Chem 5

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What is the purpose of therapeutic drug monitoring?

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Chemistry

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1

What is the purpose of therapeutic drug monitoring?

-Ensure drug dosage is in a range that produces maximal therapeutic benefits \n -Identify when the drug is outside the therapeutic range

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2

Why is TDM mostly unnecessary?

For most drug therapies, safe and effective dosages have been established

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3

What is the dose providing therapeutic benefits as statistically derived from observations in a healthy population?

Standard dosage

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4

What fraction of the drug interacts with the site of action and cause a biologic response?

Free or unbound

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5

What is the biochemical pathway responsible for a large portion of drug metabolism?

Hepatic Mixed-Function Oxidase (MFO) system

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6

How are drugs eliminated?

-Hepatic metabolism \n -Renal filtration \n -Combination of the two

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7

What are the terms for lowest and highest levels of drug concentration?

Lowest: trough \n Highest: peak

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8

Approximately how many doses are required before a steady-state oscillation?

5-7

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9

What is the term for patients benefitting from therapeutic and desired effects of drugs?

Responders

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10

What is the term for patients not benefitting from therapeutic and desired effects of drugs?

Non-responders

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11

What is the gene group family that affects drug metabolism and the family of enzymes within the MFO system?

Cytochrome P-450

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12

List 4 cardioactive drugs.

-Digoxin

-Quinidine

-Procainamide

-Disopyramide

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13

What is a cardiac glycoside used in the treatment of congestive heart failure?

Digoxin

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14

What does digoxin inhibit?

Membrane Na-K-ATPase

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15

What is a natural occurring drug used to treat various cardiac arrythmias?

Quinidine

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16

What is a group of chemically related antibiotics used to treat gram negative bacterial infections that are resistant to other less toxic antibiotics?

Aminoglycosides

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17

What are the most common aminoglycosides?

Amikacin, gentamicin, tobramycin, kanamycin

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18

What are the most serious effects of aminoglycosides?

Ototoxic & nephrotoxic

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19

What is a bactericidal antibiotic effective against both aerobic and anaerobic gram positive rods and gram positive cocci? Effectively treats MRSA.

Teicoplanin

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20

What is a glycopeptide antibiotic effective against gram positive cocci and bacilli infections?

Vancomycin

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21

List 6 antibiotics.

-Gentamicin \n -Tobramycin \n -Amikacin \n -Kanamycin \n -Teicoplanin \n -Vancomycin

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22

What are some side effects of vancomycin?

Red man syndrome, nephrotoxicity, ototoxicity

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23

List 16 antiepileptic drugs.

-Phenobarbital

-Primidone

-Phenytoin

-Fosphenytoin

-Valproic acid

-Carbamazepine

-Valproate

-Ethosuximide

-Felbamate

-Gabapentin

-Lamotrigine

-Levetracetam

-Oxycarbazepine

-Tiagabine

-Topriamate

-Zonisamide

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24

What two antiepileptic drugs are slow-acting barbiturate's that effectively control severe seizures?

Phenobarbital & Primidone

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25

What is the inactive form of phenobarbital?

Primidone

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26

What drug is most commonly used to treat seizure disorders?

Phenytoin

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27

What drug is used as monotherapy for treatment of petit mal and absence seizures?

Valproic acid

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28

List 4 psychoactive drugs.

-Lithium \n -Tricyclic antidepressants \n -Clozapine \n -Olanzapine

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29

What psychoactive drug is used to treat manic depression?

Lithium

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30

What class of drugs is used to treat depression, insomnia, extreme apathy, and loss of libido?

Tricyclic antidepressants

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31

What is an atypical antipsychotic used to treat otherwise treatment-refractory schizophrenia?

Clozapine

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32

List 4 immunosuppressive drugs.

-Cyclosporine \n -Tacrolimus \n -Sirolimus \n -Mycophenolic acid

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33

What drug's primary clinical use is the suppression of host-versus-graft rejection of heterotopic transplanted organs?

Cyclosporine

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34

What drug is 100x more potent than cyclosporine?

Tacrolimus

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35

What is an antifungal agent with immunosuppressive activity and FDA approved for patients receiving kidney transplants?

Sirolimus

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36

What drug is a lymphocyte proliferation inhibitor and most commonly used as supplemental therapy with cyclosporine and tacrolimus in renal transplant patients?

Mycophenolic acid

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37

What bronchodilator is used in the treatment of respiratory disorders, such as asthma and stable chronic obstructive pulmonary disease?

Theophylline

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38

List 1 antineoplastic drug.

Methotrexate

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39

List 1 bronchodilator.

Theophylline

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40

What is the study of adverse effects of xenobiotics in biological organisms?

Toxicology

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41

What are the 3 major disciplines within toxicology?

-Mechanistic: cellular & biochemical effects of toxins; dose-response relationship \n -Descriptive: uses results of animal experiments to predict what level of exposure will cause harm in humans; risk assessment \n -Regulatory: uses data from mechanistic & descriptive to establish standards regarding acceptable levels of exposure; oversees human safety issues associated with therapeutic drugs, cosmetics, food additives

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42

What are exogenous agents that may have adverse effects on a living organism; often used to describe environmental chemicals or drug exposures?

Xenobiotics

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43

What have an adverse effect on biological systems; terminology used when describing animal, plant, mineral, or gas?

Poison

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44

What are substances that are biologically synthesized in living cells or microorganisms?

Toxins

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45

What are 4 examples of poisoning?

-Suicide attempt \n -Accidental exposure \n -Homicide \n -Occupational exposure

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46

What are the most common routes of exposure to toxins, poisons, or xenobiotics?

Ingestion, inhalation, or transdermal absorption

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47

What factors affect oral drug absorption?

