Week 2: Basic Principles of Pharmacology - Target Tissue Receptors Flashcards
The study of drugs
Pharmacology
This can be describe as “any substance that, when taken into a living organism, may modify one or more of its functions”
Drug
True or false: When you know how the various drugs may affect a patient and the mechanisms behind those effects, you can apply that knowledge to get an optimal response from the patient’s therapy treatment.
True
What do I need to know about pharmacology as a PT?
-Types of medications patient is taking
-How drugs affect the patient
-The mechanisms behind the drug effects
How can I control the drug’s adverse responses?
-Schedule the therapy based on drug’s peak effects
-Avoid or control any adverse responses from occurring due to direct interaction between physical
therapy and certain medications
The area of pharmacology that refers to the use of specific drugs to prevent, treat or diagnose a disease
Pharmacotherapeutics
The study of how the body absorbs, distributes, and eliminates the drug
Pharmacokinetics
The analysis of what the drug does to the body, including the mechanism by which the drug exerts its effect
Pharmacodynamics
The study of the harmful effects of chemicals
Toxicology
This deals with the preparation and dispensing of medications
Pharmacy
It deals with the genetic basis for drug responses, especially variations in drug response from person to person
Pharmacogenetics
True or False: Examining the genetic code for a given patient does not help predict which drugs might be most effective for that patient and which drugs should be avoided because of potentially harmful side effects.
False
What are three ways to name drugs?
-Chemical
-Generic
-Trade
Refer to the specific compound’s structure and are usually fairly long and cumbersome
Chemical names
This name is often derived from the chemical name
Generic name
This name is assigned to the compound by the pharmaceutical company and may or may not bear any reference to the two other names.
Trade/brand name
True or False: Practitioners never select and prescribe the wrong drug if its name or looks like a different drug.
False
This drug is typically less expensive than its brand name counterparts and helps reduce healthcare costs
Generic drug
True or False: The generic form of the drug should be as safe and effective as the original brand-name product
True
Why should the generic form of a drug undergo testing?
To establish that it has the same type and amount of the active ingredients, the same administration route, the same pharmacokinetic profile, and the same therapeutic effects as the brand-name drug
If testing is done, the two drugs are said to be ___________.
Bioequivalent
True or False: PTs should refer their patient to the prescribing clinician if the patient has
concerns about a drug’s the effects.
True
In the United States, who is responsible for monitoring the use of existing drugs and for developing/approving new ones?
FDA
What are two primary concerns of the FDA (U.S.) and Health Products and Food Branch of the Department of National Health and Welfare (Canada)?
-whether the drug is effective in treating a certain condition
-whether the drug is reasonably safe for human use
The development of a new drug involves extensive ______ and ______ studies.
-preclinical (animal)
-clinical (human)
What is the purpose of preclinical testing?
Initial laboratory tests to determine drug effects and safety
How many phases is human/clinical testing?
Three
Which phase is the drug usually tested in a relatively small number of healthy volunteers?
Phase I
Which phase is the drug tested in a relatively small sample with a specific disease or pathological condition?
Phase II
Which phase does the clinical evaluation expand to include more patients and more evaluators?
Phase III
Which phase does is postmarking surveillance?
Phase IV
This is for a relatively small population (<200 people) with rare disease
Orphan drugs
The use of a drug to treat conditions other than those that the drug was originally approved to treat
Off-label prescribing
True or False: When the FDA approves a drug, the approval is only for treating the conditions indicated in the New Drug Application
True
Why is off-labeling prescribing permitted?
The FDA cannot dictate how physicians and other qualified clinicians prescribe medications if the clinician has justification that the drug could benefit a given patient.
Who might refuse to reimburse the cost of a drug regarding off-label prescribing?
Insurance companies
What is OTC?
Over-the-counter drugs
OTC meds are used for __________ problems.
minor
This type of drug is less expensive but the actual cost might be greater because of directly pay out of pocket
OTC meds
True or False: OTC use does not cause serious interactions with a patient’s medications
False
True or False: PTs should not directly prescribe or administer OTC products
True
What can a PT do for a patient if they cannot prescribe/administer OTC products?
Provide information about the proper use and potential benefits of these medications
True or False: Many drugs that were formerly available only by prescription are now available in a nonprescription form.
True
List of substances that were controlled in 1970 when the CSA (Controlled Substances Act) was enacted, as well as the substances that have been added since that time
Drug Schedule
How many categories are in the Drug Schedule?
5
These drugs are regarded as having the highest potential for abuse and are not typically sued as an acceptable medical treatment in the U.S.
