Pharmacokinetics and Pharmacodynamics Notes PDF

# Pharmacokinetics and Pharmacodynamics ## Pharmacokinetics Phase - Process of drug movement through the body - Four-part process - Absorption - Distribution - Metabolism - Excretion ## Pharmacodynamic Phase - Receptor binding - Postreceptor effects - Chemical reactions ## Pharm...

# Pharmacokinetics and Pharmacodynamics ## Pharmacokinetics Phase - Process of drug movement through the body - Four-part process - Absorption - Distribution - Metabolism - Excretion ## Pharmacodynamic Phase - Receptor binding - Postreceptor effects - Chemical reactions ## Pharmacokinetics: Absorption - Drug movement from GI tract into bloodstream - Disintegration - Breakdown of oral drug form into small particles - Dissolution - Combining small drug particles with liquid to form a solution - Eyedrops, eardrops, nasal sprays, respiratory inhalants, transdermal drugs, sublingual drugs, and parenteral drugs do not pass through the GI tract. - Excipients allow drug to be taken in a particular size and shape or enhance drug dissolution (simple syrup, elixirs etc.). - **Rate of dissolution:** the amount of time it takes for a drug to disintegrate and dissolve to become available for absorption. - Enteric-coated (EC) resist disintegration in gastric acid of the stomach allowing it to pass through the acidic stomach environment. Will dissolve in the alkaline environment of the small intestines. ## Absorption methods - **Passive transport** - **Diffusion:** drugs move across cell membrane from an area of higher concentration to an area of lower concentration. - **Facilitated Diffusion:** relies on a protein carrier to move from an area of higher concentration to lower concentration. - **Active transport:** requires a carrier such as an enzyme or protein to move against the concentration gradient. Energy is required. - Lipid-soluble drugs are able to pass rapidly through mucous membranes - Water-soluble drugs need either an enzyme or protein carrier ## Factors Affecting Absorption - Blood flow - Pain - Stress - pH - Exercise - Hunger - Fasting - Food texture - Fat content - Temperature - Route of administration - Poor circulation to the stomach decreases absorption. - Pain, stress, foods that are solid, hot, or high in fat decrease slow gastric emptying time, so drugs remain in the stomach longer. - IM drugs absorb faster. In muscles with increased blood flow (deltoid) compared to those with decreased blood flow (gluteus maximus). - Drugs given SQ have slower absorption rates, however have a more rapid and predictable absorption than oral. - Drugs given rectal are absorbed more slowly than oral d/t decreased surface area compared to the stomach. ## Drug Movement From GI Tract to Liver - Via portal vein - First pass effect - Bioavailability ## First Pass Effect - Some drugs are metabolized to an inactive form and excreted, decreasing the amount of active drug available. - Drugs delivered by other routes (IV, IM, SQ, Nasal, Sublingual, buccal) do not enter portal circulation and are not subject to the first pass effect. ## Bioavailability - Percentage of administered drug available for activity. - For oral meds, it's affected by absorption and first-pass effect (always less than 100%). ## Factors That Affect Bioavailability - Absorption - First pass metabolism - Drug form - Route of administration - Gastric mucosa and motility - Administration with food and other drugs - Changes in liver metabolism ## Drug Distribution - Movement of drug from circulation to body tissues - Influencing factors: - Protein binding - Free drugs - Volume of drug distribution (Vd) ## Distribution Influencing Factors - Vascular permeability and permeability of cell membrane - Regional blood flow and pH - Cardiac Output - Tissue perfusion ## Protein Binding - Many drugs need to bind with plasma proteins - **Free drug:** portion of drug that remains unbound - When to highly protein-bound drugs are given at the same time they compete for binding sites, increasing the amount of free drug in circulation. ## Blood-Brain Barrier - Protects the brain from foreign substances - Includes 98% of drugs ## Drug Metabolism (Biotransformation) - Process of the body chemically changing a drug into a form to be excreted - Prodrug: often designed to