C H A P T E R 2
Drugs and the body
21
under the skin, where it is slowly absorbed into circu
lation. Timing of absorption varies with subcutaneous
injection, depending on the fat content of the injection
site and the state of local circulation. Table 2.1 outlines
the various factors that affect drug absorption for differ
ent routes of administration.
Absorption processes
Drugs can be absorbed into cells through various pro
cesses, which include passive diffusion, active transport
and filtration.
Passive diffusion
is the major process by
which drugs are absorbed into the body. Passive diffu
sion occurs across a concentration gradient. When there
is a greater concentration of drug on one side of a cell
membrane, the drug will move through the membrane
to the area of lower concentration. This process does not
require any cellular energy. It occurs more quickly if the
drug molecule is small, is soluble in water and in lipids
(cell membranes are made of lipids and proteins—see
Chapter 7) and has no electrical charge that could repel
it from the cell membrane.
Unlike passive diffusion,
active transport
is a process
that uses energy to actively move a molecule across a
cell membrane. The molecule may be large, or it may be
moving against a concentration gradient. This process is
not very important in the absorption of most drugs, but
it is often a very important process in drug excretion in
the kidney.
Filtration involves movement through pores in the
cell membrane, either down a concentration gradient or
as a result of the pull of plasma proteins (when pushed
by hydrostatic, blood or osmotic pressure). Filtration
is another process the body commonly uses in drug
excretion.
Factors affecting gastrointestinal absorption
Numerous factors can affect or alter the absorption of
oral drugs. Some are physiological barriers and some are
due to the formulation of the drug. The main factors
are:
• Gastrointestinal motility
• Splanchnic blood flow
• Particle size and formulation
• Physicochemical factors
Many disease conditions can slow down drug absorp
tion. For example diabetic neuropathy and migraine are
conditions that affect gastric stasis. There are also drug
treatments that can affect gastric motility. Drugs that
block the muscarinic receptors reduce gastric motility
and some drugs such as metoclopromide increase gastric
motility. A drug taken after a meal is often more slowly
absorbed because its movement to the small intestines is
delayed in the presence of food. However, not all drugs
taken after a meal can result in slow absorption of the
drug. Propanol when taken with meals reaches higher
plasma concentration because the drug increases splanch
nic blood flow. In clinical situations where a person is
hypovolaemic, splanchnic blood flow is slow and results
in a slowing of absorption of oral drugs. Formulation
and particle size have major effects in the absorption of
oral drugs. Capsules may be designed to remain intact
for some hours after the person takes the drug in order to
delay absorption. In some cases, tablets may have a resist
ant coating to give the same effect. Slow-release capsules
and sustained release capsules are formulated to produce
rapid but sustained absorption of the drug. Physicochem
ical factors such as changes in gastric pH due to ageing
and presence of other drugs can all affect drug absorp
tion. Tetracycline, an antibiotic, binds strongly to Ca
2
+.
Absorption of this drug is prevented if administered with
calcium rich foods (especially milk).
First-pass effect
Drugs that are taken orally are usually absorbed from
the small intestine directly into the portal venous system
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TABLE 2.1 Factors that affect absorption of drugs
Route
Factors affecting absorption
IV (intravenous)
None: direct entry into the venous
system
IM (intramuscular)
Perfusion or blood flow to the
muscle
Fat content of the muscle
Temperature of the muscle:
cold causes vasoconstriction
and decreases absorption;
heat causes vasodilation and
increases absorption
Subcutaneous
Perfusion or blood flow to the
tissue
Fat content of the tissue
Temperature of the tissue:
cold causes vasoconstriction
and decreases absorption;
heat causes vasodilation and
increases absorption
Acidity of stomach
PO (oral)
Length of time in stomach
Blood flow to gastrointestinal tract
PR (rectal)
Presence of interacting foods or
drugs
Perfusion or blood flow to the
rectum
Lesions in the rectum
Length of time retained for
absorption
Mucous
membranes
(sublingual,
buccal)
Perfusion or blood flow to the area
Integrity of the mucous
membranes
Presence of food or smoking
Length of time retained in area
Topical (skin)
Perfusion or blood flow to the area
Integrity of skin
Inhalation
Perfusion or blood flow to the area
Integrity of lung lining
Ability to administer drug
properly
