Transcript Phases of Drug Action

Stressors Requiring Medication
Phases of Drug Action
NUR101 Fall 2010
Lecture # 11 & 12
K. Burger, MSEd, MSN, RN, CNE
PPP by Sharon Niggemeier RN, MS
(J. Garnar & R. Kolk) Rev kburger06,07
Three Phases of Drug Action
I. PHARMACEUTICAL PHASE
II. PHARMACOKINETIC PHASE
III. PHARMACODYNAMIC PHASE
I. PHARMACEUTICAL
PHASE
• A solid drug (tablet) has to disintegrate
before it can be absorbed
• The process where a solid (tablet) goes into
solution is known as dissolution
• ALL drugs must be in solution to cross
biologic membranes
II. PHARMACOKINETIC
PHASE
• What the body does to the drug- refers to the
study of how the body processes drugs
• It includes the 4 basic components of :
1# Absorption
2# Distribution
3# Metabolism (Biotransformation)
4# Excretion
#1 ABSORPTION
• Movement of a drug from the site of administration
into the bloodstream.
• Absorption determines how long it takes for a drug
to take effect.
• Usually the more rapid the absorption, faster the drug
works
• Drugs can be absorbed through plasma membranes
by various methods but primarily by: Diffusion (lipid
soluble molecules) & Active transport (protein bound
or water soluble molecules)
Factors Affecting Absorption
•
•
•
•
•
•
•
•
Surface area
Contact time with surface
Circulation
Solubility (water soluble vs lipid soluble)
Ionization (weak versus strong acid/base)
Drug form & drug concentration
Bioavailability ( after first pass thru liver)
Route of administration (enteral &
parenteral)
• Additives: alter the location of disintegration of
drugs as well as increase or decrease the rate of
absorption
• Enteric coating allows a drug to dissolve only in
an alkaline (pH greater than 7.0) environment such
as the small intestine.
• Sustained release drugs:allow drugs to be
released slowly over time, rather than quickly,
like conventional tablets. SR, LA
• Size of drug particles: smaller the particle, faster
the onset. Ex: The generic drug Glyburide has
trade names Micronase and Glynase. Glynase
(micronized) onset is faster than Micronase (nonmicronized)
Drug Absorption varies by form
Liquids, elixirs, syrups
Suspension solutions
Powders
Capsules
Tablets
Coated tablets
Enteric-coated tablets
Fastest





Slowest
Absorption:ENTERAL ROUTES
Mucous membranes of the mouth:
• Buccal or Sublingual forms of drugs
• Highly vascular absorbing surface
• Avoids first pass phenomenon that occurs in
the liver
• Absorptive area is small therefore…
• Only small amounts of drugs can be given
Absorption: ENTERAL ROUTES
• Oral Route: Stomach
• Has low pH (about 1.4) the rate of gastric
emptying & pH changes will affect how fast
or how slow meds are absorbed.
• Has rich blood supply
• Susceptible to first pass phenomenon
• Lipid soluble substances and those that are
relatively nonionized are well absorbed here.
Absorption:ENTERAL ROUTES
• Oral Route: Small Intestines
• Most important site for absorption of oral
drugs as it has extensive absorptive surface
due to many villi.
• Peristalsis and mixing encourage
dissolution of drugs.
• Highly vascular and has a pH of 7.0 to 8.0
Absorption:ENTERAL ROUTES
• Mucus Membranes of the Lower Intestine:
Rectal Route
• Avoids most first pass effects in the liver
• Has extensive vascularity.
• Limited surface area
• Drugs need to be in solution or absorption
is erratic and unpredictable.
Absorption: Other Routes
• PULMONARY: Lungs
• Gases or aerosols can be delivered by this
route.
• Rapid absorption occurs due to large surface
area, rich blood supply and high permeability
of the alveolar membrane.
