PHARMACOKINETICS

AND
PHARMACODYNAMICS
BACKGROUND
Learning objectives

After reading this section, you will be able to answer the following questions:
* How drugs are absorbed?
* Define pharmacokinetics?
* Define absorption?

 BACKGROUND
➢When a drug is administered via the oral route with a glass of water, it passes through the esophagus to

the stomach. In the stomach, the dosage form disintegrates and dissolves (in case the dosage form was
solid).

➢The drug is already dissolved if administered as an oral solution.

➢The half-life (t1⁄2) of the gastric emptying is about 25 min.

➢ The drug is then emptied into the small intestine from where the majority of orally administered drugs

are absorbed.

➢The interaction between the body and the drug is the subject of pharmacokinetics and

pharmacodynamics.

PHARMACOKINETICS
▪ Once the drug is administered, it is absorbed into the systemic circulation, from where
it is then distributed to the various tissues and cells of the body, where it exerts its
therapeutic and adverse actions and where it might be metabolized, and ultimately it
will be excreted from the body.

▪ The term pharmacokinetics describe these 4 processes. Pharmacokinetics is defined

in the simplest terms as what the body does to the drug.

▪ The 4 processes of pharmacokinetics are known by the acronym ADME (absorption,

distribution, metabolism, and excretion).

ABSORPTION
▪ To exert its actions in the body, the drug needs to reach the systemic circulation.

▪ What happens to the drug from its site of administration till it reaches the systemic circulation
concerns: the absorption process.

▪ Absorption in simple terms can be defined as the transfer of the drug molecules from the site
of administration to the systemic circulation.

▪ When the drug is administered intravenously, it is directly placed into the systemic
circulation, therefore the absorption phase of its pharmacokinetics does not exist.

ABSORPTION
Drugs administered orally are mainly absorbed from the small
intestine. In the small intestine, absorption occurs through two
main processes:

▪ Diffusion: in which drug molecules passively (no energy

required) move down their concentration gradient.

▪ Active transport: in which drug molecules are transported with

the help of a transporter which need energy to transport the drug.

ABSORPTION
▪ Drug molecules are absorbed into small blood vessels which then collects in
the portal vein. This means that the drug has to pass the liver before it reaches
the systemic circulation.

▪ Detoxification is a major function of the liver as hepatocytes contain many

enzymes capable of metabolizing (usually inactivating) endogenous and
exogenous materials, including drugs.

ABSORPTION
▪ Therefore it is probable that a fraction (%) of the dose of the drug absorbed might be
metabolized before the drug reaches the systemic circulation.

▪ This phenomenon is known as first pass effect which is defined as a phenomenon

in which a proportion of the drug dose is metabolized before it reaches the systemic
circulation. ( see next figure )

▪ Drugs might have a first pass effect anywhere between 0- 100%. The fraction of the
dose that reaches the systemic circulation is known as bioavailability (F).

ABSORPTION
▪ Absorption of drugs depends on physiological factors of the patient and the
physicochemical properties of the drug. The rate and extent of drug absorption
are more when:

Physiological factors:
▪ More blood flows to the site of absorption
▪ More surface area available for absorption
▪ The longer it remains at the absorption site

ABSORPTION
Physicochemical properties:
▪ The higher the solubility of the drug

▪ The higher the chemical stability of the drug

▪ The higher the lipophilicity of the drug

having an affinity for lipids

▪ The lower the fraction of drug ionized

DISTRIBUTION
➢ Once the drug reaches the systemic circulation, it is distributed to various tissues

and cells in the body where it will exert its therapeutic as well as adverse effects.

➢In this process, drugs are first distributed into body fluids. The body fluids include

plasma, extracellular and intracellular fluids.

➢ Drugs will then be taken by tissues and cells.

➢The degree to which drugs are taken by various tissues and cells depends on the

lipophilicity of the drugs and protein binding. ( see next slide)….

DISTRIBUTION
1) Lipophilic drugs are extensively distributed into various body tissues and cells,
while hydrophilic drugs remain in the body fluids. Drugs can distribute to areas
like the brain when they are relatively small and adequately lipid soluble. Usually,
a fraction of the drug will bind to plasma proteins.

2) the free “unbound” fraction of the dose available in the systemic circulation that
will distribute into various tissues and cells.

METABOLISM
▪ Drug molecules often undergo metabolism in various tissues and cells, notably those
of the liver, kidneys, lungs, intestine, and brain. In this process, drug molecules are
transformed into metabolites which are usually more polar and less active.
▪ There are two main phases of drug metabolism:

1) Phase I includes oxidation, reduction, and hydrolysis reactions.

