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Toxicolology Clin Chem
n/a
408
Chemistry
Undergraduate 4
03/29/2010

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Term
What is post-marketing surveillance?
Definition
1.) Post-marketing surveillance occurs ONLY in the US…it is the careful review of meds currently on the market to detect any harmful complications that may have not been known at the time that the drug became available
Term
2.) What is unique about Toxicology relative to Chemistry or Hematology?
Definition
2.) In toxicology we are usually measuring things that shouldn’t be there
Term
3.) Why is organic chemistry key to an understanding of toxicology?
Definition
3.) An understanding of organic chemistry is key to an understanding of toxicology because:
• Majority of drugs are small compounds
• Knowledge about structure may help understand therapeutic mechanism
• Understand drug metabolism
• Develop separation schemes
• Determine best analytical approach for monitoring drug
Term
4.) In general terms, what is a chemical bond?
Definition
4.) A chemical bond is the sharing of electrons between atoms in the outer orbitals
Term
What is the difference between an ionic and covalent bond?
Definition
5.) In an ionic bond, one atom dominates the electrons being shared, and in a covalent bond both atoms share the electrons equally
Term
6.) Arrange the following compounds in order of DECREASING polarity: H20, CH3CHOHCH3, CH3COCH3, CH3CO2H, CH3CH=CHCH3
Definition
6.) Most polar least polar: CH3CH=CHCH3, CH3COCH3, CH3CHOHCH3, CH3CO2H, H2O *****look in O chem. Book for RULES!!!!
Term
1.) What is Therapeutic Drug Monitoring? What is it’s “goal”?
Definition
1.) TDM refers to all activities used to monitor or assess a patient’s drug status for clinical purposes. Primary goal is to ensure sufficient quantity of drug ispresent to maximize the benefit of the patient. Thus, the overall goal for TDM is to provide physicians with information (data) for the purpose of maintaining the drug concentration within defined therapeutic limits.
Term
2.) What is the ADME scheme of pharmacokinetics? Define each term that ADME stands for
Definition
2.) The ADME scheme: Pharmacokinetics is often divided into several areas including, but not limited to, the extent and rate of absorption, distribution, metabolism, and excretion. Absorption is the process of a substance entering the body (many ways…skin patch, inhalation, etc). Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism is the irreversible transformation of substances into metabolites. Excretion is the elimination of the substances from the body
Term
3.) Define: pharmakodynamics
Definition
3.) Pharmakodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect
Term
4.) How can pharmakokintetics/pharmacodynamics be summarized?
Definition
4.) Pharmacodynamics is the study of what a drug does to the body, and pharmacokinetics is the study of what the body does to a drug
Term
5.) What is the major assumption we operate under by testing a blood sample for toxicological studies?
Definition
5.) The major assumption is that what is going on in that blood sample is proportional to what is going on at the anticipated site of action
Term
6.) What are 7 factors that influence TDM?
Definition
6.) Seven factors that influence TDM include:
• Patient’s Clinical Status
• Specific disease states
• Age
• Single vs. multiple does
• Time since last dose
• Intended effect (Ex: amt of aspirin for arthritis or headache)
• Other drugs/food
Term
7.) What are 5 pieces of critical information necessary for interpretation of TDM?
Definition
7.) Dosing method, dose of drug, time of dose, time of collection, drug concentration
Term
8.) What are 7 prerequisites for TDM
Definition
8.) Prerequisites for TDM:
• Analytical method-sensitive, specific, timely
• measures active drug and/or metabolites
• receptor site has minimal intolerance
• Serum concentrations reflect changes at rxn. site
• good correlation between concentration and response
• well defined therapeutic range
• proper precautions when interpreting results
Term
9.) Fill in blanks: a drug must be ____ to pass from one compartment to the next…as long as its bound to ____ it will stay in the blood
Definition
9.) A drug must be “free” to pass from one compartment to the next…as long as it’s bound to protein it will stay in the blood
Term
10.) Things that aren’t metabolized generally end up in the _____. Water-soluble drugs go to ____ and lipid-soluble things go to the ______
Definition
10.) Things that aren’t metabolized generally end up in the adipose tissue…water-soluble things go into the kidneys, and lipid soluble things go to the liver
Term
11.) Unlike testing in other areas of the lab, if we don’t find the drug we are looking for in the patient sample, we then know what?
Definition
11.) If we don’t find the drug in the patient sample, we know either the patient didn’t take the dug, we drew the wrong patient, or we mixed up the patients in the lab
Term
12.) It usually takes ___-____ half lives to get to a steady-state in testing a patient
Definition
12.) 5-7 half-lives
Term
13.) At what time do we want to measure the patient for drug levels?
Definition
13.) We want to measure the patient in the “trough” concentration of drug in their blood…it would take many samples/would be quite difficult to determine a peak sample
Term
14.) What does a trough level test for a drug reflect and what is it’s main advantage?
Definition
14.) A trough level is the drug concentration monitored at dosing intervals…usually once daily…reflects the patient’s ability to properly eliminate the parent drug or metabolite(s)…an advantage of using it is that the timing for sample collection is straightforward…prior to the next dose
Term
15.) What does a peak level test for a drug reflect and what are it’s disadvantages?
Definition
15.) A peak level of a drug provides information concerning absorption….disadvantages for using it include timing for sample collection, the fact that it might require multiple samples, and that the patient must be available
Term
16.) What 3 words describe the future for TDM
Definition
16.) The future for TDM is pharmacogenetics, pharmacogenomics, and personalized medicine
Term
1.) What is the purpose of putting an acetyl group onto salicylic acid? ( Salicylic acid was used since the time of Hippocrates…today aspirin is acetylsalicylic acid)
Definition
By putting acetate on salicylic acid the stomach is protected from heavy acids and damage
Term
2.) What are analgesics
Definition
2.) Analgesics are drugs that are effective against low to moderate pain, specifically pain associated with inflammation or chronic post-operative pain. Aspirin is a good example
Term
3.) What are antipyretic drugs?
Definition
3.) Antipyretic drugs are drugs that reduce the body temperature for individuals in a febrile state
Term
4.) What are anti-inflammatory drugs used for?
Definition
4.) Anti-inflammatory drugs are drugs used for muscle-skeletal disorders, such as rheumatoid arthritis
Term
5.) How do most analgesics work?
Definition
5.) Most analgesics work by the inhibition of prostaglandin synthesis and are NOT a cure….just a treatment
Term
6.) What are prostaglandins?
Definition
6.) Prostaglandins are a series of biological compounds derived from arachadonic (C-20) acid that have a multiplicity of responses. If prostaglandins are injected subcutaneously or intravenously there is usually immediate pain, fever, and edema
Term
7.) What are 4 side effects of chronic use of analgesics that are related to prostaglandins
Definition
7.) Side effects: prolonged bleeding times, inhibition of platelet aggregation, GI irritation/ulceration, and decreased renal function
Term
8.) Why is there a concern with aspirin use in children with viral infections?
Definition
8.) There appears to be an association between aspirin use and Reye’s syndrome…therefore aspirin is contraindicated in children with viruses
Term
9.) Why do people with an increased risk for cerebrovascular or cardiovascular disease take aspirin regularly?
Definition
9.) Aspirin inhibits platelet aggregation that may be promoting or intensifying the likelihood of cerebrovascular or cardiovascular disease
Term
10.) Why don’t we give aspirin to pregnant women?
Definition
10.) Inhibiting prostaglandins can induce labor in pregnant women
Term
11.) What are 4 overdose/side effects of aspirin use?
Definition
11.) Overdose/Side effects of Aspirin use:
• Tinnitus: ringing in the ears that can be severe enough to cause a loss of hearing…usually reverses within 24 hours after lowering the dose
• Stimulates the Central respiratory center and causes hyperventilation and respiratory alkalosis
• Enhances anaerobic glycolysis but inhibits the Krebs cycle leading to increased organic acids and metabolic acidosis
• Because of 2 and 3 patients might present with combined respiratory alkalosis and metabolic acidosis
Term
12.) Why does the half life of aspirin increase at high doses?
Definition
12.) The half life increases at high doeses because the metabolic pathways for eliminating salicylic acid is saturable
Term
13.) T or F: Salicylic acid crosses the placenta
Definition
13.) True
Term
14.) Describe acetaminophen (Tylenol)’s effectiveness as an analgesic, antipyretic, and anti-inflammatory agent
Definition
14.) Acetominohen is an effective analglesic and antipyretic but is a WEAK anti-inflammatory agent
Term
15.) What process metabolizes acetaminophen?
Definition
15.) Tyelenol is metabolized by nicrosomal enzymes
Term
16.) Describe the symptoms of a tyelenol overdose
Definition
16.) Toxicity: Initial signs are fairly mild…nausea, vomiting, abdominal discomfort…all of these are not reflective of the pending hepatic necrosis that can occur in 3-5 days after ingestion
Term
17.) What is the treatment for a tyelenol overdose?
Definition
17.) The treatment for a Tyelenol overdose is N-acetylcysteine (NAC), and this must be administered within the first 8 hours of and OD
Term
18.) How does Ibprofen achieve it’s effect?
