The Nursing Process in Drug Administration · Drug-Administration Procedures •Drug orders must be...

The Nursing Process in Drug Administration

• Nurses are expected to understand the pharmacotherapeutic principles for all medications given to each patient

Nurse Responsibilities

• What drug is ordered

• Name (generic and trade) and drug classification

• Intended purpose or use

• Effects on body

• Contraindication

• Special considerations (e.g., how age affects response)

• Side effects

• Why the medication was prescribed

• How the medication is supplied by the pharmacy

• How the medication is to be administered, including dosage ranges

• What nursing process considerations related to the medication apply to this patient

• Before drug is administered, the nurse must know all variables of the patient's condition

• Be prepared to recognize and react to adverse effects (adverse events)

Allergic Reactions

• Allergic reaction—an acquired hyperresponse of body defenses to a foreign substance

– If discovered, nurse responsible for labeling charts, informing all personnel, and placing alert bracelet on patient

Anaphylaxis

• A severe allergic reaction involving the massive, systemic release of histamine and other chemical mediators of inflammation that can lead to life-threatening shock

Five Rights of Drug Administration

• Five rights used as the basis of safe delivery of medications. They are:

– Right patient

– Right medication

– Right dose

– Right route of administration

– Right time of delivery

Three Checks of Drug Administration

• Checking drug with medication information system when removing it from storage

• Checking drug when preparing it, pouring it, taking it out of the unit-dose container, or connecting the IV tubing to bag

• Checking drug before administering it to the patient

Mistakes and Liability

• Despite five rights and three checks, mistakes still occur

• Nurses are held accountable for correct administration of drugs, but responsibility also rests on other positions like prescriber and pharmacist

Four Most Common Medication Errors

• Errors in patient assessment

– e.g., inadequate medication history

• Errors in prescribing

– e.g., wrong drug, incorrect dose

• Administration errors

– e.g., route or time of administration

• Distracting environmental factors

– e.g., interruptions during preparation

Drug Compliance

• Compliance is taking a medication in the manner prescribed by the health care provider

– Patient has an active role in ensuring compliance

Drug Compliance

• Factors that can cause a patient to deviate from compliance:

– Cost of drug

– Forgetting doses

– Annoying side effects

– Self-adjustment of doses

– Fear of dependency

• Nurse must be vigilant in questioning patients about their medications

Special Drug-Administration Abbreviations

• STAT—medication is to be given immediately, and only once

• ASAP—drug should be available for administration within 30 minutes of the written order

• PRN—drug is administered as required by the patient's condition

Drug Administration Abbreviations (1 of 2)

Table 3.1 Drug Administration Abbreviations

Abbreviation Meaning

ac before meals

ad lib as desired/as directed

AM Morning

bid twice a day

cap capsule

gtt drop

h or hr hour

IM intramuscular

IV intravenous

no number

pc after meals; after eating

PO by mouth

PM afternoon

Drug Administration Abbreviations (2 of 2)

Table 3.1 Drug Administration Abbreviations

Abbreviation Meaning

prn when needed/necessary

qid four times per day

q2h every 2 hours (even or when first given)

q4h every 4 hours (even)

q12h every 12 hours

Rx take

STAT immediately; at once

tab tablet

tid three times a day

Note: The Institute for Safe Medical Practices recommends the following abbreviations be avoided

because they can lead to medication errors: q: instead use ―every‖; qh: instead use ―hourly‖ or ―every

hour‖; qd: instead use ―daily‖ or ―every day‖; qhs: instead use ―nightly‖; qod: instead use ―every other

day.‖ For these and other recommendations, see the official Joint Commission ―Do Not Use List‖ at

http://www.jointcommission.org/assets/1/18/dnu_list.pdf

Drug-Administration Written Orders

• Single order—drug is to be given only once at a specific time

• Orders not written as STAT, ASAP, NOW, or PRN are called routine orders

• Standing order—written in advance of a situation that is to be carried out under specific circumstances

Drug-Administration Procedures

• Drug orders must be reviewed by the attending physician within specific time frames, at least every seven days

• Drugs may need administration during or between meals, depending on interaction with food

• Central nervous system drugs and antihypertensives are often best administered at bedtime