2) phase II metabolism, conjugative reactions occur.
Note: Metabolites are usually More Polar than parent compounds and thus can be
excreted easily from the body.

EXCRETION
➢Drugs and their metabolites need to be eliminated from the body. Most of the

drugs and their metabolites are eliminated in the urine via the kidneys.

➢ This process often starts with active glomerular filtration.

➢Drugs and their metabolites might also be actively secreted into the proximal

tubules of the nephron.

➢Drugs and their metabolites are then passed with the urine.

PLASMA DRUG CONCERTATION

VERSUS TIME PROFILE
▪ When a drug for systemic action is administered via any of the extravascular
routes (oral, intramuscular, rectal, ...etc), the drug will ultimately be absorbed
and reaches the systemic circulation.

▪ Figure 2.1 shows the plasma drug concentration vs. time profile for a drug that
was administered via an extravascular route.

PLASMA DRUG CONCERTATION

VERSUS TIME PROFILE
▪ Onset time is the time when the drug concentration reached the minimum
effective concentration (MEC) which is the minimum concentration that need
to be reached for a drug to exert its therapeutic action.

▪ Dosing schedule of any drug should be designed taking into account that the
drug concentration should not reach the minimum toxic concentration (MTC)
which is the minimum concentration at which the drug starts exhibiting its toxic
effects.

PLASMA DRUG CONCERTATION

VERSUS TIME PROFILE
▪ The distance between the MTC and MEC is known as therapeutic range
(therapeutic index) of the drug.

▪ Drugs with shorter ranges are known as narrow therapeutic index drugs and
drugs with longer distances are known as drugs with wide (broad) therapeutic
index drugs.

PLASMA DRUG CONCERTATION

VERSUS TIME PROFILE
▪ The maximal drug concentration is known as Cmax

▪ the time to Cmax is known as Tmax.

▪ The time from onset till the termination of drug action is known as duration of

action which can be defined as the time through which the drug concentration remains
above the MEC.

▪ The area under the curve (AUC) is the area under the plasma concentration time

which represents the extent of exposure to the drug.

PHARMACODYNAMICS
▪ In simple terms pharmacodynamics refers to what the drug does to the body.

▪ The field of pharmacodynamics includes how does the drug work in the body by
interacting with targets to produce effects ( Mechanism of action )

▪ how does the drug affect the body ( the drug effects ):

a) therapeutic effects b) side effects.

▪ How much of the drug is needed to safely treat the patient’s condition the dose.

 PHARMACODYNAMICS
Targets for drug action
▪ Many targets for drug action are extracellular proteins on the cell membrane or
intracellular proteins that can be found in the cytoplasm or in the nucleus. Drug targets
can be:

▪ Transporter proteins ( receptors)

▪ Nucleic acids
▪ Ion channels
▪ Structural macromolecules
▪ Adhesion molecules
▪ Enzymes

PHARMACODYNAMICS
▪ Drugs bind to specific targets that they have certain affinity to.

▪ The lock and key hypothesis is a scientific analogy that describes the
interaction between the drug and its target.

1) An agonist is a drug that binds to a receptor and activates it.

2) An antagonist is a drug that binds to a receptor and prevents an agonist from

binding to and activating the receptor.

ROUTES OF DRUG
ADMINISTRATION
▪ Drugs can be administered via different routes. This depends
on the many factors including the physicochemical properties of
the drug and the pathophysiologic conditions of the patient.

▪ Routes of administration can broadly be divided into:

▪ Enteral routes

▪ Parenteral routes

▪ Other routes

ENTERAL ROUTES
▪ Enteral routes (by the mouth) can be safe, convenient, and economic.
However, it is not suitable for all patients.
▪ Oral route

▪ Sublingual route

▪ Buccal route

PARENTERAL ROUTES

▪ Intravenous (IV) route or intra arterial

▪ Intramuscular (IM)
▪ Subcutaneous (SC)

 OTHER ROUTES
▪ Inhalation
▪ Intrathecal
▪ Topical
▪ Transdermal
▪ Rectal

 DRUGS DOSAGE FORMS:

Solids:
tablets , caplets , capsules , pills , lozenges , powders.
Semisolids:
Creams , ointments , gels , pastes , suppositories .
Gazes:
Inhalations , sprays , aerosols.
Solutions:
Syrup , suspension , emulsion , water for injection , solutions for
injection.