Day 9 - Drug, Toxicity, Alcohol, Lead Flashcards
IV vs oral drug - which acts faster? Which drops faster after administration?
IV
-give active form
IV
- comes up fast, declines fast
- oral drops slowly, especially with a slow release
Single compartment vs two compartment model
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
0 order vs 1st order kinetics
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
1st drug to treat epilepsy… Current anti-epileptic drugs (3)
Bromide
Phenobarbital
Phenytoin
Primidone
-primidone is a prodrug for phenobarbital
What is the Vd?
Ratio of concentration of drug in the body to concentration of drug in the plasma (ml/kg)
-an imaginary number
A high Vd indicates a high concentration of drug in… A low Vd indicates a high concentration of drug in…
Tissues
Plasma
Equation to calculate 1st order clearance rate
Cf = Ci x 0.5^ (time/half-life)
Ci = dose / Vd
Drug is cleared faster from the body with a high or low GFR?
High
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
Ionized
Higher
-higher pH = cleared more easily
Lower
-lower pH = cleared more easily
Equation to calculate 0 order clearance rate
Dosing rate = Conc x clearance rate x dosing interval (time)
- rate that drug is lost
- determines how much to replenish
What is the LD50? Is a low or high LD50 more toxic?
Dose that’s lethal in 50% of the population
Low
-very small dose causes death
What is the ED50? Is a low or high ED50 more effective?
Dose that’s effective in 50% of the population
Low
-very small dose can be effective
What is the equation for the therapeutic index? Do we want a high or low TI when determining how safe a drug is?
TI = LD50 / ED50
High
-very high to get to lethal dose, very low to get to effective dose
Which form of a drug can cross the cell membrane - ionized or unionized?
Unionized/uncharged
- via diffusion (absorption)
- lipids in cell membrane block transport of ionized molecules
Blood containing a significant amount of carboxyhemoglobin will appear…
Cherry red color
What’s the best specimen for toxicology testing and why?
Urine since it concentrates metabolites
This is the best analytical method for confirmatory testing for drug abuse and drug toxicity…
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
Almost 90% of all human drugs are metabolized by this enzyme…
CYP (CYP450 screening)
Drugs screened for in urine (8)
Amphetamines Barbiturates Benzodiazepines THC BE (cocaine) Opiates (morphine) PCP Propoxyphene
What is the drug schedule based on? How many schedules are there? Which is the most restricted?
Potential for addiction
5
Schedule I
Adulterants in drug testing can be detected by using reagent test strips that test for (4)…
Nitrate
Glutaraldehyde
Creatinine
-tampered sample has very high creatinine
pH
Drawback of using immunoassay for drug testing
Cross-reactivity
-different analyzers will have different cross-reactivity
Difference between gas chromatography and HPLC
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
GC and HPLC separate compounds based on (3)
Size
Polarity
Reactivity
- HPLC - need to know what to look for, more interference
- Mass spectrometry - don’t need to know, less interference
