Principles of Pharmacokinetics/Pharmacodynamics Review Flashcards
What is the term for first hand reports including research, clinical cases and case series?
Primary Medical Literature
What is the term for second-hand reviews of primary literature sources which include meta-analyses and systematic reviews?
Secondary Medical Literature
What is the term for publications that utilize both primary and secondary sources and includes textbooks, and online sources such as Epocrates?
Tertiary Medical Literature
What is the preferred literature source?
An original study (primary)
What is the term for a rigorous review process by experts in the field or specialty prior to publication?
Peer Review
What is the term for any literature source that is not peer reviewed prior to publication and may include professional publications and patient education?
Non-peer Reviewed
Which database contains the largest and most diverse list of references?
PubMed
Which database is more focused on literature relevant to health professions such as nursing?
CINAHL
Which database is focused on drug therapy?
International Pharmacy Abstracts (IPA)
Which database is the European equivalent to PubMed?
Embase
What is the term for the study of the action of drugs in the body?
Pharmacology
What is the term for the science that studies and describes how drugs are absorbed, distributed, transported, and eliminated form the body?
Pharmacokinetics
What is the term for the study of the relationship between drug concentrations at the site of action and the pharmacologic activity of the drug?
Pharmacodynamics
What are the five steps in the pharmacokinetic process?
1) Liberation
2) Absorption
3) Distribution
4) Metabolism
5) Elimination
What term defines the breakdown of the dosage form?
Liberation
How can liberation be enhanced?
By giving a drug already in solution
What can be controlled by regulating the process of liberation?
The rate of absorption
What term defines the process of getting the drug into systemic circulation?
Absorption
In what two ways can absorption be bypassed?
Giving a drug by IV or direct local administration
What term defines the transport and transfer of drug to the various parts of the body?
Distribution
The distribution process is influenced by what three factors?
1) Protein binding capacity
2) Water and lipid solubility
3) Size of the drug molecule
What term defines the process by which the body breaks down the the chemical compound that is administered?
Metabolism
What is the goal of metabolism?
To alter the drug chemically, so that it can be easily eliminated from the body
What term defines the process by which active drug or drug metabolites are excreted from the body?
Elimination
What organs are involved in elimination?
1) Kidney
2) Liver
3) Intestine
4) Lungs
5) Skin
What are the protein sites called where drugs bind to produce their action in the body?
Receptors
On what two sites are receptors are usually located?
1) Cell
2) Enzyme
What is the term for the relative amount of drug needed to elicit a response as compared to another drug?
Potency
What is the term for the amount of drug in a dosage form?
Strength
What term describes the relationship between the dose or concentration needed to produce a pharmacologic effect and the dose or concentration that produces toxic effects?
Therapeutic index
What term describes the time it takes for a drug to produce its pharmacological action?
Onset of action
What is the term for a drug that binds to a receptor and produces stimulation or increased activity of the receptor (mimics or enhances activity)?
Agonist
What is the term for a drug that binds to a receptor and blocks or inhibits the activity of the receptor?
Antagonist
What is the term for a drug that has both agonist and antagonist properties?
A mixed agonist-antagonist or a mixed-effects drug
On what parts of a cell can a receptor be present?
1) Membrane
2) Ion channel
3) Nucleus
4) Ribosome
What are some factors that influence drug binding to receptors?
1) Drug concentration at site
2) pH
3) # of receptors
4) Affinity for the receptor
5) Selectivity of the drug for that receptor
6) Change in shape of the receptor (caused by diseases or drugs)
What is the term for a reduction in the number of receptors or the reduced affinity of a drug for a receptor?
Down-regulation (compensation for overstimulation)
What is the term for an increased need of a higher dose of a drug to obtain the pharmacologic effects of the drug?
Tolerance
Down-regulation occurs in response to what type of drug?
Agonist
What is the term for an increased number of receptors or the increased affinity of a receptor?
Up-regulation (compensation for blockade)
Up-regulation often occurs in response to what kind of drug?
Antagonist
What are the two types of binding typically used to describe drug interaction with enzymes instead of cells?
1) Competitive binding
2) Non-competitive binding
What is the term used to describe the process of a drug binding to the actual site on an enzyme that breaks down an endogenous substance?
