The Nursing Process in Drug Administration
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- Jonathan Warren
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1 The Nursing Process in Drug Administration Nurses are expected to understand the pharmacotherapeutic principles for all medications given to each patient
2 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 Copyright 2015, 2017, 2012, 2014, Pearson Education, Inc. All Rights Reserved
3 Nurse Responsibilities 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
4 Nurse Responsibilities 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)
5 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
6 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
7 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
8 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
9 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
10 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
11 Drug Compliance Compliance is taking a medication in the manner prescribed by the health care provider Patient has an active role in ensuring compliance
12 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
13 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
14 Drug Administration Abbreviations (1 of 2) Table 3.1 Drug Administration Abbreviations Abbreviation ac ad lib AM bid cap gtt h or hr IM IV no pc PO PM Meaning before meals as desired/as directed Morning twice a day capsule drop hour intramuscular intravenous number after meals; after eating by mouth afternoon
15 Drug Administration Abbreviations (2 of 2) Table 3.1 Drug Administration Abbreviations Abbreviation prn qid q2h q4h q6h q8h q12h Rx STAT tab tid Meaning when needed/necessary four times per day every 2 hours (even or when first given) every 4 hours (even) every 6 hours (even) every 8 hours (even) every 12 hours take immediately; at once tablet 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
16 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
17 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
18 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
19 Three Systems of Measurement Used in Pharmacology Metric most common Apothecary oldest Household
20 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
21 Metric, Apothecary, and Household Approximate Measurement Equivalents Table 3.2 Metric, Apothecary, and Household Approximate Measurement Equivalents Metric Apothecary Household 1 ml minims drops 4 5 ml 1 fluid dram 1 teaspoon or 60 drops ml 4 fluid drams 1 tablespoon or 3 4 teaspoons ml 8 fluid drams or 1 fluid ounce 2 tablespoons 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 mg 1 grain mg 5 grains 1 g 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.
22 Routes of Drug Administration Three broad routes are enteral, topical, and parenteral Subsets within each
23 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
24 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
25 Enteral Route Enteral route includes drugs administered By mouth Tablets, capsules, sublingual, and buccal Via nasogastric tube or gastrostomy tube
26 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
27 Enteral Drug Administration (1 of 3) Table 3.3 Enteral Drug Administration Drug Form (Example) A. Tablet, capsule, or liquid (Orally disintegrating tablets and soluble films are placed on the tongue and then swallowed) Administration Guidelines 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.
28 Enteral Drug Administration (2 of 3) Table 3.3 Enteral Drug Administration Drug Form (Example) Administration Guidelines 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.
29 Enteral Drug Administration (3 of 3) Table 3.3 Enteral Drug Administration Drug Form (Example) D. Nasogastric and gastrostomy Administration Guidelines 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.
30 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
31 Sublingual drug administration
32 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
33 Buccal drug administration
34 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
35 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
36 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
37 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
38 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
39 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
40 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
41 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
42 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)
43 Transdermal patch administration: protective coating removed from patch
44 Transdermal patch administration: patch immediately applied to clean, dry, hairless skin and labeled with date, time, and initials
45 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
46 Instilling an eye ointment into the lower conjunctival sac
47 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
48 Instilling eardrops Source: Andy Crawford/DK Images.
49 Nasal Administration For both local and systemic administration Ease of use, avoids first-pass effect and digestive enzymes Mucosal irritation common; potential for damage
50 Nasal Administration Often used for local astringent effect shrink swollen mucous membranes or loosen secretions and facilitate drainage
51 Nasal drug administration Source: Ph College/Pearson Education, Inc.
52 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
53 Vaginal drug administration: instilling a vaginal suppository
54 Vaginal drug administration: using an applicator to instill a vaginal cream
55 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.
56 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
57 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
58 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
59 Intradermal and Subcutaneous Administrations Intradermal (ID) injection administered into the dermis layer of the skin More easily absorbed than in subcutaneous Small amount of drug
60 Intradermal drug administration: cross section of skin showing depth of needle insertion
61 Intradermal drug administration: the administration site is prepped
62 Intradermal drug administration: the needle is inserted, bevel up at 10 15
63 Intradermal drug administration: the needle is removed and the puncture site is covered with an adhesive bandage
64 Intradermal and Subcutaneous Administrations 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
65 Subcutaneous drug administration: cross section of skin showing depth of needle insertion
66 Subcutaneous drug administration: the administration site is prepped
67 Subcutaneous drug administration: the needle is inserted at a 45 angle
68 Subcutaneous drug administration: the needle is removed and the puncture site is covered with an adhesive bandage
69 Four Common Subcutaneous Injection Sites Outer upper arm Anterior thigh Upperback (Subscapular) 4-5 cm out from umbilicus
70 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
71 Intramuscular drug administration: cross section of skin showing depth of needle insertion
72 Intramuscular drug administration: the administration site is prepped
73 Intramuscular drug administration: the needle is inserted at a 90 angle
74 Intramuscular drug administration: the needle is removed and the puncture site is covered with an adhesive bandage
75 Four Common Intramuscular Injection Sites Ventrogluteal (Hip, Side) Deltoid (Shoulders) Dorsogluteal (Buttocks,Upper, Sciatic Nerve?) Vastus lateralis (Outer Thigh)
76 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 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.
