Book Chapter 2 Flashcards
(232 cards)
1
Q
What is an agonist in pharmacology?
A
A drug that activates a receptor by binding to it.
2
Q
How do most agonists bind to receptors?
A
Through a combination of ionic, hydrogen, and van der Waals interactions.
3
Q
What happens when a receptor is bound to an agonist ligand?
A
The effect of the drug is produced.
4
Q
Define antagonist in pharmacology.
A
A drug that binds to the receptor without activating it.
5
Q
What type of antagonism occurs when increasing concentrations of antagonist inhibit agonist response?
A
Competitive antagonism.
6
Q
What is noncompetitive antagonism?
A
When high concentrations of agonist cannot overcome the antagonism.
7
Q
What is a partial agonist?
A
A drug that binds to a receptor and activates it, but not as much as a full agonist.
8
Q
What effect do inverse agonists have on receptors?
A
They produce the opposite effect of the agonist by turning off receptor activity.
9
Q
True or False: Receptors have only one conformation.
A
False.
10
Q
What is the significance of receptor conformations in pharmacology?
A
They determine the receptor’s activity and response to ligands.
11
Q
What is tachyphylaxis?
A
A decreased response to the same dose of a drug due to receptor downregulation.
12
Q
What can cause upregulation of receptors?
A
Specific stimuli, such as lower motor neuron injury.
13
Q
List three types of drug targets based on location.
A
- Membrane-bound receptors
- Intracellular proteins
- Circulating proteins
14
Q
What is pharmacokinetics?
A
The quantitative study of the absorption, distribution, metabolism, and excretion of drugs.
15
Q
What does pharmacodynamics describe?
A
What the drug does to the body.
16
Q
What are the four basic principles of pharmacokinetics?
A
- Absorption
- Distribution
- Metabolism
- Elimination
17
Q
What is the central compartment in pharmacokinetics?
A
The elements of the body that dilute the drug within the first minute after injection.
18
Q
How does intravenous administration affect drug distribution?
A
Drugs mix with body tissues and are diluted from the concentrated injectate.
19
Q
Fill in the blank: Pharmacokinetics describes what the _______ does to the drug.
A
body
20
Q
True or False: All drugs interact with proteins.
A
False.
21
Q
What role do proteins play when a drug binds to a receptor?
A
They change the activity of the machine, enhancing or decreasing its activity.
22
Q
What is the central compartment in pharmacology?
A
The central compartment is the small initial mixing volume of drug in the body, including venous blood volume, heart, lungs, and upper aorta.
23
Q
What happens to drugs that are highly fat soluble during the first passage through the lungs?
A
They may be avidly taken up, reducing the concentration measured in arterial blood.
24
Q
List examples of drugs with first-pass pulmonary uptake exceeding 65%.
A
- Lidocaine
- Propranolol
- Meperidine
- Fentanyl
- Sufentanil
- Alfentanil
25
True or False: The total volume of distribution for propofol is reported to exceed 5,000 L.
t
26
What are the tissues that receive the bulk of arterial blood flow after drug injection called?
Vessel-rich group.
27
What role do muscles play in drug distribution?
Muscles have intermediate blood flow and solubility for lipophilic drugs.
28
Which plasma proteins do most drugs bind to?
* Albumin
* α1-acid glycoprotein
* Lipoproteins
29
What is the effect of protein binding on drug distribution?
Only the free or unbound fraction can readily cross cell membranes.
30
How does age or hepatic disease affect plasma protein concentration?
They can decrease plasma protein concentration.
31
Fill in the blank: The four basic pathways of metabolism are _____, _____, _____, and _____.
[oxidation], [reduction], [hydrolysis], [conjugation]
32
What is the role of hepatic microsomal enzymes?
They are responsible for the metabolism of most drugs.
33
What is the most common reaction catalyzed by CYP enzymes?
Monooxygenase reaction.
34
Which CYP enzyme is responsible for metabolizing more than one-half of all currently available drugs?
CYP3A4.
35
How can drugs alter the activity of CYP enzymes?
Through induction and inhibition.
36
What is the consequence of enzyme induction on drug metabolism?
It can render drugs less effective through increased metabolism.
37
What is the role of glucuronic acid in drug metabolism?
It is added to lipid-soluble drugs to render them water-soluble.
38
What type of reactions are phase I reactions in drug metabolism?
Oxidation, reduction, and hydrolysis.
