PHARM Chapter 1 - Pharmacokinetics and Routes of Administration

• Pharmacokinetics describes how medications travel through the body, involving absorption, distribution, metabolism, and excretion.

Absorption

• Absorption is the movement of medications from the administration site to the bloodstream (GI tract, muscle, skin, mucous membranes, or subcutaneous tissue).
• Enteral (through the GI tract) and parenteral (by injection) are common routes of administration.
• The absorption rate determines how soon the medication takes effect.
• The amount of medication absorbed determines the intensity of its effects.
• The route of administration affects both rate and amount of absorption.

Oral Route

• Barriers to absorption include the layer of epithelial cells in the GI tract.
• Absorption varies due to medication stability, solubility, GI and intestinal pH, emptying time, food presence, concurrent medications, and medication forms (enteric-coated pills or sustained-release liquids).

Sublingual, Buccal Route

• Swallowing before dissolution can lead to inactivation by gastric pH.
• Quick systemic absorption occurs through highly vascular mucous membranes.

Mucous Membranes Route (Rectal, Vaginal)

• Stool in the rectum or infectious material in the vagina limits tissue contact.
• Easy absorption with both local and systemic effects.

Inhalation Route (Mouth, Nose)

• Inspiratory effort is a barrier to absorption.
• Rapid absorption via alveolar capillary networks.

Intradermal, Topical Route

• Close proximity of epidermal cells is a barrier.
• Slow, gradual absorption with primarily local effects, but can also have systemic, especially with lipid-soluble medications.

Subcutaneous, Intramuscular Route

• No significant barriers due to large spaces between capillary cells.
• Water solubility affects absorption: highly soluble medications have rapid absorption (10-30 min), and poorly soluble medications have slow absorption.
• Blood perfusion affects absorption: high perfusion sites have rapid absorption, and low perfusion sites have slow absorption.

Intravenous Route

• No barriers to absorption.
• Absorption is immediate and complete, entering directly into the blood.

Distribution

• Distribution is the transportation of medications to action sites via bodily fluids.
• Conditions inhibiting blood flow (peripheral vascular or cardiac disease) can delay distribution.
• Lipid-soluble medications or those with a transport system cross the blood-brain barrier and the placenta.
• Medications compete for protein binding sites (primarily albumin) in the bloodstream, affecting how much medication reaches target tissues; competition can lead to toxicity.

Metabolism

• Metabolism (biotransformation) changes medications into less active or inactive forms, primarily in the liver, but also in the kidneys, lungs, intestines, and blood.
• Infants have limited medication-metabolizing capacity; hepatic metabolism generally declines with age, requiring smaller doses for older adults to prevent accumulation.
• Increased medication-metabolizing enzymes can require increased medication dosage to maintain therapeutic levels.
• The liver inactivates some medications on their first pass, requiring nonenteral routes (sublingual, IV).
• When the same pathway metabolizes two medications, it can alter the metabolism rate of one or both, leading to accumulation.
• Malnutrition can impair medication metabolism due to a deficiency in necessary factors to produce medication-metabolizing enzymes.
• Outcomes of metabolism include increased renal excretion, inactivation of medications, increased therapeutic effect, activation of pro-medications (pro-drugs), decreased toxicity of active forms, and increased toxicity of inactive forms becoming active.

Excretion

• Excretion is the elimination of medications from the body, primarily through the kidneys, but also through the liver, lungs, intestines, and exocrine glands.
• Kidney dysfunction can increase the duration and intensity of a medication's response, requiring BUN and creatinine level monitoring.

Medication Responses

• Dosing aims to maintain plasma levels between the minimum effective concentration (MEC) and the toxic concentration.
• A plasma medication level is within the therapeutic range when it is effective and not toxic.
• Medications with a high therapeutic index (TI) have a wide safety margin, negating the need for routine blood medication-level monitoring.
• Medications with a low TI require close monitoring of medication levels.
• For oral medications peak levels occur 1 to 3 hours after administration, IV peak levels might occur within 10 minutes.
• Trough levels (lowest plasma level) are obtained immediately before the next dose.
• A plateau is a medication's concentration in plasma during a series of doses.

