Term
| Explain the interrelationship of pharmacokinetics and pharmacodynamics. |
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Definition
| After a dose is administered, it undergoes pharmacokinetics (what the body does to the drug). The resulting [plasma] binds to a receptor. Pharmacodynamics (what the drug does to the body) represents the effect and the physiological response from the effect. |
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Term
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Definition
| It is the study of the characterization of the time course of the drug through ADME |
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Term
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Definition
| It's the study of relating [drug] to effect (It's what the drug does to the body). Pharmacokinetics are related to the intensity and time course of therapeutic and adverse effects. |
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Term
| Define clinical pharmacokinetics |
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Definition
| Interpreting plasma drug concentrations in a pt care setting using pharmacodynamics and pharmacokinetics. |
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Term
| Define Therapeutic Drug Monitoring |
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Definition
| Using clinical pharmacokinetics, lab technology, and clinical medicine to develop an individual drug plan. |
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Term
| List the variables that influence pharmacological response. |
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Definition
| The pharmacokinetic variables could be drug-related or pt-related. Some drug related variables are: Was the dose given on time?; was the time of the dose recored correctly?; was the pt compliant? The pt-related variables have to do with varying phenotypes and genotypes among patients. The pharmacodynamic variables are: receptor (or active site) availability, receptor (or active site) sensitivity, & receptor site binding (reversible or irreversible). |
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Term
| List the variables that influence the Dose-response relationship |
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Definition
A - (formulations, interactions, hepatic extraction) D - (age, protein binding, blood flow) M-(age, protein binding, interactions, hepatic fnctn)E-(age, protein binding, interactions, hepatic fnctn) Also if the response (or the concentration associated with the response) is inconsistent w/ the therapeutic goals, consider modifying the dose. |
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Term
| What properties must a drug possess to justify TDM? |
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Definition
A Relationship b/w drug concentration and effect has to be present. The drug's pharmacokinetics must be fairly complete. A narrow TI must be present. There should be a wide interpatient variability in the pharmacokinetic parameters for the drug (ie, someone w/ bad kidneys wouldn't eliminate drugs as well as someone w/ good kidneys. A sensitive and specific assay must be available. |
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Term
| Give 4 instances in which we would want to draw serum drug concentrations. |
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Definition
When we want a drug to rapidly attain an effect. When there's an insufficient response (maybe due to lack of pt compliance or lack of drug in body). We want to see if a drug is producing toxic effects. We want to know the pharmacokinetic parameters of a patient. |
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Term
| What are some limitations when monitoring drug therapy? |
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Definition
When a person has a dynamic clinical status, their pharmacokinetic parameters change a lot. Drug interactions may occur. The biggest limitations are errors: wrong amount of dose, wrong time of dose, sample is taken (or documented) at wrong time, "failure to flush", or a sample is taken from the same arm the IV is in. |
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Term
Why do we use SI units? How do you convert to SI units? How do you convert from SI units? |
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Definition
B/c biological components react in vivo on a molar basis, SI allows for better understanding of comparison of the pharmacodynamic and toxicology of similar drugs; it also allows for a better understanding of protein binding and receptor binding. CF = 1000/MW To convert to SI units: (μg/ml) x CF = (μmol/L) To convert from SI units: (μmol/L)= (μg/ml) CF |
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Term
| Explain mean error and % mean error |
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Definition
| Mean error measures bias. The smaller the number, the lesser the bias. Mean error identifies the magnitude of the systematic component of error. % mean error is used to adjust for the magnitude of differences b/w big differences in numbers. |
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Term
| Explain the coefficient of variation |
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Definition
| The smaller the CV, the greater the reliability. A CV should be less than 10% for clinical work. |
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Term
| What is the root mean squared error? |
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Definition
| It is a measure of reliability (absolute magnitude of error - demonstrates variance (accuracy)). |
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Term
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Definition
| It's the ability of an assay to quantitate low drug concentrations. You don't want to interpret any value lower than the sensitivity of the assay. |
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Term
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Definition
| It's the ability of an assay to differentiate the drug in question from similar or like substances. |
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Term
| Which assay is the primary type of drug analysis performed in TDM? |
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Definition
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Term
| What info is required for a clinical pharmacokinetics assessment? |
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Definition
Dosage form Dosage strength Dosing frequency Dosing Hx over last 5 half-lives Duration of infusion (time of absorption) Potential interacting drugs Sample time Sample type (plasma, serum) Sample collection method Type of sample tube |
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Term
| What happens if the color of the stopper on the sampling tube is red? |
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Definition
| There are no additives, so the sample will clot. After it clots, you spin it down to get serum. |
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Term
| What does it mean if the color of the stopper on the sampling tube is lavender? |
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Definition
| It contains EDTA, & it's used for cyclosporine whole blood. EDTA binds calcium to prevent coagulation. So, the blood is anti-coagulated, and the elements are spun out to give you plasma. |
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Term
| What is the additive if the stopper on a sample tube is red and gray? What is the additive if the stopper is green, and why do you have to be careful w/ this additive? |
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Definition
SST (serum separator tube) Heparin can alter protein binding |
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Term
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Definition
| The measured value should reflect the true value |
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Term
| What do mean square and root mean square measure? |
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Definition
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Term
What is acute renal failure, and what all may it be due to? What happens to the creatinine and BUN during renal failure? |
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Definition
