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Adv. Clinical Chem
Exam 1 - TDM
Question | Answer |
---|---|
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. |