Schedule I
These drugs have the lowest relative abuse potential. Drugs in this category consist primarily of low doses of opioids that are used in cough medications and antidiarrheal preparations.
Schedule V
Drugs in this category are approved for specific therapeutic purposes but still have a high potential for abuse and possible addiction.
Schedule II
Drugs in this category may cause a person to still develop mild to moderate physical and/or strong psychological dependence.
Schedule III
These drugs may cause a person to have a limited possibility of physical and/or psychologic dependence.
Schedule IV
Why does a drug change the function of a cell?
-To help restore normal physiological function
-Prevent a disease process from occurring
This provides information about the dosage range over which the drug is effective, as well as the peak response that can be expected from the drug.
Dose-response curve
Very _____ doses do not produce any observable effect.
low
At ___________ dose, the response begins to occur and continues to increase in magnitude before reaching a plateau.
threshold
The ________ indicates that there will be no further increment in the response, even if the dosage continues to be increased.
plateau
The point at which there is no further increase in the response.
Ceiling/maximal effect
This term is related to the dose that produces a given response in a specific amplitude
Potency
When two drugs are compared, the more potent drug requires a _______ dose to produce the same effect as a ________ dose of the second drug.
-lower
-higher
A dose of 10 mg of drug A would lower blood pressure by 25%, whereas 80 mg of drug B would be required to produce the same response. Which drug is more potent?
Drug A
True or False: Potency and maximal efficacy fully indicate a drug’s therapeutic potential.
False
This curve shows the percentage of the population that exhibits a specific response as the dosage is increased.
Quantal Dose-Response Curve
This is the dose at which 50 percent of the population responds to the drug in a specified manner (ex: absence of headache)
Median effective dose (ED 50)
True or False: Higher doses of the same medication is not is not associated with the appearance of a specific toxic effect.
False
This is the dose at which 50 percent of the group exhibits the adverse effect.
Median toxic dose (TD 50)
Two doses that are used to determine the therapeutic index (TI)
Median effective and toxic doses
This indicates a drug’s safety
Therapeutic Index (TI)
The greater the value of the TI, the __________ the drug is considered to be
safer
A large TI indicates that it takes a ________ dose to evoke a toxic response than it does to cause a beneficial effect
larger
What are the routes of drug administration?
-Alimentary canal (enteral administration)
-Non alimentary canal (parenteral administration)
The most common method of enteral medication administration, especially when self-administration is necessary or desired.
Oral
Most medications that are administered orally are absorbed from the ___________.
Small intestine
True or false: Drugs that are administered by mouth must have a relatively high degree of lipid solubility in order to pass through the GI mucosa and into the bloodstream.
True
___________ are absorbed very poorly from the alimentary canal and will be eventually lost through the feces.
Large, nonlipid-soluble
This structure enhances entry in the body for oral administration
Intestinal microvilli with a large surface area
Where is the drug transported after absorption from the alimentary canal?
Liver via portal vein
This occurs when a significant amount of the drug may be metabolized and destroyed prior to reaching its site of action
First-pass effect
True or False: The amount and rate at which the drug eventually reaches the bloodstream is predictable for the oral route.
False
Drugs administered by placing the drug under the tongue
Sublingual
Drugs administered by placing the drug between the cheek and gums
Buccal
True or False: Sublingual and buccal drugs can reach the systemic circulation without being subjected to first-pass inactivation in the liver.
True
True or False: Sublingual and buccal drugs have slower effects compared to swallowing the drug.
False
This method is less favorable because many drugs are absorbed poorly or incompletely
Rectal
When is the rectal method useful?
-unconscious patient
-vomiting prevents drugs from being taken orally
This method treats local conditions such as hemorrhoids
Rectal
True or false: Parenteral methods are aimed more directly to the site
True
Examples of parenteral administration include:
Inhalation, injection, topical, and transdermal
Method for rapid entry into the bloodstream through diffusion into the pulmonary circulation
Inhalation
True or false: Inhalation has a limited ability to predict exactly how much the drug eventually reaches the lungs
True
Why is pulmonary administration adventageous?
Large (alveolar) surface area for diffusion
True or False: Drug particles are never trapped by cilia and mucus in the respiratory tract
False
Various types of injection can be used to introduce the drug either _________ or __________.
-systemically
-locally
True or false: The bolus injection of a medication into a peripheral vein allows an accurate, known quantity of the drug to be introduced into the blood stream over a short period of time.
