Download 3-1General Properties of Drugs

Principles of Drug Action:
Pharmacokinetics
Pharmacodynamics
Pharmacotherapeutics
Copyright © 2006, 2001 by Mosby, Inc.
Slide 1
General Properties of Drugs
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Drugs do not perform any new functions
on a tissue or organ in the body; they only
modify existing functions.
Drugs in general exert multiple actions
rather than a single effect.
Drug action results from a physiochemical
interaction between the drug and a
molecule in the body.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 2
Definitions
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Pharmaceutics—process of dissolution when
drug becomes a solution so it can cross the
biologic membrane
Pharmacokinetics—processes by which drugs
are distributed in the body
Pharmacodynamics—processes by which
drugs influence living tissue
Pharmacotherapeutics—process of using
drugs to treat disease
Toxicology—the study of harmful effects of
chemicals (toxins and poisons) on the body
Copyright © 2006, 2001 by Mosby, Inc.
Slide 3
Phases of Drug Activity
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Slide 4
Pharmaceutical Phase
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Slide 5
Pharmacokinetic Activities
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Absorption—the process of a drug moving
from the entry site to the bloodstream
Distribution—the process of moving from the
bloodstream to target tissue or receptor site
Metabolism (biotransformation)—process by
which liver transforms drug from an active to
an inactive form by liver enzymes
Excretion—elimination of the drug from the
body (kidneys)
Copyright © 2006, 2001 by Mosby, Inc.
Slide 6
Types of Absorption
Passive transport. Molecules move across
a membrane from a region of higher
concentration to lower concentration.
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Slide 7
Types of Absorption (cont’d)
Active or carrier transport. In this example,
adenosine triphosphate (ATP) moves a
molecule across a membrane from an area of
low concentration to high concentration.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 8
Factors Affecting Absorption
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Route
Condition of site and blood supply to site
Patient age
Peristalsis
Concentration of drug
Form of oral med
Presence of food and amount of fluid taken (contact)
Pain, stress, exercise
Condition of liver (hepatic first pass)
Whether drug is lipid soluble or nonionized (faster)
The amount of drug actually absorbed is called the
bioavailability.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 9
A comparison of drug onsets and duration
of action by route of administration.
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Slide 10
Effect of pH on drug ionization and transport
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Slide 11
Factors Affecting Distribution
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Condition of target site and amount of blood
supply to target site
Circulatory status of patient
Concentration of drug
Whether drug is protein-bound
If drug can pass blood-brain or placental
barrier
Drugs affinity to tissue or receptor site
Copyright © 2006, 2001 by Mosby, Inc.
Slide 12
Factors Affecting Metabolism
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Genetic differences
Age of patient
Hormone levels (broken down by same
method and may compete with drug)
Condition of liver
Concentration of drug (overdose)
Nutritional status of patient (many enzymes
are proteins)
Stress, cigarette smoking (increases)
Copyright © 2006, 2001 by Mosby, Inc.
Slide 13
Factors Affecting Excretion
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Age of patient
Condition of and blood supply to excreting
organ (usually kidney)
pH of urine—acid urine promotes elimination
of weak basic drugs; alkaline urine promotes
elimination of weak acidic drugs
Half-life of drug—amount of time it takes for
half of the drug to be eliminated from body.
Most drugs have about 5 half-lives.
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Slide 14
Biologic half-life (t½)
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Slide 15
Time to steady-state drug concentration.
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Slide 16
Half-life timing to steady-state drug
concentration and elimination with
discontinuation of the drug.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 17
A loading dose is administered to reach a
therapeutic response level rapidly. Maintenance
doses are administered at prescribed intervals to
maintain a therapeutic drug response. The amount
of drug eliminated = amount absorbed is the ideal
condition to maintain a constant level in the blood.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 18
Pharmacodynamics: Study of the
Mechanism of Drug Action on Living Tissue
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Mechanism of action
Drug-receptor interaction
Drug-enzyme interaction
Nonspecific interaction
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Slide 19
Mechanism of Action:
Plasma level profile of a drug
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Slide 20
Highest and Lowest Levels
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Trough: lowest level of drug in bloodstream
(usually just before next dose is due)
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Peak: highest level of drug in bloodstream
(depends on route as to when this level is
achieved)
Copyright © 2006, 2001 by Mosby, Inc.
Slide 21
Therapeutic Index and Serum
Concentration
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Therapeutic index—Range of safe treatment—a
narrow index can make it easier for patient to
become toxic
Serum concentration—amount of drug in blood at a
given testing time
Therapeutic index represents the ratio between two
factors:
 Lethal dose (LD50)
 Effective dose (ED50)
TI = LD50/ED50
Copyright © 2006, 2001 by Mosby, Inc.
Slide 22
Drug-Receptor Interactions:
Once a drug binds to a receptor, a chemical or electrical
signal is transmitted via a transducer to an intermediary
effector resulting in a pharmacologic response.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 23
Affinity is how well the drug fits and is attracted
to the receptor site. This is a picture of
agonist activity. Drug has an affinity and
produces a response.
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Slide 24
This depicts competitive antagonistic activity
at the receptor site (B-blockers, antihistamines,
ARBS). Has affinity but does not produce
response—only blocks response.