Half-Life

• Half-life (t½) is the time it takes for the medication in the body to drop by 50%.
• Liver and kidney function affect half-life; it typically takes four half-lives to achieve a steady blood concentration (medication intake = medication metabolism and excretion).
• Short half-life (4-8 hr) means medications leave the body quickly requiring short-dosing intervals or experiencing MEC drops between doses.
• Long half-life (more than 24 hr) means medications leave the body more slowly, increasing the risk for accumulation and toxicity, and allowing for longer intervals between doses to maintain therapeutic effects, but taking meds longer to reach a steady state.

Pharmacodynamics

• Pharmacodynamics describes interactions between medications and target cells, body systems, and organs, resulting in functional changes or the mechanism of action.
• Agonists mimic or bind to receptor activity regulated by endogenous compounds; e.g., morphine activates receptors to produce analgesia, sedation, and constipation.
• Antagonists block the usual receptor activity regulated by endogenous compounds or other medications; e.g., losartan blocks angiotensin II receptors to prevent vasoconstriction.
• Partial agonists act as both agonists and antagonists with limited affinity, e.g., nalbuphine causes analgesia with minimal respiratory depression.

Routes of Administration

• Oral or Enteral: Tablets, capsules, liquids, suspensions, elixirs, lozenges.

• Contraindications vomiting, decreased GI motility, absence of a gag reflex, difficulty swallowing, and a decreased level of consciousness.

• Unless contraindicated, 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 if clients cannot finish 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 or with food.

• Follow the manufacturer’s directions for crushing, cutting, and diluting medications; only break or cut scored tablets.

• Ensure 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; ensure the base of the meniscus (lowest fluid line) is at the level of the dose.

• Advantages of oral administration include safety, low cost, ease, and convenience.

• Disadvantages of oral medications include variable absorption, potential inactivation in the GI tract or by first-pass effect, and the requirement for cooperative and conscious clients.

  Sublingual and Buccal

• Sublingual: under the tongue

• Buccal: between the cheek and the gum

• Enters directly into the bloodstream, bypassing the liver

• 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.

• Nasogastric and gastrostomy tubes

• Liquid forms of medications are preferred.

• If not available, consider crushing medications if guidelines allow

• Never administer sublingual medications through the NG tube.

• Do not crush specifically-prepared oral medications (extended/time-release, fluid-filled, enteric-coated).

• Administer medications separately.

• Do not mix medications with enteral feedings.

• Completely dissolve crushed tablets and capsule contents in 15 to 30 mL of sterile water before administration.

• 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 (use 15 to 30 mL of warm sterile water).

  Topical

• Medications directly applied to the mucous membranes or skin (powders, sprays, creams, ointments, pastes, oil-and suspension-based lotions)

• Are Painless

• Have limited adverse effects

• Apply with a glove, tongue blade, or cotton-tipped applicator, not with a bare hand.

• Wash the skin with soap and water, and pat dry it before application.

• Use surgical asepsis to apply topical medications to open wounds.

  Transdermal

• Medication in a skin patch absorbed through the skin, producing systemic effects

• Ensure proper dosing by way of patch application.

• Wash the skin with soap and water, and dry 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 avoiding placing it directly on the cornea, and have them close the eye gently. Repeat if they blink.

• Apply gentle pressure with your finger and a clean facial tissue on the nasolacrimal duct for 30 to 60 seconds to prevent systemic absorption.

• Wait at least 5 min between instilling multiple medications in the same eye.

• For eye ointment, apply a thin ribbon to the edge of the lower eyelid from the inner to the outer canthus.

  Ear

• 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.

• Drops may be warmed with hands, as cold drops may cause dizziness.

  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.

• Support the head with your nondominant hand, use your dominant hand to instill nasal drops.

• 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 the nose while the client inhales. Instruct the client not to blow their nose for several minutes.

  Rectal

• Position clients in the left lateral or lateral semi-prone recumbent 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

• 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.

• Wash a reusable applicator with soap and water. (Discard disposables.)

  Inhalation

• Administered through metered-dose inhalers (MDI) or dry-powder inhalers (DPI)

  MDI Client Education

• 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.

