Pharmacokinetics and Pharmacodynamics: Mechanisms and Processes PDF

Here is the converted markdown from the images of the document you sent: # Pharmacokinetics Phase * Process of drug movement through the body. * Four-part process * Absorption * Distribution * Metabolism * Excretion # Pharmacodynamic Phase * Receptor binding * Postr...

Here is the converted markdown from the images of the document you sent: # 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 Gl 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 Gl 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 stomach allowing it to pass through the acidic stomach environment. Will dissolve in the alkaline environment of the small intestines # Absorption methods | | Passive transport | Active transport | | :-------------------- | :--------------------------------------------------------------------------------------------------------------------------------------------------------------- | :---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Passive transport | | | | Active transport | | | | | Diffusion | | | Illustration | A cell with lipids shown, the substances flow with the concentration gradient.Facilitated diffusion is shown with a channel that substances also flow through. | Pores on a cell are shown, with squares needing ATP to enter. | | List of characteristics | * Passive transport | * Active transport | | | * Diffusion | Requires energy to move drug against a concentration gradient | | | Facilitated diffusion | Pinocytosis Cell carries drug across membrane by engulfing drug particles. | 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 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 stomach decreases absorption * Pain, stress foods that are solid, hot or high in fat decrease slow gastric emptying time so drugs remain in 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 stomach. # Drug Movement From GI Tract to Liver Oral (enteral) administration Sublingual administration Buccal cavity Venous return from buccal cavity Liver Hepatic vein * Via portal vein * First pass effect * Bioavailability Bile duct Liver Stomach Portal vein Intestine Lymphatics Vena cava Rectum Venous return from rectum Rectal administration First Pass Effect: Some drugs are metabolized to inactive form and excreted decreasing 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 first pass effect **Bioavailability**: percentage of administered drug available for activity. For oral meds. Affected by absorption and first-pass effect (always less than 100%) | | | | :----------------------------- | :------------------------------------------------- | | Factors thataffectbioavailability | 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 brain from foreign substances * Includes 98% of durgs | | | | :------------------------------------------ | :------------------------------------- | | Drug metabolism(biotransformation) | Process of body chemically changing drug into a form to be excreted | | **Explanation and definition of terms** | Prodrug | | | Half-life ($t{1/2}$) | | | Steady state | | | Loading dose | * Liver is the primary site * Diseases that affect the liver alter metabolism (hepatitis, cirrhosis) * 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 * Stead-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)** | Kidneys | Liver (bile) | Lungs | | ------- | ------------ | ------------ | | Saliva | Sweat | Breast milk | * 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 w/in body to mimic the actions of bodies 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** ## Potency * Amount of drug needed to elicit specific physiologic response ## Maximal efficacy * Point which increasing a drug's dosage no longer increases desired therapeutic response ## Therapeutic index * Relationship between therapeutic dose and toxic dose **Body's physiologic response to changes in drug concentration at site of action** **Therapeutic range: range of doses that produce a therapeutic response without causing significant an adverse effect in Patients.** **Important Pharmacodynamics Terms** | Parameter | Description | | :-------------------------- | :------------------------------------------------------------------------------------------ | | **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 * Trough drug level Peak drug level: Highest plasma concentration of a drug in a specific time. Measures rate of absorption * If peak is to low effective concentration has not been met * Oral medication usually 2-3 hours after admin * IV usually 30-60 min * IM usually 2-4 hours * Important to be aware of these time to draw lab at appropriate time Trough Drug Level: Lowest plasma concentration, measures rate of elimination Drawn right before admin of next dose **Receptor theory** * Drugs act by binding to receptors * To activate receptor * To produce a response * To inactivate a receptor * 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 fits in the receptor the more active the drug is Most receptors are protein in nature and found on cell surfaces **Pharmacodynamics** *Agonist:* * Produce 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 | | ----------- | ------------------------- | ------------------------------- | | Eye | Eye | Constrict pupils | | Heart | Heart | Decrease heart rate | | Bethanechol | Blood vessels | Decrease blood pressure | | | Stomach | Increase gastric secretion | | | Bronchus | Constrict bronchioles | | | Bladder | Increase bladder contraction | Ex. Bethanechol | DRUG | RECEPTOR | SITES | RESPONSES | | ----------- | ------------- | ------------- | --------------------- | | Epinephrine | Alpha | Blood vessels | Increase blood pressure | | | Beta, | Heart | Increase heart rate | | | Beta${_2}$ | Bronchus | Relax bronchioles | Nonselective Drug effects Epi affects alpha and beta 1 and beta 2 receptors. | | | | :------------ | :------------- | | **Mechanism ofDrugAction** | Stimulation | | | Depression | | | Irritation | | | Replacement | | | Cytotoxic action | | | Antimicrobial action | | | Modification of immune status | | | | | | | :------------ | :------------ | :------------ | :------------ | | Pharmacodynamics Cont. | | | | | **Side effects** | Adverse reactions | Truck toxicity | Drug interactions | | Secondary drug effects | Mild to severe Unintentional Undesirable effects | Drug level exceeds therapeutic range | Altered drug effect due to interaction with another drug | | | | | - | - | | PharmacodynamicInteractions:Changes occurring inabsorption, distribution,metabolism, and excretion | Additive Sum of effects of two drugs | | | Synergistic Effect of two drugs is much greater than effects of either drug alone. | | | Antagonistic One drug reduces or blocks 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** **NursingProcess: Pharmacokinetics andPharmacodynamics** * Concept * Caring, intervention, safety * Assessment * Determine potential for drug interactions problems. * Identify patient's current drugs. * Patient problems * Anxiety, need for health teaching * Planning * The patient willdescribe rationale for therapeutic regimen. * Nursing interventions * Advise patient not toeat high-fatfoodsbeforeingestingarenterIC-Coatedtablet, * Monitor therapeuticrangeofdrugsthataremoretoxic Orhavenarrowtherapeuticranges * Notity healthcare provider ofdrugs ordered thathave antagonistic effects * Evaluation 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. 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. 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. Which nursing actions would be most appropriate for ensuring patient safety with a medication that has a low therapeuticindex? 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 peakis too low, no therapeutic effect is achieved. 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.