39
What is a prodrug? Give an example.
An inactive parent compound that is metabolized to an active drug; example: codeine metabolized to morphine.
40
What are the potential effects of reactive metabolites produced during drug metabolism?
They may lead to organ toxicity.
41
What is the primary enzyme responsible for hydrolysis of drugs?
Enzymes responsible for hydrolysis do not involve the CYP enzyme system.
42
What is the function of glutathione-S-transferase enzymes?
Detoxification and protection against oxidative stress.
43
True or False: The rate of metabolism for most anesthetic drugs is independent of drug concentration.
44
What assumption is fundamental for anesthetic pharmacokinetics?
The clearance of the drug is constant and proportional to drug concentration.
45
What is the relationship between drug concentration and hepatic clearance?
The rate of metabolism for most anesthetic drugs is proportional to drug concentration, making the clearance of the drug constant
## Footnote
This fundamental assumption is crucial for understanding anesthetic pharmacokinetics.
46
What limits the metabolic capacity of the liver?
The liver does not have infinite metabolic capacity
## Footnote
At some drug flow rate, metabolism can no longer be proportional to concentration.
47
What is the equation for the rate of drug metabolism in the liver?
Rate of drug metabolism, R = Q (Cinflow − Coutflow)
## Footnote
Where Q is liver blood flow, Cinflow is the concentration of drug flowing in, and Coutflow is the concentration of drug flowing out.
48
Fill in the blank: The rate of drug flow into the liver is calculated as _______.
liver blood flow, Q, times the concentration of drug flowing in, Cinflow
49
What does the equation R = Q (Cinflow − Coutflow) illustrate?
The relationship between the drug rate of metabolism and liver blood flow
## Footnote
This equation is commonly used in mass-balance pharmacokinetic studies.
50
True or False: Metabolism can always be proportional to drug concentration.
False
## Footnote
Metabolism can become saturated when the liver's metabolic capacity is exceeded.
51
What is the significance of understanding hepatic metabolism in pharmacokinetics?
It provides insight into how drug clearance governs the metabolism of drugs.
52
What happens when the liver's metabolic capacity is exceeded?
Metabolism can no longer be proportional to drug concentration.
53
What factors are involved in mass balance for drug metabolism in the liver?
Rate of drug flow into the liver, rate of drug flow out of the liver, and rate of hepatic metabolism
## Footnote
This balance is essential for analyzing drug metabolism.
54
What is the range of the Response in Equation 2.2?
0 to 1
55
What does a Response of 0 indicate?
No metabolism
56
What does a Response of 1 indicate?
Metabolism at the maximal possible rate
57
What does C refer to in the context of Equation 2.2?
Drug concentration
58
What is C50 in the context of drug response?
The concentration associated with 50% response
59
What happens to the response as C becomes much greater than C50?
The response approaches 1
60
What is the primary concentration used to view the rate of metabolism in the liver?
Coutflow
61
What does Vm represent in the context of hepatic metabolism?
The maximum possible metabolic rate
62
What is Km, the 'Michaelis constant'?
The outflow concentration at which the metabolic rate is 50% of the maximum rate (Vm)
63
When is metabolism proportional to concentration?
When the outflow concentration is less than one-half of Km
64
What is the extraction ratio?
The fraction of inflowing drug extracted by the liver
65
How is clearance calculated?
Liver blood flow times the extraction ratio
66
What is the relationship between infusion rate and metabolic rate?
Infusion rate = metabolic rate = Clearance × Cinflow
67
What type of drugs have a high extraction ratio?
Drugs like propofol
68
What is flow-limited clearance?
Clearance that is nearly identical to liver blood flow for drugs with high extraction ratios
69
What is capacity-limited clearance?
Clearance limited by the liver's capacity to metabolize the drug
70
What happens to clearance for drugs with low extraction ratios when liver blood flow changes?
Clearance is nearly independent of liver blood flow
71
What is intrinsic clearance?
A term that summarizes the hepatic metabolic capacity
72
What does Clint represent?
Intrinsic clearance in the linear range
73
What are the three processes involved in renal excretion of drugs?
* Glomerular filtration
* Active tubular secretion
* Passive tubular reabsorption
74
How does pH influence renal tubular reabsorption?
It alters the fraction of drug that exists in the ionized form
75
Which equation predicts creatinine clearance?
Cockcroft and Gault equation
76
What is the effect of age on renal blood flow?