It's a rapid deterioration of renal funciton w/ an accumulation of nitrogenous wastes. It may be due to: ischemic disorders (no blood flow), diseased glomeruli, diseased blood vessels, or interstitial nephritis associated w/ infection or drugs. The creatinine and BUN increase dramatically. |
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Term
| chronic renal disease (ESRD) is due to multiple insults to the kidney. For all races, what are the 4 leading causes of ESRD? What is the leading cause for whites? Blacks? Indians? |
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Definition
Diabetes HTN Glomeruloenphritis Tubular interstitial diseases HTN is the leading cause for whites Diabetes is the leading causes for blacks & indians |
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Term
| People who are on dialysis will have a GFR below 90, 60, 30, or 15? |
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Definition
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Term
| Describe the different stages of renal impairment (what stage is a GFR of 15-30, etc). |
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Definition
Moderate renal impairment is a GFR is below 90 ml/min w/ elevated [albumin] Mild renal impairment is a GFR below 60 ml/min Severe renal impairment is a GFR below 30 ml/min ESRD is below 15 ml/min |
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Term
What is the preferred substance used to measure GFR when an accurate measurement is critical? What are the drawbacks of this substance? |
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Definition
Inulin Inulin supply is limited & it's administration is complicated. |
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Term
What conditions must be met to consider creatinine clearance a valid measure of GFR? |
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Definition
Creatine must be constantly produced by the liver. The conversion of creatine and phosphocreatine to creatinine must be constant. Non-constant sources (eg, beef) cannot exist. Creatinine is freely filtered and not reabsorbed by the kidney (but it is secreted by the tubule). The measurement of urinary and serum creatinine must be accurate (it can be challenging to get an accurate sample). |
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Term
In a 24 hr period, what is the normal urinary creatinine excretion for young females? For young males? How much does creatinine excretion decrease after age 20? At age 60, CLcr is about % of young adults. |
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Definition
B/w 15 & 20mg/kg in young females B/w 20 & 25mg/kg in young males 2 mg/kg/day/decade 70 |
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Term
| What are the average Scr levels for young women? For young men? |
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Definition
0.6 to 1.0 mg/dL for young women 0.8 to 1.3 mg/dl for young men |
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Term
| What 4 things could change Scr levels? |
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Definition
The rate of production Reduced CLcr (which means Scr has increased) Increased CO and renal blood flow Drug interactions |
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Term
If renal function has decreased by 50%, then Scr has increased how much? Conversely, GFR must be ml/min before a rise in Scr will be seen. Why is this? |
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Definition
two-fold < 50ml/min; this is b/c the body compensates with tubular secretion |
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Term
T or F Elderly pts who weigh more than their IBW will have low Scr |
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Definition
| False, elderly pts who weigh less than their IBW will have low Scr. |
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Term
| When would use the MDRD method? |
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Definition
| The Crockcroft-Gault equation may have up to 50% error when the CRcl is < 30ml/min. So, this is when you should use the MDRD. |
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Term
| Choose: Creatinine is secreted by the anionic/cationic tubular secretory system and can be blocked by anionic/cationic drugs |
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Definition
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Term
T or F BUN should not be used to assess GFR Why or why not? |
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Definition
| True, b/c numerous factors can alter BUN that are unrelated to GFR. |
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Term
| The overall effect on drug excretion is dependent on what 3 things? |
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Definition
GFR Tubular secretion Tubular reabsorption |
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Term
| Tubular secretion is dependent upon what 3 things? |
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Definition
Affinity of the tubular transport sites for the drug. Capacity of the site to transport the drug into the tubular lumen. Renal blood flow. |
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Term
| Tubular reasborption is dependent upon what 3 things? |
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Definition
degree of lipophilicity degree of ionization (pH and pKa) urine flow rate |
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Term
| When would you use the chennavasin and brater method? |
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Definition
| For people who have changing renal function (ie, burn pts, critically ill, cancer pts) |
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Term
How does ESRD affect the distribution and protein binding of acidic drugs (phenytoin, valproic acid)? |
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Definition
A decrease in binding to plasma proteins is due to a decrease in serum albumin; an accumulation of endogenous inhibitors (usually free fatty acids); qualitative changes in binding sites; and competition for binding by metabolites of the parent drug. The decreased binding will lead to an increased Vd and an increased CLtotal for drugs w/ restrictive clearances and no change in clearance for drugs w/ no restrictive clearances. |
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Term
| How does ESRD affect the distribution and protein binding of basic drugs? |
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Definition
| An increase in binding may be due to an increase in alpha-1 acid glycoprotein. |
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Term
T or F Renal failure could alter tissue binding which would change the Vd |
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Definition
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Term
| How does renal failure affect drug metabolism? |
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Definition
| It decreases the activity of the hepatic microsomal enzyme system (cyp450 enzymes); it decreases renal metabolic activity; the degree of the reduction of drugs is less than the decrease in CLrenal (in other words, there is more drug in the system than there is being filtered through the glomerulus); and, differences in disease states can affect metabolism. |
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Term
| Explain how the dialysis of drugs is dependent upon MW |
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Definition
| As the MW of the drug increases, diffusion through the dialysis membrane is reduced. Drugs that have a MW > 500 daltons will not diffuse through conventional dialysis; however, they will diffuse through synthetic or "high flux" dialyzers and their clearance is independent of flow rate (of blood & dialysate) and dependent on molecular surface area. Drugs that have a MW < 500 will diffuse through the membrane and their clearance is dependent upon flow rate and membrane surface area. |
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Term
| How much must CLDL increase overall CLtotal to be effective? How does the pts weight affect the CLDL? |
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Definition
30% As the pt's weight increases, it decreases the effect of CLDL on CLtotal. |
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Term
| What happens if the calibration of the pumps is wrong before performing clinical dialysis? |
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Definition
There can be errors in the blood flow rates up to 30 to 40% |
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