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Adv. Clinical Chem

Exam 1 - TDM

QuestionAnswer
In what situations would you utilize TDM? (7) * (1)Narrow therapeutic ranges. * (2)Prophylactic drugs. (3)Therapeutic failures. (4)Abnormal relationship between dose and plasma drug concentration. (5)Slow -OR- fast metabolism. (6)Assessing drug-to-drug interaction. (7)Unidentifiable toxic
Pharmacokinetics is what the __ does to the __. Pharmacokinetics is what the BODY does to the DRUG.
Pharmacodynamics is what the __ does to the __. Pharmacodynamics is what the DRUG does to the BODY.
What are the 4 ways the body processes drugs? (1)Absorption. (2)Distribution. (3)Metabolism. (4)Excretion.
ABSORPTION -- What is bioavailability? Bioavailability: concentration of drug in circulation after administration
ABSORPTION -- Which way of administration has 100% bioavailability? [Oral, IV, or IM] IV
DISTRIBUTION -- What type of drug enters cells easily? [hydrophilic, lipophilic, acidic, or basic] Lipophilic
DISTRIBUTION -- Which protein does basic drugs bind to? AAG
DISTRIBUTION -- What type of drug is easily transported? [hydrophilic, lipophilic, acidic, or basic] Hydrophilic
DISTRIBUTION -- Which protein does acidic drugs bind to? Albumin
DISTRIBUTION -- BOUND-drug is biologically __. UNBOUND-drug is biologically __. Bound-drug is biologically INACTIVE. Unbound-drug is biologically ACTIVE.
Vd = D/Cp ; Define Vd. Volume of distribution. The hypothetical volume in which the drug is dissolved.
Ct = Vd x k(elimination) ; Define Ct. Total body clearance. The sum of all processes by which a drug is eliminated from the body per unit time.
__ drugs have a large Vd. [hydrophilic, lipophilic, acidic, or basic] Lipophilic.
The nonpolar drugs' Vd __ polar drugs' Vd. [ > , < , ≤ , or ≥ ] nonpolar Vd > polar Vd.
METABOLISM -- What is the the hepatic first-pass effect? The reduction of drug concentration, by the liver, before it reaches circulation.
METABOLISM -- What happens during Phase I of the first-pass effect? Detoxification of the drug by an enzyme, usually hydroxylation, to inactivate.
METABOLISM -- What happens during Phase II of the first-pass effect? Glutathione, sulfate, or glucuronic acid make the drug water soluble for easy removal.
METABOLISM -- How can the drug bypass the liver and thus the first-pass effect? (6) (1)Sublingual. (2)Buccal. (3)IM. (4)Dermal. (5)Nasal. (6)Suppositories.
METABOLISM -- Which drug does NOT have a biologically active metabolite? [Imipramine, Digitoxin, Lithium, or Lidocaine] Lithium
METABOLISM -- What is the biologically active metabolite of: IMIPRAMINE Desipramine
METABOLISM -- What is the biologically active metabolite of: LIDOCAINE Monoethylglycinexylidide (MEGX) -AND- Glycinexylidide (GX)
METABOLISM -- What is the biologically active metabolite of: TAMOXIFEN 4-hydroxytamoxifen
METABOLISM -- What is the biologically active metabolite of: PROCAINAMIDE N-acetylprocainamide (NAPA)
METABOLISM -- What is the biologically active metabolite of: DIGITOXIN Digoxin
METABOLISM -- What is the biologically active metabolite of: AMITRYPTYLINE Nortriptyline
METABOLISM -- What is the biologically active metabolite of: PRIMIDONE Phenobarbitone
EXCRETION -- What factors will affect the excretion of water-soluble converted drugs? (1)Nonfunctional kidneys. (2)Drug affects kidney function. (3)Plasma constituent competing with drug.
Define the therapeutic range. The range between the minimum effective concentration and minimum toxic concentration.
How do you find the steady state using pharmacokinetic parameters? The steady state is AT LEAST 5 to 7 half-life's of the drug.
What PATHOLOGICAL CONDITIONS affect drug distribution? (4) (1)Renal disease. (2)Hepatic disease. (3)Gastrointestinal disease. (4)Cardiac disease.
What PHYSIOLOGICAL CONDITIONS affect drug distribution? (4) (1)Age. (2)Sex. (3)Genetics. (4)Nutritional status.
What enzyme with 6 isoenzymes is responsible for >90% of drug metabolism? CYP enzyme
Which of the CYP isoenzymes is responsible for antipsychotic and antidepressant metabolism? (2) CYP2c19, CYP2d6
Which of the CYP isoenzymes is responsible for >50% of ALL drug metabolism? (1) CYP3a4
To obtain PEAK LEVELS for TDM the specimen should be collected after how long for: (1)IV. (2)Oral. (3)IM. (1) IV -- after 15-30 mins . (2)Oral -- after 1-2 hrs . (3)IM -- 1-2 hrs .