Drug-Administration Procedures

• Nurses must educate patients carefully about timing of taking medications

• Nurses must document carefully the details of medications given to patient—after they have been given

– Refusal or omission of medication must be documented

Three Systems of Measurement Used in Pharmacology

• Metric—most common

• Apothecary—oldest

• Household

Nurse Must Be Able to Convert Among All Three Systems

• Metric, Apothecary, and Household Approximate Measurement Equivalents

• Joint Commission (JCAHO), the accrediting organization for health care agencies, has placed apothecary measurements on its ―do not use‖ list

• Nurses should encourage use of accurate medical dosing devices at home

Metric, Apothecary, and Household Approximate Measurement Equivalents

Table 3.2 Metric, Apothecary, and Household

Approximate Measurement Equivalents

Metric Apothecary Household

1 mL 15–16 minims 15–16 drops

4–5 mL 1 fluid dram 1 teaspoon or 60 drops

15–16 mL 4 fluid drams 1 tablespoon or 3–4 teaspoons

30–32 mL 8 fluid drams or 1 fluid ounce 2 tablespoons

240–250 mL 8 fluid ounces (½ pint) 1 glass or cup

500 mL 1 pint 2 glasses or 2 cups

1 L 32 fluid ounces or 1 quart 4 glasses or 4 cups or 1 quart

1 mg 1/60 grain

60–64 mg 1 grain

300–325 mg 5 grains

1 g 15–16 grains

1 kg 2.2 pounds

Note: To convert grains to grams: Divide grains by 15 or 16. To convert grams to grains:

Multiply grams by 15 or 16. To convert minims to milliliters: Divide minims by 15 or 16.

Routes of Drug Administration

• Three broad routes are enteral, topical, and parenteral

– Subsets within each

Common Protocols and Techniques for All Routes of Administration

• Verify medication order, check allergy history

• Wash hands and apply gloves, if indicated

• Use aseptic technique when preparing and administering parenteral medications

• Identify patient (two forms of ID)

• Ask patient about known allergies

• Inform patient about drug

• Position patient

• Remove prepackaged drug at bedside

Common Protocols and Techniques for All Routes of Administration

• Unless instructed to do so, do not leave drugs at bedside

• Document administration and pertinent patient responses

Enteral Route

• Enteral route includes drugs administered

– By mouth

Tablets, capsules, sublingual, and buccal

– Via nasogastric tube or gastrostomy tube

Enteral Route

• Tablets and capsules most common form of drugs

– Can be crushed or opened only if manufacturer instructed; enteric-coated tablets must remain intact

• Sustained-release tablets or capsules are designed to dissolve very slowly

– Created to increase compliance by reducing frequency of dosage

Enteral Drug Administration (1 of 3)

Table 3.3 Enteral Drug Administration

Drug Form

(Example) Administration Guidelines

A. Tablet, capsule,

or liquid (Orally

disintegrating tablets

and soluble films are

placed on the tongue

and then swallowed)

1. Assess that the patient is alert and has the ability to swallow.

2. Place the tablets or capsules into a medication cup.

3. If the medication is in liquid form, shake the bottle to mix the agent, and measure the

dose into the cup at eye level.

4. Hand the patient the medication cup.

5. Offer a glass of water to facilitate swallowing the medication. Milk or juice may be offered

if not contraindicated.

6. Remain with the patient until all the medication is swallowed.

B. Sublingual 1. Assess that the patient is alert and has the ability to hold the medication under the

tongue.

2. Place the sublingual tablet under the tongue.

3. Instruct the patient not to chew or swallow the tablet or move the tablet around with

tongue.

4. Instruct the patient to allow the tablet to dissolve completely.

5. Remain with the patient to determine that all the medication has dissolved.

6. Offer a glass of water after the medication has dissolved, if the patient desires.

Drug Form

C. Buccal 1. Assess that the patient is alert and has the ability to hold the medication between

the gums and the cheek.

2. Place the buccal tablet between the gum line and the cheek.

3. Instruct the patient not to chew or swallow the tablet or move the tablet around with

tongue.

