contains intracellular enzymes that usually convert lipophilic (lipid-soluble) drug molecules into water-soluble metabolites that are more easily excreted.
What is the major enzyme system in the liver?
cytochrome P450 oxidase system
The four most important isoenzyme families for drug metabolism have been designated.
CYP1,CYP2,CYP3, and CYP4
cigarette smoking can increase the breakdown of __________ in patients with chronic lung disease, shortening the half-life of the drug from approximately 7.0 to 4.3 hours.
Chronic administration or abuse of drugs that are metabolized by the enzyme systems in the liver can
induce or inhibit the levels of enzymes
When a drug is taken orally and absorbed into the blood from the stomach or intestine, the portal vein drains this blood directly into the liver. The blood from the liver is drained by the right and left hepatic veins directly into the inferior vena cava and on into the general circulation. THis is known as the?
causes difficulties with oral administration that must be overcome by increasing the oral dose (compared with the parenteral dose) or by using a delivery system that circumvents first-pass metabolism
The primary site of drug excretion in the body is
is important for removing drug metabolites produced by the liver
refers to a hypothetical volume of plasma that is completely cleared of all drug over a given period
Plasma clearance (CLp)
To achieve a steady level of drug in the body, dosing must equal the
rate of elimination
the time required for the plasma concentration of a drug to decrease by one-half) is a measure of how quickly a drug is eliminated from the body
Plasma half-life (T1/2)
indicates how quickly a drug can accumulate and reach steady-state plasma levels
Plasma half-life (T1/2)
The concentration of a drug in the plasma over time can be graphed as a
The inhalation route used for inhaled therapeutic aerosols, together with the physical/chemical nature of the drug, determine the:
Absorption, distribution, metabolism, and elimination
Inhaled aerosols are deposited on the surface of the upper or lower airway and are a form of
topically administered drug
is exemplified by a nasally inhaled vasoconstricting agent (decongestant), such as oxymetazoline (Afrin), or by an inhaled bronchodilator aerosol, such as albuterol (Proventil-HFA, Ventolin-HFA, Proair HFA), to dilate the lower airways
whats is the rational for the inhaltion route in therapy of the lung?
to max. lung depostition and minimize systemic exposure and unwanted side effects
the inhaled route of administration can involve both:
gastrointestinal and lung distribution
The systemic level of an inhaled drug and possible extrapulmonary side effects depend on both gastrointestinal and lung
what percentage of the drug impacts the mouth or oropharynx and contributes to the 90% reaching the stomach.
Use of ______ devices with MDIs or delivery through endotracheal tubes can significantly change oropharyngeal impaction or airway delivery
The aerosol drug can be absorbed from the stomach and metabolized in the liver, producing a
What is the first-pass metabolism of albuterol?
What is the first-pass metabolism of budesonide?
What is the first-pass metabolism of terbutaline?
What are the sites of action in the airway: (there are 4)
secretions in the lumen, nerve endings, cells, and brinchial smooth muscle in the airway wall
describes the mechanism of activity by which drugs cause their effects in the body. The principal concept is the drug target protein
indicates clearly how close an aerosol drug delivery system comes to the ideal of having all of the systemic drug exposure come from only the lung dose.
The mechanism of drug action by which a drug molecule causes its effect in the body is the
Most drugs exert their effects by binding to
are any cell component that combines with a drug to change or enhance the function of the cell
The matching of a drug molecule with a receptor or enzyme in the body is based on a structural similarity between the drug and its binding site. This is known as?
Structure-activity relationship (SAR)
the response to a drug is proportional to?
the drug concentration
the dose at which 50% of the response to the drug occurs is indicated and is referred to as ______, the dose of drug that produces 50% of the maximal effect.
Refers to the concentration (EC50) or dose (ED50) of a drug producing 50% of the maximal response of the drug.
The greatest response that can be produced by a drug, a dose above which no further response can be elicited.