Definition
18.) Ibuprofen achieves it’s analglesic effect through the inhibition of prostaglandin synthesis ( equivalent to aspirin)
Term
19.) For which patients is ibuprofen not recommended?
Definition
19.) For pregnant or breast-feeding women
Term
20.) Describe the linearity of the amount of ibuprofen administered and the integrated area under the serum drug concentration vs. time curve for adults and kids age 2-11
Definition
With single, oral, solid doses up to 800 mg, in adults, a linear relationship exists between the amount of drug administered and the integrated area under the serum drug concentration vs. time curve. Above 800 mg, however, the area under the curve increase is less than proportional to the increase indose. There is no evidence of age-dependent kinetics in patients 2-11 years old. With single doses of ibuprofen children’s suspension ranging up to 10 mg/kg, a dose/response relationship exists between the amount of drug administered to febrile children and the serum concentration vs. time curve. There is also a correlation between the reduction of fever and drug concentration over time
Term
21.) Why were the COX-2 Inhibitors so popular and why were they pulled off the market?
Definition
21.) The COX-2 inhibitors were used for arthritic pain and were supposed to prevent GI side effects…they were all pulled off the market because people started to have heart attacks and strokes because of them
Term
22.) What are 4 examples of COX-2 inhibitors?
Definition
22.) Example of COX-2 inhibitors: Vioxx, Celebrex, Bextra, and Mobic
Term
23.) What are opioid analglesic drugs and how do they work?
Definition
23.) Opioid analglesic drugs are drugs that have opioid or morphine-like properties….interact with the endorphin receptors in the CNS
Term
24.) What are 4 synthetic agents with morphine-like properties
Definition
24.) Synthetic agents with morphine-like properties include: meperidine, methadone, propoxyphene, and fentanyl.
Term
25.) Why are opioid analglesics used over other analglesics?
Definition
25.) Opioid analglesics are useful for controlling dull pain as opposed to sharp pain. They are usually very specific and don’t effect other sensory entities such as vision, touch, hearing, etc.
Term
26.) What are some side effects of opioid use/overuse
Definition
26.) Side effects: cause a change in mood and mental clouding=poor decisions, cause constriction of the pupils (pinpoint pupils are pathogenic), excessive dose will depress respiration, therefore the first act for an overdose is to establish the airway and ventilate
Term
27.) What drug do you administer when someone has ODed on and opioid analglesic?
Definition
27.) An antagonist, naloxone, can be administered in the case of an overdose of an opioid analglesic, and reverses the respiratory depression
Term
28.) In what 3 ways are opioid analglesics absorbed by the body?
Definition
28.) Opioid analglesics are rapidly absorbed through the GI tract, nasal mucosa, and lungs….heroin=snuff, opium=smoked
Term
1.) What are digitalis drugs?
Definition
1.) Digitalis drugs: increase to force (contractibility) of the myocardium, resulting in increased cardiac output
Term
2.) What patients need digitalis drugs?
Definition
2.) Digitalis drugs improve circulation in congestive heart failure patients
Term
3.) What is digoxin?
Definition
3.) Digoxin is the principal digitalis used today
Term
4.) How do we begin dosing patients on digoxin?
Definition
4.) The issue of digoxin usually requires a loading dose
Term
5.) ___% of digoxin is found bound to proteins
Definition
5.) 25% of digoxin is found bound to the kidneys
Term
6.) How is digoxin eliminated?
Definition
6.) Digoxin is eliminated through the kidneys
Term
7.) What are some symptoms of digoxin toxicity?
Definition
7.) Digoxin toxicity: vomiting, confused vision, slow pulse, convulsions, death
Term
8.) Describe the prevalence of digoxin toxicity on patients taking this drugs
Definition
8.) Almost all patients on digoxin experience some form of toxicity…but 25% of all patients show some sign of toxicity at therapeutic concentrations of 0.5-2.0 ng/mL
Term
9.) What laboratory technique do we use to measure digoxin?
Definition
9.) Immunoassays are required to measure the drug
Term
10.) What is the antidote for digoxin? One dose of this binds how much digoxin?
Definition
10.) The antidote for digoxin: Digibind…a goat Ab that must be injected to be effective I doseof digibind binds ~1mg digoxin
Term
11.) What is a BNP test a good indicator of?
Definition
11.) BNP is a good indicator of ejection from vevntricles
Term
12.) Individual cardiac cells undergo depolarization and repolarization to form cardiac action potentials about ___times per minute
Definition
12.) About 60 times per minute
Term
13.) Describe hoe the activity of ion channels translates into heartbeats
Definition
13.) The activity of ion channels on the surface of individual cells controls the shape and duration of each action. Therefore, each heartbeat is the highly integrated electrophysical behavior of multiple ion channels on the surface of multiple cardiac cells
Term
14.) What are the 4 major classes of antiarrhythmic drugs?
Definition
14.) Class 1: Na+ channel block
Class 2: β-blockade
Class 3: K+ channel block
Class 4 Ca+ channel block
Term
15.) How do we define tachycardia and bradycardia?
Definition
15.) Tachycardia: anything above 100 beats per min. Bradycardia: anything below 50 beats per min.
Term
16.) We need sufficient amount of what 3 ions for normal heart contraction
Definition
16.) Sufficient amounts of potassium, calcium, and magnesium
Term
17.) What is qunidine and what is it used to treat?
Definition
17.) Quinidine is a dextro stereoisomer of quinine (an old malaria treatment) that is isolated from the bark of the cinchona plant…it is used to treat “rebellious palpitations”
Term
18.) How is quinidine excreted?
Definition
18.) The hydroxylated metabolites of quinidine are excreted through the kidneys
Term
19.) What is a common metabolite of quinidine?
Definition
19.) A common metabolite of quinidine is 3-hydroxyquinidine…this is nearly as potent as quinidine
Term
20.) What are some adverse side effects of quinidine use?
Definition
20.) Common adverse effects of quinidine use: 30-50% of patients have diarrhea, nausea, vomiting, “Cinchonism syndrome”( headaches, dizziness, hearing loss, ringing in ears), hypersensitivity reactions (rashes, fever, edema, hepatitis), reversible thrombocytopenia
Term
21.) How can hypotension effect digoxin use?
Definition
21.) Hypotension (largely due to alpha-adrenergic blocking activities) can elevate serum digoxin concentrations resulting in digitalis toxicity
Term
22.) What is procainamide a derivative of?
Definition
22.) Procainamide is a derivative of procaine
Term
23.) ___% of Procainamide is bound to protein
Definition
23.) 20% of procainamide is bound to protein
Term
24.) The major metabolite of procainamide is ___
Definition
24.) The major metabolite of procainaimide is NAPA, N-acetylprocainamide
Term
25.) What are some signs of procainamide toxicity
Definition
25.) Toxicity with procainiamide involves symptoms of bradycaridia, prolonged QRS interval, arrhythmias,
Term
26.) What are some side effects seen with procainiamide use at normal levels?
Definition
26.) Adverse effects of procainamide use at normal levels include hypotension and nausea, and 20-30% of patients develop drug-induced lupus
Term
27.) What is lidocaine used for?
Definition
27.) Lidocaine is used for premature ventricular contractions (contraction of the ventricles before fully filled with blood) and ventricular arrhythmias; for this use it is primarily used as an emergency treatment…It is also used generally as an anesthetic (used in spraying ppl’s throats before putting tubes in)
Term
28.) How is lidocaine uniquely metabolized?
Definition
28.) The oral dose of lidocaine is completely metabolized on the first-pass
Term
29.) How is lidocaine administered
Definition
29.) Lidocaine is administered through an intravenous or intramuscular injection **MUST be injected because we metabolize lidocaine very quickly on the first pass!
Term
30.) What are the two major metabolites of lidocaine?
Definition
30.) Lidocaine metabolites: monoethylglycinexylidide (MEGX)…this has a fair amt of activity effecting the heart, and Glycinexylidide (GX)
Term
31.) How does mexilitene differ from lidocaine?
Definition
31.) Mextilitene is very similar structurally to lidocaine…the difference is that it is NOT metabolized in the first pass like lidocaine is
Term
32.) How is mexilitene metabolized?
Definition
32.) Mexilitene undergoes hepatic metabolism
Term
33.) What are some adverse effects of mexilitene usage?
Definition
33.) Some adverse effects of mexilitene metabolism include tremor and nausea
Term
34.) How does tocainamide differ from lidocaine?
Definition
34.) Tocainamide looks like lidocaine, but is also not metabolized on the first pass
Term
35.) How is tocainamide eliminated?
Definition
35.) Tocainamide is eliminated by renal excretion
Term
36.) What are some adverse effects of tocainamide useage?
Definition
36.) Tocainiamide can cause fatal bone marrow aplasia and pulmonary fibrosis, also a tremor and neausea
Term
37.) Why is disopyramide used?
Definition
37.) Disopyramide was first used in the early 1980’s to maintain sinus rhythm (rhythm of the heart)
Term
38.) What are some adverse effects of disopyramide useage?
Definition
38.) Adverse effects of dispyramide useage: precipitation of glaucoma/ constipation
Term
39.) How does dispyramide bind to protein?