Competitive
What is the term used to describe the process of a drug binding to an alternate site on an enzyme resulting in a conformational change that blocks the binding of an endogenous substance?
Non-competitive
Which type of binding can be overcome by the production of more endogenous substance?
Competitive
What is the term for tight capillary walls that prevent the passage of certain substances into the brain?
Blood Brain Barrier
What are some processes that can alter this barrier?
1) Infection
2) Inflammation
3) Trauma
4) Tumor growth
5) Mechanical manipulation
What type of drugs differ because of their ability to bind with cells or enzymes on infectious organisms versus those in the body?
Antibiotics
Concerning antibiotics, what is the term for the lowest concentration where the drug has any activity against bacteria growth?
Minimum Inhibitory Concentration (MIC)
Concerning antibiotics, what is the term for the lowest concentration of the drug where bacteria are killed?
Minimum Bactericidal Concentration (MBC)
If MIC values are low, the bacteria are considered _____ to the antibiotic
Sensitive
If MIC values are high, the bacteria are considered ____ to the antibiotic
Resistant
If MICs are increasing for a specific antibiotic against a particular bacteria, there is concern about __________
Increased resistance of the bacteria to the antibiotic
What is the form in which MIC data are typically reported?
An antibiogram
What are the four steps that occur for a drug to move to a receptor? (the first three are steps in the absorption process)
1) Disintegration
2) Dissolution
3) Transfer to blood
4) Distribution
What is the term for the breakdown of the dosage form to release or liberate the drug?
Disintegration
Disintegration control is altered for what three reasons?
1) Minimize adverse effects
2) Shorten time of absorption
3) Improve absorption
What is the term that means the drug has been taken up in a solution?
Dissolution
What are the four most commonly used oral dosage forms?
1) Oral disintegrating (burst release)
2) Immediate release (regular release)
3) Delayed release (pulsatile release)
4) Sustained or extended release (controlled release)
What oral dosage form mimics an IV infusion and provides a constant blood level?
Sustained or continuous release
What oral dosage form may result in a “ghost” tablet?
Sustained or continuous release
What is the term that describes movement of a drug from a higher concentration to a lower concentration?
Passive diffusion
What is the term that refers to movement across a membrane which requires help in the form of a carrier?
Active transport
What are three barriers to absorption?
1) Solubility (pH, particle size, water solubility)
2) Enzymes (P450)
3) Hepatic portal circulation
What are some other factors that influence ORAL absorption?
1) Food
2) Age
3) GI blood flow
4) Liver blood flow
5) Protein binding
Absorption is affected by the route of administration. List the fastest to the slowest using the four most common routes of administration:
IV
IM
Oral
Topical
What is the term for the rate and extent to which the active ingredient of active moiety is absorbed from a drug product and becomes available at the site of action?
Bioavailability
What is the term that describes expected in vivo biological equivalence of two proprietary preparations of a drug that are for all intents and purposes, the same
Bioequivalence
What is the value that correlates to the total amount of drug absorbed and is defined by time and concentration?
The Area Under the Curve (AUC)
For a drug to be bioequivalent, the AUC must fall within what range of the brand product?
80% - 125%
How do you calculate a loading dose of a drug?
Desired peak concentration x volume of distribution of drug in the body and divide by the bioavailability
What is the term that describes when a drug rapidly distributes to all the places it will go in the body immediately following the administration?
One compartment distribution
What is the term that describes when a drug rapidly distributes to a small part of the body (usually total body water) followed by deeper parts?
Two compartment distribution
What kind of drug can leave the bloodstream to bind to receptors, other peripheral sites and to sites of metabolism such as the liver?
Unbound drug
What do drugs typically bind to in the blood or cells?
Protein, namely albumin
What is the term for the amount of time it takes for 50% of the amount of a drug in the body to be eliminated?
Half-life
What are two important uses for half-life?
1) Determining dosing frequency
2) Determining steady-state
What is the type of elimination followed by most drugs where the rate of metabolism or elimination is directly proportional to the concentration of the drug?
First order elimination
What is the type of elimination where the rate of elimination does not change in relationship to the concentration to the drug?
