Term
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Definition
| Dependence of rate of a process on the exponent of the drug concentration |
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Term
| What is the rate equation of a drug? |
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Definition
| Rate = Constant * [Drug]n |
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Term
| What does is mean if n=0 in the rate equation (i.e. Rate = Constant)? |
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Definition
| The process is not dependent on drug concentration and proceeds at a constant rate per unit of time. |
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Term
| What does it mean if n=1 in the rate equation (i.e. rate = constant*[Drug])? |
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Definition
| The rate is directly dependent on the drug concentation. This means that a constant percent is lost per unit of time. |
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Term
| What 2 process are zero order? |
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Definition
1) Drug Administration
2) Drug elimination in overdose |
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Term
| What is the equation for rate of drug input? |
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Definition
Rate of Drug input = f(D/T)
f= bioavailability (functional absorption)
D/T = Drug given/time i.e. 24 mg/hr, etc. |
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Term
| What 2 processes are first order? |
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Definition
1) Drug metabolism under ordinary circumstances
2) Renal Excretion |
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Term
| Why is drug metabolism under normal circumstances a first order process? |
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Definition
| The plasma concentrations of most metabolized drugs are typically below Km for the metabolic enzyme. |
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Term
| How is renal excretion a first order process? |
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Definition
| The amount of drug excreted is directly proportional to the plasma drug concentration assuming a constant number of liters are being filtered per time. |
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Term
Why is elimination first order or zero order under normal conditions?
Why? |
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Definition
| First Order since it's determined by hepatic metabolism and/or renal excretion - both of which are first order. |
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Term
| Why is alcohol usually zero order elimination? |
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Definition
| Amounts of EtOH ingested is in the gram range (as opposed to the mg grange) therefore saturating the metabolizing system so it operates at Vmax. |
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Term
| When is Km of EtOH exceeded? |
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Definition
| 3 beers or 3 oz of whiskey |
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Term
| What is Vmax for EtOH elimination? |
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Definition
| 9 g/hr (3/4 of one beer per hour) |
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Term
| What is the graph test for a zero order process? |
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Definition
| Straight-line behavior when concentration data is plotted on a normal (non0logarithmic) graph. |
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Term
| What is the graphic test for first order processes? |
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Definition
| Straight-line behavior when concentration data is plotted on a logarithmic graph. |
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Term
| When in EtOH is first order behavior seen? |
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Definition
| When blood levels are below 10 mg/dl. |
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Term
| What in the rate of drug input is adjusted when there is incomplete absorption of metabolism of a drug? |
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Definition
| Increase D & then multiply by f so that f(D) = amount of drug actually reaching the systemic circulation. |
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Term
| What equation is used to determine elimination in 1st order kinetics? |
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Definition
| Michaelis-Menten Equation |
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Term
| What is the Michaelis-Menten Equation? |
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Definition
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Term
| What does the non-logarithmic plot of first order processes look like? |
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Definition
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Term
| When is elimination rate fastest? |
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Definition
| Lg. amount of drug in the body. |
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Term
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Definition
| Time required for amount to decrease to ½ of the starting amount |
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Term
| Are there half-lifes in zero order kinetics? |
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Definition
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Term
| What is assumed normal in a t½ value? |
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Definition
| normal liver & kidney function |
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Term
| What happens to t½ if there is kidney impairment? |
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Definition
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Term
| **What is the equation relating the first order elimination constant to t½? |
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Definition
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Term
| What does it mean that t½ & ke are inversely related? |
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Definition
| As t½ increases, ke decreases & vice versa. |
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Term
| What does ke help approximate? |
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Definition
| The % of drug lost per unit of time. |
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Term
| How is therapeutic dosing determined? |
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Definition
| maximum plasma level below toxic, but above minimally effective level |
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Term
| What is the equation used to maintain a constant concentration for a therapeutic steady state? |
