Glossary/Abbreviations

Ab: Amount of drug in the body.

ADE: Adverse drug event. Any actual or potential damage resulting from medical intervention related to medicines.
ADR: Adverse drug reaction. Any response to a drug which is noxious, unintended, and occurs at doses used in m
for prophylaxis, diagnosis or therapy.
AUC: Area under the plasma concentration curve vs time curve.
Biophase: The immediate vicinity of the site of activity of a drug.
CBA: Cost-benefit analysis.
CEA: Cost-effectiveness analysis.
Clearance: The volume of plasma cleared of drug per unit time. Or a constant relating the rate of elimination to the plasm
concentration.
Clinical Pharmacology: The principles behind the prescribing process.
CMA: Cost-minimization analysis.
Cmax: Maximum concentration.
Compliance: In drug therapy this describes how much a patient is able to follow a full course of medication exactly as
prescribed.
Concordance: This is the more modern, less authoritarian, interpretation of compliance that recognizes that a prescription
embraces an agreement between the patient and the doctor.
Cp: Plasma concentration.
Cp0: Plasma concentration at time zero.
Cpss: Plasma concentration at steady state.
Cpt: Plasma concentration at time t.
CrCl: Creatinine Clearance.
CUA: Cost-utility analysis.
CYP: Cytochrome P450.
Dose Interval: The time interval between administration of doses.
Dose tapering: Back-titration of a dose of a drug after effect has been achieved in order to achieve the minimum dose
commensurate with desired effect.
e: The natural logarithm (value = 2.7183)
EC50: The concentration of a drug at which effect is 50% maximum.
Emax: The maximum effect of a drug.
F: Fractional oral availability.
First-order: A number to the power of one. In pharmacokinetics, it refers to elimination that is dependent on concentration
(i.e. Cp1 = Cp), as occurs with most drugs.
First-pass metabolism: Metabolism that occurs between the gut lumen and the systemic circulation during the first passage of the
drug through the gut wall, the portal system and the liver to the inferior vena cava.
Flow-dependent The elimination of high clearance drugs is so rapid that it is susceptible to the rate of presentation to the
elimination: eliminating organ, and hence to blood flow.
fu: Fraction excreted unchanged by the kidney.
Half-life: The time for the concentration of the drug in the plasma (or the amount of drug in the body) to halve.
k: Rate constant of elimination: The fraction of drug removed per unit time. Applies to drugs with first-order
elimination (i.e. most drugs)
Km: The Michaelis constant. The concentration at which the rate of reaction is half the Vmax.
ln: The natural logarithm.
Loading dose: The dose required to achieve a target plasma concentration as soon as possible.
M/P ratio: Milk to plasma ratio.
MEC: Minimum effective concentration.
MTC: Minimum toxic concentration.
OTC: Over the counter.
P.B.: Protein Binding - usually expressed as a fraction or percentage.
pH: The negative of the log (base 10) of the concentration of hydrogen ions.
Pharmacodynamics: The study of drug effect, and mechanism of action, i.e. what the drug does to the body.
Pharmacokinetics: The study of the movement of drug into, within, and out of the body, i.e. what the body does to the drug.
Phase I metabolism: Simple chemical alteration of a molecule by oxidation (most commonly), reduction or hydrolysis. It occurs ofte
by cytochrome p450 enzymes.
Phase II metabolism: Conjugation reactions including glucuronidation (most common), acetylation, sulphation and metylation.
pH-dependent elimination: Variation in renal elimination of drugs with susceptible pKa values whose degree of ionization varies within th
range of pH values of the urine (pH 4.5-8).
PILs: Patient information leaflets.
pKa: The pH at which a drug is 50% ionized, and 50% unionized.
Potency: An index of the concentration of a drug required for a given effect. The lower the concentration the greater th
potency.
Prodrug: A drug that is inactive in itself, but which is converted to an active metabolite.
QALY: Quality adjusted life years.
RCT: Randomized controlled trial.
Saturable metabolism: Drug concentrations rise disproportionately as a result of a change from first-order to zero-order elimination.
SIADH: Syndrome of inappropriate antidiuretic hormone.
ss: Steady state.
During breathing, the inspiratory muscles must create enough pressure to overcome two
forces: the friction associated with air flow and also the increase in elastic recoil of the
lung as it inflates to a larger volume. Before we consider air flow, we must understand
the elastic properties of the lung and chest wall.

These are best studied in static situations; that is, while one holds one's breath (either by
tensing one's respiratory muscles or by closing one's glottis).

We will first discuss how the lung responds to external pressures, then how the relaxed
chest wall responds to external pressures, and finally how the two act together.

We will use the colored illustration of the lungs, pleura, trachea, and glottis to visually
demonstrate the pressures at work. We will plot the pressure-volume curves for this
individual's lung and relaxed chest wall on the graph.

In this illustration, purple is meant to indicate subatmospheric or negative pressures, and

green greater-than-atmospheric or positive pressures. The more intense the color the
farther it is from atmospheric pressure, the paler the color, the closer it is to atmospheric.

The lung is a distensible structure. It would collapse like a balloon if there were no
pressure difference across it. However, it expands quite readily when the pressure outside
(pleural pressure, Ppl) is less than the pressure inside (alveolar pressure, Palv).
The difference in pressure between the alveoli and the pleura (Palv- Ppl) may be called
the transpulmonary pressure (PL), the distending pressure of the lung, or the recoil
pressure of the lung. In this tutorial, we will use the term recoil pressure, but bear in mind
that any of these terms could be used.