improve drug bioavailability - **Half-life:** The time it takes for the amount of drug in the body to be reduced by half. - **Steady-state:** occurs when the amount of drug being administered is the same as the amount of drug being eliminated. - **Loading dose:** Large initial dose, significantly higher than maintenance dosing, allows therapeutic levels to be reached more quickly (Heparin, Phenytoin (Dilantin)). ## Drug Excretion (Elimination) - Main route is through the kidneys. - Filter free drugs, water-soluble drugs, and unchanged drugs. - Prerenal (ex. dehydration, hemorrhage), intrarenal (ex. CKD, glomerulonephritis), and postrenal (ex. prostatic hypertrophy, stones) conditions affect drug excretion. - FYI kidney function tests (BUN, Creatinine) - Lungs: Eliminate volatile drug substances. - Products metabolized to carbon dioxide and water ## Pharmacodynamics - Study of the way drugs affect the body. - **Primary effect:** Desirable response. - **Secondary effect:** Desirable or undesirable. - Drugs act within the body to mimic the actions of the body's chemical messengers. - **Primary/Secondary effect:** - Ex. Diphenhydramine (Benadryl) - Primary: antihistamine to treat allergy symptoms. - Secondary: drowsiness (bad if driving, good if it is bedtime). ## Dose-Response Relationship - Body's physiologic response to changes in drug concentration at the site of action - **Therapeutic range:** Range of doses that produce a therapeutic response without causing significant adverse effects in patients. ## Important Pharmacodynamics Terms - **Onset:** Time it takes for drug to reach minimum effective concentration. - **Peak:** Highest concentration in blood. - **Duration:** Length of time drug exerts a therapeutic effect. ## Therapeutic Drug Monitoring - **Peak drug level:** Highest plasma concentration of the drug in a specific time. Measures rate of absorption. - Oral medication usually 2-3 hours after administration. - If the peak is too low, the effective concentration has not been met. - IV usually 30-60 minutes. - IM usually 2-4 hours. - It's important to be aware of these times to draw lab at the appropriate time. - **Trough drug level:** Lowest plasma concentration, measures rate of elimination. - Drawn right before administration of the next dose. ## Receptor Theory - Drugs act by binding to receptors. - To activate a receptor. - To produce a response. - To inactivate a receptor. - To block a response. - Four receptor families: - Cell membrane-imbedded enzymes - Ligand-gated ion channels - G protein-coupled receptor systems - Transcription factors - The better the drug is in the receptor, the more active the drug is. - Most receptors are protein in nature and found on cell surfaces. ## Pharmacodynamics - **Agonist:** Produces a desired response. - **Partial agonists:** - Elicit moderate activity when binding to receptors. - Also prevent receptor activation by other drugs. - **Antagonists:** Prevent receptor activation and block response. - May increase or decrease cellular action. ## Nonspecific Drug Effects - When stimulated, all cholinergic receptors are affected. | DRUG | CHOLINERGIC RECEPTOR SITE | RESPONSES | |-------------|---------------------------|-----------------------------------| | Bethanechol | Eye | Constrict pupils | | | Heart | Decrease heart rate | | | Blood vessels | Decrease blood pressure | | | Stomach | Increase gastric secretion | | | Bronchus | Constrict bronchioles | | | Bladder | Increase bladder contraction | ## Nonselective Drug Effects | DRUG | RECEPTOR | SITES | RESPONSES | |-------------|-----------|-------------------|------------------------------| | Epinephrine | Alpha | Blood vessels | Increase blood pressure | | | Beta, | Heart | Increase heart rate | | | Beta2 | Bronchus | Relax bronchioles | - Epi affects alpha, beta 1, and beta 2 receptors. ## Mechanism of Drug Action - Stimulation - Depression - Irritation - Replacement - Cytotoxic action - Antimicrobial action - Modification of immune status ## Pharmacodynamics Cont. | | | | | |--------------------|--------------------------------|-------------------------------|-----------------------------| | **Side effects** | **Adverse reactions** | **Drug toxicity** | **Drug interactions** | | Secondary drug effects | Mild to severe | Drug