Flashcards in Pharmacokinetics Deck (32):
What are the 3 time allotments considered for routes of administration?
Time for dissolution (if solid formulation)
Time for absorption (considered 0 time for IV)
Time for circulation (to site of action/onset of action)
What are the 2 routes of passive (simple) absorption?
Filtration = through pores or channels; determined y osmotic/hydrostatic pressure differential
Diffusion = through cell membranes; determined y concentration gradient
What method of absorption is most commonly utilized by drugs?
Passive diffusion (through cell membranes y concentration gradient)
What is the difference between an ionized and unionized drug?
Ionized = charged/polar
Unionized = uncharged/nonpolar
What are the characteristics of ionized vs unionized compounds in terms of lipid solubility and PM diffusion?
Ionized compounds = lower lipid solubility and do not easily diffuse across PM
Unionized compounds = higher lipid solubility and easily diffuse across PM
Ionization status of drugs depends on 2 factors. What are they?
pKa of medication
PH of membrane gradient
Define pH versus pKa
PH = measure of acidity of a soln (0-14) and is a fnx of the amt of H+ in soln
PKa = propensity of a compound to donate (acids) or accept (bases) a proton
There are 2 important areas of the body where pH varies and commonly impacts ionization status. What are these 2 locations
When is there a 50%:50% ratio of ionized:unionized drug in the body?
When pKa = pH
Differentiate between ionized and unionized drugs in terms of absorption and elimination
HIghly ionized drugs DO NOT get readily absorbed and ARE eliminated
Highly unionized drugs DO readily get absorbed and are NOT eliminated
Facilitated diffusion is considered active transport but is unique. What are the unique characteristics of facilitated diffusion?
- does not require energy
- does not proceed against gradients
What does the alpha represent in bound/unbound fraction of a drug?
Represents the unbound fraction
**Alpha is opposite of percent protein bound
Differentiate between bound and unbound drugs
Unbound = free drug; this is active -> represented by alpha; low protein binding means low displacement
Bound = inactive drug
Explain the naming of CYPs
Family = first number
Subfamily = letter
Individual = last number
List the main sites of action of the cytochrome P450 enzyme system
What are the 3 main processes of renal elimination?
1. Passive glomerular filtration -> blood flow dependent
2. Passive tubular diffusion -> PCT or DCT, ionization & concentration status dependent
3. Active tubular secretion -> weak acids/bases secreted into PCT
Explain first order kinetics
- the percentage of the total amount of change in the plasma concentration remains constant over time
$100 - 1/2 = 50 - 1/2 = 25...
Explain zero order kinetics
- the percentage of the total amount of change in the plasma concentration is not constant over time
- saturable (Vmax)
100-50 = 50 - 50 = 0 -> lose the same amount every time instead of a proportional loss
What does Tmax stand for?
Time at Cmax
What does MEC vs MTC stand for?
MEC = minimum effective concentration
MTC = maximum therapeutic concentration
What does F stand for in terms of absorption?
Bioavailability -> represents the fraction oof a dose that enters circulation
- describes the extend of absorption NOT the rate of absorption
- always considered 100% (F=1) for IV route
- no units
What factors determine the bioavailability of a drug?
Ionizing status in various locations
First pass and GI metabolism
Dissolution -> extend vs rate
What does S stand for in terms of absorption?
Salt factor -> percentage of a dose that equals the primary serum-assessed drug
- no units
What are the 3 items that determine the amount of drug absorbed?
Salt factor (S)
What is the equation for ideal body weight (IBW)?
Female = 45kg + (2.3kg X (height in inches - 60”))
Male = same but base weight of 50kg
What is the adjusted body weight (AdjBW) equation?
(0.4 X (ABW - IBW)) + IBW
**Used for ABW >40% higher than IBW
What does Cpss stand for. In terms of elimination?
Steady state -> represents an equilibrium between drug administration and body clearance, where rate in = rate out
- units = w/v #’s
- related to dose, Cl, Kel and T1/2
What is the equation used to calculate the loading dose and what are the units of the answer?
LD = ((Vd)(Cp)) / ((S)(F))
Units = weight units
What equation do you use to calculate a supplemental loading dose (LDsuppl) and what are the units of the answer?
LDsuppl = ((Vd)(Cpd - CPI) / (S)(F))
Units = weight units
What is the equation used to calculate the maintenance dose (MD)?
((Cl)(Cp)(tau)) / ((S)(F))
What is the equation used to calculate the elimination rate constant (Kel)?
((Ln(Cpt1) - ln(Cpt2)) / (T2-T1)