Zero elimination
What are the common drugs that have zero elimination?
1) Phenytoin
2) Ethanol
3) High dose aspirin
What are the two stages of metabolism called?
1) Phase I
2) Phase II
In which phase of metabolism is the primary enzyme Cytochrome P450 (CYP)?
Phase I
In which phase of metabolism is the primary enzyme UDP/UGT?
Phase II
In which phase are active metabolites a concern for toxicity?
Phase I
Cytochrome P450 is broken down into what five common isoenzymes involved in drug metabolism?
1) CYP 1A2
2) CYP 2C9
3) CYP 2C19
4) CYP 2D6
5) CYP 3A4
What is the term for the drugs that are metabolized through specific isoenzymes?
Substrates
What is the term for drugs that increase CYP450 isoenzymes?
Inducers
If an inducer (drug) is added to a drug regimen in which a substrate (drug) is altered by an isoenzyme, the dose of the substrate would need to be _______
Increased
What is the term for drugs that reduce the activity of CYP450 isoenzymes?
Inhibitors
If an inhibitor (drug) is added to a drug regimen in which a substrate (drug) is altered by an isoenzyme, the dose of the substrate would need to be _______
Reduced
Warfarin is given as a mixture of what two types of enantiomers?
1) R-warfarin (less anticoagulation activity)
2) S-warfarin (most anticoagulation activity)
R-warfarin is metabolized by what isoenzyme?
CYP 1A2
S-warfarin is metabolized by what isoenzymes?
CYP 2C9 and CYP 3A4
Name the primary organ of elimination
The kidney
Normal kidney function is considered to be equal to or greater than _____
100 ml/min
What are some ways in which age affects the principles of pharmacokinetics?
1) Altered metabolism (children often require larger doses on a mg/kg basis)
2) Altered protein binding (neonates and elderly have low albumin)
3) Altered receptor sensitivity (elderly more sensitive)
4) Declining organ function (renal function decreases with age)
What are some ways in which physiology affects the principles of pharmacokinetics?
1) Pregnancy (altered protein binding, renal function, hepatic function and body composition)
2) Acute illness (trauma, MI, burns)
What are some ways in which organ function affects the principles of pharmacokinetics?
1) Liver function (metabolism, production of proteins)
2) Renal function (body composition, protein binding)
Name three types of drug interactions?
1) Duplication
2) Opposition
3) Alteration
What is the term for administering two drug products that contain the same drug or similarly acting drugs?
Duplication
What are common drugs for duplication?
Acetaminophen and anticholinergics
What are the acetaminophen parameters for adults?
Over 1000 mg per dose or 4000 mg per day
What are the acetaminophen parameters for children?
Over 10-15 mg/kg/dose or 2600 mg per day
What complication does an acetaminophen overdose cause?
Hepatotoxicity
What are the effects of anticholinergic duplication?
Dry mouth, blurred vision, urine retention, constipation, decreased memory, delusions and hallucinations
What is the term for giving two drugs with opposite reactions?
Opposition
What is the term for drug interactions which alter the effect of the drug itself?
Alteration
What types of drug alterations can take place?
1) Altered absorption
2) Altered metabolism or elimination
3) Altered protein binding
What is the term for the study of differences in drug response or metabolism as it relates to a specific genetic change?
Pharmacogenetics
What is the term for the study of difference in drug response or metabolism as it relates to large populations?
Pharmacogenomics
What are different genetic forms of an isoenzyme called?
Polymorphisms
for example CYP 2C9 has 6 different alleles
What is the main site of action for warfarin?
The enzyme vitamin K epoxide reductase
What is the gene that codes for the vitamin K enzyme where warfarin works?
VKORC1
Name the three VKORC1 polymorphisms:
1) 1639 GG
2) 1639 AA
3) 1639 GA
Warfarin pharmacogenetic dosing is based on what two factors?
1) VKORC1 polymorphism
2) CYP 2C9 alleles
What polymorphism is associated with increased risk factors for serious dermatological reactions when taking carbamazepine?
HLA-B*1502 allele
What ethnicities does the HLA-B affect?
1) Chinese, Thai, Malaysian, Indonesian, Filipino 10-15% of population
2) Japanese and Korean