The important point is that it is the difference between the pressures on the two sides of
the lung, rather than their absolute values, that determines the size of the lung.

As the lung deflates, each lung volume corresponds to a specific value of recoil pressure.
During inflation, the relationship is slightly different because of surface forces within the
alveoli, but for the sake of simplicity we will use only the deflation curve at this time.

If an individual exhales to residual volume ( RV) and then holds his breath with the
glottis open (that is, uses his chest wall muscles to keep the lung/chest wall unit at
residual volume, while allowing the alveolar and atmospheric pressures to equilibrate),
his alveolar pressure (Palv) will be measured as zero centimeters of water (cm H20).

His pleural pressure ( Ppl) can be measured (via an esophageal balloon) as -3 cm H20.
Thus the recoil pressure of the lung (Palv- Ppl) equals 0-(-3), or +3 cm H20.

This means that at RV (roughly 20% TLC), this person's lung is exerting a pressure of 3
cm H20 to recoil inward, and must be balanced by a distending pleural pressure 3 cm H20
less than his alveolar pressure to keep the lung open.
Notice a plot point is placed on the graph at the coordinates of 20% TLC and +3 cm H20.

The recoil pressure, or the pressure difference between the inside and outside of the lung,
will remain the same at a given volume, although the actual alveolar or pleural pressures
may change.

For instance, if negative pressure had been applied to the trachea to reach RV, his Palv
might have been -4 cm H20 rather than 0 cm H20, but his Ppl would still have to have
been 3 less, or -7 cm H20.

: You breathe in until the recoil pressure of your lung is 10 cm H20, and then you do a
Valsalva maneuver (compress the air in your lungs against a closed glottis) until alveolar
pressure is 50 cm H20. What is your pleural pressure during the Valsalva?
Answer: 40 cm H20. The recoil pressure of the lung is given as 10 cm H20; this means
that at this volume Palv is 10 cm H20 greater than Ppl. If Palv is 50, then Ppl must be 10
less, or 40 cm H20.

Since the glottis is closed, no air can escape, so the volume does not change (any volume
change produced by compressing the alveolar gas is trivial and can be ignored).

utorial: Quiet Breathing.

This module explains what happens during quiet breathing. We will be examining the
breathing cycle at 4 stages: rest, during inspiration, end inspiration (equilibrium), during
expiration, and end expiration.

Mechanics refers to the study of mechanical (as opposed to chemical or biological)

aspects of breathing, namely the interaction of pressure, volume, and air flow within the
respiratory system.

The graph (shown below) will show you where we are in the breathing cycle. Watch the
red ball as it moves through the inspiration and expiration cycle. The scale at the lower
right correlates pressure changes with the colors used in the illustration. Watch the arrows
representing alveolar and pleural pressure as they move.
In this model, purple indicates subatmospheric (negative) pressures, and green greater-
than-atmospheric (positive) pressures; the more intense the color, the farther it is from
atmospheric pressure, the paler, the closer to atmospheric pressure.

At Rest:

(After expiration ends and before inspiration begins.)

1. With the respiratory muscles at rest, the elastic recoil of the lung (Palv-Ppl=+5) and of
the chest wall (Ppl-Pbs=-5) are equal but opposite.

2. Pleural pressure is subatmospheric (note the purple color in the pleural space).

3. Pressure along the tracheobronchial tree and in the alveoli is equal to atmospheric
pressure. There is no air flow.

4. Air will only flow only from an area of higher pressure to one of lower pressure. Since
alveolar pressure equals atmospheric pressure there is no air flow.
During Inspiration:

1. The diaphragm and other respiratory muscles contract.

2. Because the diaphragm is curved, its contraction compresses the abdominal contents
and decompresses the contents of the thorax, causing pleural pressure to fall.

3. Because the volume of the lung is initially unchanged, its recoil pressure (Palv - Ppl),
which is volume-dependent, is also unchanged. Thus, as pleural pressure falls, alveolar
pressure falls by an equal amount, becoming subatmospheric.

4. Air flows into the lungs down the pressure gradient from the mouth to the alveoli.

5. The lungs and chest expand in volume, causing the recoil pressure of the lung to
increase until a new equilibrium is reached.
End Inspiration:

1. An equilibrium exists after inspiration ends and before expiration begins.

2. Air flows down the pressure gradient until the lung reaches a new equilibrium volume
at which alveolar pressure equals zero and the gradient for flow ceases to exist.

3. Lungs and chest are fully expanded.

During Expiration:

1. The respiratory muscles relax, causing an abrupt increase in pleural pressure to a less
negative value.

2. Because lung volume has not yet changed, the recoil pressure of the lung must remain
the same, so the rise in pleural pressure causes the alveolar pressure to rise by the same
amount.

3. This establishes a pressure gradient from the alveoli to the mouth, down which air
flows.

4. Lung and chest volume decrease as air flows out, causing lung recoil pressure to fall as
well, until a new equilibrium is reached at FRC, the equilibrium volume.
At the End of Expiration:

1. The pleural cavity and the alveoli return to the pressure relationship they had at the
start of inspiration:

2. Pleural pressure is -5 and alveolar pressure is 0.