Exam 1 Intro to Pharmacology and Pharmacodynamics Flashcards
9/4 Lecture 1 and 2
What is pharmacology?
The science of drugs and how they affect living systems
Why is pharmacology important to dentists?
If a patient is taking more than one drug, there is potential for drug interactions and adverse consequences
True or false: every drug can affect the entire body
True
A ____ is a substance used in the diagnosis, treatment, or prevention of a disease
Drug
Drugs are usually what type of structure?
Small molecules (smaller than proteins, smaller than polypeptides)
Why is it advantageous for drugs to be small?
- Quicker access into the body
- Reach target (chemically sensitive site) sooner
Most drugs are smaller than proteins and polypeptides. What is the exception?
- Small active peptides
- Monoclonal antibodies
What is the non-proprietary name of a drug?
Official name, such as ibuprofen
What is the proprietary name of a drug?
Brand or trade name (such as Advil)
____ is what a drug does to the body
Pharmacodynamics
____ is what the body does to a drug
Pharmacokinetics
____ is involved with the drug/receptor interaction/study of the biochemical and physiologic effects of drugs and their mechanisms of action
Pharmacodynamics
What are the 4 principles of drug action?
4 ways in which drugs act on the body
- Stimulation
- Depression
- Replacement
- Cytotoxic action
What is stimulation?
- Enhancement of the level of a specific biological activity, usually already an ongoing physiological process
- Ex: Adrenaline/epinephrine stimulates heart rate
What is depression?
- Decrease in the level of a specific biological activity, usually already ongoing physiological process
- Ex: Opioids depress the CNS
Principles of Drug Action
What is replacement?
- Replacement of the natural hormones or enzymes (any substance) which are deficient in our body
- Ex: Insulin for treating diabetes
What is cytotoxic action?
Toxic effects on invading microorganisms or cancer cells (ex: antibiotics)
In what ways do drugs produce their effects?
- Physical action
- Chemical action
- Counterfeit biochemical constituents
- Through stimulating/inhibiting enzymes
- Through receptors
During ____, the physical property is responsible for drug action
Physical action
During ____, the drug reacts extracellularly according to simple chemical equations (not entering a cell or system)
Chemical action (Ex: tums to neutralize gastric acid)
____ is the most common way of producing action
Receptor action
What are the major classifications of receptors?
- GPCR
- Ion channels
- Enzymatic receptors
- Intracellular receptors (regulates gene expression)
Where are steroid receptors located?
Intracellular
What is affinity?
The ability of a drug to bind to the receptor (just bind)
What is intrinsic activity?
It is the ability of a drug to activate a receptor following receptor occupation
What is a receptor agonist?
Any drug that binds to a receptor and activates it to produce an effect
Morphine has both ____ and ____
Affinity and maximal intrinsic activity
What is a receptor antagonist?
A drug that binds to the receptor and prevents the action of an agonist, but does not have an action on its own
Example of a receptor antagonist
Naloxone (antagonist of opioids at mu-opioid receptors)
Receptor antagonists have ____ but no ____
Affinity but no intrinsic activity
____ rapidly reverses opioid overdose
Naloxone
What is a partial agonist?
A drug that binds to the receptor and activates it, but produces a submaximal effect (less than a full agonist)
____ blocks the full agonist action
Partial agonist
A partial agonist has ____ but ____
Affinity; Submaximal intrinsic activity
What is an inverse agonist?
Any drug that activates a receptor to produce an effect in the opposite direction to that of the agonist
____ inhibits endogenous (constitutive) activity of a receptor
Inverse agonist
____ reduces background activity of a receptor
Inverse agonist
An inverse agonist has ____ and _____
Affinity and negative intrinsic activity
Describe the activity level comparing agonist and inverse agonist
- Agonist has increasing activity level with increasing drug concentration, above the baseline level
- Inverse agonist has the opposite effect (decreased activity of the receptor) with increasing drug concentration, below the baseline level
Are receptors specific?
Usually, but not always
Are there receptor subtypes?
Sometimes - for instance, there are several types of epinephrine receptors
True or false: there can be several types of receptors
True
Beta1 epinephrine receptors are located in the ____
Beta2 receptors found in ____
Heart; Bronchioles
True or false: receptor diversity may differ due to genetic differences among individuals
True
Epinephrine is a non-specific drug: it is an agonist for both ____ and ____. Why might this be a problem for someone with asthma and hypertension? What is a solution?
B1 and B2 receptors; Epinephrine will treat the asthma but also raise BP even higher; Terbutaline (more specific agonist of B2) used to treat people with asthma
In most cases of a drug-receptor interaction, drug (D) binds to a receptor (R) in a ______
Reversible bimolecular reaction
Drug-receptor interaction equation
D+R <-> DR <-> DR* —-> Response
In a drug-receptor interaction, agonists that have the appropriate structural features force the bound receptor into what?
Active conformation (DR*)
Conformational change of DR* leads to:
Series of events causing a cellular response
Antagonists participate in which part of the drug-receptor interaction equation?
First equilibrium (D+R <-> DR)
No conformational change of the receptor
____ is used as a measure of affinity of a drug for its receptor
Kd
A lower value of Kd means:
Higher affinity/receptor occupation
Generally, the intensity of a response ____ with dose
Increases
The drug receptor interaction obeys what?
