Pharmacokinetics Flashcards
Definition of “ Onset “
Time it takes for a drug to start producing its therapeutic effects
Must drugs always have at least some ability to dissolve in H2O?
Yes
What is the difference between one compartment model and two compartment model?
One compartment
-> consider the whole body as a single compartment
–> D(plasma) <-> D(tissue) is in rapid equilibrium
Two compartment
-> central compartment vs peripheral compartment
–> central compartment = rapid equilibrium
–> peripheral compartment = slower equilibrium
Which organs in the two compartment model is part of the central compartment ( high perfusion ) ?
Brain
Kidney
Heart
Liver
Lungs
What are the 4 types of drug transportation?
Passive diffusion
Carrier - mediated transport
-> active transport
-> facilitated transport
Vesicular transport
-> phagocytosis
Pore transport
-> channels
What is the equation for passive diffusion? (Fick’s Law of Diffusion)
dQ (D x A x Kp)
—- = —————- x (C1 - C2 )
dt h
-> D = constant
-> A = surface area for diffusion
-> Kp = P.C.
What is the equation for Lipid - Water Partition Coefficient ? (P.C.)
P.C. = [D] lipid / [D] water
If the polarity of a drug is high, will the P.C of the drug be high / low ?
Low
-> high polarity
–> increased ionization
—> increased conc. in water
—-> lower P.C.
Definition of “ ion trapping “
Due to pH gradient
-> ionization on one side = more total drugs
If weak acid,
what is the Handerson and Hasselbalch equation?
pH = pKa + log [A-] / [HA]
If weak base,
what is the Handerson and Haseelbalch equation?
pH = pKa - log [B+] / [BOH]
What is the percentage of ionized form of aspirin ( pKa = 3.4 ) in plasma ( pH = 7.4 )
pH = pKa + log [A-] / [HA]
-> 7.4 = 3.4 + log [A-] / [HA]
–> 4 = log [A-] / [HA]
—> [A-] / [HA] = 10 ^ (4)
—-> = 10000
Ionized form = 99.99%
Which of the following Handerson & Hasselbalch equation is wrong?
a) pH = pKa + log [B] / [BH+]
b) pH = pKa + log [A-] / [HA]
c) [BH+] / [B] = 10 ^ (pH - pKa)
d) [A-] / [HA] = 10 ^ (pH - pKa)
D
thought the ans is c???
Does ion trapping and binding of a drug to a macromolecule result in the same consequence?
Yes
they both result in difference between total drug across a membrane
Ion trapping
-> increased ionization = increased conc.
Binding to macromolecule
-> increased binding = increased conc.
How to increase drug excretion by kidney based on the concept of ion trapping?
If weak acids?
If weak bases?
Since lipid - soluble form will be absorbed by passive diffusion
-> change the pH of urine so more drugs are in ionized form
If weak acids
-> make urine more alkaline
If weak bases
-> make urine more acidic
If
mammary gland pH = 6.8
blood pH = 7.4
Is acidic or basic drug better for treating mammary gland infection?
Basic drug
-> more unionized drugs in blood => more diffusion from blood to mammary gland
–> more ionized drugs in mammary blood => ion trapping
What is the difference between zero order and first order rate of absorption / excretion ?
Zero order
-> constant amount per unit time
–> e.g. 10 = 100 -> 90 -> 80 -> 70…
First order
-> constant fraction per unit time
–> e.g. 50% = 100 -> 50 -> 25 -> 12.5…
Is rate of absorption of drugs often zero order or first order?
First order
-> usually passive diffusion
-> mechanism of absorption is often not saturated
What is the equation of First - order Kinetics of Absorption?
C = C(0) x e ^ ( -Ka t )
If high first pass effect
would bioavailability be high or low?
Low
What does ppm stands for?
parts per million
-> used to express the conc of a drug within a solution
–> e.g. 100 ppm = 100 parts of drugs for every 1 million parts of the solution
What does Ka stands for?
Absorption rate constant
-> describes the rate at which a drug is absorbed into the systemic circulation from its site of administration
memorize C = C(0) x e ^ ( -Ka t )
What does F stands for?
Bioavailability
We all know IV Bolus gives F = 100 %
While PO usually follows first order
How do we calculate the bioavailability for first order then?
Compare it to F ( IV Bolus )
F = (AUC)oral / (AUC)IV
Which of the following is used to calculate AUC?
Triangular method
Trapezoidal method
Rectangular method
Circular method
Trapezoidal method
First order rate of absorption = Ka x C(GI)
Zero order rate of absorption = Ka’
Why?
