EXAM 2 Reading 2 (B. Ch11) Flashcards
What term refers to the dose of a drug required to produce a given effect in 50 percent of subjects?
Potency
Select two Phase I reactions associated with drug metabolism.
Hydrolysis
Reduction
Select two inducers of hepatic drug metabolism.
Rifampin
Phenytoin
Which is the single most important enzyme, accounting for 40-45 percent of all mediated drug metabolism?
CYP3A4
Which drug exhibits the classic drug-drug interaction associated with serotonin syndrome when combined with MAOIs?
Meperidine.
Which route of administration exhibits absolute drug bioavailability?
IV
Most intravenous drugs exhibit absolute bioavailability. The exception are drugs such as ____Why?
fentanyl which undergo absorption into the pulmonary endothelium.
Which term refers to the theoretical volume of blood from which a drug is completely and irreversibly removed in a unit of time?
Elimination clearance.
Most cellular drug receptors are located
Within the cell membrane
few in the cytoplasm of nucleoplasm
Dose-response curves provide information about all of the following aspects of pharmacologic effects except:
The steady-state plasma concentration (CPss50)
The slope of a dose-response curve demonstrates
the rate of increasing effect with an increased dose.
The dose-response curve also demonstrates the
efficacy, or maximal effect of a drug as well as the potency (ED50)
A dose-response curve can also demonstrate variability in
drug effect if it measures multiple subjects.
The steady-state plasma concentration (CPss50) is determined by a
concentration-response curve using a continuous infusion of a drug
What pharmacodynamic value of a drug can be determined by a concentration-response curve when administering a continuous infusion of a drug?
CPss50 The steady-state plasma concentration (CPss50) is determined by a concentration-response curve using a continuous infusion of a drug.
Which Phase 1 reaction is characterized by reactions that remove electrons from a molecule?
Oxidation
The excretion of an acidic drug will be faster if
Alkaline
Weak acids are excreted more efficiently if the urine and
is alkaline
Weak bases are excreted more efficiently if the urine is
Acidic
Weak bases excreted more efficiently if the urine is acidic. An example is
An example would be the use of sodium bicarbonate in cases of aspirin poisoning. Aspirin, or salicylic acid, is obviously an acid. Because acids are excreted more efficiently if the urine is alkaline, the administration of intravenous sodium bicarbonate will alkalinize the urine and increase the rate at which the kidneys eliminate it
With regards to drug-receptor complexes, what is desensitization?
The binding of an agonist to the receptor produces a decreased response
When receptors are exposed to an agonist more than normal, they becomes
desensitized. This means that the binding of the agonist to the receptor exerts a lower-intensity response than normal.
The dose-response curve produced by the binding of an opioid to an opioid receptor represents the drug’s
efficacy
The dose-response curve produced by the binding of the opioid to an opioid receptor describes the drug’s
efficacy
It is a measure of the effect the drug produces.
Efficacy
is the ability of a drug to bind with a receptor to form a stable complex.
Affinity
Potency refers to the relative dose of a drug that is required to produce the
effect and is closely associated with the affinity of the drug for the receptor
After three half-lives, what percentage of an administered drug remains?
12.5%
The two-compartment pharmacokinetic model is most useful for explaining the characteristics of
Lipid soluble agents.
Where are most drug receptors located?
The cell membrane
Which of the following is a Phase II reaction?
Conjugation
Which of the following terms refers to compounds that bind to receptors without producing any changes in cellular function?
Antagonist
Which drug or drug class is an inhibitor of hepatic drug metabolism?
SSRIs
What is the term that describes the extent to which a drug reaches its effect site after its introduction into the circulatory system?
Bioavailability
Select two common treatments for moderate to severe serotonin syndrome.
Oral cyproheptadine is the most common treatment of serotonin syndrome but chlorpromazine has also been used in combination with supportive care
The gamma-amino butyric acid receptor is an example of
a ligand-gated ionophore
The two major ways in which a drug can bind to a receptor and cause a change in cellular function are The GABA receptor is a ligand-gated ionophore.
ionophores (ion channels) and G-proteins.
The binding of drugs or neurotransmitters to a GABA receptor opens a
chloride channel, allowing the influx of chloride into the cell.