True
This method is advantageous in emergency situations when it is necessary for medication to an immediate effect
IV
This can be used to allow the prolonged, steady infusion of a drug into the venous system
IV cannula (IV “line)
True or False: Intra-arterial injections are a relative difficult and dangerous procedure
True
This method is occasionally used in chemotherapy to minimize the exposure of the drug to healthy tissue
Intra-arterial Injection
This method has a relatively slower, more prolonged release into the system circulation (ex: local anesthesia, insulin, hormonal contraceptive products)
Subcutaneous (SC) Injection
The large quantity of skeletal muscle in the body allows this route to be easily accessible.
Intramuscular (IM) Injection
IM injections are useful for treating a problem located directly in the _____________.
Injected muscle
What is the benefit of IM injections?
They provide a relatively rapid effect while avoiding the sudden, large increase in plasma levels seen with IV injection
This method delivers the medication within a sheath (ex: spinal subarachnoid space, local anesthetics, etc.)
Intrathecal injection
True or false: Intrathecal injections do not allow certain drugs to bypass the blood-brain barrier and reach the CNS
False
Intrathecal injections may include administration of the drug for these sites to treat inflammation
Tendon sheath or bursa
Drugs given topically are applied to the surface of the _____________.
Skin/mucous membrane
Why do topical medications primarily help treat problems that exist on the skin itself?
Most medications applied directly to the skin are abosorbed fairly poorly through the epidermis and into the system circulation
What can topical drugs be used to treat?
-infections
-inflammation
-wound healing
True or false: Topical application of drugs to mucous membranes can therefore provide a fairly easy and convenient way to administer drugs systemically
True
Drugs for this method are absorbed through the dermal layers and into the subcutaneous tissues or the peripheral circulation
Transdermal
A transdermally administered drug must possess two basic properties. What are these properties?
-must be able to penetrate the skin
-must not be degraded to any major extent by drug metabolizing enzymes located in the dermis
Transdermal administration provides a ______, _______ release of the drug into the body
slow, controlled
Drugs administered transdermally are often delivered through _______ adhered to the skin.
medicated patches
True or false: The transdermal method allows the prolonged administration of drugs
True
What are iontophoresis and phonophoresis used for?
Treating pain and inflammation
Electric current “drives” the ionized form of the medication through the skin
Iontophoresis
Uses ultrasound waves to enhance transmission of the medication through the dermis
Phonophoresis
The extent to which the drug reaches the system circulation
Bioavailability
If 100 mg of a drug is given orally and 50 mg eventually make it into the systemic circulation, the drug is said to be _______% bioavailable.
50%
What is bioavailability dependent on?
The route of administration and drug’s ability to cross membrane barriers
Lipid-soluble compounds are able to pass directly through the membrane by dissolving in the _________.
Lipid bilayer
This structure is composed of primarily lipids and protein
Cell membrane
True or false: Many drugs do not affect dynamic ion channels’ abilities to open and close, altering cell excitability
False
Types of movements across membrane barriers
-passive diffusion
-active transport
-facilitated diffusion
-endocytosis
This occurs when the concentration of the substance differs on one side of the membrane compared to that on the other side
Concentration gradient
The driving forces in passive diffusion
Electrical, chemical, and pressure differences
What does the rate of passive diffusion depend on?
-magnitude of the gradient
-size of the substance
-distance
-temperature
The membrane must be _________________ to the diffusing substance
Permeable
Many drugs are ___________ soluble
Lipid
True or false: Certain nonlipid-soluble substances can be encapsulated in lipid vesicles
True
This term is often used to emphasize the fact that movement occurs without expending any energy
Passive diffusion
When will drugs diffuse more readily through a lipid layer?
If they are in their neutral, nonionized form
True or false: Ionization increased a drug’s lipid solubility
False
When a weak acid drug is the ___________ environment, it tends to be in its neutral, nonionized form.
acidic
A ________ drug is ionized in the acidic environment and poorly absorbed
weak base
pH for plasma and most other fluids in the body
neutral
When it reaches the ________, the same drug becomes nonionized and lipid soluble, allowing it to be absorbed from the _________.
-duodenum
-proximal small intestine
True or false: Urine can sometimes be acidic and at other times basic.
True
Why is it often desirable for the drug to remain ionized while in the urine?
The body will excrete the drug
What happens if the drug becomes nonionized while in the nephron?
It may be reabsorbed back into the body
What happens to the drug if the urine is basic?
Weak acid drugs are trapped in the nephron and excreted more readily.
What happens to the drug if the urine is acidic?