Definition
39.) Disopyramide binds to protein in a concentration-dependent manner…once bound to protein, can have a little more and REALLY increase effectivity
Term
40.) How is dispyramide eliminated?
Definition
40.) Elimination is thru both hepatic and renal means
Term
41.) What is Flecanide and what is it used for?
Definition
41.) Flecanide is a newer cardiac drug used to treat supraventricular arrhythmias
Term
42.) What problems might be associated with the use of Flecanide in patients recovering from an AMI?
Definition
42.) In one study, there was increased mortality noted when flecanise was used with patients recovering from an AMI….but even with this it is still used
Term
43.) What drug is similar to flecanide?
Definition
43.) Ecainide…but this drug is no longer used
Term
44.) How do Verapamil and Diltalizam work?
Definition
44.) Verapimil and Ditalizam are Calcium channel blockers
Term
45.) What is a major adverse effect of the use of Verapamil and Ditalizam?
Definition
45.) Hypotension is a major adverse effect for both drugs
Term
46.) What is unique about the metabolism of Verapamil and Ditalizam?
Definition
46.) They both have extensive first-pass hepatic metabolism…and because of this are not usually monitored….follow response instead
47.)
Term
47.) What is amiodarone used for?
Definition
47.) Amiodarone is used as an antiarrhythmic agent…is used in patients with valve replacements or post-MI
Term
48.) Describe the side effects of Amiodarone treatment
Definition
48.) Although Amiodarone is highly effective in treating many arrhythmias, its large number of adverse effects limits its clinical use…because iodine is attached, messes up thyroid function…more than 75% of patients receiving drug have adverse effects which increase after a year of treatment; some toxicities result in death: pulmonary toxicity and fibrosis which can be irreversible,constipation in 20% of patients, hepatic dysfunction…can be irreversible (DO NOT take with Tyelenol!!!), asymptomatic corneal deposits occur in all patients, CNS effects (ataxia, dizziness, depression, nightmares, hallucinations), hypothyroidism or hyperthyroidism, cutaneous photosensitivity, blue/grey discoloration of skin, peripheral neuropathy, substansial increase in LDL-cholesterol concentrations, enhances the effect of warfarin and increases the serum concentrations of digoxin, quinidine, procainamide, flecanide, theophylline, and other drugs
Term
1.) What are the 2 main mechanisms of action of anticonvulsant drugs?
Definition
1.) First: To effect pathologically altered neurons of seizure foci to prevent or reduce their excessive discharge (assumes excessive discharge is the problem) Second: Reduces the spread of the excited neurons from the seizure foci to prevent the disruption of normal neurons….in truth the mechanisms are not well understood…but the second one is more likely
Term
2.) What are anticonvulsant drugs?
Definition
2.) Anticonvulsant drugs are agents used to control or minimize epileptic seizures
Term
3.) What is epilepsy?
Definition
3.) Epilepsy is a group of CNS disorders that present with sudden and transitory episodes (seizures) of abnormal motor (convulsions), sensory, or psychic origin. Seziures almost always occur with abnormal EEC readings
Term
4.) What are febrile, primary, and secondary seizures?
Definition
4.) Febrile seizures: caused by high temperatures Primary=idiopathic=no known or identifiable cause, Secondary=symptomatic=caused by trauma, neoplasm, infection, cerebrovascular disease, etc.
Term
5.) What tissue is phenobarbitol soluble in?
Definition
5.) Phenobarbitol is soluble in lipid
Term
6.) how is the major metabolite of phenobarbital removed from the body?
Definition
6.) eliminated by renal clearance
Term
7.) What seizures are phenobarbital useful for?
Definition
7.) Phenobarbital is effective for generalized clonic-tonic, partial, or focal motor seizures
Term
8.) How is it preposed that Phenobarbital works?
Definition
8.) Phenobarb mech: The sedative nature of the drug probably inhibits the spread of the excited neurons…inhibits the GABA receptor
Term
9.) Why is Phenobarbital not really used that much anymore?
Definition
9.) Phenobarb not really used that much anymore b/c has a sedative nature
Term
10.) What is another name for phenytoin?
Definition
10.) Phenytoin=Dilantin
Term
11.) What is the major benefit of the use of phenytoin as an anticonvulsant?
Definition
11.) Phenytoin is not a sedative…therefore does not depress the CNS…this is a major benfit of its useage
Term
12.) Before phenytoin came of the market, _____ was the drug of choice
Definition
12.) Phenobarbital
Term
13.) How does the solubility of Phenytoin effect it’s absorption?
Definition
13.) Phenytoin has limited water solubility
Term
14.) ___% of Phenytoin is found bound to proteins in the body
Definition
14.) 90% of phenytoin is bound to proteins
Term
15.) For what seizure types is phanytoin useful for?
Definition
15.) Phenytoin is effective against primary or secondary generalized clonic-tonic, partial, or complex-partial seizures, and status epilepticus
Term
16.) What are 2 signs of phenytoin toxicity?
Definition
16.) Phenytoin toxicity symptoms: nystagmus (involuntary eye movement) and ataxia (lack of coordination)
Term
17.) Describe primadone absorption
Definition
17.) Primadone absorption: rapid and complete after oral dose…little protein binding
Term
18.) What are some signs of primadone toxicity?
Definition
18.) Primadone toxicity: nausea, sedation, vomiting, and dizziness
Term
19.) For what types of seizures is primadone effective?
Definition
19.) Primadone is effective for tonic-clonic and partial seizures
Term
20.) Describe the absorption of valproic acid
Definition
20.) Absorption of valproic acid is rapid from oral dose and peaks 1-4 hours
Term
21.) __-__% of valproic acid is protein bound
Definition
21.) 80%-90% of valproic acid is protein bound
Term
22.) What kind of toxicity is associated with Valproic acid?
Definition
22.) Toxicity: hepatic toxicity
Term
23.) For what type of seizure is valproic acid effective in treatimg?
Definition
23.) Absence seizures…it is often used in conjunction with other drugs too
Term
24.) What about carbamazepene is quite variable between individuals?
Definition
24.) It’s absorption is quite variable between individuals
Term
25.) Carbamazepine is ___% protein bound
Definition
25.) 80% protein bound
Term
26.) What types of seizures does carbamazepine primarily treat?
Definition
26.) Partial and clonic-tonic seizures
Term
27.) What are some signs of carbamazepine toxicity?
Definition
27.) Nausea,blurred vision, vomiting, drowsiness
Term
28.) What is another name for carbamazepine?
Definition
28.) Tegretol
Term
29.) What is another name for Clonazepam?
Definition
29.) Benzodiazepine
Term
30.) How is clonazepam absorbed?
Definition
30.) Clonazepam is well absorbed after it’s oral dose…it is a liplhilic drug
Term
31.) __% of clonazepam is bound to protein
Definition
31.) 85% is bound to preotiens
Term
32.) What amount of clonazepam exits the body unchanged
Definition
32.) Less than 1% is unchanged in the urine
Term
33.) For what types of seizures is clonazepam used?
Definition
33.) Clonazepam is used broadly for many types of seizures, except generalized clonic-tonic
Term
34.) How soon after they start the clonazepam do patients develop a tolerance?
Definition
34.) After 1-6 mo. Patients develop a tolerance and either have to raise the dose or find a different dose
Term
35.) What are signs of clonazepam toxicity
Definition
35.) Drowsiness and lethargy
Term
36.) What is Gabapentin?
Definition
36.) Gabapentin is a derivative of GABA with a lipophilic cyclohexane ring
Term
37.) What is gabapentin used for?
Definition
37.) Gabapentin is used in combination with other anticonvulsants for partial seizures…recently in really HIGH doses for chronic pain
Term
38.) What are signs of gabapentin toxicity?
Definition
38.) Dizziness, ataxia, and fatigue
Term
39.) What are some side effects of lamotrigine use?
Definition
39.) Worse seizures!! Depression, anxiety, suicidal thoughts, dizziness, double vision, and headaches.
Term
40.) How is topiramate dosed?
Definition
40.) The usual starting dosage of topiramate is 1 mg/kg of body weight per day. In order to maximize side effects of sleepiness, dizziness, and loss of coordination the dosage is slowly increased each week, until your neurologist determines you have reached a therapeutic dose
Term
41.) How is topiramate administered?
Definition
41.) Topiramate is taken 2-3 times a day and can be taken with or withour food
Term
42.) What are some side effects of topiramate?
Definition
42.) The most common side effects of topiramate include sleepiness and fatigue. Other rare side effects include dizziness, loss of coordination, confusion, memory problems, psychomotor slowing, difficulties with concentration, and speech and language, and mood problems. These symptoms usually occur early in the treatment, and most patient’s symptoms resolve by 8 weeks
Term
43.) What is tiagabine?
Definition
43.) Tiagabine is a selective GABA reuptake inhibitor that may cause seizures.
Term
44.) What are some side effects of tigabine useage?
Definition
44.) Tigabine useage:: confusion, difficulty speaking…stuttering, sedation
Term
45.) What is the main side effect of vigabatrin useage?
Definition
45.) 25% of adults develop permanent peripheral vision defects
Term
1.) What 3 techniques measure the stages of sleep?
Definition
1.) Electroenceplagram (EEG), electrooculogram (EOG), and electromyelogram (EMG)
Term
2.) What is the prevalence of sleep disorders in the population?
