NURS 5334 Exam Questions and Answers

Key Elements of a Prescription - 1) Prescriber Name 2) License Number 3) Contact Information 4) DEA number of prescriber and supervising physician 5) Patient Name 6) Patient DOB 7) Patient Allergies 8) Name of Medication 9) Indication for Medication 10) Strength of Medication 11) Dosing Frequency 12) Number of tablets/capsules to disepense 13) Number of refills 14) SIG or instructions for the prescription (E.g. "Take one tablet by mouth daily") 3 primary reasons for drug monitoring - 1) determine therapeutic dosage 2) evaluating medication adequacy: desired effect achieved 3) identifying adverse effects: presence of patient harm Pharmacokinetics - Study of drug movement throughout the body Includes drug metabolism and excretion Passage across cell membrane Absorption - Drug's movement from site of administration to the blood Rate=how soon effects begin Amount=how intense the effects will be Rate of absorption depends on - rate of dissolution surface area blood flow lipid solubility pH partitioning Distribution - Drug's movement from blood into interstitial space and then into cells Metabolism - "Biotransformation" Enzyme mediated alteration of the drug structure Excretion - How drugs and metabolites move out of the body Elimination - combination of metabolism and excretion Movement of drugs - GI Tract/Site of administration--Blood--Liver/Kidney/Site of action/Other Sites--Bile/Urine--Outside of body 3 ways for drugs to cross cell membrane - 1) Channels and pores 2) Transport systems (P-glycoprotein) 3) Direct penetration of the membrane - **Most common** P-Glycoprotein - Transmembrane protein that transports a wide variety of drugs out of cells Liver to Bile; Kidney to Urine, Placenta to Maternal blood; Brain to Blood Passage of drugs across membrane - "Like dissolves like" cell membrane composition lipid - lipid soluble drugs can cross membrane without help Must be Non-Ionized to cross from one side to the other Ions - drug will accumulate on side which favors ionization ("pH partitioning or Ion trapping") pH dependent ionization - acid (proton donor) ionizes in basic/alkaline media; base (proton accepter) ionizes in acidic media quarternary ammonium compounds - contain at least one atom of nitrogen and carry a positive charge Factors Affecting Drug Absorption - Rate of dissolution Surface Area Blood Flow Lipid Solubility pH Partitioning Routes of Administration: Intravenous (IV) - Advantages: Instaneous absorption, rapid onset Disadvantages: Expensive, invasive, inconvenient Routes of Administration: Intramuscular (IM) - Advantages: Rapid Absorption with water soluble drugs Capillary membrane easy to pass Permits use of poorly soluble drugs Disadvantages: Not comfortable to patient, inconvenient, potential for injury Routes of Administration: Subcutaneous (SQ) - Same as IM Routes of Administration: Oral - Advantages: Easy, Readily available, inexpensive Disadvantages: Variability in dosing, slow/variable absorption, some inactivation by gastric acid/enzymes, may cause nausea/vomiting, patient must be awake and able to take Additional Routes of Administration - -Topical -Transdermal -Inhaled -Rectal -Vaginal -Direct site injection Blood Flow to Tissues - Determines rate of delivery Carried by blood to tissues and organs Abscesses and tumors have low regional blood flow, pus-filled pockets versus internal blood vessels, some solid tumors will have a limited blood supply - these concerns will affect therapy Exiting the vascular system - Pass between capillary cells rather than through them Most drugs do not act within blood, but on specific site cells - must leave bloodstream in order to do so Blood Brain Barrier - Tight junctions prevent free diffusion Only lipid-soluble drugs or those with a transport system will cross blood-brain barrier to a therapeutic degree Placental drug transfer - Placenta membranes not an absolute barrier - diffusion is same as other membranes Risks: birth defects, drug-dependent baby with maternal drug abuse Protein binding - Can form reversible bond with various proteins Albumin - most abundant and important protein Albumin-bound protein cannot leave bloodstream restricting drug distribution Free drugs "active metabolites" Two drugs competing for protein binding will result in more free drug circulating Entering cells - Some sites of action are intracellular Most must undergo metabolism and excretion intracellularly Cell membrane passage determined by same factors as passage across other membranes Many effective at receptors on extracellular surface of cell membrane and do not need to cross intracellularly