Weak base drugs are excreted better
In some locations, cells form __________ with each other and not allow any appreciable space to exist between adjacent cells.
Tight junctions
What is the primary way that a drug may diffuse across the barrier via cell junctions?
Diffusing first into and then out of the other side of the cells comprising the barrier
This refers to when the diffusing substance is water
Osmosis
What occurs in osmosis?
Water moves from an area of high concentration to an area of low concentration
This involves using membrane proteins to transport substances across the cell membrane
Active Transport
Characteristics of active transport
-Carrier specificity
-Expenditure of energy
-Ability to transport substances against a concentration gradient
Energy in active transport is usually in the form of ______.
Adenosine triphosphate (ATP) hydrolysis
Active transport carries substances from ________ to ________.
-areas of low concentration
-areas of high concentration
True or false: Facilitated diffusion only has active transport features.
False
(It has both active transport and passive diffusion features)
True or false: An existing protein carrier is present and net energy is expended in transporting the substance across the cell membrane during facilitated diffusion.
False
This is an example of facilitated diffusion.
Skeletal muscle glucose uptake
The drug is engulfed by the cell via an invagination of the cell membrane
Endocytosis
Substances synthesized within the cell can be encapsulated in vesicles, merged with the inner surface of the cell membrane, and extruded through the membrane and out of the cell.
Exocytosis
What factors affect distribution?
-Tissue permeability
-Blood flow
-Binding to plasma proteins
-Binding to subcellular components
True or false: A highly lipid-soluble drug can potentially reach all of the different body compartments and enter virtually every cell it reaches.
True
A large ________ compound will remain primarily in the compartment or tissue to which it is administered.
nonlipid-soluble
The _________ limits the movement of drugs out of the bloodstream and into the CNS tissue.
Blood-brain barrier
True or false: More of a drug will reach organs that receive a great deal of blood flow (ex: brain, kidneys, exercising skeletal muscle).
True
True or false: Certain drugs will form reversible bonds to circulating proteins in the bloodstream (ex: albumin).
True
Why is it important that some drugs bind to plasma proteins?
Only the unbound or “free” drug can reach the target tissue and exert a pharmacological effect.
True or false: Several drugs that bind to organelles can be distributed to other compartments
False
The ratio (an arbitrary figure) of the amount of drug administered to the concentration of drug in the plasma
Volume of distribution (Vd)
What happens to the drug if the calculated Vd is approximately equal to the total amount of body water?
The drug is distributed uniformly throughout all of the body’s fluids
What happens to the drug if its Vd is less than the total body fluid content?
The drug is retained in the bloodstream (due to factors such as plasma protein binding)
What happens to the drug if Vd is greater than the total body fluid content?
The drug is being concentrated in the tissues
Where can drugs be stored?
-Adipose
-Bone
-Muscle
-Organs
The primary site for drug storage in the body
Adipose tissue
Why can fat deposits throughout the body serve as a reservoir?
Many drugs are lipid soluble
This acts as a storage stie for several toxic agents, especially heavy metals like lead
Bone
True or false: Binding of drugs to components within the muscle may lead to the long-term storage of these compounds.
True
True or false: Drugs cannot be stored in the liver and kidneys.
False
High concentrations of drugs, drug metabolites, and toxic compounds stored within tissues can cause ____________.
local damage
This occurs when a reservoir “soaks up” the drug and prevents it from reaching the target site
Drug storage
What can happen if a drug leaks out of the reservoir?
The storage site reintroduces the drug to the target site long after the original dose should have been eliminated
Generally designed to permit a slower and more prolonged absorption of the drug from the GI tract and other routes of administration
Controlled-release preparations
A small container placed under the skin in the abdomen that releases a small, measured dose of a drug on a pre- programmed schedule
Implanted drug delivery systems
This activates the drug only after it reaches a specific organ or tissue
Target drug delivery
True or false: Targeting drug delivery focuses on the drug’s effects and reduce the side effects
True
This involves the use of very small particles with physical properties that facilitate drug absorption or distribution within the body
Nanotechnology
Refers to the chemical changes that take place in the drug following administration
Biotransformation
Two ways the body can eliminate drugs
-biotransformation
-excretion
Result of biotransformation
Metabolite (altered version of the original compound)
Rate of biotransformation
Fast process, within minutes or horus
Rate of excretion
Slow process, not very effective
This occurs when the active form of a drug is excreted
Excretion
What causes the chemical changes that occur during drug metabolism?