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Slide 25
This depicts noncompetitive antagonist
activity at the receptor site. Usually inhibits
activity at receptor site.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 26
Drug-Enzyme Interactions
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Enzyme is a catalyst that accelerates,
activates, or inactivates a chemical reaction.
Some drugs are designed to inhibit enzyme
activity.
These drugs “look like” the chemical
substance that the enzyme usually acts on
and can “fool” the enzyme into combining to
the drug instead of to the chemical. This
inhibits the action of the enzyme on the real
chemical.
Example: ACEIs—inhibit acetylcholinesterase
Copyright © 2006, 2001 by Mosby, Inc.
Slide 27
Nonspecific Interactions
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Causing a change in cell membranes or DNA
processes in the cell (antibiotics,
antineoplastics)
Causing a change in pH of body fluids
(antacids, sodium bicarbonate)
Detoxifying a poison (Mucomyst, activated
charcoal)
Altering body chemistry (potassium,
Kayexalate)
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Slide 28
Pharmacotherapeutics
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Types of Drug Therapy
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Patient Responses to Drug
Therapy
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Slide 29
Types of Drug Therapy
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Acute—short-term for acute condition
Maintenance—long-term for chronic condition
Supplemental—what the body can’t make or
take in
Palliative—keep patient comfortable
Supportive—maintains body function while
body is recovering
Prophylactic—prevents a problem
Adjuvant—a substance added to an Rx to
assist in the action of the main ingredient
Copyright © 2006, 2001 by Mosby, Inc.
Slide 30
Patient Response to Drug Therapy
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Assessing patient condition
Assessing effects
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Therapeutic effects
 Side effects
 Adverse effects
 Placebo effect
 Cumulative effects
 Toxic effects
 Teratogenic, mutagenic, carcinogenic
Copyright © 2006, 2001 by Mosby, Inc.
Slide 31
Patient Condition
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History
Present condition
Weight and/or height if needed
Present drug tx
Compliance
How current illness may affect a chronic
condition (i.e., diabetes)
Copyright © 2006, 2001 by Mosby, Inc.
Slide 32
Therapeutic Effect, Side Effect, and
Adverse Effect Drug Responses
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Therapeutic effects—predictable, expected,
desirable and helpful effects—measured by
serum concentration (see drug profile slide)
Side effects—predictable secondary effects
such as anorexia, N/V/D, dizziness,
drowsiness, dry mouth, abdominal gas or
distress, constipation.
Adverse effects (iatrogenic)—unintended,
undesirable, and often unpredictable drug
effects that range from mild to fatal.
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Slide 33
Adverse Effects: Allergic Drug Reactions
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Type I: anaphylactic reaction—immediate, severe
with respiratory and cardiac effects; less severe
characterized by hives
Type II: cytotoxic reaction—autoimmune response
usually manifested by blood dyscrasias or
autoimmune disease
Type III: Arthus reaction—”serum sickness”—drugantibody complexes in vessels leading to
angioedema, arthralgia, lymphadenopathy,
splenomegaly
Type IV: cell-mediated reaction—delayed response
of 24-48h usually manifested as a rash
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Slide 34
Other Adverse Effects
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Tachyphylaxis—AKA tolerance—a decreased
response to repeated doses esp. with narcotics,
barbs, laxatives, psychotropics
Drug dependence
Idiosyncratic—from genetic differences in enzyme
production (pharmacogenetics and anthropology)
Cumulative—ingestion > excretion
Teratogenic—harmful to fetus 3 wk-3 mo
Mutagenic—alters chromosomes
Carcinogenic—causes cancer
Toxic—poisonous from therapeutic or intentional
overdosing or accumulation
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Slide 35
Placebo Effect
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Psychologic benefit that is not related to
chemical effect.
Effective in about 1/3 of persons.
Studied in drug research; seen in
everyday drug therapy.
Can be affected by the health
practitioner’s and patient’s attitude.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 36
Interactions
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Drug-drug: alters pharmacologic action when
drugs are combined. Can either be in either
of the pharmacokinetic phases or in
pharmacodynamics at receptor sites. Can be
beneficial or detrimental. Can alter serum
concentration.
Drug-food: can slow or enhance absorption
or can cause unusual reaction (grapefruit or
licorice)
Alcohol, tobacco—usually interferes with
absorption
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Slide 37
Interactions: Drug-Drug
Additive—smaller doses of similar drugs given
together (1+1=2; BP drugs or
Tylenol+codeine)
Synergistic—2 drugs together potentiate each
other (1+1=3; Demerol+Phenergan or
PCN+probenecid)
Antagonistic—combination of 2 is less than
either given alone and may work against
each other (1+1=1 or 1+1=0; Narcan)
Incompatibility—mixing causes precipitate or a
chemical or physical reaction (outside body)
See inside of drug book.
Copyright © 2006, 2001 by Mosby, Inc.
Slide 38
Labs Associated with Drug
Administration
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Serum concentration
Peak and trough levels
Body fluid analysis
Complete blood count (CBC)
Culture and sensitivity (C&S)
Copyright © 2006, 2001 by Mosby, Inc.
Slide 39