The lower the ED50 for a given drug, the more
potent the drug is
can be defined as the ratio of the LD50 to the ED50 for a given drug, with ED50 and LD50 indicating half of the test subjects rather than a 50% clinical response
therapeutic index (TI)
is also based on the dose-response curve of a drug
The ratio of the dose that is toxic to 50% of test subjects to the dose that provides relief to 50% of the subjects is the
is a drug used in respiratory care that has a narrow therapeutic margin.
is a drug or chemical that binds to a corresponding receptor (has affinity) and initiates a cellular effect or response (has efficacy)
is a drug or chemical that is able to bind to a receptor (has affinity) but causes no response (zero efficacy)
Direct chemical interaction between drug and biologic mediator, which inactivates the drug. An example is chelation of toxic metals by a chelating agent.
Can occur when two drugs each produce an effect, and the two effects cancel each other. For example, methacholine can stimulate parasympathetic (muscarinic) receptors in the airways, causing bronchoconstriction; epinephrine can stimulate �2 receptors in the airways, causing bronchodilation.
Occurs when a drug has affinity for a receptor but no efficacy and at the same time blocks the active agonist from binding to and stimulating the receptor. For example, fexofenadine is a competitive antagonist to histamine on specific receptors (H1) on bronchial smooth muscle and the nasopharynx and is used to treat allergies to pollens
Occurs when two drugs act on a target organ by different mechanisms of action, and the effect of the drug pair is greater than the sum of the separate effects of the drugs.
Occurs when two drugs act on the same receptors, and the combined effect is the simple linear sum of the effects of the two drugs, up to a maximal effect.
A special case of synergism in which one drug has no effect but can increase the activity of the other drug.
Effect that is the opposite of, or unusual, or an absence of effect, compared with the predicted usual effect in an individua
Allergic or immune-mediated reaction to a drug, which can be serious, requiring airway maintenance or ventilatory assistance.
Decreasing intensity of response to a drug over time.
Rapid decrease in responsiveness to a drug.
refers to hereditary differences in the way the body handles specific drugs.
Global term describing or referring to extension, auxiliary, or add-on devices attached to MDIs for administration. This term can include �spacer� and �valved holding chamber� (defined subsequently).
Simple tube or extension device with no one-way valves to contain the aerosol cloud; its purpose is simply to extend the MDI spray away from the mouth.
Describing the tendency of aerosol particles to remain in suspension.
Spacer device with the addition of one-way valve to contain and hold the aerosol cloud until inspiration occurs
Valved holding chamber
refers to the delivery of aerosol particles to the respiratory tract
What are tthe three main uses of aerosols:
Humidification, movement of secretions, and delivery of drugs
is a suspension of solid or liquid particles whose deposition in the respiratory tract is determined by inertial impaction, gravitational settling (sedimentation), and, perhaps less importantly, diffusion (brownian motion).
How small are the particles in an aerosol suspension?
0.001 and 100 micrometers
measures what is termed the aerodynamic diameter of aerosols because the measurement is based on the aerodynamic behavior (sedimentation velocity and impaction characteristics) of the particles.
What are the two main methods used to measure earosol particle size distrubutions?
cascade impactor and laser scattering
a measurement where the instrument determines the relationship between the intensity and the angle of light scattered from a particle, then calculates the particle size based on the Mie-scattering theory
is the diameter of a unit-density (1 g/cc) spherical particle having the same terminal settling velocity as the measured particle
aerodynamic diameter of a particle
consists of a series of stages, each of which has progressively smaller orifices through which the aerosol particles must pas
is considered the most sensitive technique for quantifying the amount of aerosol on each stage. Because each stage is calibrated for a unit-density sphere of specific diameter, the distribution of aerodynamic diameters can be calculated as the percentage of drug on each stage
HPLC (High-performance liquid chromatography
These methods (mechanically simulating the clinical setting within a laboratory) of aerosol measurement may not reflect conditions in the human lung, such as temperature, humidity, inspiratory flow rates, and exhalation phase
A major factor influencing aerosol deposition in the lung is
The upper airway (nose and mouth) is efficient in filtering particulate matter, so that generally there is 100% deposition in the nose and mouth of particles larger than
Particle sizes of ________ tend to deposit out in the upper airways and the early airway generations
particles the size of _______ have a greater probability of reaching the lower respiratory tract from the trachea to the lung periphery
were proposed for use in place of respirable fraction and respirable dose
fine particle fraction (FPF) and fine particle dose (FPD)
used to refer to the percentage or fraction of aerosol drug mass in a particle size range with a high probability of penetrating into the lower respiratory tract
fine particle fraction (FPF) and fine particle dose (FPD
Particles that are greater than_____are useful to treat the nasopharyngeal and oropharyngeal regions. An example is a nasal spray for perennial rhinitis, such as a corticosteroid.