-oxidation
-reduction
-hydrolysis
-conjugation
These are located within specific tissues and catalyze changes in the drug’s structures, altering the drug’s pharmacological properties
Enzymes
Occurs when either oxygen is added or hydrogen is removed from the original compound
Oxidation
Reactions that remove oxygen or add hydrogen to the original compound
Reduction
This occurs when the original compound is broken into separate parts
Hydrolysis
This occurs when the intact drug or the metabolite of one of the reactions described earlier is coupled to an endogenous substance such as acetyl CoA, glucuronic acid, or an amino acid
Conjugation
The chemical reactions involved in drug biotransformation are classified as __________ reactions.
-phase I or phase II
Reactions that consist of those using oxidation, reduction, or hydrolysis
Phase I
Reactions that involve conjugation of the parent drug or the metabolite of a drug that was already metabolized
Phase II
True or false: A metabolite is usually inactive or has a greatly reduced level of pharmacological activity.
True
What organ is the primary location for drug metabolism?
Liver
True or false: Inactivation of certain drugs may be significantly delayed in the patient with hepatitis, cirrhosis, or other liver disorders.
True
This occurs when the prolonged use of certain drugs “induces” the body to adjust and enzymatically destroy the drug more rapidly than expected
Enzyme induction
The need for increased drug dosages to produce the same effect
Tolerance
What organ is the primary site for drug excretion?
Kidneys
What is the functional unit of the kidney?
Nephron
What happens if a compound is not reabsorbed while moving through the nephron?
It will ultimately leave the body in the urine
Biotransformation plays a significant role in creating a ______,________ metabolite that can reach the kidneys through the bloodstream
polar, water-soluble
What are other routes of drug excretion besides the kidneys?
-lungs
-GI
-liver to bile
-breastmilk
-sweat
-saliva
Why is drug elimination rate useful?
It helps to determine the amount and frequency of a drug’s dosage
True or false: If a drug is administered much faster that it is limited, the drug does not accumulate excessively in the body and reach toxic levels
False
True or false: If the elimination rate is faster than administration, the concentration in the body may never reach therapeutic levels.
True
Can be described either in terms of all organs’ and tissues’ ability to eliminate the drug or in terms of a single organ or tissue’s ability to eliminate the drug
Clearance
What is clearance is dependent on?
The organ or tissue’s ability to extract the drug from the plasma and perfusion of the organ
The amount of time required for 50% of the drug remaining in the body to be eliminated
Half-life
Half-life is a function of both _______ and _______.
-clearance
-volume of distribution (Vd)
True or false: Disease states that affect either clearance or Vd will affect the drug’s half-life
True
True or false: If the drug is administered by
continuous IV administration, this can be done fairly
easily by matching the rate of administration with the
rate of drug elimination (clearance) once the desired
plasma concentration is achieved.
True
True false: In situations
where the drug is given at specific intervals, the
dosage is never adjusted to provide an average plasma
concentration over the dosing period.
False
True or false: If the dosing interval is relatively long
(ex:12 hours), the dose must be considerably large
to provide the same relative plasma concentration
that would exist in a shorter dosing interval (ex:
8 hours).
True
What do larger doses given farther apart result in?
Greater plasma fluctuations
What are primary factors that are responsible for variations in the response to drugs?
-genetics
-disease
-drug interactions
-age
-diet
-sex
Component on or within a cell that a substance can bind to
Receptor
What happens when a drug binds to a receptor?
It initiates a biochemical chain of events
Where to receptors have their binding sites located?
On the outer surface of the cell membrane
True or false: Receptors transmit a message through the cell membrane to cause a change in cell activity.
True
What are most surface receptors called?
Transmembrane proteins
Three ways receptors typically affect cell function
-act as an ion channel and directly altering membrane permeability
-act enzymatically to directly influence function within the cell
-being linked to regulatory proteins that control other chemicals and enzymatic processes
What happens when a receptor becomes an ion pore?
The receptor changes the membrane permeability
Examples of surface receptors becoming ion channels
-ACh receptors
-GABA benzodiazepine chloride ion channel
True or false: Drugs and endogenous chemicals that bind to the receptor site do not change the enzyme activity of the intracellular catalytic component
False
Example of surface receptors linked to enzymes
Tyrosine kinase protein for insulin and other growth factors
True or false: Receptors can also affect cell function by linking to an intracellular intermediate regulatory protein
True
Regulatory proteins that are activated by binding guanine nucleotides
G proteins
What happens when an appropriate substance binds to the surface receptor?
The receptor undergoes a specific conformational change that causes the receptor to attach to a nearby G protein
What happens after an attachment binds to a G protein?
