Exam 1 - TDM
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| 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
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| Pharmacokinetics is what the __ does to the __. | Pharmacokinetics is what the BODY does to the DRUG.
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| Pharmacodynamics is what the __ does to the __. | Pharmacodynamics is what the DRUG does to the BODY.
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| What are the 4 ways the body processes drugs? | (1)Absorption.
(2)Distribution.
(3)Metabolism.
(4)Excretion.
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| ABSORPTION -- What is bioavailability? | Bioavailability:
concentration of drug in circulation after administration
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| ABSORPTION -- Which way of administration has 100% bioavailability? [Oral, IV, or IM] | IV
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| DISTRIBUTION -- What type of drug enters cells easily? [hydrophilic, lipophilic, acidic, or basic] | Lipophilic
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| DISTRIBUTION -- Which protein does basic drugs bind to? | AAG
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| DISTRIBUTION -- What type of drug is easily transported? [hydrophilic, lipophilic, acidic, or basic] | Hydrophilic
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| DISTRIBUTION -- Which protein does acidic drugs bind to? | Albumin
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| DISTRIBUTION -- BOUND-drug is biologically __. UNBOUND-drug is biologically __. | Bound-drug is biologically INACTIVE.
Unbound-drug is biologically ACTIVE.
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| Vd = D/Cp ; Define Vd. | Volume of distribution.
The hypothetical volume in which the drug is dissolved.
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| 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.
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| __ drugs have a large Vd. [hydrophilic, lipophilic, acidic, or basic] | Lipophilic.
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| The nonpolar drugs' Vd __ polar drugs' Vd. [ > , < , ≤ , or ≥ ] | nonpolar Vd > polar Vd.
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| METABOLISM -- What is the the hepatic first-pass effect? | The reduction of drug concentration, by the liver, before it reaches circulation.
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| METABOLISM -- What happens during Phase I of the first-pass effect? | Detoxification of the drug by an enzyme, usually hydroxylation, to inactivate.
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| METABOLISM -- What happens during Phase II of the first-pass effect? | Glutathione, sulfate, or glucuronic acid make the drug water soluble for easy removal.
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| 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.
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| METABOLISM -- Which drug does NOT have a biologically active metabolite? [Imipramine, Digitoxin, Lithium, or Lidocaine] | Lithium
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| METABOLISM -- What is the biologically active metabolite of: IMIPRAMINE | Desipramine
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| METABOLISM -- What is the biologically active metabolite of: LIDOCAINE | Monoethylglycinexylidide (MEGX)
-AND-
Glycinexylidide (GX)
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| METABOLISM -- What is the biologically active metabolite of: TAMOXIFEN | 4-hydroxytamoxifen
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| METABOLISM -- What is the biologically active metabolite of: PROCAINAMIDE | N-acetylprocainamide (NAPA)
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| METABOLISM -- What is the biologically active metabolite of: DIGITOXIN | Digoxin
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| METABOLISM -- What is the biologically active metabolite of: AMITRYPTYLINE | Nortriptyline
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| METABOLISM -- What is the biologically active metabolite of: PRIMIDONE | Phenobarbitone
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| 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.
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| Define the therapeutic range. | The range between the minimum effective concentration and minimum toxic concentration.
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| 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.
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| What PATHOLOGICAL CONDITIONS affect drug distribution? (4) | (1)Renal disease.
(2)Hepatic disease.
(3)Gastrointestinal disease.
(4)Cardiac disease.
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| What PHYSIOLOGICAL CONDITIONS affect drug distribution? (4) | (1)Age.
(2)Sex.
(3)Genetics.
(4)Nutritional status.
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| What enzyme with 6 isoenzymes is responsible for >90% of drug metabolism? | CYP enzyme
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| Which of the CYP isoenzymes is responsible for antipsychotic and antidepressant metabolism? (2) | CYP2c19,
CYP2d6
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| Which of the CYP isoenzymes is responsible for >50% of ALL drug metabolism? (1) | CYP3a4
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| 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 .
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| What level should be taken for drugs taken on a chronic basis? [peak or trough] | Trough levels
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| CARDIOACTIVE DRUGS: digoxin. What is the therapeutic window? | 0.8 - 2.0 ng/mL
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| CARDIOACTIVE DRUGS: digoxin. What is it used for? | Improve cardiac contraction in congestive heart failure
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| 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.
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| CARDIOACTIVE DRUGS: procainamide. What is the therapeutic window? | 4-10 ug/mL
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| CARDIOACTIVE DRUGS: lidocaine. What is the therapeutic window? | 1.5-5 ug/mL
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| CARDIOACTIVE DRUGS: lidocaine. >5 ug/mL will cause what in patients? | CNS toxicity
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| ANTIEPILEPTIC DRUGS: phenobarbital. What is the therapeutic window? | 15-40 ug/mL
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| ANTIEPILEPTIC DRUGS: phenobarbital. What is the toxic concentration? | >40 ug/mL
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| ANTIEPILEPTIC DRUGS: phenobarbital. Other drugs are known to __ its metabolism. [enhance or inhibit] | Inhibit
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| ANTIEPILEPTIC DRUGS: phenobarbital. This drug is known to __ the metabolism of other drugs. [enhance or inhibit] | Enhance
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| PSYCHOACTIVE DRUGS: lithium carbonate. What is the therapeutic level? | 0.8-1.4 uEq/mL
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| PSYCHOACTIVE DRUGS: lithium carbonate. What is the toxic concentration? Adverse effects? | >2 uEq/mL.
AE: tremors, slurred speech, muscle twitching
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| PSYCHOACTIVE DRUGS: lithium carbonate. How much is biologically active? | 100% biologically active
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| PSYCHOACTIVE DRUGS: imipramine. What is the therapeutic window? | 150-300 ng/mL
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| IMMUNOSUPPRESSANT DRUGS: cyclosporine. What is the trough level for adult kidney transplant patients? | 100-375 ng/mL
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| 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: )
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| 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.
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| ANTINEOPLASTIC DRUGS: methotrexate. This drug is usually given with leucovorin, why? | Leucovorin protects viable cells as methotrexate kills cancerous cells.
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| ANTINEOPLASTIC DRUGS: methotrexate. After 72hr, what is the therapeutic range? | < 0.1uM
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| ANTIBIOTIC DRUGS: vancomycin. What is the therapeutic peak? Trough? | Peak: 30-40 ug/mL.
Trough: 5-10 ug/mL
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| ANTIBIOTIC DRUGS: vancomycin. What is the toxic peak concentration? Trough? | Peak: >80 ug/mL.
Trough: >20 ug/mL
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| ANTIBIOTIC DRUGS: vancomycin. What are some adverse effects? | AE: ototoxicity, neutropenia, and nephritis
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| TDM Analytical Methods: HPLC. What is high pressure liquid chromatography? | A method used to separate and quantify chemicals and/or drugs.
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| 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.
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| TDM Analytical Methods: HPLC. What is the stationary phase? | The stainless steel component.
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| TDM Analytical Methods: HPLC. How is the drug/metabolite ID'd? | Retention time.
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| TDM Analytical Methods: HPLC. In a multisolvent system, what type of eluate is used? [isocratic or gradient] | Gradient
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| TDM Analytical Methods: HPLC. In a single solvent system, what type of eluate is used? [isocratic or gradient] | Isocratic
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| TDM Analytical Methods: HPLC. What is the purpose of the detector? | The detector recognizes the drug and tells the computer data system.
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| 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.
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| 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.
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