(F) Lec 2: Therapeutic Drug Monitoring (Part 1) Flashcards
1
Q
TDM is done to determine the serum drug levels required to produce a ____ effect
A
Desirable
2
Q
The desirable effect is the ____ effect while avoiding the possibility of ____ effects
A
- Therapeutic
- Toxic
3
Q
TDM involves the analysis, assessment, and evaluation of circulating concentrations of drugs
Among the 3 methodologies, which is the main point of concern for Medical Technologists?
A
Analysis (assessment and evaluation are for the physicians)
4
Q
TDM is the (quantitative/qualitative) evaluation of circulating concentrations of drugs
A
Quantitative (results such as “high” and “low” are not accepted)
5
Q
The purpose of TDM is to ensure that a given drug dosage produces maximal ____ benefit and minimal ____ adverse effects
A
- Therapeutic
- Toxic
6
Q
TOF: “Side effects” are synonymous to “toxic effects”
A
True
7
Q
Red-Man Syndrome a is reaction that occurs due to rapid infusion of this drug, leading to the release of histamines characterized by redness, flushing, and itching of the upper body and face
A
Vancomycin
8
Q
TOF: We want to perform TDM if there is a large gap between the overdosage and underdosage effects of the drug
A
False (if there is a thin line, meaning there is a minimal difference separating the two)
9
Q
TOF: We perform TDM if the dosage, effect, or toxicity of the drugs is not clear or well-defined
A
True
10
Q
Indicators for TDM
- If the consequences of overdosing and underdosing are (mild/serious)
- There is a (big/small) difference between a therapeutic and toxic dose
- There is a (good/poor) relationship between the dose of the drug and circulating concentrations
A
- Serious
- Small
- Poor
11
Q
Indicators for TDM
- There is a (good/poor) correlation between the circulating concentrations and therapeutic or toxic effects
- There is a change in the patient’s (physiologic/psychologic) state that may unpredictably affect circulating drug concentrations
- A drug (interaction/breakdown) is or may be occurring
- TDM helps in monitoring patient (follow ups/compliance)
A
- Good
- Physiologic
- Interaction
- Compliance
12
Q
What physiologic conditions can influence the mechanism of elimination of the drug (4)?
A
- Inflammation
- Cancer
- Pregnancy
- Liver damage
13
Q
Refers to the mechanism when drugs are simultaneously taken
A
Drug Interaction
14
Q
Drug Interactions
- The effect of one antibiotic is potentiated by another drug
- One drug counteracts the effects of the other
A
- Synergism
- Antagonism
15
Q
If the patient is not on the therapeutic range, what does it mean in terms of their compliance to the medication?
A
They are NOT compliant
16
Q
Principles of Pharmacology
- The mechanism by which the drug exerts its effects on the human body
- It studies how it elicits its effects, mechanism, and interaction on living organisms
- It is the study of biochemical processes and the physiologic effects of drugs and the mechanisms by which they produce said effects
A
Pharmacodynamics
17
Q
Principles of Pharmacology (Pharmacodynamics)
Ibuprofen is a known pain reliever responsible for inhibiting ____ which is an important enzyme to produce ____
A
- Cyclooxygenase
- Prostaglandin
18
Q
Principles of Pharmacology
- It studies how the body deals with pharmacologic compounds
- It includes the way the drug is administered, absorbed, distributed, and eventually eliminated
- Refers to the biologic fate of drugs
A
Pharmacokinetics
19
Q
Pharmacokinetic Responses
- It describes the absorption, distribution, and elimination of drugs
- The rate of change of concentration of a drug (elimination) is dependent on/proportional to the drug concentration
A
First Order Kinetics (1st phase)
20
Q
Pharmacokinetic Responses
- It describes how the rate of change of concentration of a drug is independent to the concentration of the drug
- A constant amount of drug is eliminated per unit of time
- It typically depends on the ability of the liver to metabolize the drug
A
Zero Order Kinetics (2nd Phase)
21
Q
Refers to the unchanged fraction of the administered dose as it enters the systemic circulation; the number of drugs that successfully entered the circulation
A
Bioavailability
22
Q
Routes of Administration
This route has a constant bioavailability of 100% and surpasses all processes and directly enters the general circulation
A
Intravenous (IV)
23
Q
Routes of Administration
This route provides a longer effect as the site acts as a storage form
A
Intramuscular (IM)
24
Q
Routes of Administration
This route provides a longer effect
A
Subcutaneous (SC)
25
# Pharmacological Parameters
1. The release of the drug
2. The delivery of the drug to the tissue
3. The transport of the drug from the site of administration to the blood
4. The process by which the drug exits the body
5. The process of chemical modification
6. The recirculation of the drug
Choices: Recall LADMER
1. Liberation (in the GIT)
2. Distribution
3. Absorption
4. Excretion/Elimination (through the urine or feces)
5. Metabolism (in the liver)
6. Reabsorption (in the kidney)
26
# Pharmacological Parameters
If the route of administration is through IV, which among the LADMER steps is skipped?
