Term
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Definition
| study of the relationship btw the nature and intensity of a drug's effects and various drug formulation or administration factors |
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Term
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Definition
| Formulation/admin factor comprising solubility, pKa, partition coefficient, polymorphism, chirality, hydrates, complex formation potential |
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Term
| Physiological environment |
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Definition
| Formulation/admin factor comprising pH, GI motility, vasculature |
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Term
| inert formulation substances |
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Definition
| formulation/administration factor that can Can affect drug release, permeation and metabolism |
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Term
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Definition
| formulation/admin factor covering Type and concentration of enzymes, blood flow, barrier properties of the tissue. |
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Term
| pharmaceutical processes used to manufacture the dosage form |
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Definition
| Tablets, capsule, liquids, suspension, liposomes, emulsions, targeted drug delivery |
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Term
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Definition
| requires drug to be transported across various cell membranes |
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Term
| Drug may permeate cell membranes by: |
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Definition
| transcellular or paracellular pathways |
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Term
| do not cross membranes easily |
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Definition
| proteins and protein bound drugs |
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Term
| do not cross membranes easily |
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Definition
| proteins and protein bound drugs |
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Term
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Definition
| Transport through cellular junctions. Involves passive diffusion (Fick’s Law) and convective flow of water. |
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Term
| 3 mechanisms of Transcellular Transport |
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Definition
| Partitioning and passive diffusion, Carrier-mediated transport, Vesicular transport |
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Term
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Definition
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Term
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Definition
| transport out of the cell |
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Term
| calculate transcellular transport - passive diffusion |
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Definition
| use modified Fick's equation containing K (the oil:water partition coefficient) |
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Term
| 2 types of Carrier-Mediated Transcellular Transport |
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Definition
| Active transport, Facilitated diffusion |
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Term
| Carrier-Mediated Active Transport |
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Definition
| Involves carrier proteins or transporters |
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Term
| Carrier-Mediated Active Transport |
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Definition
| Drug can be transported against a concentration gradient i.e. from low to high |
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Term
| Carrier-Mediated Active Transport |
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Definition
| Process requires energy, carrier system is saturable, carrier may be selective, process may be competitive |
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Term
| example of influx transporters |
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Definition
| amino acid transporters and peptide transporters |
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Term
| example of efflux transporters |
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Definition
| P-glycoprotein and multidrug resistant proteins |
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Term
| Carrier-Mediated Facilitated Diffusion |
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Definition
| Transport occurs in the direction of the concentration gradient i.e. high to low.; process does not require energy |
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Term
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Definition
| Process of engulfing particles or dissolved materials by cells. |
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Term
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Definition
| process of transporting small solute or fluid volumes |
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Term
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Definition
| process of vesicularly transporting larger particles |
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Term
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Definition
| process of vesicular transport that is receptor mediated |
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Term
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Definition
| process of vesicular transport that involves movement out of the cell |
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Term
| steeper peak on plasma drug concentration vs time curve means: |
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Definition
| Faster Absorption, may result in quicker onset of action, higher intensity and shorter duration of effect |
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Term
| shallower, more delayed peak on plasma drug concentration vs time curve means: |
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Definition
| Slower Absorption, may result in delayed onset of action, lower intensity but exhibit prolonged effect |
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Term
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Definition
| The fraction of the drug dose that reaches the systemic circulation. aka F. |
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Term
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Definition
| Rate and extent to which an active ingredient is absorbed from a drug product and becomes available at the site of action |
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Term
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Definition
| The absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action. |
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Term
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Definition
| Absorption rate constant; percent absorbed per unit time |
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Term
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Definition
| absorption is rapid and extensive |
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Term
| Controlled-Release Products |
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Definition
| Usually approximate zero-order absorption as opposed to 1st-order absorption; results in more consistent plasma concentrations |
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Term
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Definition
| usually means the drug is always released at a controlled rate from beginning to end. |
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Term
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Definition
| the rate of release is not controlled. But where release occurs is controlled. |
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Term
| Repeat-action formulations |
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Definition
| release an initial dose followed by another dose later but the rate of the release is not controlled. |
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Term
| Sustained release formulations |
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Definition
| usually release initial dose followed by controlled-release |
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Term
| Common Formulations for ORAL Controlled-Release Products |
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Definition
| Wax matrix tablets, Coated pellets in tablets, Coated pellets in capsules, Osmotic pumps |
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Term
| factors affecting distribution |
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Definition