What level should be taken for drugs taken on a chronic basis? [peak or trough] Trough levels
CARDIOACTIVE DRUGS: digoxin. What is the therapeutic window? 0.8 - 2.0 ng/mL
CARDIOACTIVE DRUGS: digoxin. What is it used for? Improve cardiac contraction in congestive heart failure
CARDIOACTIVE DRUGS: digoxin. Why are hypothyroids more responsive to the drug vs. euthyroids? Hypothyroids have impaired metabolism therefore there is decreased Vd and decreased plasma clearance of the drug.
CARDIOACTIVE DRUGS: procainamide. What is the therapeutic window? 4-10 ug/mL
CARDIOACTIVE DRUGS: lidocaine. What is the therapeutic window? 1.5-5 ug/mL
CARDIOACTIVE DRUGS: lidocaine. >5 ug/mL will cause what in patients? CNS toxicity
ANTIEPILEPTIC DRUGS: phenobarbital. What is the therapeutic window? 15-40 ug/mL
ANTIEPILEPTIC DRUGS: phenobarbital. What is the toxic concentration? >40 ug/mL
ANTIEPILEPTIC DRUGS: phenobarbital. Other drugs are known to __ its metabolism. [enhance or inhibit] Inhibit
ANTIEPILEPTIC DRUGS: phenobarbital. This drug is known to __ the metabolism of other drugs. [enhance or inhibit] Enhance
PSYCHOACTIVE DRUGS: lithium carbonate. What is the therapeutic level? 0.8-1.4 uEq/mL
PSYCHOACTIVE DRUGS: lithium carbonate. What is the toxic concentration? Adverse effects? >2 uEq/mL. AE: tremors, slurred speech, muscle twitching
PSYCHOACTIVE DRUGS: lithium carbonate. How much is biologically active? 100% biologically active
PSYCHOACTIVE DRUGS: imipramine. What is the therapeutic window? 150-300 ng/mL
IMMUNOSUPPRESSANT DRUGS: cyclosporine. What is the trough level for adult kidney transplant patients? 100-375 ng/mL
IMMUNOSUPPRESSANT DRUGS: cyclosporine. What is the toxic concentration? Adverse effects? >400 ng/mL. AE: increased BP, tremors, renal dysfunction, hirsutism (excess facial, body hair in women D: )
ANTINEOPLASTIC DRUGS: methotrexate. What is the therapeutic peak? 0.1-2600 umol/L . Must give bolus dose to determine individuals' toxicity, optimal leucovorin, and future optimal dosage.
ANTINEOPLASTIC DRUGS: methotrexate. This drug is usually given with leucovorin, why? Leucovorin protects viable cells as methotrexate kills cancerous cells.
ANTINEOPLASTIC DRUGS: methotrexate. After 72hr, what is the therapeutic range? < 0.1uM
ANTIBIOTIC DRUGS: vancomycin. What is the therapeutic peak? Trough? Peak: 30-40 ug/mL. Trough: 5-10 ug/mL
ANTIBIOTIC DRUGS: vancomycin. What is the toxic peak concentration? Trough? Peak: >80 ug/mL. Trough: >20 ug/mL
ANTIBIOTIC DRUGS: vancomycin. What are some adverse effects? AE: ototoxicity, neutropenia, and nephritis
TDM Analytical Methods: HPLC. What is high pressure liquid chromatography? A method used to separate and quantify chemicals and/or drugs.
TDM Analytical Methods: HPLC. What is the function of the mobile(solvent) phase? Properties? To reconstitute the sample for analysis. The solvent must be: pure, chemically inert, and have low viscosity.
TDM Analytical Methods: HPLC. What is the stationary phase? The stainless steel component.
TDM Analytical Methods: HPLC. How is the drug/metabolite ID'd? Retention time.
TDM Analytical Methods: HPLC. In a multisolvent system, what type of eluate is used? [isocratic or gradient] Gradient
TDM Analytical Methods: HPLC. In a single solvent system, what type of eluate is used? [isocratic or gradient] Isocratic
TDM Analytical Methods: HPLC. What is the purpose of the detector? The detector recognizes the drug and tells the computer data system.
TDM Analytical Methods: HPLC. What is an advantage of using HPLC vs EIA? HPLC is able to ID many drugs in one specimen where as EIA can only ID one at a time.
What are the positive outcomes of TDM? (7) (1)Decreased morbidity. (2)Decreased hospital stay. (3)Therapeutically in control of patients. (4)Decreased in side effects and toxicity. (5)Decrease re-hospitalization. (6)Decreased drug-to-drug AE. (7)No "trial-and-method" therapy.
Created by: UTHSCSA-CLS