Definition
2.) 30-35% find it difficult to sleep, and 4-5% report excessive sleep
Term
3.) How de we define insomnia?
Definition
3.) Insomnia is the subjective complaint relating to the difficulty of sleeping, falling to sleep, maintaining sleep, or not feeling good even if there was sufficient time to sleep
Term
4.) Describe transient, short-term, and chronic insomnia
Definition
4.) Transient= problem for 2-3nights, short-term=problem for less than 3 weeks chronic=problem for greater than 3 weeks
Term
5.) What sex is insomnia more common in?
Definition
5.) Insomnia is more common in women
Term
6.) What are 2 issues involved in the controversy in the management of insomnia
Definition
6.) First: the use of pharmacological agents-sedatives, hypnotics Second: the search for medical causes and non-drug treatments.
Term
7.) Describe the perfect hypnotic drug
Definition
7.) Perfect hypnotic drug: would allow sleep to occur without disrupting the normal sleep architecture—no next day after effects, rebound anxiety, or continued sedation.the perfect drug could be used chronically without dependency or rebound effect on discontinuation of the agent
Term
8.) What was the first sedative ever made?
Definition
8.) Chloral hydrate
Term
9.) What are Mickey Finn drinks?
Definition
9.) Mickey Finn= chloral hydrate added to alcohol drink…aka knockout drops
Term
10.) Chloral hydrate was used extensively until ____were discovered….today id only used in ___
Definition
10.) Chloral hydrate was used extensively until barbiturates discovered…toady only used in veterinary medicine
Term
11.) What is the relationship between “barbiturate
and “barbital”
Definition
11.) A barbiturate is a short acting barbital
Term
12.) What are 5 problems users of barbitals have?
Definition
12.) Users of barbitals have problems with tolerance, physical and physiological dependence, overdose, withdrawal, and other drug interactions
Term
13.) Hundreds of barbital derivatives have been synthesized for use as sedatives….how come they weren’t all used
Definition
13.) Of the hundreds of barbital derivatives that have been synthesized for use as sedatives, most were long-lasting drugs with half-lives of more than 12 hours…and many exceed 24 hours…thus drowsiness lasted too long
Term
14.) What have largely replaced barbitals?
Definition
14.) Benxodiazepines
Term
15.) How many benzodiazepines have been synthesized?
Definition
15.) 3000+
Term
16.) How do benzodiazepines work?
Definition
16.) Benzodiasepines work by acting on the CNS to inhibit synaptic response to stimuli by having a structure similar to gamma-aminobutyric acid (GABA)
Term
17.) What do benzodiazepines do?
Definition
17.) Benzodiazepines work as a sedative, hypnotic, decrease anxiety, and are a muscle relaxant
Term
18.) What are 3 kinds of benzodiazepines?
Definition
18.) Flurazepam (date rape), diazepam, and chlordiazepoxide
Term
19.) What are some common symptoms involved with benzodiazepine use?
Definition
19.) Sedation, hypnosis, decreased anxiety, muscle relaxation, anterograde amnesia, and anticonvulsant activity…Impaired mental and psychomotor functions—confusion…light-headedness—increased reaction times…are dangerous with alcohol…drunkenness persists longer, assoc. with memory loss
Term
20.) What are some paradoxyl effects of benzodiazepine useage?
Definition
20.) Nightmares, anxiety, irritability, tachycardia and hallucination..significant side effects may even include paranoia, depression, suicidal or hostility and rage
Term
21.) How are benzodiazepines absorbed? What percents of them bind to proteins? What about their concentration in the CSF vs. quantity found in free form in plasma?
Definition
21.) All benzodiazepines are rapidly and completely absorbed. Most forms of benzodiazepine are lipophilic and bind to proteins—ranging from 70% for alprazolam to 99% for diazepam. Their concentration in the CSF is equivalent to the quantity found in the free form in the plasma
Term
22.) What benzodiazepine has been banned in the US?
Definition
22.) Flunitrazepam has been banned
Term
23.) What is zolpidem?
Definition
23.) Zolpidem is a prescription medication used for short-term treatment of insomnia. It is a short-acting non-benzodiazepine drug that works quickly and serves also as an anticonvulsant and muscle-relaxant
Term
24.) Why is zolpidem not used to treat seizures?
Definition
24.) Because the dose needed is 10-20x the amount required for sedation
Term
25.) What are some side effects of zolpidem useage?
Definition
25.) Amnesia, hallucinations, delusions, ataxiz, impaired judgement, headaches, increased appetite, and more
Term
26.) What is another name for zolpidem?
Definition
26.) Ambien
Term
27.) Alchemists in the Middle ages thought alcohol was ____
Definition
27.) The elixir of life
Term
28.) Describe ethanol’s impact on the CNS, vessels, Lipoprotiens, skeletal muscle, temperature, liver, and kidney
Definition
28.) Ethanol is a CNS depressant, causes vasodilation of the vessels, causes increased HDL, lessens the fatigue in small doses in the skeletal muscle, increases temp and sweating, increases acetaldehyde in the liver, and causes a diuretic effect on the kidney
Term
29.) What beneficial purpose does ethanol serve in a hospital today?
Definition
29.) Ethanol is used to treat overdose of methanol and ethylene glycol because competes for alcohol dehydrogenase
Term
30.) What Is the drug of choice now for alcohol ( ethanol, methanol, ethylene glycol) overdose?
Definition
30.) Fomepizole….shuts down alcohol dehydrogenase
Term
31.) What are cyclic antidepressants?
Definition
31.) Cyclic antidepressants are named for the rings in their structure…the older agents had 3…some of the more recent ones have 4
Term
32.) If give a patient ethanol to compete for alcohol dehydrogenase in a methanol or ethylene glycol OD….where does the ethylene glycol/methanol go?
Definition
32.) Goes into pee
Term
33.) What is amitriptyline and what is it mainly used for?
Definition
33.) Amytriptyline was first used in 1961 to treat mood disorders such as major depressive disorders, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorders, PTSD, and even eating disorders….is widely used as antipsychotic agent
Term
34.) How do most tri-cyclic antidepressants work?
Definition
34.) By impacting the neurotransmitters…increasing the levels of serotonin-norepinephrine in the CNS—low levels have been associated with mental disorders
Term
35.) What are some side effects of tricyclic/cyclic antidepressants?
Definition
35.) Dry mouth, blurry vision, GI motility, cognitive and/or memory impairment and increased body temp….other issue inclusd edrowsiness, anxiety, confusion, restlessness, and a change in appetite and weight
Term
36.) What are signs of a TCA overdose?
Definition
36.) Mortality and morbidity are associated with cardiovascular and neurological activity….significant toxicity in pediatric patients…enhanced response to alcohol
Term
1.) What is the drug’s name of the agent given to inhibit alcohol dehydrogenase activity?
Definition
1.) Agent given to inhibit alcohol dehydrogenase activity: Fomepizole (aka Antizol)
Term
2.) What is the general category in which stimulants are categorized?
Definition
2.) Methylxanthine derivatives
Term
3.) What is caffeine?
Definition
3.) Caffiene is one of three closely related alkaloids that occur in plants
Term
4.) What are the top 3 reasons people take caffeine?
Definition
4.) To elevate mood, decrease fatigue, and increase capacity for work
Term
5.) How does caffeine effect the CNS, kidney, cardiac muscle, and smooth muscle
Definition
5.) Caffiene is a CNS stimulant, is a diuretic on the kidney, stimulates cardiac muscle, and relaxes smooth muscle
Term
6.) What are 2 therapeutic uses of caffeine?
Definition
6.) Caffiene is used in bronchial asthma and in preterm infant apnea
Term
7.) The immune response in humans is composed of what 2 mechanisms?
Definition
7.) Cell mediated immunity and humoral immunity
Term
8.) What is cyclosporine and where is it found?
Definition
8.) Cyclosporine is a cyclic polypeptide composed of 11 amino acids that is isolated from fungus.
Term
9.) To what type of tissues does cyclosporine migrate? How did this effect testing of values in early preparations of the drug?
Definition
9.) Cyclosporine is a lipophillic drug…initial preparations were poorly absorbed…the lipphillic nature of the drug meant much was bound to lipoproteins and red cells. Thus, whole blood values give the best estimate of body burden
Term
10.) How have newer preparations of cyclosporine changed the dosing?
Definition
10.) Newer preparations of cyclosporine in a microemulsion have improved the bioavailability and lowered the dose required for effective immune suppression.
Term
11.) What is the most active aspect of cyclosporine..the drug itself or its metabolites?
Definition
11.) The parent cyclosporine is the most active form with over 25-30 metabolites…most are inactive
Term
12.) What lab technique is usually used to measure cyclosporine?
Definition
12.) Immunoassays are used primarily to measure the drug—cross reactivity has been a significant problem HPLC measures the parent drug…currently HPLC/MS using selected ion monitoring is the method used at UWHC.
Term
13.) What are the major types of toxicity associated with cyclosporine use?
Definition
13.) Renal or nephrotoxicity…but then again if have too little drug will have rejection
Term
14.) What are C-2 levels that are drawn for patients taking cyclosporine, and why are they used?
