Pharmacokinetics and Routes of Administration

07/24/15 April 15, 2019 3:31 PM rm_rn_2019_pharm_chp1 CHAPTER 1 PHARMACOLOGICAL PRINCIPLES UNIT 1 CHAPTER 1 Pharmacokinetics and Routes of Administration Pharmacokinetics refers to how medications travel through the body. They undergo a variety of biochemical processes that result in absorption, distribution, metabolism, and excretion. PHASES OF PHARMACOKINETICS ABSORPTION Absorption is the transmission of medications from the location of administration (gastrointestinal [GI] tract, muscle, skin, mucous membranes, or subcutaneous tissue) to the bloodstream. The most common routes of administration are enteral (through the GI tract) and parenteral (by injection). Each of these routes has a unique pattern of absorption. ● The rate of medication absorption determines how soon the medication will take effect. ● The amount of medication the body absorbs determines the intensity of its effects. ● The route of administration affects the rate and amount of absorption. Inhalation via mouth, nose BARRIERS TO ABSORPTION: Inspiratory effort ABSORPTION PATTERN: Rapid absorption through alveolar capillary networks Intradermal, topical BARRIERS TO ABSORPTION: Close proximity of epidermal cells ABSORPTION PATTERN ● ● Subcutaneous, intramuscular BARRIERS TO ABSORPTION: Capillary walls have large spaces between cells. Therefore, there is no significant barrier. ABSORPTION PATTERN ● ● BARRIERS TO ABSORPTION: Medications must pass through the layer of epithelial cells that line the GI tract. ABSORPTION PATTERN: Varies greatly due to: ● ● ● ● ● Stability and solubility of the medication GI pH and emptying time Presence of food in the stomach or intestines Other concurrent medications Forms of medications (enteric-coated pills, liquids) Sublingual, buccal BARRIERS TO ABSORPTION: Swallowing before dissolution allows gastric pH to inactivate the medication. ABSORPTION PATTERN: Quick absorption systemically through highly vascular mucous membranes Other mucous membranes (rectal, vaginal) BARRIERS TO ABSORPTION: Presence of stool in the rectum or infectious material in the vagina limits tissue contact. ABSORPTION PATTERN: Easy absorption with both local and systemic effects Solubility of the medication in water: Highly soluble medications have rapid absorption (10 to 30 min); poorly soluble medications have slow absorption. Blood perfusion at the site of injection: sites with high blood perfusion have rapid absorption; sites with low blood perfusion have slow absorption. Intravenous BARRIERS TO ABSORPTION: No barriers ABSORPTION PATTERN ● Oral Slow, gradual absorption Effects primarily local, but systemic as well, especially with lipid-soluble medications passing through subcutaneous fatty tissue ● Immediate: enters directly into the blood Complete: reaches the blood in its entirety DISTRIBUTION Distribution is the transportation of medications to sites of action by bodily fluids. Factors influencing distribution include the following. Circulation: Conditions that inhibit blood flow or perfusion, such as peripheral vascular or cardiac disease, can delay medication distribution. Permeability of the cell membrane: The medication must be able to pass through tissues and membranes to reach its target area. Medications that are lipid-soluble or have a transport system can cross the blood-brain barrier and the placenta. Plasma protein binding: Medications compete for protein binding sites within the bloodstream, primarily albumin. The ability of a medication to bind to a protein can affect how much of the medication will leave and travel to target tissues. Two medications can compete for the same binding sites, resulting in toxicity. 07/24/15 April 15, 2019 3:31 PM rm_rn_2019_pharm_chp1 METABOLISM THERAPEUTIC INDEX Metabolism (biotransformation) changes medications into less active or inactive forms by the action of enzymes. This occurs primarily in the liver, but it also takes place in the kidneys, lungs, intestines, and blood. Medications with a high therapeutic index (TI) have a wide safety margin. Therefore, there is no need for routine blood medication-level monitoring. Medications with a low TI require close monitoring of medication levels. Nurses should consider the route of administration when monitoring for peak levels (highest plasma level when elimination = absorption). For example, an oral medication can peak from 1 to 3 hr after administration. If the route is IV, the peak time might occur within 10 min. (Refer to a drug reference or a pharmacist for specific