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Definition
| Csteady state = (f*dose)/(intervaldosing*clearance)
f=functional availability (bioavailability) |
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Term
| What is the rate of drug output equation? |
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Definition
| Rate of Drug Output = X ke
or = C*Vd*ke
X = amount of drug in the body |
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Term
| What equation is used to estimate the total body amount of drug? |
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Definition
X = C*Vd
C= blood concentration
Vd= Volume of Distribution |
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Term
| What determines the amount of drug remaining from the previous day? |
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Definition
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Term
| When is steady state for drug accumulation achieved (aka plateau principle)? |
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Definition
| When rate of input = rate of output. |
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Term
| **What is the equation of steady state (input rate = output rate)? |
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Definition
| f(D/T) = css*Vd*ke
or
f(D/T) = css*Vd*(0.7/t1/2)
or
f(D/T) = css*clearance
css= steady state avg. concentration |
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Term
| How can amplitude of fluctuations in steady state be reduced? |
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Definition
| Decreasing Dose & Dose Interval |
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Term
| What completely removes the fluctuations of the steady state? |
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Definition
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Term
| What is the equation that approximates how long until steady state can be achieved? |
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Definition
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Term
| What controls accumulation kinetics? |
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Definition
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Term
| What is used when 4*t½ is too long of a time to achieve steady state? |
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Definition
| Loading Dose - dose given to immediately achieve steady state concentration |
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Term
| **What is the equation for Loading Dose? |
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Definition
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Term
| How is steady state maintained after a loading dose is administered? |
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Definition
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Term
| For saftey reasons, how are most Loading Doses given? |
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Definition
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Term
| Is loading dose dependent on elimination? |
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Definition
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Term
| **What is the equation for clearance? |
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Definition
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Term
| Does clearance apply to zero order processes? |
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Definition
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Term
| What is the equation of total body clearance? |
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Definition
| CLtotal = Σ CLorgans that eliminate |
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Term
| What is the equation for maintenance dose in steady state? |
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Definition
| Dosemaintanence = CL*csteady state |
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Term
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Definition
1) Liver 160 mg/ml, Kidney 40 mg/ml
2) 180 mg/ml: 160 Liver, 20 Kidney |
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Term
| How do we obtain an Area Under the Curve (AUC)? |
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Definition
| Plotting plasma concentation-time curve on linear axes and integrating the area under the curve. |
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Term
| How is clearance calculated using AUC? |
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Definition
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Term
| What is the equation for oral bioavailability? |
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Definition
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Term
| Drug V is administered at 4 x 1 mg tablets every 4 hours. t½ = 1 day. How long will it take the patient to reach steady state? |
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Definition
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Term
| Drug V is administered to another patient at 2 x 1 mg tablets every 4 hours. How long will it take for this patient to reach steady state? |
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Definition
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Term
| You decide that 4 days is too long to reach steady state for your patient. How much do you give your patient recieving 4 x 1 mg tablets every 4 hours? |
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Definition
| 4 mg/4 hr = 24 mg/day
f(D/T) = css*Vd*ke
24 mg/day = css*Vd*(0.7/1 day)
34.3 mg = css*Vd = Loading Dose |
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Term
Data for metoprolol"
Oral availability: 38%
Clearance: 63 L/hr/70kg
Vd: 290 L/70kg
t½ = 3.2 hr
Target Concentration: 25 ng/mL
What is the maintenance dosing rate? |
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Definition
f(D/T) = css*CL
.38(D/T) = (25 ng/mL)*(63 L/hr/70kg)*(1000mL/L)*(mg/1000 µg)
(D/T) = 4.1 mg/hr or 100 mg/day |
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Term
| Patient has been hospitalozed with cardiac arrythmia that has been treated using an IV infusion rate of 20 mg/hr of Drug X (t½ = 5 hr). Kidney problems change t½ to 10 hr. What will happen to the steady state blood level of the patient if they continue to recieve 20 mg/hr dosage? |
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Definition
Steady state will double.
f(D/T) = css*Vd*(0.7/t½)
css = [f(D/T)*t½]/[Vd*0.7] so if t½ doubles, css doubles. |
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Term
| If the therapeutic steady state level of Drug X is 100 µg/ml, and toxicity becomes evident at 150 µg/ml, how long from time of change in renal function will it take for signs of toxicity to manifest? |
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Definition
10 hr (one half life).