level exceeds therapeutic range | Altered drug effect due to interaction with another drug | | | Unintentional | | | | | Undesirable effects | | | ## Pharmacodynamic Interactions: - Changes occurring in absorption, distribution, metabolism, and excretion. - **Additive:** Sum of effects of the two drugs. - **Synergistic:** Effect of two drugs is much greater than effects of either drug alone. - **Antagonistic:** One drug reduces or blocks the effect of other drugs. ## Drug Interactions - **Drug-nutrient interactions:** Food may increase, decrease, or delay drug response. - **Drug-laboratory interactions:** Drugs may cause misinterpretation of test results. - **Drug-induced photosensitivity:** Drug-induced skin reaction caused by sunlight exposure. ## Don't Forget to... ADPIE ## Nursing Process: Pharmacokinetics and Pharmacodynamics - **Concept:** Caring intervention, safety. - **Assessment:** - Determine potential for drug interaction problems. - Identify the patient's current drugs. - **Patient Problems:** Anxiety, need for health teaching. - **Planning:** The patient will describe the rationale for the therapeutic regimen. - **Nursing Interventions:** - Advise the patient not to eat high-fat foods before ingesting an enteric-coated tablet. - Monitor the therapeutic range of drugs that are more toxic or have narrow therapeutic ranges. - Notify the health care provider of drugs ordered that have antagonistic effects. - **Evaluation** ## Quiz 1. A patient has liver and kidney disease. He is given a medication with a half-life of 30 hours. What is the expected duration of this medication? - A. Increase. - B. Decrease. - C. Remain unchanged. - D. Dissipate. **Answer: A. Increase** **Rationale:** Metabolism and elimination affect the half-life of a drug. With liver or kidney dysfunction, the half-life of the drug is prolonged, and less drug is metabolized and eliminated. 2. When assessing older adults and those with renal dysfunction, the nurse would expect the creatinine clearance to be which of the following? - A. Substantially increased. - B. Slightly increased - C. Decreased. - D. In the normal range. **Answer: C. Decreased.** **Rationale:** Creatinine clearance is the most accurate test to determine renal function. Creatinine is a metabolic byproduct of muscle that is excreted by the kidneys. Creatinine clearance varies with age and gender. Lower values are expected in older adult and female patients because of their decreased muscle mass. A decrease in renal GFR (common in older adults) results in a decrease in urine creatinine clearance. 3. A patient sustains significant burns to the skin and is experiencing fluid shift associated with edema in the fluid overload phase. The nurse would anticipate that this will interfere most with which phase of pharmacodynamics? - A. Absorption - B. Distribution - C. Metabolism - D. Excretion **Answer: B. Distribution** **Rationale:** Distribution is the process by which the drug becomes available to body fluids and body tissues. Drug distribution is influenced by blood flow, the drug's affinity to tissue, and the protein-binding effect. This distribution can be affected by the effects of edema in the fluid overload phase. 4. Which nursing actions would be most appropriate for ensuring patient safety with a medication that has a low therapeutic index? - A. Monitoring a patient's urine output - B. Assessing vital signs hourly - C. Maintaining strict isolation precautions - D. Monitoring serum peak and trough levels **Answer: D. Monitoring serum peak and trough levels** **Rationale:** Serum peak level is the highest plasma concentration of a drug at a specific time, indicating rate of absorption. Serum trough level is the lowest plasma concentration of a drug. They are drawn immediately before the next dose of the drug is to be administered. Trough levels indicate the rate of elimination of the drug. If either the peak or the trough level is too high, toxicity can occur. If the peak is too low, no therapeutic effect is achieved. 5. What is the primary site of metabolism for most drugs? - A. Kidney. - B. Small intestine. - C. Liver. - D. Brain. **Answer: C. Liver.** **Rationale:** Drugs can be metabolized in the gastrointestinal tract; however, the liver is the primary site of metabolism.