Toxicology Exam 3

1. The name of the plant from which cocaine is extracted.

Erythroxylon Coca

2. The classification of amphetamines under the Controlled Substances Act (Public law 91-513) of 1970.

Class 2

3. Which are the forms of cocaine.

   1. Hydrochloride Salt (purity >50%)

   2. Crack

4. What form of cocaine, crack is and how it is prepared.

Crack is a freebase form of cocaine

Crackling sound when smoked

Prepared by adding baking soda to aqueous cocaine HCl and heating it to remove water. After heating, the mixture is cooled and filtered. The freebase cocaine precipitates into small pellets that can be smoked in a crack pipe.

5. The complete metabolic pathway of cocaine to benzoylecgonine, ecgonine methyl ester and cocaethylene (with structures).

Cocaine →

1.  Ecgonine methyl ester → ecgonine

2.  → Norcocaine (P450) 

3. → Benzoylecgonine → ecgonine

4.  → Ethylcocaine/cocaethylene → ecgonine

6. The receptors through which cocaine mediate its activity.

Norepinephrine and Dopamine

7. The effects of cocaine mediated by dopamine.

Euphoria, psychic energy, heightened sexual excitement, self confidence, paranoia, hallucinations, dysphoria

8. The effects of cocaine mediated by norepinephrine.

Mydriasis, vasoconstriction, hypertension, tachycardia, tachypnea

9. The pharmacodynamic mechanism of action of cocaine on dopaminergic nerve terminal.

Prevents the reuptake of dopamine into the presynaptic dopaminergic neuron by binding to receptors on the dopamine transporter located on the dopaminergic nerve terminal.

Mediated by NaCl, dependent on active transport

Inhibited when coke binds to sodium binding site and alters chloride binding site

10. Which compounds are used as cutting agents in cocaine.

11. The differences on the bioavailability of cocaine after per os, intravenous and intranasal administration.

After IV and SM: peak concentration is immediate. First order elimination with a half like of 60 min

After IN and PO: peak concentration 30-60 minutes after, half-like is 4-5 hours

12. Which is the unique metabolite of cocaine which is formed only after simultaneous use of alcohol.

13. The unique metabolite of cocaine which is produced only after consumption of ethanol is:

Amphetamines

14. Which chemical class do the amphetamines represent?

Sympathomimetic drugs

15. The structures of amphetamine, methamphetamine, methylene-dioxy-amphetamine, methylene-dioxy-methamphetamine, and methylene-dioxy-ethylamphetamine.

    Methamphetamine:

    

methylene-dioxy-amphetamine:

methylene-dioxy-methamphetamine:

methylene-dioxy-ethylamphetamine:

16. The classification of amphetamines under the Controlled Substances Act (Public law 91-513) of 1970.

Schedule II

17. The receptors through which amphetamines mediate its activity.

Dopaminergic and adrenergic receptors

18. At least one synthetic route of methamphetamine.

Phenyl-2-Propanone (P2P) + methylamine + aluminum foil + HgCl2 + C2H5OH → d-methamphetamine

19. Which amphetamine can be used for therapeutic purposes and for which treatments.

Dextroamphetamine: narcolepsy and ADHD

20. The effects of amphetamine and methamphetamine.

Hyperstimulation, peripheral vasoconstriction, tachycardia, pupillary dilation, euphoria, intensification of feelings, convulsions, hyperthermia, behavioral changes.

21. The street names of methamphetamine.

MA HCl, speed, crank, go, crystal, meth, ice

22. Which adulterants are added to amphetamines formulations. What is the role of each adulterant?

Sugars: add volume

Caffeine, phenylpropanolamine, ephedrine, pseudoephedrine: cheaper stimulants

23. The metabolic pathway of methamphetamine including the structures.

Cannabis

24. The name of the plant from which cannabis is extracted.

There are four: sativa, indica, ruderalis, and hybrids

25. Which is the main factor that affects the purity on Delta 9-tetrahydrocannabinol in the plant.

more heat and less humidity means the leaves dry a bit and concentrate the THC

in more humid areas, the concentration is more dilute

26. The receptors responsible for the effects of Delta 9-tetrahydrocannabinol at CNS.

CB1 and CB2 receptors

27. What is the hysteresis effect?

Delta9-THC is rapidly absorbed and distributed to tissues. Initial changes in blood concentrations are out of phase with the physiological and behavioral changes.

