes metabolizes: CYP 2C19
Diazepam; omeprazole
66
Give examples of drugs metabolized by each of the following cytochrome P-450 enzymes metabolizes: CYP 2D6
Codeine; dextromethorphan; fluoxetine; haloperidol; loratadine; metoprolol; paroxetine; risperidone; thioridazine; venlafaxine
67
Give examples of drugs metabolized by each of the following cytochrome P-450 enzymes metabolizes: CYP 2E1
Ethanol; INH; acetaminophen (at high doses)
68
Give examples of drugs metabolized by each of the following cytochrome P-450 enzyme s metabolizes:CYP 3A4 (50%-60% of all therapeutically used drugs are metabolized via CYP 3A4)
Alprazolam; carbamazepine; cyclosporine; diltiazem; erythromycin; fluconazole; itraconazole; ketoconazole; lidocaine; lovastatin; midazolam; nifedipine; quinidine; simvastatin; tacrolimus; verapamil
69
Give examples of drugs and herbal extracts that generally induce cytochrome P-450 enzymes:
Phenobarbital; nicotine; rifampin; phenytoin; carbamazepine; St. John's wort; chronic ethanol consumption
70
Give examples of drugs and foods that generally inhibit cytochrome P-450 enzymes:
Erythromycin; ketoconazole; ciprofloxacin; quinidine; cimetidine; omeprazole; ritonavir; chloramphenicol; acute alcohol intoxication, grapefruit juice
71
Intracellular volume (ICV) makes up what fraction of TBW?
2/3 (ICV = 2/3 TBW)
72
Extracellular volume (ECV) makes up what fraction of TBW?
1/3 (ECV = 1/3 TBW)
73
Interstitial volume makes up what fraction of ECV?
2/3 (interstitial volume = 2/3 ECV)
74
Plasma volume makes up what fraction
1/3 (plasma volume = 1/3 ECV) of ECV?
75
What type of elimination involves a constant fraction of drug eliminated per unit time?
First-order elimination
76
What type of elimination involves a constant amount of drug eliminated per unit time?
Zero-order elimination
77
Define the following terms: Pharmacodynamics (PD)
Field of study that deals with the relationship between plasma concentration of a drug and the body
78
Define the following terms: Affinity
Ability of a drug to bind to a receptor; on a graded dose-response curve, the nearer the curve is to the y axis, the greater the affinity (affinity deals with drugs acting on the same receptor)
79
Define the following terms: Efficacy
How well a drug produces a pharmacological response; on a graded dose-response curve, the height of the curve represents the efficacy
80
Define the following terms: Potency
The amount of drug required to obtain a desired effect; on a graded dose-response curve, the nearer the curve is to the y axis, the greater the potency
81
Will the curves for two drugs acting on the same receptor be parallel or nonparallel to each other on a graded dose-response curve?
Parallel
82
Will the curves for two drugs acting on different receptors be parallel or nonparallel to each other on a graded dose-response curve?
Nonparallel
83
Define the following terms: Agonist
A drug that binds to a receptor, alters its conformation, and activates that receptor's function
84
Define the following terms: Full agonist
An agonist capable of producing a maximal response
85
Define the following terms: Partial agonist
An agonist incapable of producing a maximal response; less efficacious than a full agonist
86
Define the following terms: Antagonist
A drug that binds to a receptor and prevents activation of a receptor
87
Define the following terms: Competitive antagonist
An antagonist that competes with an agonist for the same receptor site; graded dose-response curve will be shifted to the right (parallel) thus decreasing the agonist's potency (and affinity); maximal response will not be affected
88
Define the following terms: Noncompetitive antagonist
An antagonist that acts at a different site from the agonist, yet still prevents the agonist from activating its receptor; potency not affected; maximal response will be decreased; causes a nonparallel shift to the right on a graded dose-response curve
89
What happens when a partial agonist is added in the presence of a full agonist?
The response of the full agonist is reduced; partial agonist is acting as an antagonist.
90
How does a competitive antagonist affect the following? Affinity (1/Km) of agonist
Decreased (thus Km will increase as it is inversely proportional to affinity)
91
How does a competitive antagonist affect the following? Maximal response (Vmax) of agonist
No change
92
How does a noncompetitive antagonist affect the following? Affinity (1/Km) of agonist
No change
93
How does a noncompetitive antagonist affect the following? Maximal response (Vmax) of agonist
Decreased
94
Will increasing the dose of an agonist completely reverse the effect of a competitive antagonist?
Yes
95
Will increasing the dose of an agonist completely reverse the effect of a noncompetitive antagonist?
No
96
Define the following terms: Pharmacologic antagonism
Antagonist and agonist compete for the same receptor site.
97
Define the following terms: Physiologic antagonism
Two different types of agonists acting at different receptors causing opposite responses, therefore,
98
Define the following terms: Chemical antagonism
Response to a drug is antagonized by another compound that binds directly to the effector drug (digoxin is antagonized by digoxin immune Fab[Digibind] which binds directly to digoxin and not its receptor)
99
Define the following terms: Potentiation
When one agonist enhances the action of another compound (benzodiazepines and barbiturates potentiate the effect of gamma-aminobutyric acid (GABA) on its receptor); graded dose-response curve is shifted to the left
100
What is a quantal (cumulative) dose-response curve?
Curve showing the percentage of a population responding to a given drug effect versus dose of drug given (or log of dose); allows you to visualize intersubject variability regarding drug response in graph form
101
What is ED50
Estimation of the effective dose in 50% of a population; the dose at which 50% of the population will
102
Can you obtain the ED50 from a graded (quantitative) dose-response curve?
No (this curve does not represent a population of individuals)
103
Can you obtain the ED50 from a quantal (cumulative) dose-response curve?
Yes (this curve represents a population of individuals)
104
What is TD50?
Estimation of the toxic dose in 50% of a population; the dose at which 50% of the population will have toxic effects from the drug
105
What is LD50?
Estimation of the lethal dose in 50% of a population; the dose at which 50% of the population will die from the drug
106
What is therapeutic index (TI)?
The relative safety of a drug by comparing the ED50 to either the TD50 or LD50; the safer the drug, the "wider" the TI, meaning the TD50 or LD50 is much greater than the ED50; drugs with a "narrow" TI have their TD50 or LD50close to the ED50
107
What is a narrow therapeutic index (NTI)?
Drugs with an NTI usually have a TI less than 2.
108
List some examples of drugs with an NTI:
Carbamazepine; digoxin; levothyroxine; lithium; phenytoin; theophylline; valproic acid; warfarin