What are the 2 non IV routes for which tissue perfusion does not affect drug onset of effect because the drug is delivered adjacent to the site of action.
The intrathecal space
Epidural space.
Is rarely the side at which drug produces their action
Blood
Absorbed faster: lipophyillic or hydrophyllic
lipophyllic because diffusion across lipid cellular barriers is faster.
Those 2 organs equillibrate fast
Brain and kidneys
Explain the redistribution
Redistribution of opioid from the highly perfused but low tissue volume brain back in the plasma will eventually decrease the concentration of drug at its site of action below the therapeutic threshold and thereby halt its effect.
What is the major determinant of the limited bioavailability of many drugs administered via the gastrointestinal tract?
This first-pass metabolism by the liver
IV methods administration is that the same impediments to rapid systemic absorption can provide
a prolonged drug effect
Drug transport, either into or from the tissue, is usually not saturable, so drug uptake by the tissue is mostly limited by)
the blood flow to the tissue (flow-limited drug uptake
What 2 things determine the rate of drug equilibration with the plasma in each tissue bed
The distribution of cardiac output to the different tissue beds and the cellular mass of the tissue
In contrast, the well-perfused muscle and splanchnic tissues take hours to approach equilibrium why?
due to their large tissue volumes relative to blood flow
When the concentration of drug in the tissue becomes higher than the plasma concentration, the overall movement of drug is
from the tissue to the plasma
This redistribution of an opioid or hypnotic from the highly perfused but low tissue volume brain back into the plasma will eventually
decrease the concentration of drug at its site of action below the therapeutic threshold and thereby halt its effect.
It is important to note that the brain may redistribute drug minutes after a bolus of drug has been administered. But tissue beds such as the muscle, which are slower to equilibrate because of the large capacity for drug uptake ,
will continue to take up drug until the plasma concentration decreases below the tissue concentration as drug is metabolized, excreted, and drug distributed throughout the bod
With repeated injections or an infusion of drug,
tissue uptake of drug will continue as long as the blood–drug concentration remains above that of tissue–drug concentration.
Thus, when drug administration is stopped or the rate is decreased, these tissues begin to act like
depots, causing net transfer of drug to blood and slowing the rate of further decrease of the plasma concentrations (Fig. 7-2).
When the rate of net tissue transfer of drug to blood is equal to the elimination rate of drug from the body, then the blood
drug concentration versus time profile enters into the terminal elimination phase where the rate of change (or half-life) remains constant (3).
most common cause of interindividual variability in the rate of drug elimination from the body.
Genetic polymorphisms of the enzymes involved in drug metabolism
The cytochrome P450 (CYP P450) superfamily of enzymes, which are found in the
endoplasmic reticulum of hepatocytes and some other cells,
Some drugs, such as____and ____ can be directly conjugated to glucuronide without phase I reactions.
propofol and morphine
Vd In a purely physical sense, the
amount (mass) of solute divided by a known physical volume of fluid will equal the concentration of the solute in the fluid.
Usually, drugs that have clearances near that of liver blood flow are very efficiently biotransformed by phase I reactions (e.g., fentanyl) or phase II reactions (e.g., propofol) in the liver and, in the case of propofol, also in the kidneys. With such drugs, the elimination clearance
is considered to be flow limited, meaning the clearance will only decrease if blood flow to the organ decreases (e.g., with low cardiac output).
For other drugs that are less efficiently biotransformed (e.g., midazolam), the clearance is more (or even solely)
influenced by the enzymatic rate.
Limit the fraction of drug eliminated from the blood flowing to the organ. In these cases, blood flow is less of a factor in determining elimination clearance, and these drugs’ clearance are referred to as
capacity limited.
Most drugs are eliminated as a fixed fraction per unit of time. This circumstance is known as
first-order kinetics and the fraction eliminated is the rate constant (units of time−1), and drug concentration decreases exponentially
have more significant clinical effects on pharmacokinetic parameters than all but the most extreme derangements of the hepatic or renal function.
Weight and age
T 1/2 combines
Vd and elimination clearance.
T 1/2 = 0.693 x Vd/Cle