Zero order is independent of drug concentration or amount
What does Cp stands for?
Plasma concentration
What does Cpss stands for?
Steady state plasma concentration
-> the point where rate of drug administration is equal to the rate of drug elimination
What happens to t(1/2) when Ke increases?
t(1/2) decreases
-> increased rate of elimination = half life decreased
What is the 2 major organs for drug elimination?
Kidney
Liver
What is 4 examples of minor ways of drug elimination?
Lungs
-> exhalation
Sweat
Saliva
Milk
What is the equation of velocity of metabolism of a drug ? ( Michaelis - Menten Equation )
Vmax = Enzyme saturation
Km = constant, half of V max
Vmax x [S] V = -----------------
Km + [S]
Since most drugs are given at a dose that produces a Cp way smaller than Km of the enzyme for the drugs
= Km»_space;> [S]
Vmax x [S] = V = -----------------
Km
What is the First - Order Kinetics of Drug Elimination?
Cp = C(p0) x e ^ ( -Ke t )
or
ln Cp = ln C(p0) x - Ke t
In log form, the first order kinetics of drug elimination is
ln Cp = ln C(p0) x - Ke t
Which constant represents the slope in a graph?
- Ke
If given a graph with both Arithmetic ordinate ( 2, 4 ,8 ,16 ) and Logarithmic ordinate ( 0.7, 1.4, 2.1, 2.8 )
Which data should be used for slope calculation?
Logarithmic ordinate
Cp = C(p0) x e ^ ( -Ke t )
Half life of elimination ( t 1/2 ) = ?
Cp = 1/2 C (p0)
What does t (1/2) equal to ? ( using the Ke )
t (1/2 ) = 0.693 / Ke
Definition of apparent volume of distribution (Vd)
Estimate of the space in the body available to contain the drug
What is the equation of Apparent volume of Distribution?
Vd = Amount of drug in body / Plasma Drug Conc.
What percentage does total body water takes up?
60%
If 60 kg dude = 36 Liters of total body water
What percentage does plasma volume takes up?
4%
What does acidic agents enjoy binding to in plasma?
Albumins
What does basic agents enjoy binding to in plasma?
Globulins
What is the difference between perfusion - dependent and permeability - dependent ?
Perfusion - dependent
-> the factor determining the amount of drugs a compartment gets depends solely on the amount of blood it gets ( proportional to drug concentration )
Permeability - dependent
-> the factor determining the amount of drugs a compartment gets depends solely on the ability of transporting across the membrane
Does administration of high doses of drug have a probability of leading to zero - order elimination?
Yes
In two compartment model,
What are the two phases?
Alpha phase
-> distribution to tissues
Beta phase
-> elimination of drugs
In two compartment model,
What is the equation for Cp?
Cp = A x e ^ ( - alpha t ) + B x e ^ ( - beta t )
A = Cp(initial) can be determined by -alpha and is tbh technically C(p0) ahaha
B = C(p0) is determined by -beta just like in one compartment model
Ke = beta = 0.693 / t(1/2)
What does loading doses in multiple doses regimen do?
Immediate boost to effective conc.
What does maintenance dose in multiple doses regimen do?
Maintain the conc. of drugs on effective conc.
What are the equations for loading dose and maintenance dose?
Loading dose
-> Vd x Cpss(max)
Maintenance dose
-> Vd x ( Cpss(max - min) )
If a multiple doses regimen is failing due to conc. of drug dropping always dropping under the effective conc. , what changes should you apply?
Increase frequency of injection
+
Lower dosage
What is the equation for Total Body Clearance ( Cl(b) )?
Cl = Ke x Vd
Does Cl(b) includes every single elimination mechanisms e.g. Cl(renal) & Cl(hepatic)?
Yes
In one compartment model,
Cl(b) = Ke x Vd
= ( 0.693 / t(1/2) ) x Vd
Cl(renal) = Ke(renal) x Vd
If Cl(b) - Cl(renal)
in theory, what Cl(?) does it give us?
Cl(liver / hepatic)
In two compartment model,
What is the equation for Cl(b)?
Cl(b) = beta x Vd
= Vd x 0.693 / t(1/2)
The 4 most important equation to remember
1) Vd = ?
2) Cl = ?
3) t(1/2) = ?
4) F = ?
Vd = Dose / C(p0)
Cl = Ke x Vd
t(1/2) = 0.693 / Ke
F = AUC(x) / AUC(iv)
