pharmacodynamics study guide Flashcards
T or F: drugs alter the physiological processes already present in the body, but they do not produce new effects.
True
How do drugs produce their effects?
Through cellular or extracellular actions, mimicking or blocking endogenous chemicals.
What is a drug target?
A site that can be functionally altered by interaction (binding) with a drug molecule.
What is a physiological receptor?
Specialized protein that receives a chemical signal, leading to a cellular change in function. Receptors are a subset of drug targets, and most drugs work by altering receptor activity.
Four Basic Types of Receptors
Intracellular Receptors
Ligand-gated ion channels
Enzyme-linked Receptors
G-protein coupled Receptors
Cellular Targets that are NOT physiological receptor proteins
o Voltage –gated ion channels
o DNA
o Structural proteins
o Intracellular enzymes
o Transporter proteins
How do drugs interact with intracellular receptors?
Drugs must be able to cross the cell membrane to interact with intracellular receptors.
What happens when a drug interacts with an intracellular receptor?
The drug alters the reading of DNA, which results in altered protein levels and changes in cellular function.
Where are intracellular receptors found?
inside the cell
What happens when a ligand binds to a ligand-gated ion channel?
The binding of the ligand opens the ion channel.
Where are ligand-gated ion channels found?
in the cell membrane and are typically made up of multiple proteins
What is the result of ion movement through ligand-gated ion channels?
Specific charged particles (ions) move into or out of the cell, leading to changes in cell function.
Where are enzyme-linked receptors found?
in the cell membrane, with the ligand binding on the outside and the enzyme on the inside.
What happens when an enzyme-linked receptor is activated?
activates the enzyme inside the membrane.
What biological processes are enzyme-linked receptors often associated with?
cell growth and multiplication, such as in the immune system.
Where are G-protein coupled receptors found?
large proteins found in the cell membrane, with the ligand binding site on the outside and the G-protein binding site on the inside.
What is binding affinity?
the strength of the bond between a drug and its receptor, and it is related to the drug’s potency (how much is needed to produce a certain effect).
What happens when a G-protein coupled receptor is activated by a ligand,?
the G-protein breaks off and interacts with different structures in the cell, causing a change in cellular function
Are drug-receptor interactions reversible?
Yes
How does a drug bind to a receptor?
structurally specific manner, similar to a lock-and-key mechanism.
What is efficacy?
drug’s ability to activate a receptor and produce the maximum possible effect it can generate.
What is an agonist?
drug that increases receptor activity
What is a direct agonist?
binds directly to the receptor and activates it
Where does a direct agonist bind?
endogenous ligand site
What is a full agonist?
drug that is highly effective at activating the receptor and will produce the maximum possible effect (full efficacy) at some dose
What is a partial agonist?
drug that activates the receptor moderately and will never produce the maximum possible effects (partial efficacy), even at very high doses
What are positive modulators?
bind to a site on the receptor other than the endogenous agonist site. They do not produce an effect on their own but enhance the receptor’s response to a direct agonist.
Where do positive modulators bind?
allosteric site
What are indirect agonists?
increase the levels of the endogenous ligand, which then binds to and activates the receptor.
Do indirect agonists bind to receptors?
No, they increase activation of receptor indirectly by increasing the level of endogenous agonists
What is an antagonist?
drug that blocks the effects of agonists, including both endogenous ligands and drugs
What is a competitive antagonist?
competes with the agonist for the binding site on the receptor. Its effect can be reduced by increasing the dose of the agonist.
Where does a competitive antagonist bind?
endogenous ligand site
What is a non-competitive antagonist?
decreases the ability of the agonist to activate the receptor. Its effect cannot be reduced by increasing the dose of the agonist
Where does a non-competitive antagonist bind?
allosteric site
What determines the size of a drug effect? (biochemical, physiological, or clinical)
function of the dose administered
How is the relationship between drug dose and effect measured?
not linear, so a log scale is used to measure dose and its corresponding effect
Characteristics of the log dose-response curve
Potency
Efficacy
Variability
How is potency related to the drug’s binding affinity?
target; a drug with higher binding affinity typically has higher potency.
What determines the potency of a drug?
the position on the X-axis (dose), which reflects the amount of drug needed to produce an effect.
When comparing the potency of two drugs, what must be done?
compare doses that produce equally effective responses (e.g., 50% effect vs. 50% effect), not different levels of response (e.g., 50% effect vs. 80% effect).
What is efficacy in terms of drug effect?
refers to the maximum level of effect a drug can produce, as shown on the Y-axis (Effect)
How is efficacy related to the drug’s action on receptors?
ability to activate receptors and produce a maximal effect
Can different drugs have different efficacies?
Yes, meaning they can produce different levels of effect even if they bind to the same receptor.
What does variability in drug response refer to?
refers to the differences in how individuals respond to the same drug, resulting in different levels of effect
What does a narrow bell curve indicate in drug variability?
indicates low variability, meaning most individuals respond similarly to the drug
What does a wide bell curve indicate in drug variability?
indicates high variability, meaning there is a larger difference in responses to the drug among individuals
What is the formula for the therapeutic index (TI)?
TI = LD50/ED50.
