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Stressors Requiring MedicationPhases of Drug Action
NUR101 Fall 2008Lecture # 11 & 12K. Burger, MSEd, MSN, RN, CNE PPP by Sharon Niggemeier RN, MS(J. Garnar & R. Kolk) Rev kburger06,07
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Three Phases of Drug Action
I. PHARMACEUTICAL PHASE
II. PHARMACOKINETIC PHASE
III. PHARMACODYNAMIC PHASE
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I. PHARMACEUTICAL
PHASE
A solid drug (tablet) has to disintegrate before it can be absorbed
The process where a solid (tablet) goes intosolution is known as dissolution
ALL drugs must be in solution to cross biologic membranes
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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# Absorption2# Distribution
3# Metabolism (Biotransformation)4# Excretion
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#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 drugworks
Drugs can be absorbed through plasma membranes
by various methods but primarily by: Diffusion (lipidsoluble molecules) & Active transport (protein boundor water soluble molecules)
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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)
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Additives : alter the location of disintegration ofdrugs as well as increase or decrease the rate ofabsorption
Enter ic coating allows a drug to dissolve only inan alkaline (pH greater than 7.0) environment suchas the small intestine.
Sustained release drugs :allow drugs to bereleased 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 hastrade names Micronase and Glynase. Glynase(micronized) onset is faster than Micronase (non-micronized)
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Drug Absorption varies by form
Liquids, elixirs, syrups FastestSuspension solutions Powders Capsules
Tablets Coated tablets Enteric-coated tablets Slowest
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Look at your Lasix Drug Guide
Is this drug available in more than oneform?
Which will have the fastest absorption? What is the absorption rate for the oral
tablet form?
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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
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Absorption: ENTERAL ROUTES
Oral Route: Stomach Has low pH (about 1.4) the rate of gastric
emptying & pH changes will affect how fastor 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.
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CONSIDER THIS
Alcohol is extremely lipid soluble Aspirin is a very weak acid Both are well absorbed in the stomach.
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Absorption: ENTERAL ROUTES
Oral Route: Small Intestines Most important site for absorption of oral
drugs as it has extensive absorptive surfacedue to many villi.
Peristalsis and mixing encouragedissolution of drugs.
Highly vascular and has a pH of 7.0 to 8.0
In what way will diarrhea affect absorption?
Why?
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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.
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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 permeabilityof the alveolar membrane.
Provides a local effect ( ex: bronchodilation ), but may also produce unwanted systemiceffects ( ex: sympathetic nervous system
stimulation)
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Absorption: Other Routes
TOPICAL ROUTE: Epidermis is low inlipid and water content, so it is a barrier toabsorption.
Dermis allows rapid absorption therefore:Abraded skin could allow an overdose of thedrug so only use intact skin.
Effects are usually local Lipid soluble drugs can penetrate lipid by-
layers of the epidermal cells.
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Critical Thinking Questions
A client has an order for Benadryl ointment for anitchy rash on his arms. To promote absorption of the
drug, the nurse should:A. Apply an ice pack to the arms after applicationB. Wash the area with mild soap and water before
applying the ointmentC. Wear sterile gloves before applying the ointmentD. Ask the client to walk around the room after the
application.
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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 instillingear drops?
Nasal mucosa - instilled in droplet form or byswab for local or systemic effect.
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Absorption: PARENTERAL
intravenous subcutaneous intramuscular intradermal
intraarticular -synovial cavity
intrathecal - spinalsubarachnoid spaceor epidural space
intraperitonealREMEMBER Parenteral meds retain 100% bioavailabilityTHEREFORE smaller doses are appropriate
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Absorption: PARENTERAL
Subcutaneous and intramuscular injectionsare affected by tissue composition
Intramuscular route is more effective thanthe subcutaneous route because there is agreater blood supply in muscle tissue.
Application of heat or massage canincrease vasodilation and improveabsorption
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Critical Thinking
CaseMr. L. is admitted to the trauma unit with
multisystem injuries from an automobile accident.
He arrived at the unit with multiple abnormalfindings, including shock, decreased cardiacoutput, and urinary output of less than 30 mL/hr.
Which route of administration would be indicated forany medications for this patient?
Explain your reasoning.
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#2 Distribution
Distribution : the transport of drugsfrom the blood to the site of action . Adrug must be distributed to its site ofaction to have an effect
Drugs are also distributed to tissueswhere it has no effect. Competition fordrug binding sites affects the amountof drug available for action in the body .
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Factors Affecting Distribution
Volume of Distribution (Vd) - Thedegree of distribution of a drug intovarious body compartments and tissue
Cardiac output and capillary
permeability affect the regional bloodflow, perfusion of tissues and thereforethe volume of distribution
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Factors Affecting Distribution
Plasma Protein Binding - drugs bind to proteins inthe blood (albumin, globulins) in varying degrees,from highly bound to poorly bound
Protein binding decreases the concentration of freedrug in circulation therefore there is a limitedamount of drug available to travel to the site ofaction. Only free drug is able to diffuse intotissues.