medication peak times.) For trough levels, obtain a blood sample immediately before the next medication dose, regardless of the route of administration. A plateau is a medication’s concentration in plasma during a series of doses. FACTORS INFLUENCING THE RATE OF MEDICATION METABOLISM ● ● ● ● ● Age: Infants have a limited medication-metabolizing capacity. The aging process also can influence medication metabolism, but varies with the individual. In general, hepatic medication metabolism tends to decline with age. Older adults require smaller doses of medications due to the possibility of accumulation in the body. Increase in some medication-metabolizing enzymes: This can metabolize a particular medication sooner, requiring an increase in dosage of that medication to maintain a therapeutic level. It can also cause an increase in the metabolism of other concurrent-use medications. First‑pass effect: The liver inactivates some medications on their first pass through the liver, and thus they require a nonenteral route (sublingual, IV) because of their high first-pass effect. Similar metabolic pathways: When the same pathway metabolizes two medications, it can alter the metabolism of one or both of them. In this way, the rate of metabolism can decrease for one or both of the medications, leading to medication accumulation. Nutritional status: Clients who are malnourished can be deficient in the factors that are necessary to produce specific medication-metabolizing enzymes, thus impairing medication metabolism. OUTCOMES OF METABOLISM ● ● ● ● ● ● Increased renal excretion of medication Inactivation of medications Increased therapeutic effect Activation of pro-medications (also called pro-drugs) into active forms Decreased toxicity when active forms of medications become inactive forms Increased toxicity when inactive forms of medications become active forms EXCRETION Excretion is the elimination of medications from the body, primarily through the kidneys. Elimination also takes place through the liver, lungs, intestines, and exocrine glands (such as in breast milk). Kidney dysfunction can lead to an increase in the duration and intensity of a medication’s response, so it is important to monitor BUN and creatinine levels. MEDICATION RESPONSES Medication dosing attempts to regulate medication responses to maintain plasma levels between the minimum effective concentration (MEC) and the toxic concentration. A plasma medication level is in the therapeutic range when it is effective and not toxic. Nurses use therapeutic levels of many medications to monitor clients’ responses. HALF-LIFE Half-life (t½) refers to the time for the medication in the body to drop by 50%. Liver and kidney function affect half-life. It usually takes four half-lives to achieve a steady blood concentration (medication intake = medication metabolism and excretion). SHORT HALF-LIFE ● ● Medications leave the body quickly (4 to 8 hr). Short-dosing interval or MEC drops between doses. LONG HALF-LIFE ● ● ● Medications leave the body more slowly: over more than 24 hr, with a greater risk for medication accumulation and toxicity. Medications can be given at longer intervals without loss of therapeutic effects. Medications take a longer time to reach a steady state. PHARMACODYNAMICS Pharmacodynamics describes the interactions between medications and target cells, body systems, and organs to produce effects. These interactions result in functional changes that are the mechanism of action of the medication. Medications interact with cells in one of two ways or in both ways. Agonists are medications that bind to or mimic the receptor activity that endogenous compounds regulate. For example, morphine is an agonist because it activates the receptors that produce analgesia, sedation, constipation, and other effects. (Receptors are the medication’s target sites on or within the cells.) Antagonists are medications that can block the usual receptor activity that endogenous compounds regulate or the receptor activity of other medications. For example, losartan, an angiotensin II receptor blocker, is an antagonist. It works by blocking angiotensin II receptors on blood vessels, which prevents vasoconstriction. Partial agonists act as agonists and antagonists, with limited affinity to receptor sites. For example, nalbuphine acts as an antagonist at mu receptors and an agonist at kappa receptors, causing analgesia with minimal respiratory depression at low doses. 