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CLS 701 > Day 9 - Drug, Toxicity, Alcohol, Lead > Flashcards

Day 9 - Drug, Toxicity, Alcohol, Lead Flashcards

1
Q

IV vs oral drug - which acts faster? Which drops faster after administration?

A

IV
-give active form

IV

  • comes up fast, declines fast
  • oral drops slowly, especially with a slow release
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2
Q

Single compartment vs two compartment model

A

Single compartment - equal drug distribution in all tissues or only in plasma

Two compartment - distribution differences:

  • plasma vs liver
  • plasma vs bone
  • plasma vs muscle
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3
Q

0 order vs 1st order kinetics

A

0 order = drug is removed at a constant rate
-independent of concentration and changes to concentration

1st order = rate of drug removal is proportional to concentration

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4
Q

1st drug to treat epilepsy… Current anti-epileptic drugs (3)

A

Bromide

Phenobarbital
Phenytoin
Primidone
-primidone is a prodrug for phenobarbital

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5
Q

What is the Vd?

A

Ratio of concentration of drug in the body to concentration of drug in the plasma (ml/kg)
-an imaginary number

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6
Q

A high Vd indicates a high concentration of drug in… A low Vd indicates a high concentration of drug in…

A

Tissues

Plasma

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7
Q

Equation to calculate 1st order clearance rate

A

Cf = Ci x 0.5^ (time/half-life)

Ci = dose / Vd

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8
Q

Drug is cleared faster from the body with a high or low GFR?

A

High

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9
Q

Do ionized or bound drugs go into urine more easily? Are weak acids (aspirin) ionized more at lower or higher pH? Are weak bases ionized more at lower or higher pH

A

Ionized

Higher
-higher pH = cleared more easily

Lower
-lower pH = cleared more easily

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10
Q

Equation to calculate 0 order clearance rate

A

Dosing rate = Conc x clearance rate x dosing interval (time)

  • rate that drug is lost
  • determines how much to replenish
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11
Q

What is the LD50? Is a low or high LD50 more toxic?

A

Dose that’s lethal in 50% of the population

Low
-very small dose causes death

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12
Q

What is the ED50? Is a low or high ED50 more effective?

A

Dose that’s effective in 50% of the population

Low
-very small dose can be effective

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13
Q

What is the equation for the therapeutic index? Do we want a high or low TI when determining how safe a drug is?

A

TI = LD50 / ED50

High
-very high to get to lethal dose, very low to get to effective dose

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14
Q

Which form of a drug can cross the cell membrane - ionized or unionized?

A

Unionized/uncharged

  • via diffusion (absorption)
  • lipids in cell membrane block transport of ionized molecules
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15
Q

Blood containing a significant amount of carboxyhemoglobin will appear…

A

Cherry red color

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16
Q

What’s the best specimen for toxicology testing and why?

A

Urine since it concentrates metabolites

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17
Q

This is the best analytical method for confirmatory testing for drug abuse and drug toxicity…

A

Gas chromatography/Mass spec

  • sample is vaporized and injected onto chromatographic column for GC
  • MS fragments vaporized molecules into charged molecules
  • separation into mass and charge
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18
Q

Almost 90% of all human drugs are metabolized by this enzyme…

A

CYP (CYP450 screening)

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19
Q

Drugs screened for in urine (8)

A 
Amphetamines
Barbiturates
Benzodiazepines
THC
BE (cocaine)
Opiates (morphine)
PCP
Propoxyphene
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20
Q

What is the drug schedule based on? How many schedules are there? Which is the most restricted?

A

Potential for addiction

5

Schedule I

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21
Q

Adulterants in drug testing can be detected by using reagent test strips that test for (4)…

A

Nitrate

Glutaraldehyde

Creatinine
-tampered sample has very high creatinine

pH

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22
Q

Drawback of using immunoassay for drug testing

A

Cross-reactivity

-different analyzers will have different cross-reactivity

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23
Q

Difference between gas chromatography and HPLC

A

GC uses gas phase

HPLC uses liquid phase

  • solid phase and mobile phase
  • analytes with greater affinity for stationary phase elute later than those with greater affinity for mobile phase
24
Q

GC and HPLC separate compounds based on (3)

A

Size

Polarity

Reactivity

  • HPLC - need to know what to look for, more interference
  • Mass spectrometry - don’t need to know, less interference
25
Q

The primary product of ethanol metabolism that is toxic is… The process uses this enzyme…

A

Acetaldehyde

ADH (alcohol dehydrogenase)

26
Q

Too much alcohol triggers an imbalance in this molecule…

A

NADH/NAD+

  • too much NADH buildup
  • interferes with glycolysis
27
Q

What process is alcohol interfering with in fetuses?

