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