Definition
14.) C-2 Levels: It is not easy to derive peak cyclosporine levels for an individual. Instead, cyclosporine levels are determined at 2 hours post dose, which reflects the individual’s ability to absorb the dose plus provides some possible information concerning how rapidly the drug was metabolized
Term
15.) What is Tacrolimus’s mode of action?
Definition
15.) Similar to Cyclosporine, Tacrolimus is able to inhibit T-Cell activation
Term
16.) To what tissues does tacrolimus migrate?
Definition
16.) Tacrolimus is a very lipophillic drug
Term
17.) Which is more potent: Cyclosporine or tacrolimus?
Definition
17.) Tacrolimus is more potent than cyclosporine (about 100 times more!!)
Term
18.) What kind of toxicity is noted with tacrolimus use?
Definition
18.) Nephrotoxitcity is noted with tacrolimus use
Term
19.) What sample do we obtain for tacrolimus determination? And what technique do we use to measure it?
Definition
19.) Use HPLC/MS assay to quantitate the drug in the patient’s whole blood
Term
20.) What is another name for Sirolimus?
Definition
20.) Rapimmune
Term
21.) What is another name for tacrolimus?
Definition
21.) FK-506
Term
22.) What technique/sample type do we use to measure sirolimus?
Definition
22.) Use HPLC/MS assay to quantitate drug in patient’s whole blood
Term
23.) What is “triple Therapy”
Definition
23.) Triple therapy: when patients also receive glucocorticoids in combination with immunosuppressive agents…usually this is Prednisone. In addition, patients receive cytotoxic drugs; azothioprine is the primary agent.
Term
24.) What aspect of cellular proliferation do antineoplastic drugs usually target?
Definition
24.) Protein synthesis
Term
25.) How does the antineoplastic drug cyclophosphamide work?
Definition
25.) It is an alkalating agent that causes cross-linking of DNA
Term
26.) How does the antineoplastic drug methotrexate work?
Definition
26.) Methotrexate is a folic acid antagonist that is also one of the oldest chemotherapy agents
Term
27.) How does the antineoplastic drug 5-Fluorouracil work?
Definition
27.) It is a pyrimidine antagonist…since the 1950s 5-fluorouracil has been one of the major drugs used in a variety of solid cancers
Term
28.) Describe the pathway from purine/pyrimidine synthesis to proteins
Definition
28.) Purine/pyrimidine synthesisribonucleotidesdeoxyribonucleotidesDNARNAProteins
Term
29.) Describe the role of TDM in chemo drugs
Definition
29.) TDM has been of limited use during the administration of most chemotoxic drugs. The exception is the use of methotrexate for the treatment of various cancer and non-cancer issues
Term
30.) Describe hoe methotrexate is administered
Definition
30.) Typically, methotrexate is administered in extremely toxic doses to maximize the killing effect of the drug towards the cancer cells. After a short period of time(4-8 hours) the patient is rescued with leucovorin. The methotrexate levels are measured. If after 48 hours the methotrexate levels have not fallen below toxic concentrations, the patient receives leucovorin.
Term
31.) Why must the urine of many patients on chemo be maintained as alkaline?
Definition
31.) Urine must be maintained as alkaline to avoid precipitation of methotrexate in the renal tubules when urine is acidic
Term
32.) What is an aminoglycoside?
Definition
32.) An aminoglycoside is a molecule composed of a sugar group and an amino group
Term
33.) What is amikacin?
Definition
33.) Amikacin is an aminoglycoside antibiotic used to treat different types of bacterial infections
Term
34.) How does amikacin work?
Definition
34.) Amikacin works by binding to the bacterial 30s ribosomal subunit, causing the misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth
Term
35.) How is amikacin administered?
Definition
35.) Amikacin may be administered once or twice daily but must be given by the intravenous or intramuscular route, which tends to be painful. There is no oral form available. Dosage must be adjusted in people with kidney failure
Term
36.) When is amikacin most often used?
Definition
36.) Amikacin is most often used for treating severe, hospital-acquired infections with multidrug resistant gram-negative bacteria such as pseudomonas aeruginosa, acinetobacter, and enterobacter.
Term
37.) What is is vancomycin?
Definition
37.) Vancomycin is a glycopeptides antibiotic
Term
38.) When is vancomycin used?
Definition
38.) Vancomycin is used in the prophylaxis and treatment of infections caused by Gram-positive bacteria infections. It has traditionally been used as a drug of “last resort”, used only after treatment with other antibiotics has failed, although the emergence of vancomycin-resistant organisms means that it is increasingly being displaced from this role by linezolid and daptomycin
Term
39.) What is gentamicin?
Definition
39.) Gentamicin is an aminoglycoside antibiotic
Term
40.) When is gentamicin used?
Definition
40.) Gentamicin is used to treat many types of bacterial infections, particularily those caused by gram-negative bacteria. However, gentamicin is NOT useful in the treatment of neisseria gonorrhoeae, neisseria meningitides, or Legionella pneumophilia bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin found in these gram negative organisms
Term
41.) All aminoglycosides are toxic to what part of the body?
Definition
41.) All aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their relative effects on hearing vs. balance.
Term
42.) How can gentomicin be toxic?
Definition
42.) Gentamicin is a vestibulotoxin, and can cause permanent loss of equilibrocation, caused by damage to the vestibular apparatus of the inner ear, usually if taken at high doses or for prolonged periods of time…but there are well documented cases in which gentamicin completely destroyed the vestibular apparatus after 3-5 days on the drug
Term
43.) What is chloramphenicol and where does it come from?
Definition
43.) Chloramphenicol is a bacteriostatic antimicrobial originally derived from the bacterium Streptomyces venezuelae and introduced into clinical practice in 1949. It was the first antibiotic to be manufactured synthetically on a large scale
Term
44.) When is chloramphenicol used?
Definition
44.) Chloramphenicol is effective against a wide variety of microorganisms; it is still very widely used in low income countries because it is very inexpensive…but has fallen out of favor in the Midwest b/c of fear of a very rare but serious side effect: Aplastic anemia In the West, the main use of chloramphenicol is in eye drops or ointment for bacterial conjuntivitis
Term
45.) Besides it’s clinical use, what other use has chloramphenicol been used for in recent years?
Definition
45.) Chloramphenicol has recently been discovered to be a ife saving cure for chytridomycosis in amphibians. Chytridiomycosis is a fungal disease that has been blamed for the extinction of 1/3 of the 120 frog species lost since 1980
Term
46.) What is the way in which pharmaceutical companies approach finding new drugs today?
Definition
46.) They want to develop new drugs that work at specific cellular levels to regulate a given process
Term
47.) What are some examples genetically-variable mechanisms that may contribute to individual variability
Definition
47.) Altered drug absorption, increased first-pass metabolism, altered rate of systematic inactivation, inc/dec metabolism, conversion to an active metabolite, competition for binding sites, altered abundance/function of enzyme, altered affinity of enzyme, altered abundance or binding to receptor
Term
48.) What is “personalized medicine”?
Definition
48.) The new approach that will focus on the use of genetic information to determine how an individual might metabolize a drug before they receive their first dose
Term
1.) What are schedule 1 Drugs?
Definition
1.) Schedule 1 drugs are drugs that have a high potential for abuse and no accepted medical use ( heroin, LSD, dihybromorphine, marijuana, etc)
Term
What are Schedule 2 Drugs?
Definition
2.) Schedule 2 drugs are drugs with a high potential for abuse with severe liability for physical dependence and limited medical usefulness (codeine, morphine, meperdine, etc.)
Term
3.) What are Schedule 3 Drugs?
Definition
3.) Schedule 3 drugs are ;drugs with a high potential for abuse but less than that of schedule 1 or 2 drugs…also have a low to moderate physical dependency (certain opioid and non-opioid compounds, barbituates and methprylon)
Term
4.) What are schedule 4 drugs?
Definition
4.) Schedule 4 drugs are drugs with a low potential for abuse…includes most barbituates, benzodiazepines, and propoxyphene
Term
5.) What are schedule 5 drugs?
Definition
5.) Schedule 5 drugs are drugs with the lowest potential for abuse
Term
6.) How do we acquire scheduled drugs?
Definition
6.) All of the scheduled compounds require a physician’s superscription to acquire. Severe penalties are in place for possession or selling of any of the scheduled drugs
Term
7.) What are the 2 types of special laboratories established to perform drugs of abuse testing?
Definition
7.) Special laboratories perform drug of abuse testing: those certified by NIDA (Natioinal Institute for drugs of abuse) and those certified by SAMHSA (Substance abuse and mental health service administration)…equipment in these labs cannot be used for medical purposes
Term
8.) How do we choose the levels we want our controls to be at for DOA testing?
Definition
8.) Controls should be near the cut points for medical decisions
Term
9.) What is the most widely used illicit drug in the world?
Definition
9.) Cannabinoids (marijuana)
Term
10.) What is the active compound in marijuana?