• 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.

• Wait at least one minute between inhalations when two inhalations of the same medication are needed.

• 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.

• 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.

• 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.

  DPI Client Education

• Do not shake the device.

• Take the cover off the mouthpiece.

• 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.

  Parenteral

• Parenteral routes include intradermal, subcutaneous, intramuscular, and intravenous.

• The vastus lateralis is best for infants (1 year and younger) and toddlers (12 months-2 years).

• The ventrogluteal site is preferable for IM injections and for injecting volumes exceeding 2 mL.

• The deltoid site has a smaller muscle mass and can only accommodate up to 1 mL of fluid.

• Use a needle size and length appropriate for the type of injection and the client’s size; the syringe size should approximate the volume of medication.

• Use a tuberculin syringe for solution volumes smaller than 0.5 mL.

• Rotate injection sites to enhance medication absorption, and document each site.

• Do not use injection sites that are edematous, inflamed, or have moles, birthmarks, or scars.

• For IV administration, immediately monitor clients for therapeutic and adverse effects.

• Discard all sharps (broken ampule bottles, needles) in leak- and puncture-proof containers.

  Intradermal

• For tuberculin testing or checking for medication or allergy sensitivities.

• Use small amounts of solution (0.01 to 0.1 mL) in a tuberculin syringe with a fine-gauge needle (1/4- to 5/8-inch, 25- to 27-gauge) in lightly pigmented, thin-skinned, hairless sites (the inner surface of the mid-forearm or scapular area of the back) at a 10° to 15° angle.

• Insert the needle with the bevel up; a small bleb should appear.

• Do not massage the site after injection.

  Subcutaneous and Intramuscular

• Subcutaneous use is for small doses of nonirritating, water-soluble medications, such as insulin and heparin.

• Use a 3/8- to 5/8-inch, 25- to 31-gauge needle. Use an insulin syringe when administering insulin. Inject no more than 1.5 mL of solution.

• Select sites that have an adequate fat-pad size (abdomen, upper hips, lateral upper arms, thighs).

• For average-size clients, pinch up the skin and inject at a 45° to 90° angle; for obese clients, use a 90° angle.

• Intramuscular use is for irritating medications, solutions in oils, and aqueous suspensions.

• The most common sites are ventrogluteal, deltoid, and vastus lateralis (pediatric).

• Use a needle size 18- to 25-gauge, 5/8- to 1.5-inch long, and inject at a 90° angle. Solution volume is usually 1 to 3 mL; divide larger volumes into two syringes and use two different sites.

• Advantages use for poorly soluble medications.

• Use for administering medications that have slow absorption for an extended period of time (depot preparations).

• Disadvantages injections are more costly.

• Injections are inconvenient.

• There can be pain with the risk for local tissue damage and nerve damage.

• There is a risk for infection at the injection site.

  Intravenous

• Use for administering medications, fluid, and blood products.

• Vascular access devices can be for short-term use (peripheral catheters) or long-term use (peripherally inserted central catheter, tunneled and non-tunneled catheter, and implantable port).

• Use 16-gauge devices for clients who have trauma, 18-gauge during surgery and for blood administration, and 22- to 24-gauge for children, older adults, and clients who have medical issues or are stable postoperatively (general guidelines).

• Peripheral veins in the arm or hand are preferable; ask clients which site they prefer; for newborns, use veins in the head, lower legs, and feet.

  Advantages

• Onset is rapid, and absorption into the blood is immediate, providing an immediate response.

• This route allows control over the precise amount of medication to administer.

• It allows for administration of large volumes of fluid.

• It dilutes irritating medications in free-flowing IV fluid.

  Disadvantages

• IV injections are even more costly.

• IV injections are inconvenient.

• Absorption of the medication into the blood is immediate. This is potentially dangerous if giving the wrong dosage or the wrong medication.

• There is an increased risk for infection or embolism with IV injections.

• Poor circulation can inhibit the medication’s distribution.

Epidural

• Use for IV opioid analgesia (morphine or fentanyl).
• The clinician advances the catheter through the needle into the epidural space at the level of the fourth or fifth vertebra.
• Use an infusion pump to administer medication.