| body tissue characteristics, disease states, lipid solubility of drug, regional pH differences, extent of protein binding |
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Term
| relative perfusion of tissues |
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Definition
| heart/lungs/kidneys > skeletal muscle > fat and bone |
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Term
| diseases decreasing perfusion |
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Definition
| liver failure, CHF, renal failure |
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Term
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Definition
| get a higher distribution of the drug. (So, diseases that decrease the perfusion will decrease the distribution.) |
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Term
| failure in an organ of elimination |
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Definition
| adverse health condition that can cause buildup of drug in the body |
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Term
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Definition
Crosses membranes easily
Distributes into fat |
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Term
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Definition
Polar or charged molecules
Don’t cross membranes easily
Doesn’t distribute much into fat |
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Term
| Hydrophilic vs Lipophilic solubility |
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Definition
| plays a big role in calculating doses by weight. |
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Term
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Definition
| plasma protein concentrations 35-45 g/L; anionic, cationic, ex. phenytoin |
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Term
| alpha-1-acid glycoprotein |
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Definition
| plasma protein concentration 0.4-1.0 g/L; cationic; ex. lidocaine |
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Term
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Definition
| plasma protein concentration is variable, lipophilic binding, ex. cyclosporine |
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Term
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Definition
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Term
| protein binding is NOT constant because of |
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Definition
Changes in protein concentration
Displacement by other substances
Changes due to disease states |
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Term
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Definition
| Inactive form; Bioactive after biotransformation or metabolism; ex. Levodopa |
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Term
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Definition
| oxidation, reduction, hydrolysis |
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Term
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Definition
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Term
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Definition
| are the major hepatic enzyme system responsible for Phase I reactions; can be induced or inhibited by drugs |
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Term
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Definition
| performs phase I and phase II metabolic reactions; completes phase I metabolism using CYP450 enzymes |
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Term
| biotransformation can be affected by: |
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Definition
| functioning of metabolic enzyme systems; social habits; diseases; concomitant drug use; genetic variation |
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Term
| biotransformation can be affected by: |
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Definition
| functioning of metabolic enzyme systems; social habits; diseases; concomitant drug use; genetic variation |
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Term
| Extent of hepatic extraction depends on: |
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Definition
| physical and chemical properties of the drug. |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| E; fraction of drug removed during one pass; between 1 and 0; The efficiency of the liver in removing drug from the bloodstream |
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Term
| Intrinsic clearance (CLi) |
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Definition
| the liver’s innate ability to clear unbound drug from intracellular water via metabolism or biliary excretion |
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Term
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Definition
| significant for drugs with high extraction ratio |
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Term
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Definition
| removal of drug by the liver AFTER absorption but BEFORE reaching systemic circulation. |
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Term
| When assessing clinical significance consider the following: |
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Definition
Route of administration (IV vs PO)
Extraction ratio (high = >0.8, low = <0.2)
Protein binding (high = >80%, low = <50%) |
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Term
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Definition
| made up of metabolism and excretion. |
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Term
| Drugs can be excreted through: |
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Definition
| urine, bile, sweat, expired air, breast milk, seminal fluids |
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Term
| three mechanisms of renal excretion |
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Definition
| glomerular filtration, tubular secretion, tubular reabsorption |
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Term
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Definition
Passive diffusion of fluids and solutes.
Influenced by molecular size(≤60,000), protein binding (only free fraction), integrity of and number of nephrons. |
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Term
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Definition
| Active process therefore may be subject to competition e.g to enhance half-life of penicillin coadminister probenecid |
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Term
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Definition
Depends on the effect of pH on the drug.
Drugs that are ionized in the urine have less reabsorption so they stay in the urine and are excreted. Urine flow rate may also be important for some compounds e.g. urea (low flow rate higher reabsorption). |
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Term
| If a drug is only eliminated renally and the only renal process is glomerular filtration the relationship between total body clearance and GFR is: |
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Definition
| Double GFR = double clearance; if GFR=0, then Cl=0 |
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Term
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Definition
| drug Cl constant at 1st order; as dose increases, plasma C increases proportionally and AUC increases in a linear manner; doubling dose will double Css; as dose increases |
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Term
| non-linear/dose-dependent |
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Definition
| the type of kinetics the drug follows actually changes with the dose |
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Term
| Michaelis-Menten Equation (MME) |
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Definition
| Used in biochemistry to describe kinetics of saturable enzymes systems. |
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Term
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Definition
| drug concentration when the rate of the process is half the maximum rate |
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Term
| Nonlinear Elimination usually occurs because: |
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Definition
| the drug elimination process is saturable |
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Term
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Definition
| prediction of plasma drug concentrations for drugs with saturable elimination. |
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Term
| in clinical pharmacokinetics using MME, drug elimination rate |
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Definition
| Rate of decline in plasma drug |
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Term
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Definition
at a small dose, the kinetics will approximate 1st-order.