Definition
10.) THC: tetrahydrocannabinol
Term
11.) Describe the pharmacokinetics of marijuana
Definition
Principal route of administration: inhalation of smoke…30% of THC is destroyed by pyrolysis…drug is quickly ad efficiently delivered from the lungs to the brain. Bioavaliability is 18-50%
Term
12.) What tissue does marijuana like to bind to and how much of it is protein bound
Definition
12.) Marijuana is a lipophilic drug that is 97-99% protein bound—primarily to lipoproteins metabolized to inactive 11-oh metabolite by the cytochrome p-450 enzyme system
Term
13.) Define: Hallucinogenic drugs
Definition
13.) Psychedelic compounds that produceillusions (perceptual distortions of colors, sounds, distance, shapes) and rapidly changing emotions from ecstacy to depression and paranoia
Term
14.) Describe the physical effects of LSD use
Definition
14.) The effects of LSD are unpredictable. They depend on the amount taken; the user’s personality, mood, and expectations; and the surroundings in which the drug is taken. The physical effectsinclude dilated pupils, higher body temperature, increased heart rate and blood pressure, sweating, loss of appetite, sleeplessness, dry mouth, and tremors
Term
15.) Describe the sensation/emotional effects that LSD use creates..how long do these last?
Definition
15.) Sensations and feelings change much more dramatically than the physical signs. The user may feel several different emotions at once or swing rapidly from one emotion to another. If taken in a large enough dose, the drug produces delusions and visual hallucinations. The user’s sense of time and self changes. Sensations may seem to “cross over”, giving the user a feeling of hearing colors and seeing sounds. These chnges can be frightening and can cause panic. …These experiences are long, and typically begin to clear after about 12 hours
Term
16.) Describe the phenomenon of LSD flashbacks
Definition
16.) Many LSD users experience flashbacs…recurrences of certain aspects of a person’s experience, without the user taking the drug again. These happen suddenly a few days after to up to a year after use. Flashbacks usually occur in people who use hallucinogens chronically or have an underlying personality problem; however they can occur in anybody..in addition to flashbacks, LSD users may manifest relatively long-lasting psychoses, such as schizophrenia or severe depression
Term
17.) What is peyote and what is its active ingredient?
Definition
17.) Peyote is a mind-altering drug found in cactus..the active ingredient is mescaline…Indians in the SW used this for religious purposes
Term
18.) What is the active ingredient in hallucinogenic mushrooms?
Definition
18.) Psilocin
Term
19.) What is ephedrine and what is it used for?
Definition
19.) Ephedrine is a strong CNS stimulant which was used for more than 5000 years by Chinese physicians….it is recommended as an antipyretic and antitussive
Term
20.) What is amphetamine and what was its original purpose?
Definition
20.) Amphetamine is a synthetic stimulant used in the 50s and 60s in inhalers to relieve congestions
Term
21.) What are the effects of amphetamine abuse? How does it cause death?
Definition
21.) Abuse of amphetamine leads to a high degree of psychosis and schizophrenia…Death usually occurs due to arrhythmic complications
Term
22.) More than __% of amphetamines will be in the urine unchanged
Definition
22.) More than 40% of meth will be in the urine unchanged….the drug will appear in the urine over several days
Term
23.) Why is the meth on the streets so dangerous?
Definition
23.) Many of the illicit preparations of meth contain contaminants ( solvent, lead, mercury) that are delivered with the drug
Term
24.) What is “Vin mariani”?
Definition
24.) Wine mixed with cocaine
Term
25.) What are all the routes whereby one can take cocaine?
Definition
25.) Different routes of administration: leaf chewing, snorting, smoking, and intravenous…cocaine can be absorbed through the skin
Term
26.) What is “freebasing cocaine”
Definition
26.) In the 1980s cocaine was mixed with volatile solvents and inhaled, called “freebasing”…this gave way to smoking “crack”
Term
27.) What are the confidentiality issues/puposes of medical testing for DOA?
Definition
27.) In medical testing a physician requests a DOA test for treatment purposes. Information obtained is not usable in a court of law…intended primarily for the good of the patient…may occur frequently in a treatment center for individual that have addictive disorders…tests are used to monitor abstinance
Term
28.) What are some legal issues that the lab must keep in mind when performing DOA testing for the purpose of employee testing? How are confirmatory tests run?
Definition
All testing performed on employees fall under different criteria and must provide full documentation as to the validity of a given test result. Therefore, all specimens are collected and managed under rules that maintain “chain of custody” Any presumptive positive of a screening test must be confirmed by a second and usually more reliable method. Often the confirmatory assay is GC-MS
Term
29.) Describe the costs of screening tests vs. confirmatory tests for DOA vs. regulatory costs vs. liability costs
Definition
29.) Screening tests are fairly inexpensive…personnel can be easily trained and unit cost is less than $10…instrumentation is little or no cost …confirmatory tests are expensivs though…need personnel that are highly trained…costs for reagents is minimal but instrumentation is expensive…regulatory costs for lab certification is very expersive, ($500,000 to start and then $100,000 yearly)… also the liability of inappropriate testing or test results is very costly
Term
30.) Describe Chain of Custody as it relates to DOA
Definition
30.) Chain of Custody: All specimens (urine, blood, hair) must be collected under a strict set of rules to validate the results…sample collection must be observed and documented, transport to lab must be documentedwho/when…sample storage, who did analysis and what parts of it, who reported results/ran confirm tests….ALL of this is incredibly expensive and medical testing ould likely go up if this same management scheme were required of all samples collected in a hospital
Term
1.) Define: Chromatography
Definition
1.) Chromatography refers to any technique that separates molecules based on their affinity for a stationary phase relative to a mobile phase. The elution pattern of the chemicals is referred to as the chromatogram
Term
2.) The stationary phase is generally a ____. It remains in a _____ position during the chromatographic procedure
Definition
2.) The stationary phase is generally a solid or liquid. It remains in a fixed position during the chromatographic procedure.
Term
3.) The mobile phase is generally a ____ . It is the phase that ___ during the chromatographic procedure
Definition
3.) The mobile phase is generally a liquid or a gas. It is the phase that moves during the chromatographic procedure
Term
4.) Generally a compound will be ____ to one of the two phases in an affinity column
Definition
4.) Generally a compound will be attracted to one of the two phases in an affinity column
Term
5.) What is partition chromatography?
Definition
5.) Patition chromatography involves separation of a compound as it moves from a mobile phase to a stationary phase
Term
6.) What is normal phase chromatography?
Definition
6.) Normal phase chromatography: non-polar mobile phase and stationary polar phase
Term
7.) What is reverse phase chromatography?
Definition
7.) Reverse-phase chromatography: polar mobile phase and non-polar stationary phase…this is preferred for use in the hospital because things from a patient are usually polar
Term
8.) What is ion exchange chromatography? (difference between cation-exchange and anion-exchange?)
Definition
8.) Ion-exchange chromatography: separation of compounds based on exchanges of ions between two phases….cation-exchange: negatively charged stationary phase…anion-exchange: positively charged stationary phase
Term
9.) What is adsorption chromatography?
Definition
9.) Adsorption chromatography: Separation is achieved through a weak interaction between the analyte and stationsry phase such as electrostatic attraction or H bonding
Term
10.) What is size exclusion chromatography?
Definition
10.) Size-exclusion chromatography: separation is achieved by smaller analytes being trapped in channels of stationary phase while larger particles go around
Term
11.) What is affinity chromatography?
Definition
11.) Affinity Chromatography: separation achieved on the basis of the specific biological interaction between analyte and stationary phase
Term
12.) What are the 3 types of affinity chromatography?
Definition
12.) Antigen:antibody, enzyme:substrate, hormone:receptor
Term
13.) How do you calculate resolution?
Definition
13.) Resolution= (retention volume of B – retention volume of A)/((base peak width of A +base peak width of B)/2)
Term
14.) What level of resolution is generally deemed acceptable?
Definition
14.) Generally want resolution to be 0.8 and above
Term
15.) Two well-resolved peaks that are pointy are probably due to…
Definition
15.) Good resolution due to column efficiency
Term
16.) Two well-resolved peaks that aren’t pointy are probably due to…
Definition
16.) Good reolution due to column selectivity
Term
17.) What are some reasons for poor resolution?
Definition
17.) Overloaded sample, low temp., increased flow rate, short column length
Term
18.) What is the equation for number of theoretical plates?
Definition
18.) Number of theoretical plates: 16(RT/W)2 where RT is retention time..measured from 0 to center of peak….and W is the width of the peak at its widest point
Term
19.) What does a calculation of theoretical plates tell us?
Definition
19.) The calculation of theoretical plates tells us about the peak quality…higher values show better peak quality, and the TP equation describes the peak’s sharpness
Term
20.) A gas chromatograph peak has a retention time of 130 seconds, peak height of 7.5 cm, and base width of 2mm. The chart speed is 10mm/minute. What is the number of theoretical plates for this column?
Definition
20.) 1800…have to first convert base width to seconds
Term
21.) What are 5 detector types used on an HPLC?
Definition
HPLC: Refractive index, spectrophotometer (UV/vis or fixed/variable), diode array, fluorescence, electrochemistry (conductivity, amperometrically)
Term
22.) What are 5 detector types used on a GC?
Definition
22.) GC: Thermal conductivity, flame ionization, nitrogen-phosphorus, electron-capture, mass spectrometer
Term
23.) What was the internal standard used in the alcohol lab?