Particles _________ may shift deposition to the more central airways, although significant oropharyngeal deposition is expected. An example is a nasal spray, but there is no one standard device that creates this specific particle size. Most aerosol devices use a smaller particle size, which is discussed subsequently.
As particle size decreases to less than ____ , deposition shifts from the oropharynx and large airways to the overall lower respiratory tract (large airways to periphery
Increased delivery of an aerosol to the lung parenchyma, including the terminal airways and alveolar region, can be achieved with particles less than
Three physical mechanisms usually are considered for aerosol particle deposition in the human lung:
Inertial impaction, Gravitation settling, and diffusion
is a function of particle size (mass) and velocity and increases with larger size and higher velocities
is a function of particle size and time. Settling is greater for larger particles with slow velocities, under the influence of gravity
Gravitational settling, or sedimentation
affects particles less than 1 �m and is a function of time and random molecular motion. Particles 0.1 to 1.0 �m may remain suspended or even exhaled because the time required to diffuse to the airway surface tends to be greater than the inspiratory time of a normal breath
Diffusion (brownian motion)
What are tthe common devices for the delivery of inhaled aerosol drugs.
SVN, pressurized MDI (pMDI) , DPI
Traditional aerosol-generating devices all deliver about _______% of the dose produced to the lung, although different types of devices vary in their loss patterns.
inhaled drugs are more stable with this, but the breakdoen of a drug can be cumulative effect of surface denaturation, heat, cavitation, and direct pressure.
device is a large-reservoir nebulizer, capable of holding 300 mL of solution for long periods of nebulization. It operates on a jet-shearing principle.
small particle aerosol generator (SPAG)
What was used during the clinical trials of the aerosolized antiviral drug ribavirin (Virazole) and is marketed for delivery of that drug by its manufacturer
An SVN fitted with inspiratory and expiratory one-way valves and with an expiratory filter is used during the administration of aerosolized
used with the SVN prevent second-hand exposure of pentamidine by eliminating the contamination of the ambient environment with exhaled aerosol
What are the factors that effect jet nebulizer performance?
residual volume, filling vol., flow rate, output, cont vs inspir., gas, physiocal nature, humdity and temp., and interface
Jet nebulizers do not aerosolize below a minimal volume, termed the _______,which is the amount of drug solution remaining in the reservoir when the device begins to sputter and aerosolization ceases
How much is the typical dead volume?
At less than __ mL, most pneumatic nebulizers do not perform well because the volume is close to the dead volume�that is, the residual amount that does not nebulize
At ___ mL, an excessively long time is required for treatment (more than 10 minutes) with most brands. Although 5 minutes seems to be a short time, even this can be inconveniently long as a way of taking medication three or four times a day
affects two variables: the length of treatment time and the size of the particles produced
Use of gases other than oxygen or air can change
Hess and associates35 showed that the use of _________ to nebulize albuterol caused particle size and inhaled drug mass to decrease, along with a more than twofold increase in nebulization time
Device interfaces used for aerosol drug administration include
Mouthpiece and mask
should be used because studies suggest that the mouthpiece provides greater lung dose than a standard pediatric aerosol mask
is related to surface tension and viscosity of the solution and is partially determined as well by the baffles in the device
droplet size of nebulized solutions
Additives to the drug solution can also affect aerosol