4. Instruct the patient to allow the tablet to dissolve completely.

5. Remain with the patient to determine that all of the medication has dissolved.

6. Offer a glass of water after the medication has dissolved, if the patient desires.

Drug Form

D. Nasogastric

and gastrostomy

1. Administer liquid forms when possible to avoid clogging the tube. Contact the

pharmacist or health care provider if unsure if the medication may be given through

the tube.

2. If the medication is solid, crush finely into a powder and mix thoroughly with at least

30 mL of warm water until dissolved. Enteric-coated, extended-release, and other

dosage types may not be crushed. Always check the drug information before

crushing.

3. Assess and verify tube placement per agency protocol.

4. Turn off the enteric feeding, if applicable to the patient.

5. Aspirate stomach contents and measure the residual volume as per agency

protocol. If greater than 100 mL for an adult, check agency policy.

6. Return the residual via gravity and flush with water.

7. Pour the medication into the syringe barrel and allow to flow into the tube by gravity.

Give each medication separately, flushing between with water.

8. Keep the head of the bed elevated for 1 hour to prevent aspiration.

9. Reestablish continual feeding, as scheduled. Keep the head of the bed elevated 45°

to prevent aspiration.

Sublingual and Buccal Drug Administration

• Tablet is kept in mouth

• Sublingual

– Medication is placed under the tongue and allowed to dissolve slowly

Rich blood supply causes rapid onset

– Used only after oral medications have been swallowed, if multiple drugs are ordered

– No food or drink until completely dissolved

Sublingual drug administration

Sublingual and Buccal Drug Administration

• Buccal

– Tablet or capsule placed in oral cavity between the gum and the cheek

– Preferred for sustained delivery

– Generally does not cause irritation

– Like sublingual drugs, buccal drugs are formulated to bypass first-pass metabolism

Buccal drug administration

Rapid-Dissolving Tablets and Films

• Orally distintegrating tablets (ODTs) or oral dissolving films

– Medication placed on the tongue

– Dissolves in less than 30 seconds

– Eliminates need for external source of water and aids compliance

– Ondansetron first FDA-approved drug in this form

Nasogastric and Gastronomy Drug Administration

• Nasogastric (NG) tube is a soft, flexible tube inserted by way of the nasopharynx with the tip lying in the stomach

– Generally for short-term treatment

Nasogastric and Gastronomy Drug Administration

• Gastrostomy (G) tube is surgically placed directly into the patient's stomach

– Longer-term treatment

• Both methods generally use liquid drugs

Enteral Drug Administration Advantages

• Convenient

• Overdose can be countered by retrieval of undigested medicines through vomiting

• Safest route because skin barrier not compromised

• Uses vast absorptive surfaces of the oral mucosa, stomach, or small intestine

Enteral Drug Administration Disadvantages

• Difficulty swallowing by some patients

• May be inactivated if tablets or capsules crushed or opened

• Can be inactivated by enzymes

• Depends on patient gastrointestinal motility and mobility

• First-pass metabolism: inactivation of drug by processing in the liver

Topical Drugs Applied to Skin or Mucous Membranes

• Applications:

– Dermatologic preparations: applied to skin—most common

– Instillations and irrigations: applied into body cavities and orifices. (Antineoplastic UBC).

– Inhalations: applied to the respiratory tract by inhalers or positive-pressure breathing

Purposes of Topical Drugs

• Many intended for local effect—for example antibiotics to treat a skin infection

• Fewer side effects because generally absorbed very slowly

Purposes of Topical Drugs

• Some given for slow absorption into general circulation, designed for their systemic effects

– Systemic vs local effect is important distinction for a nurse

Transdermal Delivery System

• Transdermal patches provide effective means of delivering some medications

• Rate of delivery and dose may vary with drug

• Avoids first-pass effect of liver and enzymes

• Full documentation by nurses applies (old removed-new applied)

Transdermal patch administration: protective coating removed from patch

Transdermal patch administration: patch immediately applied to clean, dry, hairless skin and labeled with date, time, and initials

Ophthalmic Administration

• Used to treat local conditions of the eye and surrounding structures

• Common indications of problems:

– Excessive dryness, infections and dilation of the pupil during eye examinations

• Special procedures, sometimes even immobilization, may be needed for children

Instilling an eye ointment into the lower conjunctival sac

Otic Administration

• Used to treat local conditions of the ear, including infections and soft blockages of the auditory canal

• Eardrops, irrigations

• Usually used for cleaning purposes

Instilling eardrops Source: Andy Crawford/DK Images.