There is an alteration in the activity of an intracellular effector, leading to a change in cell function
Receptors linked to G proteins
G protein-coupled receptors
True or false: A drug may bind to the cell for only a short period, but long enough to initiate the interaction of the G protein with the intracellular effector system
True
Intracellular compound created by drugs and other substances that exert their effects through receptor G protein enzyme systems
Second messenger
True or false: The drug acts as the first messenger, which triggers a biochemical change in the cell, and the drug itself enters.
False
(Drug does not enter)
True or false: The second messenger, the substance produced in the cell, mediates the change in function.
True
Primary example of second messenger strategy
adenylate cyclase-cyclic adenosine monophosphate (cAMP)
Where are intracellular receptors located?
Within the cytoplasm and/or nucleus
What are intracellular receptors specific for?
Certain endogenous hormones and hormone-like drugs
Examples of intracellular receptors
Steroids, steroid-like compounds, thyroid hormones
What does the drug’s ability to bind to any receptor depend on?
The drug’s size and shape relative to the configuration of the receptor’s binding site and electrostatic attraction between the drug and the receptor
True or false: Some drugs bind readily to the receptor, some moderately, some very little, or some not at all.
True
The amount of attraction between a drug and a receptor
Affinity
What is affinity related to?
The drug amount that is required to bind to the unoccupied receptors
True or false: A drug with high affinity binds readily to the open receptors, even if the concentration of the drug is relatively low
True
True or false: Drugs with moderate or low affinity do not require a higher concentration in the body before the receptors become occupied
False
These local regulators can bind to specific sites on the receptor that are distinct from the primary (drug) binding site and increase/decrease affinity of the drug
Allosteric modulators
What is affinity influenced by?
Local regulators (allosteric modulators) and environments (membrane’s fluidity and organization)
Term used to describe a drug that affects only one type of cell or tissue and produces a specific physiological response
Selective
What is the selectivity of a particular drug a function of?
Its ability to interact with specific receptors on the target tissue and not with other receptors on the target tissue or on other tissues
Why is drug selectivity a relative term?
No drug produces only one effect
What is drug selectivity related closely to?
Many receptor populations can be divided into various subtypes according to specific structural and functional differences between subgroups of the receptor
True or false: The fact that we can classify many receptors into
subtypes means we can develop drugs that will affect only one receptor subtype and therefore produce
fairly selective effects with fewer side effects
True
What is the shape of a dose-response curve related to?
The number of receptors that are bound by the drug
True or false: Increasing the
dosage beyond the point at which the maximal effect
is reached will not produce any further increase in response because all the receptors are bound by the drug.
True
A drug that can bind to a receptor and initiate a change in the cell’s function
Agonist
What does an agonist have?
Affinity and efficacy
Term used for when the drug will activate the receptor and change the function of the cell
Efficacy
What does an antagonist have?
Affinity
Why are antagonists significant?
By occupying the receptor, they prevent the agonistic compound from having any effect on the cell
Another term for antagonists
Blockers
How are pharmacological antagonists characterized?
Competitive and noncompetitive
These vie for the same receptor as the agonist
Competitive antagonists
True or false: Only agonists have the opportunity to occupy the receptor
False
(BOTH the agonist and antagonist have an equal opportunity to occupy the receptor)
Regarding agonists and competitive antagonists, whichever drug concentration is _______ tends to have the predominant effect.
Greater
True or false: Raising the concentration of the agonist with a competitive antagonist present can overcome the original inhibition.
True
Form strong, essentially permanent, bonds to the receptor
Noncompetitive antagonists
These also refer to noncompetitive antagonists
Irreversible antagonists
True or false: Irreversible antagonists either have an
extremely high affinity for the receptor or form irreversible covalent bonds to it.
True
True or false: The noncompetitive antagonist can be displaced
by the agonist
False
How are noncompetitive antagonists terminated?
Only after the receptor has been replaced as part of the normal protein turnover within the cell
True or false: The inhibition produced by a noncompetitive blocker tends to remain in effect for long periods (ex: several days)
True
Drugs are classified as this when they do not evoke a maximal response compared to a strong agonist
Partial agonists
True or false: The lack of a maximal response
is caused by decreased drug–receptor affinity.
False
What is the possible reasoning for partial agonists not evoking a maximal response?