Definition
23.) N-propanol
Term
24.) What is the purpose of an internal standard in GC/HPLC?
Definition
24.) An internal standard is a known amount of a compound, different from analyte, that is added to the unknown. It is a compound similar to those being analyzed. The signal from the analyte is compared with the signal from the internal std to figure out how much analyte is present. Internal stds are especially useful for analyses in which the quantity of the sample analyzed or the instrument response varies slightly from run to run for reasons that are difficult to control. For example, gas or liquid flow rates or injection volumes. If a known quantity of std is added to the unknown prior to any manipulation, the ratio of std to analyte remains constant because the same fraction of each is lost in any operation
Term
25.) How do you determine your concentration of your unknown for an HPLC/GC analysis?
Definition
25.) Conc Unknown= Ceonc IS x peak unknown/peak IS
Term
26.) Compare HPLC/GC wrt sample type/separation
Definition
26.) HPLC: biological samples that are separated based on solubility GC: organic samples that are separated based on volatility
Term
27.) Compare HPLC/GC wrt what phase separation occurs in and at what temp
Definition
27.) HPLC: separation is achieved in both phases, and occurs at a lower temp, GC: separation is achieved in the stationary phase and occurs at a higher temp
Term
28.) Compare HPLC/GC wrt types of detectors used for each
Definition
28.) There are a variety of detectors available for both
Term
29.) Compare HPLC/GC wrt ease of sample recovery
Definition
29.) HPLC: easy to recover sample GC: difficult to recover sample
Term
30.) What are some areas in which chromatography is clinically useful?
Definition
30.) Clinical usefulness of chromatography: TDM, toxicology/DOA, neurochemicals, endocrinology, Amino acids, vitamins, proteins, peptides, nucleic acids, lipids/lipoproteins, creatinine, bilirubin, uric acid
Term
16.) Name the cell that has altered function in the presence of aspirin
Definition
16.) Platelets! Aspirin irreversibly disrupts platelet function by inhibiting cyclooxygense (COX-1), and hence normal hemostasis
Term
In the sulfonamide experiment, why do we not have to make a TCA filtrate of the standard?
Definition
17.) The purpose of the TCA filtrate is to precipitate out and remove any protein in the sample that might interfere with our measurement of sulfonamide. Because the standard is only composed of sulfamethoxazole in water…there is no protein to precipitate out…unlike in human samples.\
Term
18.) Why is it alright in the sulfonamide procedure to have an aqueous standard when the unknown sample is not aqueous but serum?
Definition
18.) It is OK because we precipitate out any protein that might interfere with the sulfonamide measurement
Term
19.) What would you do if the TCA filtrate from the sulfonamide exp was not clear? Would it matter?
Definition
19.) Re-filter…it would matter
Term
20.) Why must the reagents of the sulfonamide experiment need to be added in the specified order? Why is the timing of the reaction so important?
Definition
20.) The reagents need to be added in the right order because each reagent changes the sulfanilamide in just the right way so that it can eventually produce a red dye…the timing is crucial because a color is produced, which would continue to be generated if not stopped by the addition of ethylenediamine dihydrochloride reagent..if this happened we wouldn’t be able to judge any differences between the samples.
Term
21.) What is the purpose of the Triton X-100 in the alcohol method?
Definition
21.) The Triton-X-100 serves is a surfactant and hemolyzes the RBCs so that we can get a better estimate of alcohol content in blood
Term
22.) Generally, how is the retention time related to the molecular size in GC analysis?
Definition
22.) MW is directly proportional to retention time…it takes more time for larger compounds to volatilize
Term
23.) Isopropanol and n-propanol are 3 carbon alcohols of identical MW. How would you explain the longer retention of the straight chain alcohol, n-propanol
Definition
23.) If you increase the carbon chain length, you increase the retention time
Term
24.) In the GC/Alcohol lab, why do the compounds separate after they have been injected together?
Definition
24.) The compounds separate because they interact to different degrees with the stationary phase
Term
25.) Would the TLC procedure be limited just to the separation and identification of narcotics?
Definition
25.) NO! TLC is used for many purposes…the adsorbant material coated on the plate (Stationary phase) can be made of many different compounds …separation is based on competition of the solute and the mobile phase for binding sites on the stationary phase…this phenomenon is not unique to narcotics
Term
26.) For each TLC plate run, is it necessary to have standards along with the unknowns on the TLC plate?
Definition
26.) Yes this is necessary because different conditions inside the developing chamber may cause the solvents to spread farther/not as far
Term
27.) What is the purpose of the pH9.0 buffer in the EXTUBE in the TLC experiment?
Definition
27.) The buffer is necessary so that the wanted substance that is clinging to the stationary phase of the column (the narcotic) will fall off and we can measure it
Term
28.) Why is a negative control run on the TLC plate?
Definition
28.) To guard against false positives
Term
What is the equation we use to calculate resolution?
Definition
Resolution= (retention volume of B- retention volume of A)/((base peak width of B+base peak width of A)/2)
Term
What class of drug is acetylsalicylate?
Definition
analgesic
Term
What class of drug is aspirin? And what is another name for aspirin?
Definition
Aspirin is aka acetylsalicylic acid...it is an analgesic...specifically a NSAID
Term
What class of drug are salsalate and diflunisal?
Definition
analgesics...specifically NSAIDS!
Term
What class of drug is acetominophen?
Definition
analgesic...specifically a NSAID
Term
What class of drug is ibuprofen?
Definition
An analgesic...specifically an NSAID
Term
What are four "other NSAIDS?"
Definition
naproxen (alleve), fenoprofen, flurbiprofen, ketoprofen
Term
What class of drug are COX-2 inhibitors?
Definition
analglesics
Term
What are four types of COX-2 inhibitors?
Definition
vioxx, celebrex, bextra, mobic
Term
what are four opioid analglesic drugs
Definition
morphine, codeine, thebaine, oxycodone
Term
What class of drug is digoxin?
Definition
a digitalis
Term
What class of drug is quinidine?
Definition
an antiarrhythmic
Term
what class of drug is procainamide?
Definition
an antiarrhythmic
Term
What class of drug is lidocine?
Definition
an antiarrhythmic
Term
What class of drug is mexilitene?
Definition
it is an antiarrythmic
Term
What class of drug is lidocaine?
Definition
an antiarrythmic
Term
What class of drug is tocainamide?
Definition
an antiarrythmic
Term
What class of drug is disopyramide
Definition
a antiarrythmic
Term
What class of drug is flecanide
Definition
an antiarrythmic
Term
What class of drug is verapamil and diltalizam?
Definition
an antiarrythmic
Term
What class of drug is amiodarone?
Definition
an antiarrythmic
Term
What class of drug is dronedarone
Definition
an antiarrrythmic
Term
What class of drug is ephedrine?
Definition
an amphetamine
Term
What class of drug is pseudoephedrine?
Definition
an amphetamine
Term
What class of drug is ephedrone?
Definition
an amphetamine
Term
What class of drug is cathinone
Definition
an amphetamine
Term
What class of drug are methylxanthine derivatives?
Definition
stimulants
Term
What class of drug is caffiene?
Definition
stimulant
Term
What class of drug is theobromine?
Definition
stimulant
Term
What class of drug is theophylline
Definition
a stimulant
Term
What class of drug is cyclosporine?
Definition
an immunosuppressive agent
Term
What class of drug is tacrolimus?
Definition
an immunosuppressant
Term
What class of drug is sirolimus?
Definition
an immunosuppressant
Term
What class of drug is cyclophosphamide?
Definition
an antineoplastic drug
Term
What type of drug is methotrexate?
Definition
an antineoplastic drug
Term
What class of drug is 5-fluorouracil?
Definition
an antineoplastic drug
Term
What class of drug is amikacin
Definition
an aminoglycoside antibiotic
Term
What class of drug is vancomycin?
Definition
a glycopeptide antibiotic
Term
What class of drug is gentamicin?
Definition
an aminoglycoside antibiotic
Term
What class of drug is chloramphenicol?
Definition
a bacteriostatic antimicrobial
Term
What class of drug is chloral hydrate?
Definition
a sedative
Term
What class of drug are barbituates
Definition
sedatives
Term
What class of drug is barbital?
Definition
A sedative...specifically a barbituate
Term
What class of drug is flurazepam?
Definition
A sedative..specifically a benzodiazepine
Term
What class of drug is diazepam?
Definition
A sedative...specifically a benzodiazepine
Term
What class of drug is chlordiazepoxide?
Definition
A sedative...specifically a benzodiazepine
Term
What class of drug is flunitrazepam?
Definition
A sedative...specifically a benzodiazepine..is now banned in the US though
Term
What class of drug is zolpidem?
Definition
a sedative..a non-benzodiazepine
Term
What class of drug is ethanol?
Definition
a sedative
Term
What class of drug are tricyclic antidepressants?
Definition
sedatives
Term
What class of drug is phenobarbital?
Definition
an anticonvulsant
Term
What class of drug is phenytoin?
Definition
an anticonvulsant
Term
What class of drug is primadone?
Definition
an anticonvulsant
Term
What class of drug is valproic acid?
Definition
an anticonvulsant
Term
What class of drug is carbamazepine?
