TDM / Toxicology
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| Define "therapeutic window" | The range between the minimum effective concentration and the maximum toxic concentration
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| Define MEC | minimum effective concentration: lowest dosage given to receive results
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| Define MTC | Maximum toxic concentration: The highest dosage possible to give a patient before it causes toxicity
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| Explain the LADME system | The system of changes in drug concentration over time.
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| What is the "L" in LADME system for? | Liberation - Active ingredients are released
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| What is the "A" in LADME system for? | Absorption - drug molecule is taken up into the circulation (or plasma)
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| What is the "D" in LADME system for? | Distribution - distributing active contents to blood and tissues
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| What is the "M" in LADME system for? | Metabolism - biotransformation. the conversion of the parent form into a metabolite
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| What is the "E" in LADME system for? | Elimination - excreted from the body
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| Describe high performance liquid chromatography | The sample is injected into a column full of beads that have reaction sites. The liquid in the column carries the sample through. It is released at different times and this is measured.
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| Felbamate | partial seizures
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| Gabapentin | drug-resistant partial seizures
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| Lamotrigine | binds to GABA receptors
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| Levetiracetam | partial on-set seizures
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| Oxcarbazepine | partial seizures
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| Phenobarbital | Seizures (NOT petite mal)
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| Phenytoin | Seizures
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| Tiagabine | partial seizures
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| Topiramate | Broad Spectrum anti-epileptic
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| Valproic acid | Absence seizures
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| Digoxin | Cardiac contractions
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| Lidocaine | PVC and atrial fibrillation after AMI
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| Quinidine | Tachycardia
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| Procainamide | Tachycardia
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| Amiodarone | Supraventricular and ventricular tachyarrhythmias
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| Theophyllines | Bronchodilators. Relax smooth muscle to relieve or prevent asthma
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| Aminoglycosides | Antibiotics. Prevent protein synthesis of the bacteria
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| Lithium | Anti-psychotic drugs. Manic depressive illnesses
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| Imiprimine | Antidepressants. Endogenous depression
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| Methotrexate | Antimetabolite drugs. Used for ALL in children. Breast, Testicular, Tongue cancers.
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| Cyclosporine | Suppresses host vs. graft rejection
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| Mycophenolate mofetil (Cellcept) | Inhibits IMPDH
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| 5 parameters determined on patients with toxic reactions: | - amount of reagent introduced
- route of administration
- number of doses
- time period of administration
- lethal dosage
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| list 5 ways a toxic agent can affect the body | - interference of enzyme systems
- blockage of Hb/O2 transport
interference of general cell function
- interference of DNA/RNA synth.
- hypersensitivity
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| Example of a toxin that causes irreversible enzyme inhibition | insecticides
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| Example of a toxin that causes blockage of Hb/O2 transport | carbon monoxide
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| Example of a toxin that causes interference with general function of the cell | anesthetics
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| Example of a toxin that causes inhibition of oxygen transfer | cyanide
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| Example of a toxin that causes interference with DNA and RNA synthesis | mustard gas
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| What are the 7 most commonly ordered drug tests? | Volatiles (alcohols)
Barbiturates
Hypnotics
Salicylates
Opiates
Amphetamines
Phenytoin (dialantin)
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| Barbituates (Phenobarbital, pentobarbital, secobarbital) | Depressants
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| Benzodiazepine (valium, librium) | Depressants
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| Lowers body temperature. Anti-inflammitory. Compound that reduces pain without causing loss of consciousness | Analgesics
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| Narcotics, Salicylates, and Acetominophen | Analgesics
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| What can cause an accidental poisoning in children? | Salicylates
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| Imipramine (trofranil) | Tricyclics
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| LSD, Mescaline | Hallucinogens
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| Amphetamine and Cocaine | Stimulants
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| Very potent toxin. Affects the CNS. Widely abused. No longer used therapeutically | Stimulants
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| Minimal medicinal use for glaucoma and nausea | Cannabis
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| Serum level decreases in 1 day by 10%. Half life is 1 day, 3-5 days in chronic users | THC
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| There are very few _____ on the market for toxins | Antidotes
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| Treatment methods to remove toxins from the body: | - Gastric levage.