Liberation (hence absorption will be the first step)
27
# Formulation of the Drugs (Absorption)
1. Tablets and capsules require ____ before being absorbed
2. Liquid solutions tend to be absorbed (rapidly/slowly)
3. Weak acids are efficiently absorbed in the ____ while weak bases are absorbed in the ____ where the pH is more neutral
1. Dissolution
2. Rapidly
3. Stomach; Intestines
28
# Formulation of the Drugs (Absorption)
1. Most drugs are absorbed via ____ diffusion
2. For most drugs, absorption from the ____ occurs
3. After the drug is absorbed in the GIT, one of the organs it will also encounter is the ____
1. Passive (no energy consumption)
2. Gastrointestinal Tract
3. Liver
29
Familiarize yourself with the factors affecting the absorption of drugs
1. Changes in intestinal movement or peristalsis
2. pH
3. Inflammation
4. Food and other drugs
30
# Absorption
- Once the drug is absorbed and has interacted with the liver, it will implement its detoxification function
- It refers to drug metabolism occurring before the drug enters the systemic circulation
- It results in decreased bioavailability therefore a decrease in therapeutic response
First-Pass Metabolism
31
# Absorption
- Occurs when the drugs go straight to the circulation
- Includes the IV route and sublingual route
Bypassing the First-Pass Metabolism
32
# Absorption
1. This goes directly to the general circulation therefore bypassing the liver (there is 100% bioavailability)
2. This is administered under the tongue as there are a lot of blood vessels present there (bioavailability is not 100% but still high)
1. IV route
2. Sublingual route
33
# Distribution
Among the bound and free fractions, which is biologically active?
Free
34
# Distribution
1. Most drugs that circulate in the blood are bound to ____ proteins
2. Drugs compete with other ingested drugs as well as endogenous molecules such as (2) ____ and ____ for protein binding sites
3. Bound proteins are pharmacologically ____
1. Plasma
2. Steroids and Bilirubin
3. Inactive
35
# Distribution
1. Acidic drugs bind to ____
2. Basic drugs bind to ____
1. Albumin
2. A1-acid glycoprotein (AAG)
| Acidic binds to basic while basic binds to acidic (opposite)
36
# Distribution
In cases of inflammation, malignancies, and pregnancy, there is a/an (increase/decrease) in serum and bound fractions and a/an (increase/decrease) in free fractions
1. Increase
2. Decrease
37
# Distribution
In cases of inflammation, malignancies, and pregnancy, the effectiveness of the drug is (enhanced/reduced) so it is recommended to (increase/decrease) the dosage of the drug
1. Reduced
2. Increase
38
# Distribution
In cases of hepatic diseases, nephrotic syndrome, and malnutrition, there is a/an (increase/decrease) in serum and bound fractions and a/an (increase/decrease) in free fractions
1. Decrease
2. Increase
39
# Distribution
This is the fraction that best correlates with both the therapeutic and toxic effects of a drug
Free Fraction
40
# Distribution
1. Describes how the patient is supposed to be within the therapeutic range (the dosage that is already proven to be within the therapeutic range)
2. This defines when the patient is to experience toxic adverse effects
3. Describes when the therapeutic benefit is unrealized
1. Standard Dose Total Plasma Content
2. High Free Fraction
3. Low Free Fraction
41
# Distribution
In cases wherein there is competition for binding sites by urea, bilirubin, and hormones, there is a/an (increase/decrease) in serum and bound fractions and a/an (increase/decrease) in free fractions
1. Increase
2. Decrease
42
# Factors Affecting Distribution
If there is slow blood flow, the distribution is ____
Slow
43
# Factors Affecting Distribution
Familiarize yourself with the 4 factors affecting drug distribution
1. Organ blood flow
2. Protein binding capacity
3. Tissue permeability
4. Lipid solubility
44
- Refers to the ratio of the "amount of drug administered" to the "concentration of drug in the plasma"
- The volume of fluid in which a dose of a drug would need to be dissolved to have the same concentration as it does in plasma
Volume Distribution
45
# Drug Storage Sites
1. The best storage site
2. Mostly for toxic agents such as heavy metals
3. A form of long-term storage
1. Adipose tissue
2. Bone
3. Muscle
46
# Metabolism
This organ is primarily responsible in inactivating or detoxifying the drug as part of its function
Liver
47
# Metabolism
This system allows the drug to undergo biotransformation which alters its chemical formula
Hepatic Mixed Function Oxidase (MFO) System
48
# Metabolism
The enzymes of biotransformation are located where?