Decreased efficacy (the partial agonist does not completely activate the receptor after it bind)
Agents that stimulate certain receptor subtypes while simultaneously blocking the effects of endogenous substances on other receptor subtypes
Mixed agonist-antagonists
Example of mixed agonist-antagonist
Selective estrogen receptor modulators (SERMS)
These drugs bind to the same receptor as the agonist but have the effect of the agonist on cellular function
Inverse agonists
When is it helpful to use inverse agonists?
When the receptor is too active or overstimulated
True or false: A prolonged
increase in the stimulation of various receptors will lead to a decrease in receptor function, and decreased
stimulation will lead to an increase in receptor numbers or sensitivity
True
Term used to describe a fairly brief and transient decrease in responsiveness
Desensitization
Why does desensitization occur?
Phosphorylation (addition of phosphate residues) or other chemical modification to the receptor protein
This occurs when receptors are withdrawn from the cell membrane by endocytosis and sequestered temporarily within the cell
Receptor internalization
This describes a slower, more prolonged process in which the number of available receptors is diminished
Down-regulation
True or false: During down-regulation, the cell undergoes a decrease in responsiveness that remain in effect long after the agonist is removed
True
What kind of system is densenitization and down-regulation?
Negative feedback
Why does down-regulation occur?
Increased receptor removal, decreased receptor synthesis, or both
The need to progressively increase the dose to achieve therapeutic effects
Drug tolerance
Why does drug tolerance happen?
There may be changes in receptor sensitivity and function
What can a prolonged decrease in the stimulation of a post-synaptic receptor result in?
Functional increase in receptor sensitivity
Examples of receptor supersensitivity
-Denervation in the PNS
-Parkinson disease
-Taking receptor antagonist drugs for prolonged periods
Loss of nerve supply
Denervation
The use of specific drugs to prevent, treat, or diagnose disease is known as:
-toxicology
-pharmacokinetics
-pharmacotherapeutics
-toxicokinetics
pharmacotherapeutics
Toxicology is
-the study of harmful effects of chemicals
-the study of a drug’s beneficial effects
-the analysis of drug absorption, distribution, and metabolism
-the preparation and dispensing of therapeutic medications
-the study of harmful effects of chemicals
The generic name of a drug
-is also known as the “official” or “nonproprietary” name
-is often derived from the chemical name
-tends to be somewhat shorter than the drug’s chemical name
-all of the above are true
all of the above are true
The generic form of a drug is considered to be as safe and effective as the original, brand-name product if the generic form _________
as the brand-name drug.
-has the same type and amount of the active ingredient(s)
-uses the same administration route
-has the same pharmacokinetic profile (drug absorption, plasma levels, and so forth)
-produces the same therapeutic effects
-all the above are true
all the above are true
Regarding drug development and approval, an “orphan drug” is a drug that is
-used exclusively in children prescribed for conditions other than those approved by the FDA
-given special funding for development because it is used in a small patient population with a relatively rare disease
-available directly to consumers without a prescription
-only available in countries outside the United States
given special funding for development because it is used in a small patient population with a relatively rare disease
Prescription use of a drug to treat conditions other than those that the drug was originally approved to treat (off label prescribing)
-is illegal and punishable by revoking a physician’s license
-is legal only if the Center for Disease Control provides written permission to the physician
-is legal only if the drug is not a controlled substance
-is legal and quite common in the United States
-is legal only after the patent for a drug has expired
is legal and quite common in the United States
When two drugs are compared, the drug that requires a lower dosage to produce the same effect as a higher dose of the second drug is said to
-be more potent
-be impotent
-have a great maximal efficacy
-have a greater therapeutic index
be more potent
The ______ effect occurs when drugs are transported initially to the liver where a significant amount of the drug may be metabolized and destroyed before the drug reaches its primary site of action.
-malabsorptive
-first pass
-Bohr
-bioequivalence
-pharmacodynamic
first pass
The extent to which a drug reaches the systemic circulation is referred to as
-bioequivalence
-biotransformation
-bioavailability
-biodistribution
-lass pass metabolism
bioavailability
Osmosis refers to the special case of diffusion where the diffusing substance is
-a lipid soluble drug
-a non-lipid soluble drug
-a protein
-a carbohydrate
-water
water
A drug that has a volume of distribution of approximately 42 L in a healthy 70-kg man will typically be
-bound extensively to plasma proteins
-retained in the bloodstream
-concentrated in the tissues
-stored in the liver and kidneys
-distributed uniformly throughout all of the body fluids
distributed uniformly throughout all of the body fluids
Drug developers are exploring nanotechnology (i.e., the use of very small particles with specific physical properties) as a way to
-target and deliver drugs to specific tissues within the body
-facilitate drug absorption from the GI tract
-enable drugs to cross the blood brain barrier more easily
-all the above
all the above
Drug metabolism that occurs when a drug is changed chemically following administration is also known as
-biotransformation
-excretion
-retoxification
-degradation
-allosterification
biotransformation
Most drugs are metabolized by _____ to the drug molecule, and the enzymes that catalyze these reactions are typically located at the ____ of specific cells.