Inversely correlated
77
True or False: Elderly patients with normal serum creatinine have the same GFR as younger patients.
78
What equation predicts creatinine clearance from age and weight?
The equation of Cockcroft and Gault.
79
How does age affect glomerular filtration rate (GFR)?
Elderly patients with normal serum creatinine have about half the GFR than younger patients.
80
Why is absorption placed at the end of the pharmacokinetics list in this textbook?
Because most anesthetic drugs are administered intravenously, making absorption less relevant.
81
What forms do most drugs exist in solution?
Ionized and nonionized forms.
82
Which drug form is usually pharmacologically active?
The nonionized form.
83
What is the impact of a high degree of ionization on drug absorption?
It impairs absorption from the gastrointestinal tract and limits access to drug-metabolizing enzymes.
84
What factors determine the degree of drug ionization?
Dissociation constant (pK) and the pH of the surrounding fluid.
85
What phenomenon occurs when a weak base accumulates in an acidic environment?
Ion trapping.
86
What is the first-pass hepatic effect?
Drugs absorbed from the gastrointestinal tract pass through the liver before entering systemic circulation.
87
What is a common consequence of first-pass hepatic metabolism?
Large differences in pharmacologic effect between oral and intravenous doses.
88
What is a key advantage of sublingual and buccal administration?
Bypasses first-pass metabolism for the initial dose.
89
What is the primary site of drug absorption after oral administration?
The small intestine.
90
Fill in the blank: The _______ route of administration allows for rapid drug effect bypassing the liver.
sublingual
91
What are the characteristics of drugs suitable for transdermal absorption?
* Combined water and lipid solubility
* Molecular weight of <1,000
* pH 5 to 9 in a saturated aqueous solution
* Absence of histamine-releasing effects
* Daily dose requirements of <10 mg
92
True or False: The rate-limiting step in transdermal absorption is diffusion across the stratum corneum.
True.
93
What is the effect of increased blood flow at the site of drug absorption?
Enhances systemic absorption.
94
What type of drugs are usually highly ionized at alkaline pH?
Acidic drugs, such as barbiturates.
95
What happens to local anesthetics when they cross the placenta?
They are converted to the poorly lipid-soluble ionized fraction in the more acidic environment of the fetus.
96
What is the extraction ratio for propofol?
Nearly 1.
97
What is the consequence of the first-pass hepatic effect on nitroglycerin?
Oral nitroglycerin tablets are ineffective due to extensive first-pass hepatic metabolism.
98
What is the primary mechanism of drug elimination by the kidneys?
Excretion of unchanged drugs or their metabolites.
99
What is a common characteristic of drugs delivered via transdermal systems?
Sustained therapeutic plasma concentrations.
100
What can cause variability in transdermal delivery of drugs?
Differences in the thickness and chemistry of the stratum corneum.
101
What is the primary reason for the ineffectiveness of oral administration of propofol?
Extensive first-pass hepatic metabolism.
102
Fill in the blank: _______ is a route of drug administration that provides rapid onset of effect due to bypassing liver metabolism.
Sublingual
103
What is one reason that scopolamine patches are placed behind the ear?
To utilize skin with different thickness for better absorption.
104
What are the initial sites of absorption for drugs through the skin?
Sweat ducts and hair follicles
## Footnote
These structures function as diffusion shunts, aiding in the absorption process.
105
How does the thickness of the stratum corneum affect drug absorption?
It reflects the skin’s permeability to drug absorption
## Footnote
Skin thickness varies, with 10-20 microns on the back and abdomen versus 400-600 microns on the palmar surfaces.
106
Why are scopolamine patches placed behind the ear?
Due to the thin epidermal layer and higher temperature
## Footnote
This area allows for predictable and sustained absorption of scopolamine.
107
What is the regeneration cycle of the stratum corneum?
About 7 days
## Footnote
This cycle limits the adhesion duration of transdermal delivery systems.
108
What is a common reaction at the site of transdermal patch applications?
Contact dermatitis
## Footnote
This occurs in a significant number of patients and contributes to limiting patch duration.
109
Where are drugs administered rectally absorbed into?
Superior hemorrhoidal veins
## Footnote
This leads to transport via the portal venous system to the liver.
110
What is the effect of rectal administration on first-pass metabolism?
Drugs undergo the same first-pass metabolism as orally administered drugs
## Footnote
This is applicable for drugs placed in the proximal rectum.
111
What happens when drugs are placed more distally in the rectum?
