Transcript Phases of Drug Action

Stressors Requiring Medication
Phases of Drug Action
NUR101 Fall 2008
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
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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
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Slowest
Look at your Lasix Drug Guide
• Is this drug available in more than one
form?
• Which will have the fastest absorption?
• What is the absorption rate for the oral
tablet form?
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.
CONSIDER THIS…
• Alcohol is extremely lipid soluble
• Aspirin is a very weak acid
• Both are well absorbed in the stomach.
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
In what way will diarrhea affect absorption?
Why?
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.
Critical Thinking Questions
A client has an order for Benadryl ointment for an
itchy rash on his arms. To promote absorption of the
drug, the nurse should:
A. Apply an ice pack to the arms after application
B. Wash the area with mild soap and water before
applying the ointment
C. Wear sterile gloves before applying the ointment
D. Ask the client to walk around the room after the
application.
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
How should you position a client after instilling
ear drops?
• Nasal mucosa - instilled in droplet form or by
swab for local or systemic effect.
Absorption:PARENTERAL
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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
Critical Thinking
Case
Mr. L. is admitted to the trauma unit with
multisystem injuries from an automobile accident.
He arrived at the unit with multiple abnormal
findings, including shock, decreased cardiac
output, and urinary output of less than 30 mL/hr.
Which route of administration would be indicated for
any medications for this patient?
Explain your reasoning.
#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.
Critical Thinking
What effect would an
albumin level of 2.8 have
on distribution?
What should the nurse be
alert to happening ?
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.
• What effect might sudden weight loss or starvation
have on a client taking lipid soluble drugs?
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 )
What other substance did we talk about that is
highly lipid soluble????????
• 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
CONSIDER THIS…
• The elderly have less effective blood-brain
barriers.
• Symptoms of dizziness and lightheadedness
are more common as side effects to many
drugs taken by the elderly.
Look at your Lasix Drug Guide
• What is the site of action for distribution?
• What does it have to say about the drug’s
distribution properties?
• Is this drug highly protein bound?
• What does this mean in regards to distribution?
#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 !
Consider this…
• Enzymes within the liver called
cytochromes metabolize lipid soluble drugs.
• People with liver disease have a reduced
amount of cytochromes
• What will the overall effect then be??
Variations in Metabolism
• Pharmacogenetics - hereditary influences on drug
responses, refers to variations in which individuals
metabolize drugs.
Remember our discussion of Acetylator Rates?
• 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 )
Look at your LASIX drug guide
• What is the half-life of this drug?
• What does that mean in regards to dosing?
• Look at the Route/Dosage for the IV route
for adults. What correlation can you make
between the instructions there and the drugs
half-life’s Time Action Profile?
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.
Consider This…
• Bronchodilators (ie: albuterol ) used for
asthma attacks are classified as betaagonists. They attach to adrenergic
receptors in the sympathetic nervous system
(SNS) and mimic the action of
norepinephrine.
• Adrenergic antagonists such as betablockers (ie: atenolol) attach to the
adrenergic receptors in the SNS and block
the action of norepinephrine
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.
Look at your Lasix Drug Guide
• What is the onset time for the PO route?
• Compare this to the onset for IV.
• If you gave your client 40mg of Lasix @
10am PO, when would you expect the
greatest amount of diuresis?
• 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.
Consider this…
• Certain drugs, such as aminoglycoside antibiotics
( Gentamycin ) are extremely ototoxic and
nephrotoxic and are administered once daily.
• It is the responsibility of the nurse administering
these medications to utilize therapeutic drug
monitoring procedures
• Check trough levels 18-24 hrs after previous dose
for a < 1mcg/ml level ( or previously set # from
MD / Lab / Pharmacy)
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
Look at your Lasix Drug Guide
• Do you think the therapeutic index of Lasix
is high or low?
• Explain your answer.
• 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.
Back to our Case Study
• The 72 y.o. client with hypertension was
prescribed 40 mg of Lasix p.o. b.i.d.
• Would you say this is a maintenance dose?
• Why or why not?
• What is the highest loading dose you see in
your Lasix drug guide for the p.o. route.
• Why didn’t the MD order this dosage?
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.
Look at your Lasix Drug Guide
• Are there any toxic LIFE THREATENING
side effects to Lasix therapy?
• What are the most common side effects?
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)
Our Case Study
• Our 72 y.o. client has developed pneumonia
and a DVT as complications from his
immobility while hospitalized. The MD has
ordered Gentamicin IVPB ( an aminoglycoside
antibiotic ) and Heparin (an anticoagulant).
What type of drug interactions should the
nurse be alert to in conjunction with his
Lasix therapy?
Case Study - continued
The oral Lasix that our client is taking is not
producing the desirable effect, and the MD
orders a STAT dose of Lasix 40 mg IV. You
prepare to inject this into the client’s IV line,
but see that the Gentamicin previously ordered
is currently infusing.
Is it OK to proceed with giving the Lasix IV?
Why of why not?
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)
Case Study
After starting a new IV line, you administer the
Lasix IV. The client almost immediately begins to
experience an anaphylatic type reaction. He did
not report any past allergies to Lasix, but he is
allergic to “sulfa drugs”.
• Should this information have impacted your
administration of the Lasix?
• Was this a preventable, predictable drug reaction?
• Was it a medication error?
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