Nasal Administration

• For both local and systemic administration

• Ease of use, avoids first-pass effect and digestive enzymes

• Mucosal irritation common; potential for damage

Nasal Administration

• Often used for local astringent effect—shrink swollen mucous membranes or loosen secretions and facilitate drainage

Nasal drug administration Source: Ph College/Pearson Education, Inc.

Vaginal Administration

• For treating local infections and to relieve vaginal pain and itching

• Suppositories, creams, jellies, or foams

• Nurse must explain purpose of treatment and provide for privacy and patient dignity

Vaginal drug administration: instilling a vaginal suppository

Vaginal drug administration: using an applicator to instill a vaginal cream

Rectal Administration

• Local or systemic administration

• Usually suppository form, but sometimes administered as enema

• First-pass effect and digestive enzymes avoided (Blood is not transported to the liver)

– Comatose,vomiting.

Parenteral Drugs Are Administered via Needle

• Types: intradermal, subcutaneous, intramuscular, intravenous

• Require aseptic technique

• Nurse must have knowledge of anatomical locations

• Nurse must know correct equipment to use

• Nurse must know procedure for disposing of hazardous equipment

Parenteral Locations

• Intradermal: dermis layer of skin

• Subcutaneous: deepest layers of the skin

• Intramuscular: specific muscles

• Intravenous: directly into bloodstream

• Advanced parenteral delivery may be directly into body cavities or organs

Intradermal and Subcutaneous Administrations

• Avoid the hepatic first-pass effect and digestive enzymes; offer method for those who cannot take medicine orally

• Only small volumes can be administered; injections can cause pain and swelling

• Intradermal (ID) injection administered into the dermis layer of the skin

– More easily absorbed than in subcutaneous

– Small amount of drug

Intradermal drug administration: cross section of skin showing depth of needle insertion

Intradermal drug administration: the administration site is prepped

Intradermal drug administration: the needle is inserted, bevel up at 10–15°

Intradermal drug administration: the needle is removed and the puncture site is covered with an adhesive bandage

• Subcutaneous injection delivered to the deepest layers of the skin

• Used for easy access and rapid absorption

• Important to rotate injection sites

• Aspiration not usually necessary, but depends on drug

Subcutaneous drug administration: cross section of skin showing depth of needle insertion

Subcutaneous drug administration: the administration site is prepped

Subcutaneous drug administration: the needle is inserted at a 45° angle

Subcutaneous drug administration: the needle is removed and the puncture site is covered with an adhesive bandage

Four Common Subcutaneous Injection Sites

• Outer upper arm

• Anterior thigh

• Upperback (Subscapular)

• 4-5 cm out from umbilicus

Intramuscular Administration

• Delivers medication into specific muscles

• More rapid onset of action than with oral, ID, or subcutaneous administration

• Can accept larger volume of medication than subcutaneous

• Injection site very important; must avoid bone, blood vessels, and nerves

Intramuscular drug administration: cross section of skin showing depth of needle insertion

Intramuscular drug administration: the administration site is prepped

Intramuscular drug administration: the needle is inserted at a 90° angle

Intramuscular drug administration: the needle is removed and the puncture site is covered with an adhesive bandage

Four Common Intramuscular Injection Sites

• Ventrogluteal (Hip, Side)

• Deltoid (Shoulders)

• Dorsogluteal (Buttocks,Upper, Sciatic Nerve?)

• Vastus lateralis (Outer Thigh)

Table 3.5 Parenteral Drug Administration (1 of 5)

Table 3.5 Parenteral Drug Administration

Drug Form Administration Guidelines

A. Intradermal route 1. Verify the order and prepare the medication in a tuberculin or 1-mL syringe with a

preattached 26- to 27-gauge, 3/8- to 5/8-inch needle.

2. Apply gloves and cleanse the injection site with antiseptic swab in a circular motion.

Allow to air dry.