Only free drug is able to diffuse into tissues, interactwith receptors, and produce biological effects.Bound drugs are pharmacologically inactive.
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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 competefor the binding site resulting in a greater
proportion of free drug . This effect may increase the free drug to toxiclevels .
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What effect would analbumin level of 2.8 haveon distribution?What should the nurse bealert to happening ?
Critical Thinking
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Factors Affecting Distribution
Tissue Binding/Affinity: force by which atomsare held together in chemical compounds
Lipid soluble drugs have a high affinity for fattissue and this is where these drugs are stored.Drugs can be held in reservoirs such as adiposetissue or bone.
What effect might sudden weight loss orstarvation have on a client taking lipid solubledrugs?
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Factors Affecting Distribution Blood Brain Barrier - The structure of brain
capillaries are less permeable than other bodycapillaries. Most drugs cant pass this blood brain
barrier. This protects the brain from the harmfuleffects of many drugs. Drugs that DO cross are
highly lipid soluble. ( Ex: phenytoin,antidepressants, caffeine, nicotine )What other substance did we talk about that ishighly lipid soluble????????
Placenta : the placental membrane is lipid innature and readily allows non-ionized, lipidsoluble drugs to cross the membrane. The use ofmany drugs has resulted in teratogenic effects onthe developing fetus
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CONSIDER THIS
The elderly have less effective blood-brain barriers.
Symptoms of dizziness and lightheadednessare more common as side effects to manydrugs taken by the elderly.
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Look at your Lasix Drug Guide
What is the site of action for distribution?
What does it have to say about the drugsdistribution properties?
Is this drug highly protein bound?
What does this mean in regards to distribution?
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#3 METABOLISM
Biotransformation: process by whichthe body changes the chemicalstructure 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 theliver
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METABOLISM (BIOTRANSFORMATION )
First Pass Phenomenon - Drugs are firstabsorbed through the small intestine thanarrive at the liver via the portal circulation
There they undergo considerable biotransformation before entering thesystemic circulation.
There will be less active drug availablefor action in the body cells after thisfirst Pass through the Liver !
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Consider this
Enzymes within the liver calledcytochromes metabolize lipid soluble drugs.
People with liver disease have a reducedamount of cytochromes
What will the overall effect then be??
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Variations in Metabolism
Pharmacogenetics - hereditary influences on drugresponses, refers to variations in which individualsmetabolize 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 thetime of day a drug is administered.
Effects of Gender and Age BMR differencesGERIATRIC CHGS
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#4 ExcretionExcretion: process where drugs are removed from
the body. Kidneys are the major organs ofexcretion.
Lungs excrete gaseous drugs.
Biliary excretion (bile & feces) is important for afew drugs. These drugs may be reabsorbed when passing through the intestines from the liver( enterohepatic re-circulation ).
Intestines, sweat, saliva and breast milk constituteminor routes of drug excretion.
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Excretion
Clearance of drugs - elimination ofdrugs from circulation by all routes. Itaffects the time a drug remains in the
body and the dosage required.Renal ClearanceHepatic clearance
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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 )
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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- lifes Time Action Profile?
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III. PHARMACODYNAMIC PHASE
What a drug does to the body- refers to thestudy of the mechanism of drug action on livingtissue.
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: antibioticsand antineoplastic drugs .
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THEORY OF DRUG-RECEPTORINTERACTIONS
The majority of drugs are believed to exert theireffects by combining with a specialized area onthe cell or within the cell called receptors . Drug+ Receptor Drug receptor (binding) =Response
A drug receptor may be on the cell surface orwithin the cell
Receptors come in many shapes that are specificfor particular drugs.
The greater the degree of specificity andselectivity for receptors, the fewer undesirableside effects and the greater drug efficacy.
T f D g R t
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Types of Drug-ReceptorInteractions
Agonists : Drug that has the ability to produce a desired therapeutic effectwhen bound to the receptor.
Antagonists : Drugs that bind well tothe receptor but produce no receptorresponse. This can prevent other drugsfrom having an effect, thus they arecalled blockers.
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Consider This Bronchodilators (ie: albuterol ) used for
asthma attacks are classified as beta-agonists . They attach to adrenergic
receptors in the sympathetic nervous system(SNS) and mimic the action ofnorepinephrine.
Adrenergic antagonists such as beta- blockers (ie: atenolol) attach to theadrenergic receptors in the SNS and blockthe action of norepinephrine
T f D R
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Types of Drug-ReceptorInteractions
Competitive antagonist : agonist drugand antagonist drug are eachcompeting for the same site.
The drug present in the greatestnumber will get bound.
Therefore a higher dose of agonist isrequired to overcome this response
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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 WILLincrease the risk of adverse side effects
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Other Ways Drugs Work
Enzyme InteractionSome 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 andinterrupt their cell processes leading to celldeath
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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 acontinuous infusion, variations willoccur in the level of drug in the body.
