Pharmacodynamics and
pharmacokinetics
E N S U R I N G PAT I E N T S AF E T Y I N H E ALT H C AR E N U 2 1 0 0 0 5
Concepts
Pharmacology= study of drug action/ how
chemical substances affect living tissue
Divided in:
Pharmacodynamics = studies the effects of
a drug on biological systems
Pharmacokinetics = phases of the drug in
the body- the absorption, distribution,
metabolism, and excretion (ADME)
Pharmacodynamics
Refers to the effect of a drug on the body, organs, cells and molecules
Information on the mechanisms of action of drugs is needed, for example, to
assess the potential for drug interactions
The drug strengthens or prevents the body's own reactions. A therapeutically
useful drug only selectively affects the desired site or function of the body!
It is good to identify these basic terms of drug effects:
AGONIST = A drug that binds to the receptor and mimics the effects of the body's
own substances is called an agonist.
ANTAGONIST = The antagonist also binds to the receptor, but it inhibits the
response of the agonist
Stages and effects of the medicine in the
body
Pharmacokinetics
Absorption- how a drug gets into the
body
Distribution- how the drug gets
distributed throughout the body and
where
Metabolism- how the drug is broken
down into waste products
Elimination- how the drug leaves the
body
Cont…
Understanding how drugs travel in the body and how they work helps
to understand why drugs are administered using different routes of
administration
to administer medication to the patient correctly
to guide the patient in the proper use of medications
to manage the side effects of drugs
to monitor the effects of drugs on the patient
to guide and support the patient in the proper use of medications
Absorption
The movement of a medicine from the site of
administration to the bloodstream
Drug must cross several semipermeable cell
membranes before it reaches the systemic
circulation
Cell membranes are biologic barriers that
selectively inhibit passage of drug molecules
Lipid soluble drugs tend to be absorbed more
quickly than water-soluble agents
Bioavailability
Each drug will have a unique
bioavailability
Fraction of an administered dose that
reaches the systemic circulation
I.V 100%
P.O 0-100%
A drug’s bioavailability is determined
by
its pharmacokinetics
Factor that reduce the availability of drugs
• Route of administration • Gastrointestinal poor mobility
• Physical properties of the drug /Gastric emptying rate
• The drug formulation • Blood circulation
• The additives (inactive ingredients • Interactions with other drugs/foods
such as diluents, stabilizers,
disintegrants, and lubricants) are • Stomach pH, food, drink can
mixed with the drug to make it change absorption
easier to swallow or help break it • Disease state
up in the gastrointestinal tract
• Level of physical activity
• Dosage forms (eg, tablets,
capsules, solutions) • Stress
• Absorption from the digestive tract
is impaired
Distribution
Drug distribution is the process of delivering a drug from the bloodstream
to the tissues of the body – especially the tissue(s) where its actions are
needed
Intravascular (blood/plasma) and extravascular (intracellular &
extracellular) compartments of the body
Drugs penetrate different tissues at different speeds, depending on
the drug’s ability to cross membranes
the location, extent, and degree of distribution are dependent on the drug's properties
and individual patient characteristics such as organ perfusion and blood flow
Drugs penetrate different tissues
at different speeds, depending
on the drug’s ability to cross
membranes
Often the idea of some tissues
being “barriers” to drug
distribution is discussed (e.g.
blood-brain-barrier; placental
barrier)
Video
Medications will be more quickly distributed to areas of the body that
receive large amounts of blood flow than to areas that receive little blood
flow
Commonly, drugs bind non-specifically to albumin in the plasma
A medication is bound non-specifically to a protein, it cannot have a
therapeutic action, nor can it be eliminated
Non-specific binding to drugs can also play a role in drug-drug interactions;
if two or more drugs are competing for the same binding site, one drug will
displace the other, thereby, leading to potential toxicity caused by the drug
that was displaced
Apparent Volume of distribution-
Jakautumistilavuus
The volume of distribution is the extent to which a
medicine distributes out of the bloodstream and
into the tissues of the body
If the volume of distribution is a large: medicine
builds up in the tissues (liver, heart, kidneys) and
leaves the body slowly
If the volume is small: the medicine is almost non-
circulating
Some medicine leave the bloodstream very slowly
because they bind tightly to proteins circulating in
the blood
Only medicines that are unbound to proteins and
other components in the blood are free to diffuse
across the cell membranes into the tissues of the
body
Metabolism
The liver is one of the largest organs
in the body
It has many important metabolic
functions
It converts the nutrients in our diets
into substances that the body can
use, stores these substances, and
supplies cells with them when
needed
It also takes up toxic substances
and converts them into harmless
substances or makes sure they are
released from the body
Metabolism describes the chemical reactions that change drugs into
compounds which are easier to eliminate
Metabolites
This stage the drug is broken down
This takes place mostly in the body’s largest internal organ, the liver
Metabolism is often divided into two phases of biochemical reaction -
phase 1 and phase 2
Functionalization reactions
Oxidation (via cytochrome P450), reduction
and hydrolysis reactions
During this phase, proteins called enzymes
break down the drug molecules, which
creates metabolites
In some cases the reverse occurs: inactive
drugs (or prodrugs) are converted to active
metabolites
The primary objective of drug metabolism is
to facilitate a drug’s excretion by increasing
its water solubility (hydrophilicity)
Why does the drug not work if swallowed?
Some medicines should not be formulated for oral use at all
This may be because the drug becomes ineffective as soon as it is
absorbed from the gut and first reaches the liver
Consequences of first-pass metabolism:
1. Low bioavailability per os when administered:
If the drug has poor bioavailability when administered orally, its
bioavailability may be lower than usual when administered rectally.
The fact that the drug cannot take full effect when taken orally does not
affect e.g. bioavailability of drugs absorbed intravenously, intramuscularly
or orally
Oral dose requirement of some drugs is higher
Cont..
2. Individual dosage requirements per os for medicinal products with
extensive first-pass metabolism may vary significantly
diseases
interactions
Age
genetic factors
food or tobacco
Cont…
3. First-pass metabolism may saturate
For example, nitrate on the market as a sublingual tablet (sublingual) must
be allowed to melt and be absorbed in the mouth
If the tablet is swallowed, it loses its potency due to extensive first-pass
metabolism
Conjugation reactions
Phase II liver neutralizes the
byproducts of Phase I liver
detoxification and other remaining
toxins making the toxins water-
soluble can be excreted from the
body conjugation
Glutathione, sulphate, and glycine are
the primary molecules responsible for
this process
Glucuronidation, the most common
phase II reaction, is the only one that
occurs in the liver microsomal enzyme
system. Glucuronides are secreted in
bile and eliminated in urine
Elimination
The half-life of a drug
The symbol for half-life is T½
For example, if 100mg of a drug with a half-life
of 60 minute is taken, the following is
estimated:
60 minutes after administration, 50mg remains
120 minutes after administration, 25mg
remains
Actual half-life of a drug varies from person to
person, because it depends on a number of
different patient- and drug-specific variables
Cumulation
Cumulation means the accumulation of a drug in the body
The amount of drug that accumulates in the body depends on it
the dose used
Bioavailability
half-life
time between doses
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