Law of mass action
____ is usually equal to EC50
Kd
The dose-response curve increases in response until it reaches a ____. Later it remains ____ despite increase in dose which is called the ____
Maximum; constant; Plateau effect
What is threshold concentration?
Lowest concentration to elicit a measurable response
At EMax, increasing doses have what effect?
Progressively smaller incremental effect
____ refers to the maximal response produced by a drug
Efficacy
What does efficacy depend on?
The number of drug-receptor complexes formed
____ is a measure of how much drug is required to elicit a given response
Potency
The ____ the dose required to elicit the response, the more potent the drug is
Lower
Which scale is used to graph dose-response curves to be able to compare two drugs?
Log scale (difficult to compare with arithmetic scale)
What is EC50?
The dose of the drug at which it gives 50% of the maximal response
A drug with a low EC50 is more ____ than a drug with larger EC50
Potent
The further ____ a DRC is, the more potent it is
Left (relative position on x-axis)
The height of the DRC indicates:
Efficacy of the drug
The taller the DRC, the ____ efficacious the drug
More
____ relates only to binding of drug to receptor
Affinity
____ and ____ both encompass binding and subsequent signal transduction events leading to a response
Intrinsic activity and potency
Full agonists are those that have what?
Emax that is the highest for any agonist at that receptor
Partial agonists have ____ and therefore have lower intrinsic activity
Lower Emax values
A steep slope in a DRC indicates what?
A small increase in dose produces a large change in response
True or false: the slope of the mid-portion of the DRC varies from drug to drug
True
Is a steep DRC desired?
No
In a steep DRC, moderate increase in dose leads to what?
More increase in response
In a flat DRC, moderate increase in dose leads to what?
Little increase in response
True or false: If a drug has a steep DRC, dose needs no individualization for different patients
False - does need individualization
If a drug has a flat DRC, does the dose need individualization for different patients?
No
What DRC is desired and common?
Flat DRC (drug is administered more safely)
What is ED50?
Looks like EC50 but indicates the dose for a therapeutic effect in 50% of the population
Therapeutic index is a measurement of:
Drug safety
What is TD50?
Median toxic dose
Formula to calculate Therapeutic Index
TD50/ED50
Safer drugs have ____ TI values
Higher
Toxic dose (TD50) and Lethal dose (LD50) is estimated in what kind of studies?
Preclinical animal studies
NOT HUMAN STUDIES
Is LD50 calculated in humans?
NO
What is therapeutic window?
- Clinically relevant index of safety
- Describes the dosage range between the minimum effective therapeutic concentration or dose, and the minimum toxic concentration or dose
Drugs with a ____ should be used with caution and needs periodic monitoring, such as warfarin and theophylline
Narrow therapeutic window
Drugs with a ____ can be used relatively safely and does not need close monitoring
Large therapeutic window
When 2 drugs are given together or in quick succession, what 3 things can happen?
- Nothing (indifferent to each other)
- Synergism (action of one drug is facilitated by the other)
- Antagonism (action of one drug may decrease or inhibit the action of the other drug)
What are the two types of synergism?
- Additive effect
- Supra-additive effect
____ is when the effect of two drugs are in the same direction and simply add up
Additive effect
Synergism
____ is when the effect of combination is greater than the individual effect of the components
Supra-additive effect
Synergism
What are the different types of antagonism?
- Physical
- Chemical
- Physiological antagonism
- Receptor antagonism
Physical antagonism is based on:
Physical property of a drug
Chemical antagonism is based on:
Chemical properties resulting in an inactive product
Ex. chelating agent like EDTA
What happens in physiological antagonism?
Two drugs act on different receptors or by different mechanisms, but have opposite effects
What happens in receptor antagonism?
Antagonist interferes with the binding of the agonist with its receptor and inhibits the generation of a response
Is receptor antagonism specific?
Yes
Receptor antagonism can be ____ and ____
Competitive and noncompetitive
____ antagonism is surmountable
Competitive
In ____, antagonist competes with agonist in reversible fashion for the same receptor site
Competitive antagonism
If competitive antagonism occurs, it is necessary to have:
Higher concentration of agonist to achieve same response
____ antagonism is insurmountable
Noncompetitive
What happens during noncompetitive antagonism?
Antagonist binds to a different site to that of an agonist
True or false: in noncompetitive antagonism, no matter how much agonist, antagonism cannot be overcome
True
How does the DRC change in competitive antagonism?
Parallel rightward shift
How does the DRC change in noncompetitive antagonism?
Flattens
True or false: Number and affinity of receptors do not change
False, may change
Upregulation or downregulation of receptors
Upregulation
Increase in receptor number
Downregulation
Decrease in receptor number
What is the clinical relevance of downregulation?
Patient’s response to drug therapy may change over time
Prolonged/frequent use of a drug may decrease number of receptors
What is tolerance?
Gradual reduction in response to drugs that occurs over a period of time
What are 2 reasons for tolerance?
- Receptor downregulation (pharmacodynamic reasons)
- Chronic use leads to enhanced clearance (pharmacokinetics), leading to a less effective concentration