• Provides a local effect ( ex: bronchodilation ),
but may also produce unwanted systemic
effects ( ex: sympathetic nervous system
stimulation)
Absorption: Other Routes
• TOPICAL ROUTE: Epidermis is low in
lipid and water content, so it is a barrier to
absorption.
• Dermis allows rapid absorption therefore:
Abraded skin could allow an overdose of the
drug so only use intact skin.
• Effects are usually local
• Lipid soluble drugs can penetrate lipid bylayers of the epidermal cells.
Absorption: Other Routes
• Transdermal: A disk or patch containing a days
or weeks medication-Absorbed at a steady rate
• Eyes - produces a local effect. Instruct patient to
put pressure on the side of the nose after placing
drops to decrease possibility of systemic effect.
• Ears - used for local treatment of infection or wax
• Nasal mucosa - instilled in droplet form or by
swab for local or systemic effect.
Absorption:PARENTERAL
•
•
•
•
intravenous
subcutaneous
intramuscular
intradermal
• intraarticular synovial cavity
• intrathecal - spinal
subarachnoid space
or epidural space
• intraperitoneal
REMEMBER – Parenteral meds retain 100% bioavailability
THEREFORE smaller doses are appropriate
Absorption: PARENTERAL
• Subcutaneous and intramuscular injections
are affected by tissue composition
• Intramuscular route is more effective than
the subcutaneous route because there is a
greater blood supply in muscle tissue.
• Application of heat or massage can
increase vasodilation and improve
absorption
#2 Distribution
• Distribution: the transport of drugs
from the blood to the site of action. A
drug must be distributed to its site of
action to have an effect
• Drugs are also distributed to tissues
where it has no effect. Competition for
drug binding sites affects the amount
of drug available for action in the body.
Factors Affecting Distribution
Volume of Distribution (Vd) - The
degree of distribution of a drug into
various body compartments and tissue
• Cardiac output and capillary
permeability affect the regional blood
flow, perfusion of tissues and therefore
the volume of distribution
Factors Affecting Distribution
Plasma Protein Binding - drugs bind to proteins in
the blood (albumin, globulins) in varying degrees,
from highly bound to poorly bound
Protein binding decreases the concentration of free
drug in circulation therefore there is a limited
amount of drug available to travel to the site of
action. Only free drug is able to diffuse into
tissues.
Only free drug is able to diffuse into tissues, interact
with receptors, and produce biological effects.
Bound drugs are pharmacologically inactive.
Plasma Protein Binding
Continued
• When free drug is eliminated by the body some
bound drug is released from protein binding.
• Some drugs persist in the body for three days by
this mechanism.
• (2) drugs given concurrently & highly bound to
the same site on a plasma protein will compete
for the binding site resulting in a greater
proportion of free drug.
• This effect may increase the free drug to toxic
levels.
Factors Affecting Distribution
• Tissue Binding/Affinity: force by which
atoms are held together in chemical
compounds
• Lipid soluble drugs have a high affinity for
fat tissue and this is where these drugs are
stored. Drugs can be held in reservoirs such
as adipose tissue or bone.
Factors Affecting Distribution
• Blood Brain Barrier - The structure of brain
capillaries are less permeable than other body
capillaries. Most drugs can’t pass this blood brain
barrier. This protects the brain from the harmful
effects of many drugs. Drugs that DO cross are
highly lipid soluble. ( Ex: phenytoin,
antidepressants, caffeine, nicotine )
• Placenta: the placental membrane is lipid in
nature and readily allows non-ionized, lipid
soluble drugs to cross the membrane. The use of
many drugs has resulted in teratogenic effects on
the developing fetus
#3
METABOLISM
• Biotransformation: process by which
the body changes the chemical
structure of a drug to another form
called a metabolite.
• Metabolite: a more water soluble
compound that can be easily excreted.
The major organ for this process is the
liver
METABOLISM (BIOTRANSFORMATION)
• First Pass Phenomenon - Drugs are first
absorbed through the small intestine than
arrive at the liver via the portal circulation
• There they undergo considerable
biotransformation before entering the
systemic circulation.