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Onset of drug action is the time it takesafter the drug is administered to reach aconcentration that produces a response.
Duration of action is the time during whichthe drug is present in a concentration largeenough to produce a response.
Peak effect is the time it takes for the drugto reach its highest effective action.
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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 thegreatest amount of diuresis?
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Trough level will occur immediately before
a drug is given, or once sufficient drug iseliminated. This is the lowest point of drugconcentration
Plasma blood levels may be taken for peakand trough levels. The drug must beadministered precisely as ordered and a
blood sample must be taken just before thenext drug dose is scheduled for an accuratetrough level.
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Consider this Certain drugs, such as aminoglycoside antibiotics
( Gentamycin ) are extremely ototoxic andnephrotoxic and are administered once daily.
It is the responsibility of the nurse administeringthese medications to utilize therapeutic drugmonitoring procedures
Check trough levels 18-24 hrs after previous dosefor a < 1mcg/ml level ( or previously set # fromMD / Lab / Pharmacy)
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Therapeutic Responses
Toxicity studies of drugs determine twodosage levels for drugs.
The effective dose is the dose of a drug
necessary to produce the desired intensity ofeffect in one-half of all patients.
The lethal dose is the dose of a drug that
elicits an undesirable toxic or lethal reactionin one-half of all patients.
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Therapeutic Index
A drug with a wide therapeutic indexhas a high safety margin and is relativelysafe; 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 normaldoses may induce toxic reactions . Peakand trough levels may need to be monitored
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Look at your Lasix Drug Guide
Do you think the therapeutic index of Lasixis high or low?
Explain your answer.
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Therapeutic range : plasma drugconcentration between minimum andtoxic concentrations.
Loading doses : higher amount ofdrug given once or twice to achievemaximum effective dose quickly
Maintenance dose : intermittentdoses given to maintain plasmalevels.
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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 didnt the MD order this dosage?
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Adverse Drug Event (ADE)
General broad term that describes anyadverse outcome to medication
administration. Can be due to: staff error (preventable) OR Can be an adverse drug reaction (non-
preventable)
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ADVERSE DRUG REACTIONS
(ADR) Unintended, undesirable or
unpredictable drug effects. More than50% of adverse reactions occur fromdrug-drug, drug-food, or drug-
laboratory test interactions.
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ADR
Adverse Effects : are unwanted and/orunintended action that may occurduring drug therapy. Every drug hasthe potential to produce adverseeffects.
Side Effects : Undesirable but mildunavoidable/predictable pharmacological effects of a drug.
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ADR
Toxic Effects : More serious effect. Lifethreatening. Each drug has characteristic
toxic effects. May be due to theaccumulation of the drug in the body r/tdecreased renal function
Teratogenic Effects : Drug induced birthdefects which follow drug therapy in pregnant women.
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Look at your Lasix Drug Guide
Are there any toxic LIFE THREATENINGside effects to Lasix therapy?
What are the most common side effects?
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Drug Interactions
Occur when 1 drug and a 2 nd drug orelement such as food may have aneffect on each other.
These interactions may or thetherapeutic effect of 1 or both drugs,create a new effect or incidence ofadverse effects
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Drug Interactions Additive effects : 2 or more similar effect drugs
are combined. The result equals the sum of theindividual agents Each drug is given in a lower dosefor an equal effect of either drug givenseparately. 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 thetotal effects of each drug acting by itself. 1+1=3 .Ex: Advicor ( niacin + statin drugs) improves lipidlowering action.
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Drug Interactions Potentiation : One drug improves the performance of the
other drug. This is a particular type of synergistic effect. + 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. Sometimesthe person will react with the opposite effect to thedesired one. (Also called paradoxical reaction)Ex: Genetic G6PD enzyme deficiency (prevents RBChemolysis) idiosyncratic reactions to ASA, sulfonamides(African American and Kurdish Jewish populations)
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Our Case Study Our 72 y.o. client has developed pneumonia
and a DVT as complications from hisimmobility while hospitalized. The MD has
ordered Gentamicin IVPB ( an aminoglycosideantibiotic ) and Heparin (an anticoagulant).
What type of drug interactions should thenurse be alert to in conjunction with hisLasix therapy?
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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 clients 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?
ll
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Allergic Reactions
Increased reactions with repeatedexposure to the drug.
Hypersensitivity reactions areexaggerated 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)
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Case Study
After starting a new IV line, you administer theLasix IV. The client almost immediately begins toexperience an anaphylatic type reaction. He didnot report any past allergies to Lasix, but he isallergic to sulfa drugs.
Should this information have impacted youradministration of the Lasix?
Was this a preventable, predictable drug reaction? Was it a medication error?
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Nursing Considerations
Take a careful drug history Know what interactions to anticipate
Identify the drug reaction by monitoringthe patient response to the drug.
Educate the patient and the family re therisks and benefits of the drug.
Document any drug reactions clearly andspecifically
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