lect11&12 med admin

8/12/2019 Lect11&12 Med Admin

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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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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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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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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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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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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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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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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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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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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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