3. With the thumb and index finger of the nondominant hand, spread the skin taut.

4. Insert the needle, with the bevel facing upward, at an angle of 10–15°.

5. Advance the needle until the entire bevel is under the skin; do not aspirate.

6. Slowly inject the medication to form a small wheal or bleb.

7. Withdraw the needle quickly, and pat the site gently with a sterile 2 × 2 gauze pad. Do

not massage the area.

8. Instruct the patient not to rub or scratch the area.

9. Draw a circle around the perimeter of the injection site. Read in 48 to 72 hours.

B. Subcutaneous route 1. Verify the order and prepare the medication in a 1- to 3-mL syringe using a 23- to 25-

gauge, 1⁄2- to 5⁄8-inch needle. For heparin, the recommended needle is 3⁄8 inch and 25–26

gauge.

2. Choose the site, avoiding areas of bony prominence, major nerves, and blood vessels. For

heparin and other parenteral anticoagulants, check with agency policy for the preferred

injection sites.

3. Check the previous rotation sites and select a new area for injection.

4. Apply gloves and cleanse the injection site with antiseptic swab in a circular motion.

5. Allow to air dry.

6. Bunch the skin between the thumb and index finger of the nondominant hand.

7. Insert the needle at a 45° or 90° angle depending on body size: 90° if obese; 45° if average

weight. If the patient is very thin, gather the skin at the area of needle insertion and

administer at a 90° angle.

8. Inject the medication slowly.

9. Remove the needle quickly, and gently massage the site with antiseptic swab. For heparin

and other parenteral anticoagulants, do not massage the site, as this may cause increased

bruising or bleeding.

C. Intramuscular route:

ventrogluteal (different

administration

guidelines

would apply to the

dorsogluteal, vastus

lateralis, and deltoid

muscle sites)

1. Verify the order and prepare the medication using a 20- to 23-gauge, 1- to 1.5-inch needle.

2. Apply gloves and cleanse the ventrogluteal injection site with antiseptic swab in a circular

motion. Allow to air dry.

3. Locate the site by placing the hand with the heel on the greater trochanter and the thumb

toward the umbilicus. Point to the anterior iliac spine with the index finger, spreading the

middle finger to point toward the iliac crest (forming a V). Inject the medication within the V-

shaped area of the index and third finger. (Note: This is how to locate the ventrogluteal

site.)

4. Insert the needle with a smooth, dartlike movement at a 90° angle within the V-shaped

5. Depending on agency policy and type of drug, aspirate, and observe for blood. If blood

appears, withdraw the needle, discard the syringe, and prepare a new injection.

6. Inject the medication slowly and with smooth, even pressure on the plunger.

7. Remove the needle quickly.

8. Apply pressure to the site with a dry, sterile 2 × 2 gauze and massage to promote

absorption of the medication into the muscle.

D. Intravenous route 1. To add a drug to an IV fluid container:

2. Verify the order and compatibility of the drug with the IV fluid.

3. Prepare the medication in a 5- to 20-mL syringe using a 1- to 1.5-inch, 19- to 21-gauge

needle from the original medication vial or ampule. If a needleless system is used, use the

appropriate syringe or tip required per the system in use.

4. Apply gloves and assess the injection site for signs and symptoms of inflammation or

extravasation.

5. Locate the medication port on the IV fluid container and cleanse with antiseptic swab.

6. Carefully insert the needle or needleless access device into the port and inject the medication.

7. Withdraw the needle and mix the solution by rotating the container end to end.

8. Hang the container and check the infusion rate.

9. To add drug to an IV bolus (IV push) using an existing IV line or IV lock (reseal):

10. Verify the order and compatibility of the drug with the IV fluid.

D. Intravenous route 11. Determine the correct rate of infusion.

12. Determine whether IV fluids are infusing at the proper rate (IV line) and that the IV site is

adequate.

13. Prepare the drug in a syringe, following the procedure described above.

14. Apply gloves and assess the injection site for signs and symptoms of inflammation or

extravasation.

15. Select the injection port, on tubing, closest to the insertion site (IV line).

16. Cleanse the tubing or lock port with antiseptic swab and insert the needle into the port.

17. If administering medication through an existing IV line, occlude tubing by pinching just

above the injection port.