A

Vitamin A

28
Q

Alcohol will cause the osmolar gap to be…

A

> 10 (elevated)

29
Q

The chemical in antifreeze is… These crystals form in the urine in patients with antifreeze toxicity…

A

Ethylene glycol

Calcium oxalate crystals
-found in normal urine

30
Q

How do we treat lead poisoning?

A

Chelating therapy

  • add something to bind to heavy metal so it can be removed from the body
  • nonspecific
  • patient can develop deficiency in other trace metals
  • chelaters: EDTA, DMSA
31
Q

Lead poisoning is detected by testing this specimen… What is the lead testing called and how is it performed?

A

Blood

Anodic stripping voltammetry

  • lead inside RBCs will leech out into reagent
  • add electrode and run current to determine amount of lead that leaked out
  • uses gas chromatography for confirmation (no need for GCMS)
32
Q

Lead poisoning affects this body system…

A

CNS

33
Q

In the body, lead is deposited into (2)…

A

RBCs
-inhibits hemoglobin synthesis

Bone
-stays for decades, slowly releasing into circulation

34
Q

A person with lead poisoning will show a blood smear with RBCs showing… What does lead do inside RBCs?

A

Basophilic stippling

Inhibits hemoglobin synthesis by inhibiting ALA

  • rate limiting step in heme synthesis
  • severe anemia results
35
Q

Lead causes this hemoglobin protein to build up in the blood and urine

A

ALA

36
Q

What does lead do in the kidneys? How does lead cause gout?

A

Inhibits ion transport and excretion

Inhibits uric acid excretion
-uric acid buildup causes gout

37
Q

Lead exposure - routes of entry (2)

A

Inhalation (organic lead gasoline)

Food/ingestion

38
Q

For therapeutic drug monitoring, when do drugs peak for an IV dose? Oral dose?

A

10 mins

1 hr

-trough = just before next oral or IV dose

39
Q

Aminoglycosides, gentamicin, amikacin, tobramycin, vancomycin are examples of this group of drugs…

A

Antibiotics

40
Q

Digoxin (Lanoxin), procainamide (Pronestyl), lidocaine (Xylocaine) are used to treat…

A

Heart/cardiac

41
Q

Acetaminophen (Tylenol) and aspirin are…

A

Analgesics (painkillers)

42
Q

Cyclosporin (Sandimmune) is used as an…

A

Immunosuppressant

  • used for transplant patients
  • inhibits IL-2
  • stops lymphocyte proliferation
43
Q

Lithium (Eskalith) is used to treat…

A

Bipolar depressive disorders

44
Q

Overdose on aspirin can cause… Overdose on acetaminophen (Tylenol) can cause…

A

Bleeding
-interferes with platelet aggregation

Hepatic necrosis, liver failure
-drug is metabolized in the liver to glucuronide and metabolites

45
Q

Bound vs free drug - which is active and which is inactive?

A

Bound = inactive

Free = active

46
Q

Biotransformation of a drug is when a ___ is metabolized into a ___. Which is hydrophobic and which is hydrophilic?

A

Parent compound = hydrophobic

Drug metabolite = hydrophilic
-can be eliminated in body through blood, bile, urine

47
Q

Are parent compounds more or less active than their metabolites? The exceptions are called…

A

More active

  • metabolites less active
  • this is usually the case

Prodrug
-metabolites more active

48
Q

What are the 4 outcomes once a parent compound is converted into a drug metabolite?

A

Active metabolite

Inactive metabolite

Toxic metabolite

No change (from parent compound)

49
Q

The clearance rate of aspirin is affected by…

A

Blood pH

  • aspirin is a weak acid
  • can be ionized and cleared faster at higher pH
50
Q

What is the urine clearance time for 1 joint of THC? The test can be adulterated by degrading THC with…

A

5 days

Bleach
-also Visine, Urinaid, Joy Soap

51
Q

How is ethylene glycol poisoning treated?

A

Give ethanol to compete with ADH (alcohol dehydrogenase)

-alternative: fomepizole at 10 mg/kg for 3 doses total (expensive)

52
Q

What is ethanol’s metabolic effect on: lipogenesis, ketone bodies, glycolysis

A

Increase

Increase

Decrease

53
Q

Upon a breathalyzer test, there must be a waiting period of ___ and there must be a time of ___ since the last rinsing of the mouth

A

15 minutes since last drink of alcohol

6-7 minutes

54
Q

Ethylene glycol lab results: pH, pCO2/CO2, osmolality, anion gap

A

Low

Low

High

High

55
Q

In a mass spectrometry reading, what are the smaller peaks after a large spike?

A

Isotopes

-C13 atoms in atmosphere give +1 to molecular weight

56
Q

A mass spectrometry quantifies based on… There is a tradeoff between these two things…

A

Mass to charge ratio upon ionization

Resolution and signal

  • high resolution = low signal
  • high signal = low resolution

CLS 701 (10 decks)

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