• There will be less active drug available
for action in the body cells after this
first Pass through the Liver !
Variations in Metabolism
• Pharmacogenetics - hereditary influences on drug
responses, refers to variations in which individuals
metabolize drugs.
• Circadian Rhythms - the rate of drug absorption,
hepatic clearance, half-life and duration of action,
have all been shown to differ depending upon the
time of day a drug is administered.
• Effects of Gender and Age – BMR differences
GERIATRIC CHGS
#4
Excretion
Excretion: process where drugs are removed from
the body. Kidneys are the major organs of
excretion.
Lungs excrete gaseous drugs.
Biliary excretion (bile & feces) is important for a
few drugs. These drugs may be reabsorbed when
passing through the intestines from the liver
( enterohepatic re-circulation ).
Intestines, sweat, saliva and breast milk constitute
minor routes of drug excretion.
Excretion
Clearance of drugs - elimination of
drugs from circulation by all routes. It
affects the time a drug remains in the
body and the dosage required.
Renal Clearance
Hepatic clearance
PLASMA HALF-LIFE
• The amount of time a drug stays in the body is measured
by the elimination half-life.
• This is the time required for the concentration of drug in
the blood to decrease by 50%.
• Half-life affects the frequency of administration
• Drugs with short half-lives are quickly eliminated from
the body. ( Ex: PCN given several X per day )
• Drugs with longer half-lives stay in the body longer
(Ex: Digoxin given once a day )
III. PHARMACODYNAMIC PHASE
• What a drug does to the body- refers to the
study of the mechanism of drug action on living
tissue.
• Drugs may increase, decrease or replace
enzymes, hormones or body metabolic functions.
• Chemotherapeutic drugs alter an abnormal
parasite or growth on the body such as bacteria,
viruses or neoplastic tissue. examples: antibiotics
and antineoplastic drugs.
THEORY OF DRUG-RECEPTOR
INTERACTIONS
• The majority of drugs are believed to exert their
effects by combining with a specialized area on
the cell or within the cell called receptors. Drug
+ Receptor  Drug receptor (binding) =
Response
• A drug receptor may be on the cell surface or
within the cell
• Receptors come in many shapes that are specific
for particular drugs.
• The greater the degree of specificity and
selectivity for receptors, the fewer undesirable
side effects and the greater drug efficacy.
Types of Drug-Receptor
Interactions
• Agonists: Drug that has the ability to
produce a desired therapeutic effect
when bound to the receptor.
• Antagonists: Drugs that bind well to
the receptor but produce no receptor
response. This can prevent other drugs
from having an effect, thus they are
called blockers.
Types of Drug-Receptor
Interactions
• Competitive antagonist: agonist drug
and antagonist drug are each
competing for the same site.
• The drug present in the greatest
number will get bound.
• Therefore a higher dose of agonist is
required to overcome this response
Saturability
• Drug receptor binding is saturable
• This occurs when all available receptors are
occupied
• Once all available receptors are saturated,
increasing the drug concentration WILL NOT
increase therapeutic effect but it WILL
increase the risk of adverse side effects
Other Ways Drugs Work
• Enzyme Interaction
Some drugs bind to enzymes and block their
action on cells ( ie ACE inhibitor)
• Non-specific Interactions
No receptor action. Some drugs (ie
antibiotics) get into bacteria cells and
interrupt their cell processes leading to cell
death
Time Course of Drug Action
• The frequency and duration of drug
dosing can influence the safety and
efficacy of drug therapy.
• Unless a drug is administered by a
continuous infusion, variations will
occur in the level of drug in the body.
• Onset of drug action is the time it takes
after the drug is administered to reach a
concentration that produces a response.
• Duration of action is the time during which
the drug is present in a concentration large
enough to produce a response.
• Peak effect is the time it takes for the drug
to reach its highest effective action.