07/24 07/24/15 April 15, 2019 3:31 PM rm_rn_2019_pharm_chp1 Routes of administration ORAL OR ENTERAL Tablets, capsules, liquids, suspensions, elixirs, lozenges Most common route NURSING ACTIONS ● ● ● ● ● ● ● ● ● ● Contraindications for oral medication administration include vomiting, decreased GI motility, absence of a gag reflex, difficulty swallowing, and a decreased level of consciousness. Have clients sit upright at a 90° angle to facilitate swallowing. Administer irritating medications, such as analgesics, with small amounts of food. Do not mix with large amounts of food or beverages in case clients cannot consume the entire quantity. Avoid administration with interacting foods or beverages, such as grapefruit juice. Administer oral medications as prescribed, and follow directions for whether medication is to be taken on an empty stomach (30 min to 1 hr before meals, 2 hr after meals) or with food. Follow the manufacturer’s directions for crushing, cutting, and diluting medications. Break or cut scored tablets only. (See the Institute for Safe Medication Practices website.) Make sure clients swallow enteric-coated or time-release medications whole. Use a liquid form of the medication to facilitate swallowing whenever possible. For liquids, including suspension and elixirs, follow directions for dilution and shaking. To prepare the medication, place a medicine cup on a flat surface before pouring, and ensure the base of the meniscus (lowest fluid line) is at the level of the dose. ADVANTAGES ● ● ● Safe Inexpensive Easy and convenient DISADVANTAGES ● ● ● Oral medications have highly variable absorption. Inactivation can occur in the GI tract or by first-pass effect. Clients must be cooperative and conscious. Sublingual and buccal TOPICAL Medications directly applied to the mucous membranes or skin. Includes powders, sprays, creams, ointments, pastes, oil-and suspension-based lotions. ● Painless ● Limited adverse effects NURSING ACTIONS ● ● ● ● Transdermal Medication in a skin patch for absorption through the skin, producing systemic effects CLIENT EDUCATION ● ● ● CLIENT EDUCATION ● ● Keep the medication in place until complete absorption occurs. Do not eat or drink while the tablet is in place or until it has completely dissolved. Apply patches to ensure proper dosing. Wash the skin with soap and water, and dry it thoroughly before applying a new patch. Place the patch on a hairless area, and rotate sites daily to prevent skin irritation. Eye ● ● ● ● ● Have clients sit upright or lie supine, tilt their head slightly, and look up at the ceiling. Rest your dominant hand on the clients’ forehead, hold the dropper above the conjunctival sac about 1 to 2 cm, drop the medication into the sac, avoid placing it directly on the cornea, and have them close the eye gently. If they blink during instillation, repeat the procedure. Apply gentle pressure with your finger and a clean facial tissue on the nasolacrimal duct for 30 to 60 seconds to prevent systemic absorption of the medication. If instilling more than one medication in the same eye, wait at least 5 min between them. For eye ointment, apply a thin ribbon to the edge of the lower eyelid from the inner to the outer canthus. Ear ● ● ● Sublingual: under the tongue Buccal: between the cheek and the gum Directly enters the bloodstream and bypasses the liver Apply with a glove, tongue blade, or cotton-tipped applicator. Do not apply with a bare hand. For skin applications, wash the skin with soap and water. Pat dry before application. Use surgical asepsis to apply topical medications to open wounds. ● Have clients sit upright or lie on their side. Straighten the ear canal by pulling the auricle upward and outward for adults or down and back for children less than 3 years of age. Hold the dropper 1 cm above the ear canal, instill the medication, and then gently apply pressure with your finger to the tragus of the ear unless it is too painful. Do not press a cotton ball deep into the ear canal. If necessary, gently place it into the outermost part of the ear canal. Have clients remain in the side-lying position if possible for 2 to 3 min after instilling ear drops. 