They may be absorbed directly into systemic circulation
## Footnote
This bypasses the liver, making rectal drug delivery unpredictable.
112
True or False: The absorption of rectally administered drugs is always predictable.
False
## Footnote
Rectal drug delivery is exceptionally unpredictable due to various factors.
113
What is a zero-order process?
A process where the rate of change is constant
## Footnote
In pharmacokinetics, it refers to processes like oxygen consumption and carbon dioxide production.
114
What is the equation for a zero-order process?
x(t) = x0 + k · t
## Footnote
Here, x0 is the value of x at time 0, k is the rate constant, and t is time.
115
What is a first-order process?
A process where the rate of change is proportional to the amount present
## Footnote
Examples include interest payments and water draining from a bathtub.
116
What is the equation for a first-order process?
x(t) = x0 e−kt
## Footnote
In this equation, k is a positive number, and x0 is the initial amount.
117
What does the term half-life (t½) represent?
The time required for a quantity to decrease to half its initial value
## Footnote
It is directly related to the rate constant k.
118
What is the relationship between the rate constant (k) and half-life (t½)?
t½ = 0.693/k
## Footnote
The natural log of 2 is approximately 0.693.
119
What is a physiologic pharmacokinetic model?
A model that analyzes volumes and clearances for each organ in the body
## Footnote
These models can be complex but are useful for understanding drug distribution.
120
What are compartmental pharmacokinetic models?
Models that simplify the pharmacokinetics by grouping tissues into compartments
## Footnote
They can be one-, two-, or three-compartment models.
121
What is the definition of concentration in pharmacokinetics?
Concentration (C) = amount of drug (x) / volume (V)
## Footnote
This relationship is fundamental for calculating doses and clearances.
122
What is the equation to calculate the bolus dose for a desired target concentration?
Dose = CT × V
## Footnote
CT is the target concentration, and V is the volume of the compartment.
123
What is the fundamental identity of linear pharmacokinetics?
Cl = k × V
## Footnote
Where Cl is clearance, k is the rate constant, and V is the volume.
124
How does volume and clearance affect half-life?
Half-life is proportional to volume and inversely proportional to clearance
## Footnote
A larger volume with smaller clearance leads to longer half-life.
125
What is linear pharmacokinetics?
A situation where metabolism is proportional to concentration
## Footnote
In linear pharmacokinetics, clearance remains constant regardless of dose.
126
What is the area under the curve (AUC) in pharmacokinetics?
The integral of the concentration over time curve
## Footnote
It is used to calculate clearance.
127
What is the equation for calculating clearance from AUC?
Cl = Dose / AUC
## Footnote
This applies to any type of intravenous drug dosing.
128
What does the steady-state concentration (Css) represent during an infusion?
The concentration of drug in the plasma when the rate of drug input equals the rate of drug output
## Footnote
Css is achieved when I = C · Cl.
129
What is the equation for steady-state concentration during an infusion?
Css = I / Cl
## Footnote
I is the infusion rate, and Cl is the clearance.
130
What is the equation for infusion rate in pharmacokinetics?
CT · Cl
131
What does volume relate to in the context of bolus dose?
Initial concentration
132
What does clearance relate to during a continuous infusion?
Steady-state concentration
133
Is the initial concentration following a bolus dependent on clearance?
No
134
Is the steady-state concentration during a continuous infusion dependent on volume?
No
135
What represents the rate of change in the amount of drug, x, during an infusion?
Rate of inflow, I, minus the rate of outflow, k · x
136
How can we calculate x at any time t during an infusion?
Integral from time 0 to time t
137
What happens to e^(-kt) as t approaches infinity?
It approaches 0
138
What is xss in the context of infusion?
Steady state amount
139
How long does it take to reach half of the steady-state amount?
t1/2
140
How many half-lives does it take to reach 75% of steady state?
2 half-lives
141
What is first-pass hepatic metabolism?
Metabolism of drugs by the liver before reaching systemic circulation
142
What is the bioavailability fraction represented by in pharmacokinetics?
f
143
What is the absorption rate equation for oral drugs?
A(t) = f · Doral · ka · e^(-kat)
144
What is the differential equation for the amount, x, with oral absorption?
Rate of absorption at time t, A(t), minus the rate of exit, k · x
145
What model is often used to describe the pharmacokinetics of intravenous anesthetics?
Multicompartment models
146
What are the three distinct phases of drug concentration after a bolus injection?