• Trough level will occur immediately before
a drug is given, or once sufficient drug is
eliminated. This is the lowest point of drug
concentration
• Plasma blood levels may be taken for peak
and trough levels. The drug must be
administered precisely as ordered and a
blood sample must be taken just before the
next drug dose is scheduled for an accurate
trough level.
Therapeutic Responses
• Toxicity studies of drugs determine two
dosage levels for drugs.
• The effective dose is the dose of a drug
necessary to produce the desired intensity of
effect in one-half of all patients.
• The lethal dose is the dose of a drug that
elicits an undesirable toxic or lethal reaction
in one-half of all patients.
Therapeutic Index
• A drug with a wide therapeutic index
has a high safety margin and is relatively
safe; the lethal dose is greatly in excess
of the therapeutic dose.
• A drug with a narrow therapeutic
index is more dangerous for the patient
because small increases over normal
doses may induce toxic reactions. Peak
and trough levels may need to be monitored
• Therapeutic range: plasma drug
concentration between minimum and
toxic concentrations.
• Loading doses: higher amount of
drug given once or twice to achieve
maximum effective dose quickly
• Maintenance dose: intermittent
doses given to maintain plasma
levels.
Adverse Drug Event (ADE)
• General broad term that describes any
adverse outcome to medication
administration.
• Can be due to: staff error (preventable) OR
• Can be an adverse drug reaction (nonpreventable)
ADVERSE DRUG REACTIONS
(ADR)
• Unintended, undesirable or
unpredictable drug effects. More than
50% of adverse reactions occur from
drug-drug, drug-food, or druglaboratory test interactions.
ADR
• Adverse Effects: are unwanted and/or
unintended action that may occur
during drug therapy. Every drug has
the potential to produce adverse
effects.
• Side Effects: Undesirable but mild
unavoidable/predictable
pharmacological effects of a drug.
ADR
• Toxic Effects: More serious effect. Life
threatening. Each drug has characteristic
toxic effects. May be due to the
accumulation of the drug in the body r/t
decreased renal function
• Teratogenic Effects: Drug induced birth
defects which follow drug therapy in
pregnant women.
Drug Interactions
• Occur when 1 drug and a 2nd drug or
element such as food may have an
effect on each other.
• These interactions may ↑ or ↓ the
therapeutic effect of 1 or both drugs,
create a new effect or ↑ incidence of
adverse effects
Drug Interactions
• Additive effects: 2 or more “similar effect” drugs
are combined. The result equals the sum of the
individual agents Each drug is given in a lower dose
for an equal effect of either drug given
separately.
1+1=2.
Ex: Percodan ( oxycodone + acetominophen)
improves pain relief
• Synergism: The harmonious action of two “unlike”
drugs producing an effect which is greater than the
total effects of each drug acting by itself.
1+1=3.
Ex: Advicor ( niacin + statin drugs) improves lipid
lowering action.
Drug Interactions
• Potentiation: One drug improves the performance of the
other drug. This is a particular type of synergistic effect.
½+1=2
Ex: amoxicillen + probenecid (anti-gout)
prolongs serum levels of the antibiotic
• Idiosyncratic Reactions: Unusual, unexpected reactions
to a drug, which may be genetically caused. Sometimes
the person will react with the opposite effect to the
desired one. (Also called paradoxical reaction)
Ex: Genetic G6PD enzyme deficiency (prevents RBC
hemolysis) idiosyncratic reactions to ASA, sulfonamides
(African American and Kurdish Jewish populations)
Allergic Reactions
• Increased reactions with repeated
exposure to the drug.
• Hypersensitivity reactions are
exaggerated in response to a drug.
• Anaphylaxis: A systemic reaction, the
most severe of all the allergic reactions.
(edema of airways, severe hypotension,
cardiac arrhythmia, death)
Nursing Considerations
• Take a careful drug history
• Know what interactions to anticipate
• Identify the drug reaction by monitoring
the patient response to the drug.
• Educate the patient and the family re the
risks and benefits of the drug.
• Document any drug reactions clearly and
specifically