If you increase Cp you will increase the elimination too. |
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Term
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Definition
approximate zero order.
Larger dose. If you increase Cp the elimination does NOT increase. |
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Term
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Definition
| represents the maximum amount of drug that can be eliminated in a given time period |
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Term
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Definition
| represents the concentration above which saturation of drug elimination is likely |
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Term
| when plasma concentrations are > Km, |
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Definition
| small dose changes can lead to large increases in Css |
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Term
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Definition
| as dose increases elimination rate changes as does time to reach steady state |
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Term
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Definition
| the time it takes to reach 90% of steady-state concentration |
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Term
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Definition
| it takes a longer time to achieve Css, Plasma drug concentration continues to rise, more adverse/toxic effects may be observed at high doses |
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Term
| Sources of Pharmacokinetic Variation |
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Definition
Age
Disease states
Genetic factors
Obesity |
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Term
| organ function is decreased in: |
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Definition
| the elderly (GFR decreases 1 mL/min/year after 40, decreased Phase I hepatic) and neonates (initial low GFR, reduced hepatic phase II) |
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Term
| increase dosing interval when |
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Definition
| clearance is decreased but volume of distribution is relatively unchanged, the dose administered may be similar to that in a healthy person. |
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Term
When the volume of distribution is
altered the dose administered: |
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Definition
should change in proportion
to the change in volume of distribution, but the dosing interval can remain the same |
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Term
| in an obese person the amount of body water/kg of total body weight is |
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Definition
| lower than that of a non-obese person |
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Term
| fat tissue contains ____ water than lean tissue |
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Definition
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Term
| during pregnancy, renal drug clearance: |
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Definition
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Term
| Sources of Error in Samples: |
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Definition
Sample collection and handling
Physicochemical factors
Instrument calibration and controls
Drug administration and sampling times |
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Term
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Definition
| the fluid portion of whole blood before clotting |
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Term
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Definition
| the fluid portion of whole blood AFTER CLOTTING |
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Term
| sample collecting and handling errors: |
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Definition
Delays in assaying
Absorption or adsorption to barrier |
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Term
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Definition
| structurally related drug compounds or metabolites for which the assay method measures as if they were the desired assay compound |
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Term
| A gentamicin concentration from a sample stored at controlled room temperature and assayed 24 hr after it was collected from a patient receiving both ampicillin and gentamicin |
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Definition
| The accuracy of the drug concentration is of concern and should be redrawn |
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Term
| A plasma tobramycin concentration from a sample stored at controlled room temperature and assayed 24 hours after it was collected from a patient receiving both tobramycin and ceftazidime |
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Definition
| The accuracy of the drug concentration is not of particular concern |
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Term
| Drug administration and sampling times error examples: |
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Definition
Deviations in drug administration times
Accurate sampling times
Other medications |
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Term
| Most frequently used model-independent parameters: |
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Definition
AUC
Elimination rate constant
Elimination half-life
Total Body Clearance
Mean Residence Time
Volume of distribution at steady state
Formation Clearance |
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Term
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Definition
| Average time intact drug molecules transit or reside in the body |
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Term
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Definition
| Average time intact drug molecules transit or reside in the body |
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Term
| Volume of Distribution at Steady State |
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Definition
| Relates total amount of drug in the body to a particular plasma concentration after a single dose. |
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Term
| Formation Clearance (CLP→Mx) |
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Definition
| Provides a meaningful estimate of the portion of total body clearance that is accounted for by production of a specific metabolite |
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Term
| T/F drugs that are very lipid soluble tend to distribute well into body tissues |
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Definition
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Term
| T/F drugs that are predominantly un-ionized at physiologic pH have a limited distribution when compared to drugs that are primarily ionized |
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Definition
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Term
| T/F Drugs are generally less well distributed to highly perfused tissues compared to poorly perfused tissues |
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Definition
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Term
| Estimate the volume of distriubution for a drug when the vol of plasma and tissue are 5 and 20 L, respectively, and the fraction of drug unbound in plamsa and tissue are both 0.7. |
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Definition
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Term
| T/F the portion of drug that is not bound in plasma protein is pharmacologically active |
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Definition
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Term
| T/F penetration of drug into tissues is directly related to the extent bound to plasma proteins |
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Definition
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Term
| cationic drugs and weak bases are more likely to bind to |
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Definition
| alpha-1-acid glycoprotein |
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Term
| anionic drugs and weak acids are more likely to bind to |
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Definition