Rapid distribution phase, slow distribution phase, terminal elimination phase
147
What characterizes the terminal elimination phase?
Plasma concentration is lower than tissue concentrations
148
What does a mammillary model consist of?
Central compartment with peripheral compartments connecting to it
149
What is the equation that describes plasma concentrations over time after bolus injection?
C(t) = Ae^(-αt) + Be^(-βt) + Ce^(-γt)
150
What are A, B, and C in the polyexponential equation?
Coefficients
151
What are α, β, and γ in the polyexponential equation?
Exponents
152
What is the significance of adding more exponent terms in pharmacokinetic models?
Improves description of observed concentrations but decreases confidence in coefficients
153
What do micro-rate constants, kij, define?
Rate of drug transfer from compartment i to compartment j
154
What are the differential equations for a two-compartment model?
Equations derived from the micro-rate constants
155
What happens to the complexity of interconversions between micro-rate constants and exponents as more exponents are added?
It becomes exceedingly complex.
156
Where can individuals find interconversion data for micro-rate constants and exponents?
In the Excel spreadsheet 'convert.xls' available at https://github.com/StevenLShafer/Pharmacokinetics/blob/master/convert.xls.
157
What is the time lag between plasma drug concentration and effect site drug concentration for anesthetic drugs called?
Hysteresis.
158
Which drug shows a greater time lag between arterial concentration and electroencephalogram effect?
Fentanyl.
159
What is the effect of alfentanil on the time lag compared to fentanyl?
Alfentanil has less hysteresis (delay) than fentanyl.
160
What model describes the relationship between plasma concentration and drug effect site concentration?
An effect site model.
161
What does the constant ke0 represent in pharmacokinetics?
The rate constant for elimination of drug from the effect site.
162
At what point do plasma and effect site concentrations equal each other?
At the time of peak effect.
163
How is the volume of distribution at the time of peak effect denoted?
Vdpe.
164
What is the formula for calculating the bolus dose that provides the desired peak effect site concentration?
Bolus dose = CT × Vdpe.
165
What is the C50 for fentanyl to attenuate hemodynamic response to intubation?
Approximately 2 ng/mL.
166
What are the two volumes relevant for calculating fentanyl dosing?
V1 (central compartment) and Vdss (volume of distribution at steady state).
167
What is the typical V1 for fentanyl?
13 L.
168
What is the typical Vdss for fentanyl?
360 L.
169
What does the decline in plasma concentration after a bolus represent?
A dilution of the bolus into a larger volume.
170
What is the time to peak effect for fentanyl?
3.6 minutes.
171
What is the half-life at the site of drug effect (t½ ke0) for fentanyl?
4.7 minutes.
172
What is the maintenance infusion rate formula at steady state?
Maintenance infusion rate = CT × Cl.
173
When does the maintenance infusion rate underestimate the infusion rate?
When peripheral tissues have not fully equilibrated with the plasma.
174
What is the equation for maintaining the desired concentration after bolus injection?
Maintenance infusion rate = CT × V1 × (k10 + k12e−k21t + k13e−k31t).
175
What is the relationship between infusion rate and time after a bolus?
The infusion rate starts high and gradually decreases over time.
176
What is the apparent volume of distribution at the time of peak effect for alfentanil?
5.9 L.
177
True or False: Plasma is the primary site of drug effect for anesthetic drugs.
False.
178
What is the time to peak effect for alfentanil?
1.4 minutes.
179
What is the purpose of a dosing nomogram in anesthesia?
To show infusion rates necessary to maintain desired drug concentrations over time.
## Footnote
The nomogram illustrates how infusion rates must be adjusted as drug accumulates in the body.
180
What does the y-axis represent in the dosing nomogram for anesthetics?
The target concentration, CT.
## Footnote
Target concentrations are based on previous research and scaled appropriately for different drugs.
181
Which anesthetic drugs are mentioned in the dosing nomogram?
* Fentanyl
* Alfentanil
* Sufentanil
* Propofol
182
What is the suggested infusion rate for maintaining a fentanyl concentration of 1.0 ng/mL at 15 minutes?
3.0 μg/kg/hour.
183
What is the function of a specialized slide rule in anesthesia?
To calculate the bolus dose and infusion rate required to reach a desired target plasma concentration.
## Footnote
The slide rule accounts for patient weight and time elapsed since the start of the infusion.