18. Slowly inject the medication over the designated time—usually not faster than 1 mL/min,

unless specified.

19. Withdraw the syringe. Release the tubing and ensure proper IV infusion if using an existing

IV line.

20. If using an IV lock, check agency policy for use of saline flush before and after injecting

medications.

Intravenous Administration (IV)

• Medications and fluids are administered directly into the bloodstream and are immediately available for use by the body

• Fastest drug onset action, but also most dangerous method

– Contamination

– Swift adverse reactions

Injecting a medication by IV push

Three Types of Intravenous Administration

• Large-volume infusion: for fluid maintenance, replacement, or supplementation

• Intermittent infusion: small amount of IV solution arranged tandem with or piggybacked to primary large-volume infusion; used to instill adjunct medications

Three Types of Intravenous Administration

• IV bolus (push) administration: concentrated dose delivered directly to circulation via syringe to administer single-dose medications

An infusion pump is used for both continuous and

intermittent IV administration (Universal Images Group Limited/Alamy).

Parenteral Advantages and Disadvantages

• Advantages:

– Bypasses first-pass effect and enzymes

– Available to patients unable to take medication orally

• Disadvantages:

– Only small doses can be used

– Possible pain and swelling at injection site

Pharmacokinetics

Application of Pharmacokinetics to Clinical Practice

• Pharmacokinetics: the study of drug movement throughout the body

• Know how the body deals with medication

• Understand and predict actions and side effects of medications

• Understand obstacles that a drug faces to reach target cells

Drugs in the Body

• Greatest barrier for many drugs is crossing many membranes

• Enteral route drugs are broken down by stomach acids and digestive enzymes

• Organs attempt to excrete medicines

• Phagocytes may attempt to remove medicines seen as foreign

Four Categories of Pharmacokinetic Processes

• Absorption

• Distribution

• Metabolism

• Excretion

Figure 4.1 The four processes of pharmacokinetics: absorption, distribution, metabolism, and excretion

Drugs Cross Plasma Membranes to Produce Effects

• Active transport

• Diffusion or passive transport

Active Transport

• Chemicals move against concentration or electrochemical gradient

• Usually large, ionized, or water-soluble molecules

• Cotransport involves the movement of two or more chemicals across the membrane

Diffusion or Passive Transport

• Molecules move from higher to lower concentration

• Usually small, nonionized, or lipid-soluble molecules

Absorption

• Movement from site of administration, across body membranes, to circulating fluids

• Primary pharmacokinetic factor determining length of time for drug to produce effect

Factors Affecting Drug Absorption

• Drug formulation and dose

• Dose

• Route of administration

• Size of drug molecule

• Surface area of absorptive site

• Digestive motility

• Blood flow

• Lipid solubility of drug

Factors Affecting Drug Absorption

• Degree of ionization of drug

– In stomach acid, aspirin nonionized and easily absorbed by bloodstream

– In small intestine alkaline, aspirin ionized and less likely to be absorbed

• pH of local environment

• Drug-drug/food-drug interactions

• Dietary supplement/herbal product–drug interactions

Figure 4.2 Effect of pH on drug absorption: (a) a weak acid such as aspirin (ASA) is in a nonionized form in an acidic environment and absorption occurs

Figure 4.2 Effect of pH on drug absorption: (b) in a basic environment, aspirin is mostly in an ionized form and absorption is prevented

Distribution of Medications

• Distribution—transport of drugs throughout the body

– Simplest factor determining distribution is the amount of blood flow to body tissues

• Physical properties of drug have great influence

• Certain tissues (bone marrow, teeth, eyes, adipose tissue) have a high affinity, or attraction, for certain medications

Drugs Bind with Plasma Proteins

• Many drug molecules form drug–protein complexes—binding reversibly to plasma proteins—and thus never reach target cells

• Cannot cross capillary membranes

• Drug not distributed to body tissues

Plasma protein binding and drug availability: (a) drug exists in a free state or bound to plasma protein; (b) drug–protein complexes are too large to cross membranes

• Drugs and other chemicals compete for plasma protein–binding sites

– Drug–drug and drug–food interactions may occur when one drug displaces another from plasma proteins