-pH \n -Rate of dissolution \n -Gastric motility \n -Resistance to degradation in GI tract

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48

The body's response to a drug is dependent mostly upon?

Dosage

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49

What is a single, short-term exposure to a substance?

Acute toxicity

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50

What is a repeated, frequent exposure for extended periods?

Chronic toxicity

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51

What are some general toxic effects?

Disorientation, confusion, euphoria, unconsciousness, paralysis, death

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52

What are some toxic effects from ethanol?

Diminution of judgment & motor performance

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53

What is the established statutory limit of blood alcohol concentration when operating a vehicle?

80 mg/dL or 0.08%

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54

What is a common solvent ingested accidentally as a component of many commercial products or as a contaminant of homemade liquors?

Methanol

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55

What can ingestion of methanol cause?

Severe acidosis, death, blindness

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56

What can cause severe acute-phase ethanol-like symptoms?

Isopropanol

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57

What is a common component of hydraulic fluid and antifreeze?

Ethylene glycol

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58

What is an important specimen requirement for measuring alcohols?

Specimen needs to be capped to avoid evaporation

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59

What enzyme do we NOT measure metabolizes alcohol?

ADH

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60

What is a colorless, odorless, tasteless gas that rapidly absorbs into blood from inspired air?

Carbon monoxide

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61

What is found in industrial processes, insecticides, rodenticides; produced by burning of some plastics; common suicide agent?

Cyanide

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62

What exists in both naturally occurring and manmade substances; exposure occurs in various settings, groundwater being the primary source?

Arsenic

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63

What's main use is being in electroplating and galvanizing though it is also commonly encountered during the mining and processing of other metals?

Cadmium

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64

What was a common constituent of household paints before 1972 and is still found in commercial paints and art supplies?

Lead

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65

How is lead analyzed?

AAS & ICP-MS

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66

Consumption of contaminated foods is the major source of exposure to what in the general population?

Mercury

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67

Which metal is important for healing and immune function?

Zinc

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68

Which 2 enzymes are measured due to pesticide exposure?

Acetylcholinesterase & butyrlcholinesterase

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69

What is a commonly used analgesic drug and is associated with severe hepatotoxicity?

Acetaminophen

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70

How is acetaminophen quantified?

Immunoassay or HPLC (reference)

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71

What are the toxic effects of cocaine?

Hypertension, arrhythmia, seizure, myocardial infarction

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72

How is cocaine analyzed?

Immunoassay and GC w/MS (confirmation)

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73

List the drugs of abuse.

-Methamphetamines \n -Opioids \n -Fentanyl \n -Cannabinoids \n -Cocaine \n -Phencyclidine (PCP) \n -Barbiturates \n -Benzodiazepines \n -Anabolic steroids

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74

Which addictive drugs can be used for weight loss?

Amphetamines

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75

What are the toxic effects of anabolic steroids?

Males: testicular atrophy, sterility, impotence \n Females: masculine traits, breast reduction, sterility

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76

Cholesterol is the base substance for synthesizing which type of drugs?

Anabolic steroids

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77

All toxicology measurements in a laboratory must have what?

Screen & confirmatory test

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78

State the steps of cancer staging and progression.

Stage 1: Localized primary tumor \n Stage 2: Invasion of primary tumor through epithelium and into blood vessels \n Stage 3: Migration of tumor into regional lymph nodes \n Stage 4: Metastasis and invasion of tumor to distant tissues

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79

What is the 2nd leading cause of death in developed countries?

Cancer

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80

What makes an ideal tumor marker?

Tumor specific, absent in healthy individuals, and readily detectable in body fluids

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81

List the types of tumor markers.

-Enzymes \n -Serum proteins \n -Receptors \n -Oncofetal antigens

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82

CK-BB can be used as a tumor marker for?

Prostate & breast

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83

Tumor markers are not normally used to screen populations, what is the tumor marker that is the exception to this rule?

PSA

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84

When does annual screening for PSA for men begin?

50 years old or younger if at high risk

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85

What is the normal range for PSA?

<4 ng/mL

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86

What factors contribute to interpreting tumor marker immunoassays?

-Linearity \n -Hook effect \n -Heterophile antibodies

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87

What is determined by analyzing specimens spanning the reportable range?

Linearity

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88

What is the span of analyte concentrations over which a linear relationship exists between the analyte and signal?

Linear range

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89

What is when analyte concentrations exceed the analytical range excessively, there is potential for antigen excess?

Hook effect

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90

What are circulating antibodies against animal immunoglobulins that can cause significant interference in immunoassays?

Heterophile antibodies

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91

What is used to detect neuroblastoma, pheochromocytoma, and carcinoid tumors?

HPLC

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92

What are serotonin-secreting tumors that arise from the small intestine, appendix, or rectum?

Carcinoid tumors

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93

What tumor marker is often elevated in patients with hepatocellular carcinoma and germ cell tumors?

AFP

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94

What tumor marker is useful in detecting ovarian tumors at an early stage?

CA-125

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95

What is the most widely used tumor marker for colorectal cancer; also elevated in lung, breast, and GI tumors?

CEA

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96

What tumor marker is used for diagnosis of testicular cancer, prognosis of ovarian cancer, and the most useful marker for gestational trophoblastic diseases?

HCG

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97

List the ABCDE's in assessing nutrition.

A: anthropometric or body composition measurements

B: biochemical analyses

C: clinical examination

D: dietary analysis

E: environmental assessment

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98

List 4 nutritional macronutrients.

-Thyroxine-binding prealbumin \n -Albumin \n -Transferrin \n -Nitrogen balance

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99

What macronutrient has a long half life and is not a good indicator of short term malnutrition?

Albumin

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100

What is an early indicator of iron deficiency or protein depletion?

Transferrin

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