- Skin decontamination
- Charcoal to absorb
- Increase urine flow
- Vomiting
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| What is the most common of the poisonous gases | Carbon monoxide
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| Which toxic gas is present in fossil fuels and organic fuels? | Carbon monoxide
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| What specimen is used for carbon monoxide testing? | Whole blood samples. Determine the % saturation of the hemoglobin by CO
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| 10% CO | shortness of breath with vigorous exercise
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| 30% CO | irritated. fatigued. headaches.
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| 60-70% CO | unconscious. respiratory failure
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| 80% CO | rapidly fatal
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| Colorless gas with the odor of almond | Cyanide
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| Rapidly bound to the heme of hemoglobin causing hypoxia | Cyanide
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| How can levels of Cyanide be measured? | ISE and isotopic GC-MS
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| What is cyanide attracted to? | Iron in the ferrous state
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| Highest blood level of all toxins studied in class: | Alcohols
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| How is a specimen collected for alcohol poisoning? | Venapuncture. Do NOT use alcohol wipe to clean
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| What are the two main alcohols | Ethanol and Methanol
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| Which of the two alcohols is most common? | Ethanol
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| What is the metabolite of ethanol? | Alcohol Dehydrogenase
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| Which alcohol is a contaminant in moonshine? | Methanol
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| How do you treat someone with a methanol toxicity? | Give ethanol to saturate the heme molecules
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| What binds with keratin and will combine with proteins to precipitate the proteins? | Arsenic
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| What is the favorite homicidal poison? | Arsenic
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| What specimen should be used to determine acute arsenic poisoning? | urine samples, testing for metabolites
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| What specimen should be used to determine chronic arsenic poisoning? | hair and nail samples
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| What is one of the most serious metallic poisons? | Lead
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| How are adults exposed to lead? | Industry - fumes.
Soil
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| How are children exposed to lead? | Ingestion
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| What does lead inhibit? | heme production.
increase in ALA
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| In what settings are drug tests most often performed? | ERs, Sports medicine, Insurance Companies, driving fatality investigations, Military, Workplace
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| How is a specimen collected for a drug test? | Very specifically and properly to avoid a lawsuit
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| Chain of custody of drug test specimen: | - monitored
- written ID
- documentation of transport, storage, and testing
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| Used to separate a negative from a positive | Drug Screen
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| Performed on all positive screens | Drug Confirmatory
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| Accurate | Close to the right answer
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| Precise | Able to reproduce same result
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| Thin Layer Chromatography | Sample preparation is mixed with solvent. Drug goes into solvent to be isolated. Chromatography. Visualization. Interpretation.
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| What specimens can be used for TLC? | Urine, Serum, or Gastric
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| What is the weakness of TLC? | less sensitive and precise. no permanent records.
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| Immunoassay | Different "labels" are used to monitor the presence of drug
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| What are the strengths of EIA | Very specific. Sensitive and accurate. Precision may vary.
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| How does mass spectrometry identify drugs? | Fragmentation of drug by a bombardment of electrons. Shatters molecule in the same pattern every time.
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| What is the strength of GC-MS? | Accurate, precise, sensitive, and specific
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| What are the weaknesses of GC-MS? | Expensive. Labor intensive. Requires special training. Data interpretation is hard. Time consuming. Large analyzer.
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| What does a "negative" drug screen mean? | The levels of the drug may not be in large enough amounts to show up on test
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| What does a "positive" drug screen mean? | Drug or metabolite may be present. Follow up with a confirmation test.
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| What does a "positive" drug confirmation test mean? | The person has recently used drugs. Does NOT show intoxication or impairment. Can not determine if patient is a chronic abuser.
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