184
What is the advantage of target-controlled drug delivery in anesthesia?
It allows the user to set desired plasma or effect site concentration, and the computer calculates the necessary drug dose.
## Footnote
This method provides controlled adjustments to drug concentrations.
185
What is stanpumpR?
An online pharmacokinetic simulator for intravenous anesthetic drugs and oral opioids.
## Footnote
It helps model specific anesthetic strategies and ongoing anesthetic drug levels.
186
What does context-sensitive half-time refer to?
The time for plasma concentration to decrease by 50% from an infusion that maintains a constant concentration.
## Footnote
It is influenced by the duration of the infusion.
187
How does context-sensitive half-time change with longer infusion durations?
It increases, as it takes longer for concentrations to fall if the drug has accumulated in peripheral tissues.
188
What is the difference between context-sensitive half-time and context-sensitive effect site decrement time?
Context-sensitive half-time refers to plasma concentration, while effect site decrement time relates to the time for effect site concentrations to decrease.
## Footnote
This is particularly relevant for drugs with slow plasma-effect site equilibration.
189
Define pharmacodynamics.
The study of the intrinsic sensitivity or responsiveness of the body to a drug and the mechanisms by which these effects occur.
190
What is the significance of the Hill equation in pharmacology?
It describes the concentration versus response relationship of a drug, indicating potency and efficacy.
## Footnote
The equation includes parameters like E0, Emax, C, C50, and the Hill coefficient.
191
What does potency refer to in pharmacology?
The relative dose of a drug required to produce a specific effect.
## Footnote
Potency is indicated by the position of the concentration versus response curve.
192
What is the difference between potency and efficacy?
Potency refers to the amount of drug needed for a specific effect, while efficacy indicates the maximum effect achievable by the drug.
193
What is the definition of ED50?
The dose of a drug required to produce a specific desired effect in 50% of individuals receiving the drug.
194
What is the definition of LD50?
The dose of a drug required to produce death in 50% of patients (or animals) receiving the drug.
195
What does the therapeutic index indicate?
The safety of a drug, calculated as the ratio of LD50 to ED50.
## Footnote
A larger therapeutic index indicates a safer drug.
196
What is the therapeutic index of a drug?
The ratio between the LD50 and ED50 (LD50/ED50)
## Footnote
A larger therapeutic index indicates a safer drug for clinical administration.
197
What is the LD1/ED99 ratio in anesthetics?
A more effective ratio showing a smaller margin of safety
## Footnote
It indicates appreciable risk of death, even at subtherapeutic doses in some individuals.
198
Why are anesthetic drugs considered to have low therapeutic ratios?
They have a narrow margin of safety and require enormous vigilance for safe use
## Footnote
For example, the LD50 for sevoflurane has been estimated to be 2.6.
199
How do opioids affect the minimum alveolar concentration (MAC) of inhaled anesthetics?
They potently reduce the MAC required to suppress movement to noxious stimulation
## Footnote
A modest amount of opioid dramatically reduces the concentrations of inhalational anesthetics required.
200
What happens to the MAC after an initial reduction with fentanyl?
There is fairly limited benefit from additional fentanyl
## Footnote
This means that a modest dose is very effective, but larger doses have diminishing returns.
201
What is the interaction of propofol with alfentanil?
It is markedly synergistic, greatly decreasing the amount of propofol needed for response
## Footnote
This interaction has implications for intubation and surgical procedures.
202
What are the two endpoints examined by Hendrickx and colleagues regarding anesthetic drug interactions?
* Hypnosis (loss of consciousness)
* Immobility (loss of movement response to noxious stimulation)
## Footnote
The interaction typically shows synergistic effects, except for NMDA antagonists like ketamine and nitrous oxide.
203
What does a 'response surface' in drug interactions illustrate?
It illustrates the concentrations of two drugs and their combined response
## Footnote
Minto et al proposed a mathematical framework for these interaction surfaces.
204
What is chirality in stereochemistry?
The study of how molecules are structured in three dimensions
## Footnote
Chirality involves molecules with centers of three-dimensional asymmetry.
205
What are enantiomers?
A pair of molecules that are mirror images of one another but cannot be superimposed
## Footnote
They are chemically identical but differ in their interaction with polarized light.
206
What is a racemic mixture?
A mixture of two enantiomers in equal proportions (50:50)
## Footnote
It does not rotate polarized light due to equal clockwise and counterclockwise rotations.