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Term
| predict how the volume of distribution (V) would change if the phenytoin unbound fraction in plasma decreased from 90% to 85%. Assume that unbound fraction in tissues (Ft) and volumes of plasma (Vp) and tissues (Vt) are unchanged. |
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Definition
| decrease. if the fraction bound decreases, then V will also decrease. |
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Term
| a new drug has a tissue volume (Vt) of 15 L, an unbound fraction in plasma (Fp) of 5%, and an unbound fraction in tissues (Ft) of 5%. what will the resulting volume of distribution be if the plasma volume (Vp) is reduced from 5 to 4? |
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Definition
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Term
| How is the volume of distribution (V) of digoxin likely to change if a patient has been taking both digoxin and quinidine and the quinidine is discontinued? Assume that plasma volume (Vp), tissue volume (Vt), and unbound fraction of drug in plasma (Fp) are unchanged |
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Definition
| increase. quinidine with digoxin compete for same binding sites, so when quinidine is discontinued, the unbound digoxin decreases. |
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Term
| the body converts drugs to less active substances through a process called |
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Definition
|
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Term
| biotransformation is also known as |
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Definition
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Term
| in total, hepatic elimination encompasses both the processes of |
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Definition
| biotransformation and excretion |
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Term
| T/F glucoronidation is a phase II biotransformation |
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Definition
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Term
| biotransformation may be dependent on factors such as age, |
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Definition
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Term
| What are the phase I reactions? |
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Definition
| oxidation, reduction, hydrolysis |
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Term
| the basic functional unit of the liver is: |
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Definition
|
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Term
| the liver receives its blood from the |
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Definition
| portal vein and hepatic artery |
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Term
| T/F a drug adminstered orally must go through the liver before it is available to the systemic circulation. |
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Definition
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Term
| because the extraction ratio can maximally be 1, the minimum value that hepatic clearance can approach is that of: |
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Definition
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Term
| T/F intrinsic clearance is the maximal ability of the liver to eliminate drug in the absence of any blood flow limitations |
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Definition
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Term
| smoking is known to increase the enzymes responsible for theophylline metabolism ( a drug with low hepatic extraction). Would a patient with a history of smoking likely require a higher, lower, or equivalent theophylline total daily dose compared to a nonsmoking patient? |
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Definition
| higher. smoking raises the concentrations of enzymes that also metabolize theophylline, so more theophylline would be metabolized, requireing a higher theophylline dose. |
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Term
| T/F heart failure reduces cardiac output and hepatic blood flow. consequently, the total daily dose of lidocaine may need to be decreased in a patient with heart failure who has a myocardial infarction. |
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Definition
|
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Term
| drugs with a high extraction ration undergo a significant amount of this type of metabolism: |
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Definition
|
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Term
| significant first-pass metabolism means that much of the drug's metabolism occurs before it's arrival at the |
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Definition
|
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Term
| the liver receives blood supply from the GI tract via the |
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Definition
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Term
| for a drug that is totally absorbed without any presystemic metabolism and then undergoes hepatic extraction, the correct equation equation for F is: |
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Definition
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Term
| T/F Route of administration, extraction ratio, and protein inding are all factors taht should be considered when trying to asses the effect of disease states on plasma concentrations of drugs eliminated by the liver. |
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Definition
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Term
| will drugs that inhibit the hepatic CYP450 system likely increase or decrease the plasma clearance of theophylline? |
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Definition
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Term
| T/F Disease states may increase or decrease drug protein binding |
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Definition
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Term
| Drug elimination encompasses both |
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Definition
|
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Term
| two important routes of drug excretion are |
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Definition
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Term
| T/F fluid is filtered across the glomerulus through active transport |
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Definition
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Term
| T/F tubular secretion most often occurs with weak organic acids |
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Definition
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Term
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Definition
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Term
| renal clearance can be calculated from the ratio of which of the following drug's rates to the drug's concentration in plasma? |
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Definition
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Term
| for aminoglycoside doses, which of the following must be calculated to estimate an individual patient's drug elimination rate? |
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Definition
| pulmonary clearance and creatinine clearance |
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Term
| drugs demonstrating nonlinear pharmacokinetics |
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Definition
| phenytoin, salicylate, penicillin G, and ascorbic acid |
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Term
| T.F linear pharmacokinetics means that the plot of plasma drug concentration vs time after dose is a straight line |
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Definition
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Term
| T/F when hepatic metabolism becomes saturated, any increase in dug dose will lead to a proportionate increase in teh plasma concentration achieved |
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Definition
|
|
Term
| when the rate of drug elimination proceeds at half the maximum rate, the drug concentration is known as: |
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Definition
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