28. The endogenous compounds that regulate the endocannabinoid system.

29. The complete metabolic pathway of delta9-Tetrahydrocannabinol to 11-OH-tetrahydrocannabinol and 11-nor-tetrahydrocannabinolic acid (with structures).

30. If the metabolites of delta 9-tetrahydrocannabinol are active.

31. Which is the disadvantage after per os use of cannabis product in terms of the bioavailability of Delta 9-tetrahydrocannabinol.

32. Cannabis’ behavioral effects.

33. Cannabis’ acute toxic effects.

34. What is the volume of distribution (number with units) of Delta 9-tetrahydrocannabinol and how it affects its partition in the human body.

35. Which is the main tissue at which Delta 9-tetrahydrocannabinol is accumulated.

36. The elimination half life for cannabis acute and long-term users.

37. The lipophilicity factor of Delta 9-tetrahydrocannabinol.

38. How the normalization of urine cannabinoid concentrations is calculated and how this can be used to decide if a new episode of drug exposure has been occurred.

ASB036 standard

39. The definitions:

Accuracy/Bias: An estimate of systematic measurement error, calculated as the difference between the mean of several measurements under identical conditions, to a known “true” value. Often reported as a percent difference.

Precision: The measure of the closeness of agreement between a series of measurements obtained from multiple samplings of the same homogenous sample.

Biological Fluid: Any liquid biological specimen that is typical pipetted for analysis

Fortified Matrix Sample: A blank matrix sample spiked with target analyte and/or internal standard using reference materials.

Interferences: Non-targeted analytes which may impact the ability to detect, identify, or quantitate a targeted analyte.

Carryover: The appearance of unintended analyte signal in samples after the analysis of a positive sample.

Blank Matrix Sample: A biological fluid or tissue (or synthetic substitute) without target analyte or internal standard.

Limit of Detection (LOD): An estimate of the lowest concentration of an analyte in a sample that can be reliably measured with acceptable bias and precision.

Lower limit of quantitation (LLOQ)/Decision Limit: An estimate of the lowest concentration of an analyte in a sample that can be reliably measured with acceptable bias and precision.

Stability: An analyte’s resistance to chemical change in a matrix under specific conditions for given time intervals.

Tissues: Any solid biological specimen that is generally weighed for analysis.

Reference material: Material, sufficiently homogeneous and stable with reference to specified properties, which have been established to be fit for its intended use in a measurement or in examination of nominal properties.

Dilution Integrity: the process of assessing whether diluting a sample impacts the accuracy and precision of the measured concentration of an analyte

Matrix effect: the influence of sample components other than the analyte (the substance being measured) on the analytical signal, potentially leading to inaccurate or inconsistent results. 

Calibration modeling: the process of ensuring a measuring instrument or method produces accurate results

Specificity: the ability of an enzyme or assay to specifically recognize and interact with its target molecule or analyte, without reacting with other similar molecules

Selectivity: the ability of a process or reagent to preferentially react with or discriminate between different components in a mixture, leading to the formation of a specific product or the separation of specific components

40. Which are the two phases of method development.

Instrumental and data acquisition/processing parameters

Sample preparation

41. The required validation parameters for Immunoassay screening methods.

Limit of detection

Precision (at the decision point)

Processed sample stability (if applicable)

42. The required validation parameters for screening methods other than Immunoassays.

Interference studies

Limit of detection

Ionization suppression/enhancement (for applicable techniques, such as LC/MS

Processed sample stability

43. The required validation parameters for qualitative identification methods.

Carryover

Interference studies

Ionization suppression/enhancement (for applicable techniques, such as LC/MS)

Limit of detection

Processed sample stability (if applicable)

44. The required validation parameters for quantitative methods.

Bias

Calibration Model

Carryover

Interference Studies

Ionization suppression/enhancement (for applicable techniques, such as LC/MS)

Limit of detection

Limit of quantitation

Precision

Dilution integrity (if applicable)

Processed sample stability (if applicable)

45. How the Within-Run and Between-Run bias and precision are calculated.

46. The acceptance criteria for %CV of bias and precision.

The maximum acceptable bias shall be +/-20% at each concentration

For precision, %CV shall not exceed 20% at each concentration

The grand mean +/- two standard deviations of the low and high concentration pools shall not overlap with the mean of the decision point 

47. Which are the calibration models used.

Simple linear regression model using the least squares method

48. Which is the least number of non-zero concentration calibrator samples that must be used to establish a calibration model.

Four

49. How the Limit of Detection can be calculated.

50. How the Limit of Quantification can be calculated.

LOQ = 10(Sy/Avgm)