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Pharmacology > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Definition of “ Onset “

A

Time it takes for a drug to start producing its therapeutic effects

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2
Q

Must drugs always have at least some ability to dissolve in H2O?

A

Yes

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3
Q

What is the difference between one compartment model and two compartment model?

A

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

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4
Q

Which organs in the two compartment model is part of the central compartment ( high perfusion ) ?

A

Brain
Kidney
Heart
Liver
Lungs

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5
Q

What are the 4 types of drug transportation?

A

Passive diffusion

Carrier - mediated transport
-> active transport
-> facilitated transport

Vesicular transport
-> phagocytosis

Pore transport
-> channels

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6
Q

What is the equation for passive diffusion? (Fick’s Law of Diffusion)

A

dQ (D x A x Kp)
—- = —————- x (C1 - C2 )
dt h

-> D = constant
-> A = surface area for diffusion
-> Kp = P.C.

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7
Q

What is the equation for Lipid - Water Partition Coefficient ? (P.C.)

A

P.C. = [D] lipid / [D] water

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8
Q

If the polarity of a drug is high, will the P.C of the drug be high / low ?

A

Low
-> high polarity
–> increased ionization
—> increased conc. in water
—-> lower P.C.

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9
Q

Definition of “ ion trapping “

A

Due to pH gradient
-> ionization on one side = more total drugs

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10
Q

If weak acid,
what is the Handerson and Hasselbalch equation?

A

pH = pKa + log [A-] / [HA]

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11
Q

If weak base,
what is the Handerson and Haseelbalch equation?

A

pH = pKa - log [B+] / [BOH]

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12
Q

What is the percentage of ionized form of aspirin ( pKa = 3.4 ) in plasma ( pH = 7.4 )

A

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%

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13
Q

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)

A

D

thought the ans is c???

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14
Q

Does ion trapping and binding of a drug to a macromolecule result in the same consequence?

A

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.

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15
Q

How to increase drug excretion by kidney based on the concept of ion trapping?
If weak acids?
If weak bases?

A

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

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16
Q

If
mammary gland pH = 6.8
blood pH = 7.4

Is acidic or basic drug better for treating mammary gland infection?

A

Basic drug
-> more unionized drugs in blood => more diffusion from blood to mammary gland
–> more ionized drugs in mammary blood => ion trapping

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17
Q

What is the difference between zero order and first order rate of absorption / excretion ?

A

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…

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18
Q

Is rate of absorption of drugs often zero order or first order?

A

First order
-> usually passive diffusion
-> mechanism of absorption is often not saturated

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19
Q

What is the equation of First - order Kinetics of Absorption?

A

C = C(0) x e ^ ( -Ka t )

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20
Q

If high first pass effect
would bioavailability be high or low?

A

Low

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21
Q

What does ppm stands for?

A

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

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22
Q

What does Ka stands for?

A

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 )

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23
Q

What does F stands for?

A

Bioavailability

24
Q

We all know IV Bolus gives F = 100 %
While PO usually follows first order
How do we calculate the bioavailability for first order then?

A

Compare it to F ( IV Bolus )

F = (AUC)oral / (AUC)IV

25
Q

Which of the following is used to calculate AUC?

Triangular method
Trapezoidal method
Rectangular method
Circular method

A

Trapezoidal method

26
Q

First order rate of absorption = Ka x C(GI)
Zero order rate of absorption = Ka’
Why?

A

Zero order is independent of drug concentration or amount

27
Q

What does Cp stands for?

A

Plasma concentration

28
Q

What does Cpss stands for?

A

Steady state plasma concentration
-> the point where rate of drug administration is equal to the rate of drug elimination

29
Q

What happens to t(1/2) when Ke increases?

A

t(1/2) decreases
-> increased rate of elimination = half life decreased

30
Q

What is the 2 major organs for drug elimination?

A

Kidney
Liver

31
Q

What is 4 examples of minor ways of drug elimination?

A

Lungs
-> exhalation
Sweat
Saliva
Milk

32
Q

What is the equation of velocity of metabolism of a drug ? ( Michaelis - Menten Equation )

A

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&raquo_space;> [S]

       Vmax x [S]             = V =  -----------------
             Km
33
Q

What is the First - Order Kinetics of Drug Elimination?

A

Cp = C(p0) x e ^ ( -Ke t )

or

ln Cp = ln C(p0) x - Ke t

34
Q

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?

A
  • Ke
35
Q

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?

A

Logarithmic ordinate

36
Q

Cp = C(p0) x e ^ ( -Ke t )

Half life of elimination ( t 1/2 ) = ?

A

Cp = 1/2 C (p0)

37
Q

What does t (1/2) equal to ? ( using the Ke )

A

t (1/2 ) = 0.693 / Ke

38
Q

Definition of apparent volume of distribution (Vd)

A

Estimate of the space in the body available to contain the drug

39
Q

What is the equation of Apparent volume of Distribution?

A

Vd = Amount of drug in body / Plasma Drug Conc.

40
Q

What percentage does total body water takes up?

A

60%

If 60 kg dude = 36 Liters of total body water

41
Q

What percentage does plasma volume takes up?

A

4%

42
Q

What does acidic agents enjoy binding to in plasma?

A

Albumins

43
Q

What does basic agents enjoy binding to in plasma?

A

Globulins

44
Q

What is the difference between perfusion - dependent and permeability - dependent ?

A

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

45
Q

Does administration of high doses of drug have a probability of leading to zero - order elimination?

A

Yes

46
Q

In two compartment model,
What are the two phases?

A

Alpha phase
-> distribution to tissues

Beta phase
-> elimination of drugs

47
Q

In two compartment model,
What is the equation for Cp?

A

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)

48
Q

What does loading doses in multiple doses regimen do?

A

Immediate boost to effective conc.

49
Q

What does maintenance dose in multiple doses regimen do?

A

Maintain the conc. of drugs on effective conc.

50
Q

What are the equations for loading dose and maintenance dose?

A

Loading dose
-> Vd x Cpss(max)

Maintenance dose
-> Vd x ( Cpss(max - min) )

51
Q

If a multiple doses regimen is failing due to conc. of drug dropping always dropping under the effective conc. , what changes should you apply?

A

Increase frequency of injection
+
Lower dosage

52
Q

What is the equation for Total Body Clearance ( Cl(b) )?

A

Cl = Ke x Vd

53
Q

Does Cl(b) includes every single elimination mechanisms e.g. Cl(renal) & Cl(hepatic)?

A

Yes

54
Q

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?

A

Cl(liver / hepatic)

55
Q

In two compartment model,
What is the equation for Cl(b)?

A

Cl(b) = beta x Vd
= Vd x 0.693 / t(1/2)

56
Q

The 4 most important equation to remember

1) Vd = ?
2) Cl = ?
3) t(1/2) = ?
4) F = ?

A

Vd = Dose / C(p0)

Cl = Ke x Vd

t(1/2) = 0.693 / Ke

F = AUC(x) / AUC(iv)

Pharmacology (5 decks)

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