207
What is the difference between D/L and R/S designations?
D/L refers to enantiomers based on rotation of polarized light, while R/S is based on atom numbering around the chiral center
## Footnote
R/S designations do not relate to light rotation.
208
What is the significance of enantiomers in drug interactions?
Enantiomers can exhibit differences in absorption, distribution, clearance, potency, and toxicity
## Footnote
They may even antagonize each other's effects.
209
What is the clinical relevance of chirality in synthetic drugs?
More than one-third of synthetic drugs are chiral, often used as racemic mixtures
## Footnote
The majority of inhaled anesthetics are chiral, with notable exceptions like sevoflurane.
210
What is the role of pharmacogenetics in drug response?
It may help predict patient responses to drugs based on genetic differences in metabolism
## Footnote
Variability in drug responses can also be influenced by factors like age and enzyme activity.
211
What factors contribute to variations in drug responses between individuals?
* Pharmacokinetics
* Renal function
* Hepatic function
* Cardiac function
* Patient age
* Pharmacodynamics
* Enzyme activity
* Genetic differences
* Drug interactions
## Footnote
These factors can lead to significant differences in drug effects even with identical doses.
212
What is the impact of interpatient variability on drug administration in clinical practice?
It may be masked by high doses but can affect levels of neuromuscular blockade and duration of action
## Footnote
Dosing based on body weight may not always align with pharmacokinetic principles.
213
What is the significance of using computerized infusion systems in anesthesia?
They aim to minimize interindividual variability in drug delivery
## Footnote
These systems are designed to achieve target concentrations for drugs like alfentanil and propofol.
214
What is the common practice in anesthesia regarding drug administration?
Administer drugs in proportion to body weight
## Footnote
This practice may not always be supported by pharmacokinetic and pharmacodynamic principles.
215
What are target-controlled infusion systems used for?
To deliver intravenous drugs to achieve a desired target concentration
## Footnote
Examples include alfentanil, remifentanil, etomidate, and propofol.
216
What factors contribute to variations in drug response in elderly patients?
1. Decreased cardiac output
2. Increased fat content
3. Decreased protein binding
4. Decreased renal function
217
How does decreased cardiac output affect drug metabolism in elderly patients?
It decreases hepatic blood flow, leading to prolonged duration of action for drugs like lidocaine and fentanyl.
218
What effect does increased fat content have on drug distribution in elderly patients?
It increases the volume of distribution (Vd) for lipid-soluble drugs such as diazepam and thiopental.
219
What is a consequence of decreased plasma protein binding in elderly patients?
Increased volume of distribution (Vd) and vulnerability to cumulative drug effects.
220
What can alterations in enzyme activity lead to?
Variations in drug responses among individuals due to enzyme induction.
221
What effect does cigarette smoke have on drug metabolism?
Induces mixed-function hepatic oxidases, increasing dose requirements for drugs like theophylline.
222
What is the effect of acute alcohol ingestion on drug metabolism?
It inhibits the metabolism of drugs.
223
How does chronic alcohol use affect drug metabolism?
Induces microsomal enzymes that metabolize drugs, leading to accelerated metabolism.
224
What is pharmacogenetics?
The study of genetically determined disease states revealed by altered responses to specific drugs.
225
What are some examples of diseases unmasked by drugs?
1. Atypical cholinesterase enzyme
2. Malignant hyperthermia
3. Glucose-6-phosphate dehydrogenase deficiency
4. Intermittent porphyria
226
What defines a drug interaction?
When a drug alters the intensity of pharmacologic effects of another drug given concurrently.
227
What are the two types of drug interactions?
1. Pharmacokinetics
2. Pharmacodynamics
228
What is an example of a beneficial drug interaction?
Concurrent administration of propranolol with hydralazine to prevent compensatory heart rate increases.
229
What typically manifests as adverse drug interactions?
Impaired therapeutic efficacy and/or enhanced toxicity.
230
Fill in the blank: A common adverse drug interaction can impair _______.
absorption
231
What can happen when two incompatible drugs are mixed in the same solution?
A physicochemical drug interaction may occur, leading to precipitation.
232
What is a typical composition of a balanced anesthetic?
1. Benzodiazepines
2. Sedative-hypnotics
3. Opioids
4. Neuromuscular blocking drugs
5. Anticholinergics
6. Anticholinesterases
7. Sympathomimetics
8. Sympathetic nervous system blocking drugs
9. Antibiotics