07/24/15 April 15, 2019 3:31 PM rm_rn_2019_pharm_chp1 Nose ● ● ● ● ● ● ● Use medical aseptic technique when administering medications into the nose. Have clients lie supine with their head positioned to allow the medication to enter the appropriate nasal passage. Use your dominant hand to instill nasal drops, supporting the head with your nondominant hand. Instruct clients to breathe through the mouth, stay in a supine position, and not blow their nose for 5 min after drop instillation. For nasal spray, prime the spray if indicated, insert tip into nare, and point nozzle away from the center of the nose. Spray into nose while the client inhales. Instruct the client not to blow their nose for several minutes. ● ● ● ● Rectal suppositories ● ● ● Position clients in the left lateral position or Sims’ position. Insert the suppository just beyond the internal sphincter. Instruct clients to remain flat or in the left lateral position for at least 5 min after insertion to retain the suppository. Absorption times vary with the medication. Vaginal ● ● ● ● ● ● DPI CLIENT EDUCATION ● ● ● ● Position clients supine with their knees bent and their feet flat on the bed and close to their hips (modified lithotomy or dorsal recumbent position). Provide perineal care, if needed. Lubricate the suppository or fill the applicator, depending on the formulation. Insert the medication along the posterior wall of the vagina (7.5 to 10 cm [3 to 4 in] for suppositories; 5 to 7.6 cm [2 to 3 in] for creams, jellies or foams) or instill irrigation as indicated. Instruct clients to remain supine for at least 5 min after insertion to retain the suppository. If using a reusable applicator, wash it with soap and water. (If it is disposable, discard it.) INHALATION ● ● ● ● ● ● ● ● MDI ● ● ● ● ● ● ● ● Remove the cap from the inhaler’s mouthpiece. Shake the inhaler vigorously five or six times. Hold the inhaler with the mouthpiece at the bottom. Hold the inhaler with your thumb near the mouthpiece and your index and middle fingers at the top. Hold the inhaler about 2 to 4 cm (1 to 2 in) away from the front of your mouth or close your mouth around the mouthpiece of the inhaler with the opening pointing toward the back of your throat. Take a deep breath and then exhale. Tilt your head back slightly, press the inhaler, and, at the same time, begin a slow, deep inhalation breath. Continue to breathe in slowly and deeply for 3 to 5 seconds to facilitate delivery to the air passages. Do not shake the device. Take the cover off the mouthpiece. Follow the manufacturer’s directions for preparing the medication, such as turning the wheel of the inhaler or loading a medication pellet. Exhale completely. Place the mouthpiece between your lips and take a deep inhalation breath through your mouth. Hold your breath for 5 to 10 seconds. Take the inhaler out of your mouth and slowly exhale through pursed lips. Resume normal breathing. If more than one puff is needed, wait the length of time the provider specifies before self-administering the second puff. Rinse the mouth out with water or brush the teeth if using a corticosteroid inhaler to reduce the risk of fungal infections of the mouth. Remove the canister and rinse the inhaler, cap, and spacer once a day with warm running water and dry them completely before using the inhaler again. Nasogastric and gastrostomy tubes Administered through metered dose inhalers (MDI) or dry-powder inhalers (DPI) CLIENT EDUCATION Hold your breath for 10 seconds to allow the medication to deposit in your airways. Take the inhaler out of your mouth and slowly exhale through pursed lips. Resume normal breathing. A spacer keeps the medication in the device longer, thereby increasing the amount of medication the device delivers to the lungs and decreasing the amount of medication in the oropharynx. If using a spacer: ◯ Remove the covers from the mouthpieces of the inhaler and of the spacer. ◯ Insert the MDI into the end of the spacer. ◯ Shake the inhaler five or six times. ◯ Exhale completely, and then close your mouth around the spacer’s mouthpiece. Continue as with an MDI. ● ● ● ● Use liquid forms of medications; if not available, consider crushing medications if appropriate guidelines allow. Do not administer sublingual medications through the NG tube (can give sublingual medications under the tongue). Do not crush specifically-prepared oral medications (extended/time-release, fluid-filled, enteric-coated). Administer each medication separately. Do not mix medications with enteral feedings. Completely dissolve crushed tablets and capsule contents in 15 to 30 mL of sterile water prior to administration. NURSING ACTIONS ● ● ● ● Verify proper tube placement. Use a syringe and allow the medication to flow in by gravity or push it in with the plunger of the syringe. To prevent clogging, flush the tubing before and after each medication with 15 to 30 mL of sterile water. Flush with another 15 to 30 mL of warm sterile water after instilling all the medications. 07/24