Transcript 01_CLIN_PHARMACOKYNETIC_PHARMACODYNAMIC

Clinical Pharmacokinetics. Clinical
Pharmacodynamics. Drugs’ Interaction.
Adverse Effects of Drugs
DRUG NAMES
The generic
name often indicates the drug group (eg, drugs with generic
names ending in “cillin” are penicillins). The trade name is
designated and patented by the manufacturer. For example,
amoxicillin is manufactured by several pharmaceutical companies,
some of which assign a specific trade name (eg,
Amoxil, Trimox) and several of which use only the generic
name.
Amoxicillin
Metronidazole
Ranitidin
.
ENTRY AND MOVEMENT OF DRUG MOLECULES
THROUGH THE BODY
TO SITES OF ACTION, METABOLISM, AND
EXCRETION
ABSORPTION is the process that occurs from the time a drug enters
the body to the time it enters the bloodstream to be circulated.
Onset of drug action is largely determined by the rate
of absorption; intensity is determined by the extent of absorption.
Dosage form
is a major determinant of a drug’s bioavailability (the portion
of a dose that reaches the systemic circulation and is available
to act on body cells). An intravenous drug is virtually
100% bioavailable; an oral drug is virtually always less than
100% bioavailable because some is not absorbed from the GI
tract and some goes to the liver and is partially metabolized
before reaching the systemic circulation.
Most oral drugs must be swallowed, dissolved in gastric
fluid, and delivered to the small intestine (which has a large
surface area for absorption of nutrients and drugs) before they
are absorbed. Liquid medications are absorbed faster than
tablets or capsules because they need not be dissolved.
Sustained blood levels
 The size and frequency of
dosing is determined by the
pharmacodynamic and
pharmacokinetic properties of
the drug. The slower the rate
of absorption, the less the
blood concentrations fluctuate
within a dosing interval. This
enables higher doses to be
given less frequently. For
drugs with relatively short
half-lives, the use of extendedrelease products may
maintain therapeutic
concentrations over
prolonged periods
Drug transport pathways. Drug molecules cross cell
membranes to move into and out of body cells by directly
penetrating
the lipid layer, diffusing through open or gated channels,
or attaching to carrier proteins.
Plasma proteins, mainly albumin (A), act as carriers for
drug molecules (D). Bound drug (A–D) stays in bloodstream
and is
pharmacologically inactive. Free drug (D) can leave the
bloodstream
and act on body cells.
Half-life of a drug
Elimination of a
hypothetical drug with
a half-life of 5 hours.
The drug concentration
decreases by 50%
every 5 hours
(i.e., T1/2 5 hours). The
slope of the line is the
elimination rate (Ke).
THE LIVER IS THE PRINCIPAL
ORGAN OF DRUG
METABOLISM. Other tissues
that display considerable
activity include the
gastrointestinal tract, the lungs,
the skin, and the kidneys.
Following oral administration,
many drugs (eg, isoproterenol,
meperidine, pentazocine,
morphine) are absorbed intact
from the small intestine and
transported first via the portal
system to the liver, where they
undergo extensive metabolism.
This process has been called a
first-pass effect.
Pharmacodynamic Variables
 Clearance is the single most important
factor determining drug concentrations.
Clearance is readily estimated from the
dosing rate and mean steady-state
concentration. Blood samples should be
appropriately timed to estimate steady-state
concentration.
Вioavailability is defined as the fraction of a
given drug dose that reaches the circulation
in unchanged form and becomes available
for systemic distribution. The larger the
presystemic elimination, the smaller is the
bioavailability of an orally administered
drug.
Сеll membrane contains receptors for physiologic substances
such as hormones (H) and neurotransmitters (NT). These
substances
stimulate or inhibit cellular function. Drug molecules (Da and
Db)
also interact with receptors to stimulate or inhibit cellular
function
Presystemic elimination
Factors that influence on drug metabolism
Factor
Reaction type
Age (newborns, Decreasing of metabolism speed
children, elderly)
Pregnancy
Increasing of metabolism speed
Genetic factor Various reactions
Liver pathology Decreasing of excreation speed of drugs, depending on their kinetics, type
and stage of liver disease, increasing of bioavailability and decreasing of
excretion speed of orally administered drugs with high hepatic clearence
GI pathology
Changes in metabolism in GI epithelium
Nutrition
character
Increasing of metabolism speed of certain drugs in case of diet with
dominance of proteins and carbohydrates
Decreasing of metabolism speed in case of heavy digestive disorders linked
with starvation (total or protein)
Environment
Alcohol
— one time
consumption
— chronic
consumption
Smoking
Way of
excretion
Increasing of metabolism speed if in contact
with chlorine insecticides
Depressing of enzymes that metabolise drugs
Induction of enzyme system
Increasing of metabolism of certain drugs (i.e.
theophyllin)
Metabolism in liver before entering system
circulation (first going-through effect) after
peroral administration of drugs
Circade changes in drugs metabolism
Time of
introduction of
drugs
Interaction of Stimulation
drugs
reaction
and
depression
of
enzyme
Client-Related Variables
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Age
Body Weight
Genetic and Ethnic Characteristics
Gender (еxcept during pregnancy and
lactation, gender has been considered a
minor influence on drug action).
 Pathologic Conditions
 Psychological Considerations
TOLERANCE AND CROSS-TOLERANCE
Drug tolerance occurs when the body becomes accustomed
to a particular drug over time so that larger doses must be
given to produce the same effects. Tolerance may be acquired
to the pharmacologic action of many drugs, especially opioid
analgesics, alcohol, and other CNS depressants. Tolerance to
pharmacologically related drugs is called cross-tolerance.
For example, a person who regularly drinks large amounts of
alcohol becomes able to ingest even larger amounts before
becoming intoxicated—this is tolerance to alcohol. If the person
is then given sedative-type drugs or a general anesthetic,
larger-than-usual doses are required to produce a pharmacologic
effect—this is cross-tolerance.
Tolerance and cross-tolerance are usually attributed to activation
of drug-metabolizing enzymes in the liver, which accelerates
drug metabolism and excretion. They also are attributed
to decreased sensitivity or numbers of receptor sites.
1. Drug-drug interaction
2. Drug-food interaction
1. Drug-others(herbs, supplements and
DNA)
Fixed drug eruptions
Erythema nodosum
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