• Some have greater affinity

• Displaced drug can reach high levels

– Can produce adverse effects

• Blood-brain barrier and fetal-placenta barrier: special anatomic barriers that prevent many chemicals and medications from entering

– Makes brain tumors difficult to treat

– Fetal-placenta barrier protects fetus; no pregnant woman should be given medication without strong consideration of condition

Metabolism of Medications

• Also known as biotransformation

• Chemically converts drug so it can be easily removed from body

• Involves complex biochemical reactions

• Liver—primary site

• Addition of side chains, known as conjugates, makes drugs more water soluble and more easily excreted by the kidneys

Metabolism in the Liver

• Hepatic microsomal enzyme system (P-450 system)

– Inactivates drug

– Accelerates drug excretion

– Some agents, known as prodrugs, have no pharmacologic activity unless first metabolized to active form by body

Enzyme Induction

• A drug increases metabolic activity in the liver

• Changes in the function of the hepatic microsomal enzymes can significantly affect drug metabolism

Oral Drugs Enter Hepatic Portal Circulation (First-Pass Effect)

• Drug is absorbed

• Drug enters hepatic circulation, goes to liver

• Drug is metabolized to inactive form

• Drug conjugates and leaves liver

• Drug is distributed to general circulation

• Many drugs are rendered inactive by first-pass effect

First-Pass Effect: Oral Drug Is Metabolized to an Inactive Form Before It Has an Opportunity to Reach Target Cells

Metabolism and Pharmacotherapy

• Metabolic activity may be decreased in some patients:

– Infants and elderly

– Patients with severe liver disease

– Patients with certain genetic disorders

• Dosages in patients with decreased metabolic activity must be reduced to prevent toxicity

Primary Site of Excretion of Drugs Is Kidneys

• Free drugs, water-soluble agents, electrolytes, and small molecules are easily filtered

• Drug-protein complexes and large substances are secreted into distal tubule of nephron

• Secretion mechanism is less active in infants and older adults

• pH of filtrate can increase excretion

Renal Failure Diminishes Excretion of Medications

• Drugs are retained for extended times

• Dosages must be reduced

Other Organs Can Be Sites of Excretion

• Respiratory system

• Glands

• Biliary system

Enterohepatic Recirculation of Drugs

• Drugs are excreted in bile

• Bile recirculates to liver

• Percentage of drug may be recirculated numerous times

• Prolongs activity of drug

– Activity of drug may last after discontinuation

Figure 4.4 Enterohepatic recirculation

Drug Plasma Concentration and Therapeutic Response

• Concentration of medication at target tissue is often impossible to measure, so it must be measured in plasma

– Minimum effective concentration—amount of drug required to produce a therapeutic effect

– Toxic concentration—level of drug that will result in serious adverse effects

– Therapeutic range—plasma drug concentration between the minimum effective concentration and the toxic concentration

Plasma Half-Life (t½) of Drugs

• Length of time needed to decrease drug plasma concentration by one half

• The greater the half-life, the longer it takes to excrete

• Determines frequency and dosage

How Drug Reaches and Maintains Therapeutic Range

• Repeated doses of drug are given

• Drug accumulates in bloodstream

• Plateau is reached

• Amount administered equals amount eliminated

Figure 4.5 Single-dose drug administration: pharmacokinetic values for this drug are as follows: onset of action = 2 hours; duration of action = 6 hours; termination of action = 8 hours after administration; peak plasma concentration = 10 mcg/mL; time to peak drug effect =5 hours; t½= 4 hours

Figure 4.6 Multiple-dose drug administration: drug A and drug B are administered every 12 hours; drug B reaches the therapeutic range faster, because the first dose is a loading dose

Loading Dose

• Higher amount of drug given

• Plateau reached faster

• Quickly produces therapeutic response

Maintenance Dose

• Keeps plasma-drug concentration in therapeutic range

Pharmacodynamics

Pharmacodynamics and Interpatient Variability

• Pharmacodynamics—how a medicine changes the body

• Helps to predict if drug will produce change

• Will ensure that drug will provide safe, effective treatment

• Combination of drug guides and intuitive experience will guide safe treatment

Frequency Distribution Curve

• Graphical representation of number of patients responding to a drug action at different doses