77 Table 3.5 Parenteral Drug Administration (2 of 5) Table 3.5 Parenteral Drug Administration Drug Form Administration Guidelines 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 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.
78 Table 3.5 Parenteral Drug Administration (3 of 5) Table 3.5 Parenteral Drug Administration Drug Form C. Intramuscular route: ventrogluteal (different administration guidelines would apply to the dorsogluteal, vastus lateralis, and deltoid muscle sites) Administration Guidelines 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 area. 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.
79 Table 3.5 Parenteral Drug Administration (4 of 5) Table 3.5 Parenteral Drug Administration Drug Form Administration Guidelines 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.
80 Table 3.5 Parenteral Drug Administration (5 of 5) Table 3.5 Parenteral Drug Administration Drug Form Administration Guidelines 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.
81 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
82 Injecting a medication by IV push
83 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
84 Three Types of Intravenous Administration IV bolus (push) administration: concentrated dose delivered directly to circulation via syringe to administer singledose medications
85 An infusion pump is used for both continuous and intermittent IV administration (Universal Images Group Limited/Alamy).
86 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
87 Pharmacokinetics
88 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
89 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
90 Four Categories of Pharmacokinetic Processes Absorption Distribution Metabolism Excretion
91 Figure 4.1 The four processes of pharmacokinetics: absorption, distribution, metabolism, and excretion
92 Drugs Cross Plasma Membranes to Produce Effects Active transport Diffusion or passive transport
93 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
94 Diffusion or Passive Transport Molecules move from higher to lower concentration Usually small, nonionized, or lipid-soluble molecules
95 Absorption Movement from site of administration, across body membranes, to circulating fluids Primary pharmacokinetic factor determining length of time for drug to produce effect
96 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
97 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
98 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
99 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
100 Distribution of Medications Distribution transport of drugs throughout the body Simplest factor determining distribution is the amount of blood flow to body tissues
101 Distribution of Medications Physical properties of drug have great influence Certain tissues (bone marrow, teeth, eyes, adipose tissue) have a high affinity, or attraction, for certain medications
102 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
103 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
104 Distribution of Medications 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
105 Distribution of Medications 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
106 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
107 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
108 Enzyme Induction A drug increases metabolic activity in the liver Changes in the function of the hepatic microsomal enzymes can significantly affect drug metabolism
109 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 firstpass effect
110 First-Pass Effect: Oral Drug Is Metabolized to an Inactive Form Before It Has an Opportunity to Reach Target Cells
111 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
112 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
113 Renal Failure Diminishes Excretion of Medications Drugs are retained for extended times Dosages must be reduced
114 Other Organs Can Be Sites of Excretion Respiratory system Glands Biliary system
115 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
116 Figure 4.4 Enterohepatic recirculation
117 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
118 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
119 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
120 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; t ½ = 4 hours
121 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
122 Loading Dose Higher amount of drug given Plateau reached faster Quickly produces therapeutic response
123 Maintenance Dose Keeps plasma-drug concentration in therapeutic range
124 Pharmacodynamics
125 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
126 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
127 Figure 5.1 Frequency distribution curve: interpatient variability in drug response
128 Median Effective Dose (ED 50 ) 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
129 Nurse s Skill Critical in Determining if Average Dose is Effective Patient observation Taking of vital signs Monitoring lab data
130 Median Lethal Dose (LD 50 ) 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
131 Median Toxicity Dose (TD 50 ) 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
132 Therapeutic Index Measure of a drug's safety margin The higher the value, the safer the drug
133 Calculating Therapeutic Index
134 Example of Therapeutic Index Therapeutic index of 4: need error four times dose to be lethal
135 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.
136 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
137 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
138 Three Phases of Graded Dose Response Curve Phase 3: plateau reached Increasing dose has no therapeutic effect Increased dose may produce adverse effects
139 Figure 5.3 Dose response relationship
140 Two Ways to Compare Medications Potency Efficacy
141 Potency Drug with higher potency produces a therapeutic effect at a lower dose, compared with another drug in the same class
142 Efficacy Magnitude of maximal response that can be produced from a particular drug From a pharmacotherapeutic perspective, efficacy almost always more important than potency
143 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
144 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
145 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
146 Figure 5.5 Cellular receptors. The red triangle represents the drug binding directly with receptors.
147 Receptor Subtypes Still Being Discovered Permit fine-tuning of pharmacology Two basic receptor types Alpha Beta Drugs affect each subtype differently
148 Nonspecific Cellular Responses Caused by drugs that act independently of receptors Example: changing the permeability of cellular membranes
149 Drugs That Act as Agonists Bind to receptor Produce same response as endogenous chemical Sometimes produce greater maximal response
150 Drugs That Act as Partial Agonists Bind to receptor Produce weaker, less effective response than agonists
151 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
152 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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