Drug Metabolism - Biotransformation Enzymatic alteration of drug structure Most often takes place in the liver P450 system - Hepatic microsomal enzyme system Key component: Cytochrome P450 12 closely related enzyme families CYP1, CYP2, CYP3 - metabolize drugs Other 9 families metabolize endogenous compounds Therapeutic consequences of drug metabolism - Promotion of renal drug excretion - cannot excrete lipid-soluble drugs, drugs must be converted to water soluble forms Drug inactivation - *most common* Improve effectiveness or therapeutic action of some drugs Some drugs are activated by metabolism (prodrugs) Usually decrease toxicity, but may actually increase toxicity for some drugs Special Consideration in drug metabolism - Age Induction or inhibition of drug-metabolizing enzymes First Pass Effect Nutritional status Competition among drugs Induction versus inhibition of drug-metabolizing enzymes - Can act as PY450 inducers or inhibitors Substrates - metabolized by PY450 Inducers increase rate of metabolism by acting on liver to stimulate enzyme synthesis ("induction") causing drug levels to fall; must adjust dosage in order to achieve therapeutic levels Inhibitors decrease rate of metabolism causing increased active drug accumulation; may lead to increased adverse effects and toxicities Some can be both a substrate and an inducer First Pass Effect - Rapid hepatic inactivation of certain oral drugs After GI absorption, carried directly to liver through hepatic portal vein Results in complete inactivation upon first pass through liver No drug is then passed into systemic circulation Nutritional status - Hepatic drug metabolism requires various cofactors to function Malnourished patients do not produce cofactors in sufficient amounts compromising drug metabolism Competition among drugs - two drugs that follow same metabolic pathway will compete will decrease metabolic rate of one or both drugs leading to accumulation/toxicity Enterohepatic Recirculation - Repetitive cycle that transports drug from liver through bile duct to duodenum and back to liver via portal blood Only glucuronidated drugs Glucuronidation: binding of lipid soluble drugs to glucuronic acid to convert to water-soluble drugs allowing passage into duodenum with bile Excretion of drugs - Removal of drugs from the body Exit the body via urine, bile, sweat, saliva, breast milk or expired air Kidney is most important organ in drug excretion Renal routes of drug excretion - Are the kidneys healthy? Poor kidney function may increase duration and intensity of drug responses Steps: 1) glomerular filtration 2) passive tubular reabsorption - lipid soluble drugs passively move through tubule membrane into blood due to concentration gradient; non lipid soluble drugs remain in urine to be excreted 3) active tubular secretion - pump drugs from blood to tubular urine; relatively high capacity Varies from person to person Factors that may modify renal drug excretion: 1) pH-dependent ionization 2) Competition for active tubular transport 3) Age - may need to consider renal dosing Nonrenal Routes of Drug Excretion - Breast milk Bile - Enterohepatic recirculation Lungs (especially anesthesia and alcohol) Sweat/saliva (toxicologically insignificant) Plasma Drug Levels - Titration Seems odd since drug responses are related to site of action concentration; for most drugs site of action is not the blood - site of action drug concentration usually not measurable For most drugs, plasma levels and therapeutic effect/toxicity directly correlated Important plasma drug levels: 1) minimum effective concentration (MEC) - just below where drug effects occur 2) toxic concentration therapeutic range: between MEC and toxicity narrow therapeutic range increases difficulty of safe administration Single-Dose Time Course - Latent period between administration and onset determined by rate of absorption Duration of effect determined by combination of metabolism and excretion Half-life - Time required for amount of drug in body to decrease by half; percentage not amount Takes 4.5-5 half-lives for drug to reach steady state Determines dosing interval; the shorter the half life the more frequent the dosing Drug levels produced with repeated doses - in order to achieve plateau drug levels with succeeding doses, drug levels climb to a steady state whereby the amount of drug eliminated is equal to the dose administered Plateau is achieved in approximately 4 half lives If plateau must be achieved quickly, a loading dose or large initial dose is used followed by maintenance dosing Generally takes approx. 4 half lives for drug to be eliminated from body