Steady state increases from 100 to 200 µg/ml. Therefore in one half life (10 hr), the level increases to 150 µg/ml where signs of toxicity become evident. |
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Term
| If the therapeutic steady state level of Drug X is 100 µg/ml, and toxicity becomes evident at 150 µg/ml. What happens to the level after 2 half-lives? |
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Definition
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Term
| Suppose that in the previous patient, the plasma level was at 200 µg/ml before the treating physician figured out that the t½ had doubled. How do we treat this patient to get the plasma level back to 100 µg/ml and then maintain the correct steady state? |
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Definition
First, stop administering the drug. If we wait 1 half life of 10 hr, the drug concentration will be at 100 µg/ml.
To maintain this level, we must decrease the input rate from the original 20 µg/ml to half of that to compenstate for the doubling of the half life (i.e. 10 µg/ml). |
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Term
| Why does decreased cardiac output affect hepatic metabolism? |
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Definition
| decreased cardiac output => decreased hepatic blood flow. |
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Term
| Which drugs are most affected by decreased cardiac output? |
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Definition
| Those affected by first pass metabolism |
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Term
| What are the 2 effects all drugs have? |
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Definition
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Term
| What increases the chance of a DDI? |
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Definition
| The more medications a person is on |
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Term
| Why is there no standard dose for all people? |
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Definition
| People vary genetically, ht, wt, age, sex, body fat, etc. |
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Term
| What age is drug metabolism rate low? |
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Definition
| infants/neonates therefore infants should not be treated as small adults |
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Term
| What age is a decline in renal function seen? |
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Definition
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Term
| Why is nephrotoxicity an issue with AMGs? |
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Definition
| AMGs are renally eliminated, so toxic levels can be incurred if nephrotoxicity isn't monitored. |
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Term
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Definition
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
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Term
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Definition
Same as potentiation
3+4>7 |
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Term
| What is used to test candidate compounds as potential drugs? |
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Definition
| Population studies in animals & healthy human volunteers |
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Term
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Definition
| use matched grouped of animals or humans to study responses at various dose levels to determine tolerated doses & toxic doses |
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Term
def
Phase II & III double-blinded clinical trials |
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Definition
| measure effective and lethal doses (in animals) & efficacy (in humans). Responses are usually measured using a quantal response (all or nothing). |
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Term
| What 2 curves can be plotted in a population study? |
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Definition
| Effective Dose & Lethal Dose |
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Term
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Definition
| Effective Dose that 50% of participants will observe a quantal response. |
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Term
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Definition
| The lethal dose of 50% of the population |
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Term
| How is the Therapeutic Index (TI) calculated? |
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Definition
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Term
| What does the TI tell us? |
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Definition
Separation of dose from effect to toxicity.
Low TI = narrow window
Large TI = wide window |
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Term
| What are the 4 problems with TI? |
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Definition
| 1) Animals are used to avoid killing human patients => uncertain applicability
2) In human studies, toxic dose is used instead of lethal dose
3) ED50 isn't a realistic dose. ED99 would be better, but isn't possible in clinical trials.
4) ED & LD are assumed parallel, though not always true. |
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Term
| What is the goal when designing a drug regimen? |
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Definition
| Maintain drug concentration in therapeutic window. |
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Term
| When is it necessary to monitor drug levels? |
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Definition
| When there is significant toxicity whose threshold level is close to the therapeutic window, or in life-threatening situations where optimal plasma levels must be maintained. |
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Term
| What must be done special while monitoring drugs that are highly bound to plasma proteins? |
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Definition
| Ask lab to determine level of FREE drug, not bound, since free drug is what interacts to cause action. |
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Term
| When monitoring drug levels, when should blood samples be taken? |
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Definition
| At the trough, just before the next dose is administered. |
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