Kaplan Section 1 Chapter 1 Pharmacokinetics
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| What is the pKa? | pH at which the drug or any compound is 50% ionized (doesn't cross membranes, but better cleared from the body) and 50% nonionized (crosses membranes)
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| Weak acids are better cleared in which environment? Slightly acidic or slightly basic? | Slightly basic because in a more basic environment, weak acids will be ionized and therefore, not cross membranes as easily.
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| Weak bases are better cleared in which environment? Slightly acidic or slightly basic? | Slightly acidic because in a slightly acidic environment, weak bases are protonated (ionized) and therefore doesn't cross membranes as easily.
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| Henderson Hasselbalch equation for weak acids | pH - pKa = log ([ionized]/[nonionized])
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| Henderson Hasselbalch equation for weak bases | pH - pKa = log ([nonionized]/[ionized])
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| T or F: both bound and unbound drugs are filtered | F. Only unbound drug is filtered in the kidney.
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| T or F: Both ionized and nonionized forms of a drug are filtered. | True
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| Acidification of urine increases renal clearance of what type of drugs? | Weak bases
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| Alkalinization of urine increases renal clearance of what type of drugs? | Weak acids
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| What percentage of a drug is absorbed if it is administered via IV? | no absorption involved because IV --> therefore, no loss of blood.
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| What is the bioavailability of an IV bolus of a drug? | 100% bioavailability, f = 1
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| T or F: Only unbound drugs cross biomembranes | T.
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| What types of drugs can cross the BBB? | lipid soluble or very low molecular weight
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| What is volume of distribution (Vd)? | How much of a drug actually gets through the plasma, into the tissues.
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| What does a high Vd mean? | More drug made it into the tissues, and therefore, less left in the plasma.
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| what drugs cause SLE-like syndromes? In what type of people do they occur? | Hydralazine > Procainamide > INH. In slow acetylators (can't break down/conjugate the drug).
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| What drug is the most common cause of fulminant hepatitis? When would this happen? | Acetominophen. When GSH (glutathione) is depleted in the liver -- you need glutathione to conjugate/break down acetominophen.
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| What does t1/2 (half life) really mean? | Time it takes to eliminate 50% of a given amount of drug
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| What does it mean when a drug has a zero order elimination rate? Give an example | Rate of elimination is indep of the [ ] of the drug in the plasma (or amnt of drug already in the body). CONSTANT amnt of drug is eliminated per unit time. Examples include: EtOH, phenytoin (high therapeutic doses), and salicylates (high toxic doses)
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| What is the t1/2 of a drug that has zero order elimination? | No fixed t1/2 because a constant amount is eliminated per unit time. t1/2 depends on how much drug you gave in the first place
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| What is the t1/2 of a drug that has first order elimination? | t1/2 is CONSTANT
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| What does it mean when a drug has first order elimination? | the rate of elimination is proportional to the [ ] of drug already in the plasma. (the higher the [ ], the faster the elimination)
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| What can you say about the clearance of a drug that has first order elimination? | Clearance is CONSTANT
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| Formula to find a dose of a first order drug | Dose = Vd x C0. Vd is volume of distribution, C0 is plasma [ ] at time 0. CO VetoeD the DOSE.
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| Formula to find the t1/2 of a first order drug | t1/2 = 0.7/k (k is first order rate constant of elimination)
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| What forms of a drug are filtered? | Ionized, nonionized, and unbound drug (bound forms of drugs do NOT get filtered)
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| What is renal clearance? | Volume of blood cleared of the drug per unit time. (volume of blood that is cleared of the blood)/(time)
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| What are the conditions under which renal clearance = GFR (glomerular filtration rate)? | If there is no active secretion or reabsorption. (ie. Inulin)
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| What is a normal GFR? | 120 mL/min
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| What is the formula for clearance? | Cl = k (elim constant) x Vd (volume of distribution). Cleared means OKed and not VetoeD.
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| What is the formula for rate of infusion of a drug? | Infusion rate = Cl (clearance) x Css ([ ] of drug in the steady state). Clara and Cassie were INFUriated with the infusion of coloreds into their school.
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| Formula for loading dose | LD = Vd (vol of distrib) x Css ([ ] drug in steady state). Laura DG VetoeD Cassie from the club.
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| Formula for maintenance dose | MD = clearance x Css ([ ] drug in steady state) x dosing interval. Clara, Cassie, and DosiDo graduated with their MDs.
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| What does steady state for a drug mean? | that rate in = rate out.
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| What is the plateau principle for a drug? | Time to reach steady state is dependent only on the t1/2 of a drug and is independent of dose size and frequency of administration
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| How many half lives does it take a first order drug to reach clinical steady state? | 4 to 5 (95% of [ ] of the drug in steady state)
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| For a first order drug, how does the amount of time needed to reach steady state change as you increase the rate of infusion? | Takes the same amount of time to reach steady state. The difference is that with a higher rate of infusion, you get a greater concentration of the drug in the plasma at steady state. Steady state is simply what goes in = what is eliminated.
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| If doses of a drug are to be administered at each half life of the drug, then what should the loading dose be? | Loading dose should then be double the amount of the dose used for maintenance.
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| Formula for renal clearance of a protein-bound drug | Cl(renal) = GFR x free fraction
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| What is the Vd if the drug is distributed into total plasma volume? | 3 L
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| What is the Vd if the drug is distributed into total blood volume? | 5 L
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| What is the Vd if the drug is distributed into extracellular fluid? | 12-14 L
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| What is the Vd if the drug is distributed into total body water? | 40-42 L
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| Which of these inhibits CYP450? Carbamazepine, EtOH, Ketoconazole, Phenobarbital, Rifampin | Ketoconazole is the only inhibitor. All the rest are inducers.
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| A 500mg dose of a drug has therapeutic efficacy for 6 hr. If the half-life of the drug is 8 hr, for how long would a 1g dose be effective? | Drug stays in therapeutic range for 6 hours so the therapeutic level is somewhere above 250 mg. With 1 g dose, after 8 hours, the [ ] will still be 500mg, so the drug will be efficacious for 8 hr, then 6 additional hr, so the total is 14 hr.
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