What does the therapeutic index (TI) represent?
represents the ratio of the lethal dose (LD50) to the effective dose (ED50), helping to estimate a drug’s relative safety
What does a higher therapeutic index indicate?
indicates a greater margin of safety between the effective dose and the lethal dose
What does “toxic dose” refer to in the context of the therapeutic index?
the “use-limiting” toxicity, which is the dose causing undesirable or toxic side effects, potentially limiting the drug’s use in patients
What is the basic principle regarding patient factors and drug response?
significantly influence drug effects, and drug dosages must be adjusted to the individual patient to avoid dangerous blood levels.
Why is it important to adjust drug dosages based on individual patient factors?
Incorrect dosage decisions can lead to blood drug levels that are too high or too low, both of which can have serious consequences.
How does body size affect drug dosing?
The lower the safety margin (therapeutic index) of a drug, the more precise the dosing needs to be based on body size.
How is weight used in drug dosing?
OTC drugs typically use an “adult dose,” while prescription drugs often base dosages on drug amount per unit of body weight. However, this does not account for body composition.
How does lean body mass affect dosing for water-soluble drugs?
Lean body mass is an important consideration for dosing water-soluble drugs since they are distributed in body water, which can vary with body composition.
Why is surface area considered for pediatric patients or cancer chemotherapy dosing?
more accurate as it reflects body size and composition, and metabolic rate
How is drug dosage determined for children?
weight or surface area, with surface area being a more accurate method.
How does drug biotransformation in children differ from adults?
may be more rapid in children for some drugs due to higher metabolic rates.
What are compliance issues in pediatric patients?
include unreliable measurement, spillage, and potential subterfuge (e.g., refusal to take medication).
T or F: There are differences in the number and types of drug targets in children, which can affect drug response.
True
T or F: Drug use can influence growth and development, as children’s bodies are still developing, including their organ systems.
True
How does aging affect metabolic function?
Aging leads to diminished metabolic function, particularly a decrease in the cytochrome P-450 enzyme system in the liver, affecting drug metabolism.
How does aging affect body composition?
Elderly patients typically have less water and more fat, which can affect drug distribution, especially for water-soluble drugs.
How does renal function change with age?
Renal function diminishes with age, potentially leading to slower elimination of drugs and increased risk of toxicity.
What is polypharmacy, and why is it a concern in the elderly?
use of multiple medications, which increases the risk of drug-drug interactions and adverse effects.
What are compliance issues in elderly patients?
confusion, behavioral problems, and challenges in remembering to take medications as prescribed.
How do body composition differences affect drug clearance between sexes?
Women typically have more body fat and less lean body mass compared to men, which can influence how drugs are distributed and cleared from the body.
How does aging affect sensitivity to drugs?
Elderly patients are generally more sensitive to adverse drug effects due to changes in organ function and overall body composition.
How do men and women differ at the cellular level in drug response?
Sex differences can lead to variations in how drugs interact with receptors, enzymes, and other cellular components, affecting the overall drug response.
How does pregnancy affect drug therapy?
consideration of the benefits versus risks. Special caution is needed during the first trimester (organogenesis) and at term (effects on neonate).
How does pregnancy alter drug distribution?
Pregnancy increases total body water, which can affect drug distribution, and changes in blood flow can alter drug delivery to tissues.
How does pregnancy influence drug clearance?
Pregnancy can cause both increases and decreases in drug clearance due to changes in organ function, such as renal and hepatic alterations.
How does lactation affect drug use in mothers?
Drugs may be transmitted to the nursing infant through breast milk, so it’s important to consider the potential impact on the infant when prescribing medications to lactating women.
How do liver and kidney diseases affect drug metabolism and excretion?
impair the body’s ability to metabolize and excrete drugs, leading to altered blood levels and potentially toxic effects due to reduced clearance.
How does a disease alter the response to normal drug levels?
Certain diseases can alter the body’s sensitivity to drugs, either enhancing or diminishing the therapeutic effects. In some cases, the drug may worsen the disease condition.
Do all drugs get affected in the same way by diseases?
No, this typically applies to specific drugs or drug classes, with some medications having their effects altered depending on the underlying pathological state.
What is pharmacogenetics?
studies how genetic differences affect an individual’s response to drugs
How can pharmacogenetics impact drug response?
Genetic differences can alter drug metabolism (pharmacokinetics) or the drug’s effect on the body (pharmacodynamics).
What are the benefits of pharmacogenetic testing?
It helps prevent adverse drug reactions and tailor drug treatments to an individual’s genetic profile.
Can pharmacogenetics influence both the effectiveness and safety of drugs?
Yes, genetic variations may increase or decrease the drug’s effect, impacting both its safety and effectiveness.
What is the role of pharmacogenetics in drug dosage?
It can guide the adjustment of drug dosages to ensure effectiveness and minimize side effects.
What is drug tolerance?
reduced effect of a drug with repeated administration
Can tolerance develop equally to all effects of a drug?
No
Can tolerance be cross-tolerant?
Yes, tolerance to one drug may lead to tolerance to other pharmacologically related drugs.
What is metabolic (pharmacokinetic) tolerance?
occurs when the body alters its handling of the drug, such as through enzyme induction, leading to lower blood levels
What is cellular (pharmacodynamic) tolerance?
when cells adapt to the presence of the drug, and blood levels do not change, but the drug’s effect is reduced