• Peak of curve indicates largest number of patients responding to drug

• Does not show magnitude of response

Figure 5.1 Frequency distribution curve: interpatient variability in drug response

Median Effective Dose (ED50)

• Middle of frequency distribution curve

• Dose that produces therapeutic response in 50% of a group

• Sometimes called ―average‖ or ―standard‖ dose

• Many patients require more or less

Nurse’s Skill Critical in Determining if Average Dose is Effective

• Patient observation

• Taking of vital signs

• Monitoring lab data

Median Lethal Dose (LD50)

• Used to assess safety of a drug

• Shown on frequency distribution curves

• Determined in preclinical trials

• Is lethal dose in 50% of group of animals

• Cannot be experimentally determined in humans

Median Toxicity Dose (TD50)

• Dose that will produce given toxicity in 50% of group of patients

• Value may be extrapolated from

– Animal data

– Adverse effects in patient clinical trials

• Needed because median lethal dose cannot be tested in humans

Therapeutic Index

• Measure of a drug's safety margin

• The higher the value, the safer the drug

Calculating Therapeutic Index

Example of Therapeutic Index

• Therapeutic index of 4: need error four times dose to be lethal

Figure 5.2 Therapeutic index: (a) drug X has a therapeutic index of 4; (b) drug Z has a therapeutic index of 2. In a human clinical study, LD50 is labeled as TD50.

Graded Dose-Response Relationship

• Graphically visualizes differences in responses to medications in a single patient

• Obtained by observing and measuring patient's response at different doses of the drug

Three Phases of Graded Dose–Response Curve

• Phase 1: occurs at lowest dose

– Few target cells affected by drug

• Phase 2: straight-line portion of curve

– Most desirable range

– Linear relationship between amount of drug administered and degree of patient response

Three Phases of Graded Dose–Response Curve

• Phase 3: plateau reached

– Increasing dose has no therapeutic effect

– Increased dose may produce adverse effects

Figure 5.3 Dose–response relationship

Two Ways to Compare Medications

• Potency

• Efficacy

Potency

• Drug with higher potency produces a therapeutic effect at a lower dose, compared with another drug in the same class

Efficacy

• Magnitude of maximal response that can be produced from a particular drug

• From a pharmacotherapeutic perspective, efficacy almost always more important than potency

Figure 5.4 Potency and efficacy: (a) drug A has a higher potency than drug B; (b) drug A has a higher efficacy than drug B

Receptor Is Macromolecule

• Molecule to which medication binds in order to initiate its effects

• Binds endogenous molecules

– Hormones, neurotransmitters, growth factors

• Most drug receptors are protein agonists

• Associated with plasma membrane or intracellular molecules

Drug Attaches to Receptor

• Comparable to how thumb drive docks to USB

port in a computer

• May trigger second messenger events

– e.g., activation of specific G proteins and associated enzymes

• Initiates drug action

• Can stimulate or inhibit normal activity

Figure 5.5 Cellular receptors. The red triangle represents the drug binding directly with receptors.

Receptor Subtypes Still Being Discovered

• Permit ―fine-tuning‖ of pharmacology

• Two basic receptor types

– Alpha

– Beta

• Drugs affect each subtype differently

Nonspecific Cellular Responses

• Caused by drugs that act independently of receptors

• Example: changing the permeability of cellular membranes

Drugs That Act as Agonists

• Bind to receptor

• Produce same response as endogenous chemical

• Sometimes produce greater maximal response

Drugs That Act as Partial Agonists

• Bind to receptor

• Produce weaker, less effective response than agonists

Drugs That Act as Antagonists

• Occupy receptor

• Prevent endogenous chemical from acting

• Often compete with agonists for receptor

• Functional antagonists inhibit the effects of an agonist not by competing for a receptor, but by changing pharmacokinetic factors

In the Future: Customized Drug Therapy

• End of single-drug, one-size-fits-all policy

• DNA test before receiving drug

• Prevention of idiosyncratic (unpredictable and unexplained) drug reactions

• Pharmacogenetics—area of pharmacology that examines role of heredity in drug response

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