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Class: PHAR - Pharmacology; Subject: Pharmacology; University: Samuel Merritt College; Term: Forever 1989;
Typology: Quizzes
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Most drugs ionized in aqueous environment.Ionization of a drug depends on pH of aqueous environment.pKa low for acid drugpKa high for basic drugIONIZED DRUGS DO NOT CROSS MEMBRANES. Non-ionized drugs are lipid soluble, ionized drugs are water soluble. Drug po into stomachStomach pH ~ 2, little to no absorptionDuodenum pH ~ 6.5, major site of absorption TERM 2
DEFINITION 2 High Vd = high conc in extravascular tissues; lipid soluble drugs, digoxin. Low Vd = Often found mostly in the blood (plasma) compartment. Water soluble drugs, neuromuscular agents.Drugs are not homogenously distributed in the body TERM 3
DEFINITION 3 Capacity limitedEnzymes saturates NonlinearMichaelis- MentonEliminationConstant amount of drug elimianted per unit of time. Aspirin, phenytoin, ethanol TERM 4
DEFINITION 4 Clearance is constant fraction of drug.Rate of elimination is proportional to CpDose-independent kinetics TERM 5
DEFINITION 5 Patient presents with Cp of 4 ng/mLHow many days after stopping dosing will Cp return to therapeutic level (1- 2 ng/mL)0 Day = 4 ng/mL1.6 Days = 23.2 Days = 1 So , 3 days from now you start the dosing again
CL = 1.386 L/HrVd = 80 L/KgT1/2 = Vd (0.7/CL) = 80 (0.7/1.386) = 40 hours TERM 7
DEFINITION 7 Controlled by lipophilicityP-glycoprotein transportersOther factors (tetracycline + milk) TERM 8
DEFINITION 8 F is calculated from the ratio of the AUC after po dose to AUC after iv dose.F for iv always equals 100 % TERM 9
DEFINITION 9 Most of the drug eliminated during first pass through the organ through which it perfuses, First-Pass Effect (liver)Elimination depends on rate of perfusion through organ. TERM 10
DEFINITION 10 Presentation in the ER at 6 PM. Patient claims morphine self- injected at Noon.Blood level at 6 PM = 0.25 mg/LVd = 200 L/Kg t1/2 = 3 Hours Dose at Noon? T1/2 = 3 H 6 PM Cp = 0.25 mg/L6 Hours is 2 half-lives agoCp at Noon was 4x higher = 1 mg/L Total Drug in Body = Vd (Cp) = 200 L (1 mg/L) = 200 mg dose
Female Male 72 - 110 94 - 140 mL/minUse 100 mL/min as average.Renal Function Impairment:Slight 52 - 63 mL/minMild 42 - 52Marked < 28If 90 then kidney function has reduced by 10%It is a measure of how you need to change the dose in order to remove the drug TERM 17
DEFINITION 17 Use for drugs that are 100% (or nearly) cleared through the kidney.Assume CC of 100 mL is normal.Determine the % reduction in CC from normal.Reduce the dose by a % equal to the % reduction in CC. TERM 18
DEFINITION 18 Use for drugs that are ALSO cleared by the liver.Normal Dose = 200 mgHepatic and Renal CL are 50% each (liver and kidney each remove half of the drug given)Dose = 100 mg liver + 100 mg renalNow, correct dose for impaired liver function but kidney function is normal.Corrected Dose = Kidney 100 + Liver [100 (0.5)]Corrected Dose = 150 mg TERM 19
DEFINITION 19 Ex) a patient is on a drug that is mostly cleared by the kidney. The drug is administered at 10mg q 8h. The patients creatinine clearance (CC) is 50 mL/min. what should be the new adjusted dose?Answer: 5 mg q 8h Or 10 mg q 16hOr 15mg / day TERM 20
DEFINITION 20 500 mg total dose/day 50% cleared by liver CC = 30 mL/minLiver clears 50% of dose Kidney clears 50% of dose 250 mg 250 mg CC reduced by 70% 70% of 250 mg = 175 mg (250) - (175) = 75 mg 250 mg) + (75 mg) = 325 mg/day