Definition
an anticonvulsant
Term
What class of drug is clonazepam?
Definition
an anticonvulsant
Term
What class of drug is felbamate?
Definition
an anticonvulsant
Term
What class of drug is gabapentin?
Definition
an anticonvulsant
Term
What class of drug is lamotrigine?
Definition
an anticonvulsant
Term
What class of drug is topiramate?
Definition
an anticonvulsant
Term
What class of drug is tigabine?
Definition
an anticonvulsant
Term
What class of drug is vigabatrin?
Definition
an anticonvulsant
Term
Describe how color is produced in the salicylate reaction
Definition
The salicylate method is based on the reaction of salicylate ion with ferric salts in a weakly acid solution to give a purple color without removal of proteins or interfering substances
Term
In the salicylate experiment, what do we add to the blank tubes instead of ferric nitrate?
Definition
nitric acid
Term
How did we measure the results of the salicylate experiment?
Definition
on a standard curve
Term
Describe why the salicylate experiment doesn't actually measure aspirin
Definition
Aspirin is the acetylated form of salicylic acid and is converted to the free form in the body. Since this method determines only the free form of salicylic acid, aspirin itself would not participate in the reaction
Term
Why is the measurement of salicylates clinically useful?
Definition
Accidental ingestion of salicylic acid derivatives is one of the primary causes of morbidity and mortalibty in young chilren. The ubiquitous presence of aspirin in every home is a constant initation to accidental ingestion. The blood salicylate concentration is a reasonable indication of the extent of toxicity, and hence is a diagnostic aid. It is also valuable in the treatment of paitnets with rheumatic fever, whose blood salicylate concentration should be maintained between 20mg/dL and 30mg/dL. The normal value for salicylate is negative
Term
Salicylates may produce harmful effects with concentrations greater than ___mg/dL in the serum
Definition
50mG/dL
Term
Which experiment: protein-free filtrate of serum
Definition
sulfonamide
Term
How is color generated in the sulfonamide experiment?
Definition
The procedure uses the amino group of the sulfonamides for production of a dye that can be measured colorimetrically. the amino group is diazotized with nitrous acid. The excess nitrous acid is converted by the addition of sulfamate, and the diazo compound is coupled with N-(1-naphtyl)-ethylenedediamine to produce an intense color, which enables the original drug to be estimated in dilutions greater than 1 ppm
Term
Describe the solubility of sulfonamides
Definition
As a rule, sulfonamides are not very soluble in water, but more solubl in ethanol, ether, and chloroform. However, the sodium salts of the sulfonamides are readily soluble in water
Term
Describe the clinical use of sulfonamides
Definition
Sulfonamides have a wide range of antimicrobial activity against both gram-positive and gram-negative organisms. In general, the sulfonamides exert only a bacteriostatic effect in the body, and cellular and humoral defense mechanisms of the host are essential for the final eradication of the infection
Term
How are sulfonamides administered?
Definition
Sulfonamides are given orally, intravenously, or used topically. The highly soluble and rapidly excreted sulfonamides are given orally for treatment of systematic as well as urinary tract infections. However, oral administration of the "insoluble" sulfonamides results in a temporaty inhibition of the intestinal microbial flora
Term
discribe the differences in protein binding and excretion between the long-acting and short-acting sulfonamides
Definition
The long-acting sulfonamides are more strongly bound to proteins and more slowly excreted than sulfonamides with a short duration of action. The concentration in the plasma muxt be higher to achieve the same therapeutic effect as that given by the short-acting sulfonamides, and the possibility of toxicity is thereby increased.
Term
What are the two main reactions of the sulfonamide procedure?
Definition
sulfanilamide + Nitrous acid --> p-diazobenzenesulfonamide

p-benzenesulfonamide + N-(1-Napththyl)ethyleneamine --> RED DYE

p-
Term
What equatino does the nitrous acid undergo in the sulfonamide procedure?
Definition
nitrous acid + N-(1-Napththyl)ethyleneamine
Term
IN what experiment did we use filter paper?
Definition
IN the sulfonamide experiment..b/c we were removing the protein
Term
In what experiment was "timing critical"...and we almost ran out of time doing the experiment
Definition
the sulfonamide experiment
Term
How did we calculate the concentration of the unknown in the sulfonamide experiment
Definition
(Abs 540-Abs 650 of unknown)/(Abs 540- Abs 650 of standard) X Concentration of standard = Concentratino of unknown
Term
What is the principle of the gas chromatographic method for alcohols
Definition
A whole blood sample is diluted with a water solution of Triton X-100 containing N-propanol as an internal standard and reference peak. Particulate material from the hemolyzed cells is centrifuged out and the clear supernatant is analyzed by gas chromatography
Term
what four alcohols did we measure in the GC lab?
Definition
methanol, ethanol, isopropanol, and acetone
Term
How did we calculate the concentrations of the unknowns in the GC lab?
Definition
(peak height ratio of unknown)/(peak height ratio of standard) x conc. of standard = conc. of unknown
Term
Describe the pharmacology and metabolism of alcohols?
Definition
ethanol, isopropanol, and methanol are water soluble substances that are rapidly absorbed in the GI tract by simple diffusion. At equilibrium, these alcohols are distributed throughour the water compartments of the body according to water content. These alcohols are widely avaliable. The alcohols and their metabolites are potentially toxic
Term
how is ethanol metabolized by the liver??
Definition
ethanol--> acetaldehyde-->acetic acid-->CO2 + H20
Term
How is isopropanol metabolized?
Definition
ISOPROPANOL--> ACETONE--> CO2 + H20
Term
How are ethanol and its metabolizes excreted in the body?
Definition
Some ethanol and acetaldehyde are excreted in the lungs. Some of the ethanol is excreted in the urine with its glucoronide conjugate.
Term
How is isopropanol and its metabolites excreted in the body?
Definition
Isopropanol is excreted in the lungs as well as in the urine along with its glucoronide conjugate.
Term
What is the major effect of isopropanol on the body and why is it more toxic than ethanol?
Definition
Isopropanol can act in a manner similar to ethanol. Its greater toxic effect is partially due to the slower metabolism of isopropanol, resulting in a level that will be sustained longer than a similar ethanol concentratino. Isopropanol has the added effect of causing a more prominent gastritis, pain, nausea, vomiting and hemorrhage. The possibility of vomiting and aspiration is a serious threat with this ingestion.
Term
what is methanol metabolized into>
Definition
methanol--> formaldehyde-->formic acid--> Co2 + H20
Term
Why is methanol toxiC?
Definition
The metabolites of methanol mare much more toxic than the parent methanol. They inhibit cellular metabolism and cause acidosis. Because methanol and the metabolites are high in tissues with high water content, the eye and the optic nerve are particularly susceptile to damage. The approximate half life of methanol in the body is 24 hours.
Term
What is the most important factor in assuring the integrity of tooxicological samples?
Definition
Chain of custody
Term
What is the primary metabolite of cocaine? What forms when alcohol is present?
Definition
The primary metabolite is benzoylecgonine, when alcohol is present cocaethylene is formed
Term
How does cocaine exhibit cardiotoxicity>?
Definition
it is an anesthitic (sodium channel blockage), catecholamine potentiation (coronary vasospasms thru alpha receptor and increased myocardial work thru beta receptor) contraction band necrosis, chronic changes resulting in microfocal fibrosis, coronary artery disease ( accelerated aterosclerosis and intimal hyperplasia)
Term
What is another name for heroin
Definition
DAM (diacetylmorphine)
Term
What is heroin metabolized into?
Definition
6-MAM (6-acetyl morphine) and then morphine
Term
If morphine is greater than heroin concentration, what do you know?
Definition
That either hroin or morphine was taken
Term
What is methadone used for?
Definition
is a morphine substitute...but has more significant sedative properties than morphine...is used to treat heroin addicts
Term
What is methadone metabolized into?
Definition
EDDP
Term
What toxicity is related to methamphetamine?
Definition
elevation and potentiation of catecholamines (arrhythmia)...same cardiac changes that are seen in chrinic cocaine use
Term
How ethanol metabolized in casual drinkers?
Definition
95% is metabolized by aldehyde dehydrogenase and 5% is metabolized by the MEOS..microsomal ethanol oxidizing system
Term
How ethanol metabolized in heavy drinkers?
Definition
75% is metabolized by aldehyde dehydrogenase and 25% is metabolized by the MEOS..microsomal ethanol oxidizing system
Term
What crystals form by ethylene glycol ingestion, and where will you see them?
Definition
Oxalic crystals (oxalate) in the kidneys..renal tubules
Term
What is the best indicator of time of death?
Definition
vitreous potassium levels...potassium is the primary intracellular cation so when the cell dies the NA/K pump stops and the membrane loses integrity..the potassium leaks into the estracellular space or vitreous at a predictable rate..so potassium levels slowly rise after death
Term
Are serum glucose/electrolye values useful is post-mortem studies?
Definition
NO...the glucose and vitreous falls to zero after death bc of cellular metabolism in very high glucose states such as diabetic ketoacidosis the glucose in the vitreous will remain high (> or equal to 200mg/dl)after death allowing diagnosis of diabetes post mortem
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