Smooth ER of cells belonging to the Drug Microsomal Metabolizing System (DMMS)
49
# Metabolism (Phases)
In this phase, the goal is to modify or alter the compound through oxidizing, reducing, and hydrolyzing
Phase 1 Biotransformation
50
# Metabolism (Phases)
Identify the chemical process in Phase 1:
1. The addition of oxygen or the removal of hydrogen (the predominant method)
2. The removal or addition of oxygen (enzymes are located in the cytoplasm)
3. The compound is broken into separate parts
1. Oxidation
2. Reduction
3. Hydrolysis
51
# Metabolism (Phases)
- Drug molecules/metabolites undergo conjugation (binding) with an endogenous substance (present in the liver) so that the kidney is able to de-filter it
- The intact drug is coupled to substances like Acetyl CoA, glucuronic acid, or amino acids
Phase 2 Biotransformation
52
# Metabolism (Phases)
In Phase 2 Biotransformation, conjugation enzymes form what kind of metabolites (which are more easily secreted)?
Water-soluble
53
# Metabolism (Phases)
After Phase 2 Biotransformation, what is produced?
Metabolites
54
# Elimination or Excretion
The removal of drugs from body fluids occurs primarily in what specimen?
Urine
55
# Elimination or Excretion
TOF: If metabolites are present in the urine, then the drug or parent compound is not present in the circulation
False (definitely present)
56
# Elimination or Excretion
What other substances can drugs be found in aside from urine?
1. Feces
2. Sweat
3. Expired air
4. Saliva
57
# Elimination or Excretion
What are the 4 organs of excretion?
1. Kidney
2. Skin
3. Lungs
4. GIT
58
This equation defines how the change in concentration per unit time is directly related to the concentration of the drug and the constant
𝛥𝑪/𝜟𝑻 = −𝒌𝑪
59
In the formula: 𝛥𝑪/𝜟𝑻 = −𝒌𝑪, what is the elimination constant/rate of elimination?
"K" - it describes the percentage change per unit time
60
# Factors Considered in Elimination
- The plasma free fraction of a parent drug or its metabolites is subject to glomerular filtration, renal secretion, or both
- It is the ability of all organs and tissues to eliminate the drug
- Is affected by blood flow to the organ and the extraction ratio
Renal Clearance
61
- The study of genes that affect the performance of a drug in an individual
- Can be used to predict drug interactions or as an indicator if the drug will provide any therapeutic benefit
Pharmacogenomics
62
# Pharmacogenomics
What is one of the most prominent gene families that affect drug metabolism?
Cytochrome P450 (CYP 450)
63
# Pharmacogenomics
CYP 450 codes for enzymes used where?
Within the MFO system (in the liver)
64
# Definition of Terms
This is statistically derived from observations in a healthy population
Standard Dose
65
# Definition of Terms
The concentration range of a drug that is beneficial to the patient without being toxic
Therapeutic Range
66
# Definition of Terms
The time after administration until a drug reaches its peak/highest concentration in the body
Peak Drug Level
67
# Definition of Terms
As a rule of thumb, the peak for the drug level should be from a specimen collected how many hours after administration?
1 hour
68
# Definition of Terms
Refers to the lowest concentration of drug obtained in the blood
Trough Drug Level
69
# Definition of Terms
Trough levels should be drawn immediately (before/after) the next dose
Before
70
# Definition of Terms
- This is the time required for 50% of the drug remaining in the body to be eliminated
- It is the time needed for the serum concentration to decrease by one half
Half Life
71
# Definition of Terms
- This refers to the value of the peak and trough when they are within the therapeutic range
- It is complete with peaks and troughs
Steady State Drug Level
72
# Sample Collection
What is the single most important factor in TDM?
Timing of Specimen Collection
73
# Sample Collection
What are the 3 screening tests?
1. Enzyme Immunoassays
2. Fluorescence-polarized Immunoassays
3. Gas Chromatography
74
# Sample Collection
What is the confirmatory test?
High Pressure Liquid Chromatography
75
# Sample Collection
Screening tests are mostly used for ____ while confirmatory tests are for ____
1. Clinical applications
2. Court rulings
76
# Sample Collection
What is the specimen of choice for drug analysis?
Serum or Plasma (urine metabolites are also measured in some cases)
77
# Sample Collection
In serum or plasma, ____ is being analyzed while in urine it is the ____
1. Parent drug
2. Metabolites
78
# Sample Collection
It is not recommended to use any gel or serum/plasma separator tubes (SST/PST) because?
Some drugs have a tendency to be absorbed into the gel (leads to falsely decreased)
79
# Sample Collection
Which additive is most suitable for most drug analysis?
Heparinized plasma
80
# Sample Collection
These types of anticoagulants add a variety of anions and cations that may interfere with analysis or cause a drug to distribute differently between cells and plasma
Calcium-binding Anticoagulants
81
# Sample Collection
TOF: EDTA, citrate, and oxalate are acceptable in TDM
False (these are calcium chelators)
| + Citrate is acidic therefore it can alter results