-adding an oxygen or removing a hydrogen; mitochondria
-adding a hydrogen or removing an oxygen; mitochondria
-adding an oxygen or removing a hydrogen; rough (granular) endoplasmic reticulum
-adding an oxygen or removing a hydrogen; smooth (agranular) endoplasmic reticulum
adding an oxygen or removing a hydrogen; smooth (agranular) endoplasmic reticulum
Prolonged administration of therapeutic drugs and other substances (alcohol, nicotine) may enhance the liver’s ability to metabolize certain drugs, thus decreasing their therapeutic effect. This process is known as _______ .
-glomerulonephritis
-enzyme induction
-biliary cirrhosis
-decreased hepatic blood flow
enzyme induction
Drugs and their metabolites are excreted from the body primarily by
-kidneys
-liver
-lungs
-adipose tissue
kidneys
To calculate drug elimination rates, blood flow to an organ and the fraction of drug removed from the plasma as it passes through the organ are measured to determine drug
-biotransformation
-clearance
-deactivation
-esterification
clearance
Drug metabolism by the liver and other organs typically creates a more ____ compound, thus enabling the compound to be ____ when it reaches the nephrons in the kidney.
-polar; excreted
-neutral; excreted
-polar; excreted
-polar; reabsorbed
-neutral; reabsorbed
polar; excreted
The acetylcholine receptor located on the postsynaptic membrane of the skeletal neuromuscular junction is an example of a membrane receptor that
-is linked directly to an intracellular enzyme
-is linked directly to a regulatory G protein
-functions as an ion channel or pore
-moves (translocates) to the cell’s nucleus when stimulated
functions as an ion channel or pore
Some drugs affect the function of the adenylate cyclase, an enzyme located on the inner surface of the cell membrane. This enzyme is responsible for hydrolyzing adenosine triphosphate (ATP) into _____, which acts as a second messenger that activates other enzymes (i.e., protein kinases) throughout the cell.
-adenosine diphosphate (ADP)
-cyclic adenosine monophosphate (cAMP)
-acetylcholine
-norepinephrine
cAMP
A drug that binds readily to available receptors even if the concentration of drug is relatively low is said to have _______ for that receptor.
-low specificity
-high affinity
-a short half life
-none of the above are true
high affinity
The ability of a drug to bind to its receptor can be influenced by local chemicals such as guanine nucleotides, ammonium ions, and divalent cations. These local regulators are commonly known as _____.
-competitive agonists
-noncompetitive agonists
-allosteric modulators
-partial antagonists
-chelators
allosteric modulators
In contrast to an agonist, a pharmacologic antagonist
-has affinity for the receptor, but lacks efficacy
-is also known as a “blocker”
-can be used prevent endogenous chemicals from overstimulating the receptor
-all the above are true
all the above are true
A drug that fails to evoke a maximal response even though it occupies all available receptors is known as
-a competitive antagonist
-a noncompetitive antagonist
-a partial agonist
-a competitive agonist
-an inverse antagonist
partial agonist
Overstimulation of postsynaptic receptors may lead to a decrease in responsiveness of the receptors. A fairly brief and transient decrease in receptor responsiveness is known as _____, whereas a more prolonged process in which the actual number of available receptors is diminished is known as _________.
-down-regulation; desensitization
-desensitization; up-regulation
-up-regulation; desensitization
-down-regulation; autophosphorylation
-desensitization; down-regulation
desensitization; down-regulation
Common Drug Suffixes: Drug Class and Common Examples
-Beta blockers
-Calcium channel blocker
-HMG CoA reductase inhibitors (stains)
-Angiotensin converting enzyme (ACE) inhibitor
-Angiotensin II receptor blockers
-Propanolol
-Nifedipine
-Pravastatin
-Enalapril
-Candesartan
Common Drug Suffixes: Primary Indication (or Desired Effect) and Common Examples
-Antihypertensive, congestive heart failure
-Antihypertensive, antianginal, antiarrhythmic, congestive heart failure
-Antihypertensive, antianginal
-Hyperlipidemia
-Captopril
-Metoprolol
-Nifedipine
-Pravastatin
