Administration and Absorption
of Drugs
Factors that effect the action of a
drug
• 1. Rate of accumulation
at its site of action
• 2. Concentration of the
drug at the site of action
• 3. The duration of the
drug’s contact at those
sites
Pharmocokinetics
• Refers to the movement
of chemicals in a
biological system
• This includes:
– Administration and
absorption
– Distribution
– Binding properties
– Metabolic mechanisms
– Elimination from the
system
Administration of drugs
•
To be effective a drug must enter
the body and get to its site of
action
•
Best method of administration of a
drug depends on the drug
•
Most drugs dissolved in a fluid
(saline) or contained in a mixture
as in pills or capsules – type of
substance is important
•
Injections tend to be fast acting,
oral administration is usually slow
acting and of a longer duration
Routes of administration – Enteral
routes
• Administered through the
alimentary canal – oral or anal
• Common problem is that
absorption rate can be highly
variable
– Absorption of orally
administered drugs is greatly
influenced by stomach
contents
– Hostile acid environment can
interfere with absorption
• Other problems:
– Some people cannot take pills
– Uncooperative patients may
refuse or “cheek” them
Routes of administration –
Parenteral routes
• Injection
– Intravenous – drug injected
into vein
• Advantages – fastest way
administer drug and dosage
most accurate
• Disadvantages – chance of
infection if conditions not
sterile and no way to retrieve
the drug in case of allergic or
toxic reaction
– Intramuscular – drug injected
into muscle mass – slower but
safer
– Subcutaneous – injection
under the skin or implanted
under the skin
– Direct injection in the nervous
system
Routes of administration –
Parenteral routes
• Pulmonary routes –
inhalation into the lungs
• Topical routes – placing
drug on the surface
usually a surface with a
mucous membrane
– Sublingual – placed under
the tongue
– Intranasal – powder or
liquid absorbed through
mucous membrane in the
nose
– Skin – skin patches or
topical anesthesia
Absorption of Drugs
• With the exception of
drugs directly injected
into the nervous system
and topical anesthesia,
drugs have to cross at
least 2 membranes to
reach its site of action
– At a minimum, it has to
cross into the blood
stream, out of the blood
stream, and into the cell
• Walls of blood vessels
and cell membranes are
semi-permeable
The bloodstream and drug
movement
• How fast a drug gets
into the bloodstream
depends on route of
administration
• Once in the blood, a
drug has access to all
types of tissue,
muscle, fat skin,
lungs, etc.
Structure of capillaries
• Capillaries in most of the body
are made up of cells with gaps
in between the cells
• These gaps allow some
substances, but not blood cells
of large proteins, to move in
and out of the capillaries
• Some drug molecules will bind
to these large proteins
reducing the amount of “free”
molecules in the blood
• When these free molecules
leave the blood stream, bound
molecules become unbound to
maintain a stable
concentration
Blood – brain barrier
• In the brain, the cells are
more tightly packed so
molecules have to move
through the cells
themselves – this makes
up part of the blood-brain
barrier
• Astrocytes make up the
rest of the blood-brain
barrier by sending out
“feet” that help seal the
capillary walls
Blood-brain barrier
• Very few substances can
cross this barrier
• Membranes of the
capillary cells and
astrocytes are made up
of lipids
• Only lipid soluble
substances can be
absorbed into the cells
and pass through them
• This barrier important
because the brain has no
immune system
Movement across semi-permeable
membranes
• Three types of fluid
– Fluid in the bloodstream
– Fluid outside the cells – extra
cellular fluid
– Fluid inside the cells –
intracellular fluid
• These fluids can move back
and forth across membranes
• Example thirst
– Lack of fluid in blood
– Extra cellular fluid moves into
bloodstream
– Intracellular fluid moves out of
the cells
– Loss of fluid detected; signal
sent to drink
Movement across semi-permeable
membranes
• Filtration – as fluid moves into
a cell the membrane filters out
large molecules which include
many drug molecules
• Movement through diffusion –
follows chemical gradient –
chemicals flow from areas of
high concentration to areas of
low concentration
– If a chemical is highly
concentrated outside a cell,
and openings exist, it will
move into the cell
Placental Barrier
• A weak barrier between
mother and fetus
• Large amounts of
materials are exchanged
between mother and
fetus
• Most drugs easily cross
the placental barrier –
almost every drug a
mother takes the fetus
takes
Solubility
• Lipid soluble drugs –
drugs that can be
dissolved in lipids – fatty
substances that make up
cell membranes –
including the blood-brain
barrier
• Water soluble drugs –
drugs that can dissolve in
water – they will not
passively move through a
cell membrane so they
require active transport