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PHAR 226 > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Do other healthcare professionals recieve extensive education aout pharmacokinetics?

A

No, pharmacists are the only healthcare professional that is qualified to use pharmacokinetics in their practice

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2
Q

What factors affect drug concentrations at the pharmacological receptor?

A
  1. Size and frequency of dosing
  2. ADME
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3
Q

What are the goals of dosage regimens?

A

They are used to attain and maintain therapeutic plasma drug concentrations

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4
Q

What does the variable Cther represent?

A

Drug plasma concentration that results in therapeutic effect

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5
Q

What is the therapeutic window?

A

This is the range of plasma drug concentration that produces desired clinical response in a patient (between MTC and MEC).

Plasma drug concentrations the fall beyond the therapeutic index are either toxic or sub-therapeutic

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6
Q

What variables describe clinical response?

A
  1. Onset (When Cp reaches the therapeutic window).
  2. Duration (Length of time Cp stays within therapeutic window)
  3. Intensity (Height of Cp within TW or toxic range)
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7
Q

What does the variable Css represent?

A

Average steady state plasma concentration

Pharmacists aim to position the Css within the therapeutic window

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8
Q

What is the relationship between drug concentration at site of action and clinical response?

A

They are proportionately related to each other to a point. Beyond the MTC, symptoms of toxicity develop

As one increases, so does the other

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9
Q

Can pharmacists use plasma drug concentrations to make inferences about tissue drug concentrations?

A

Yes, pharmacists can use plasma concentration as a proxy for tissue drug concentration.

Blood is more accessible, which is why it is preferred over actual measurement from tissue

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10
Q

What is Kinetic Homeogeneity?

A

Strong relationship between plasma and drug concentration

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11
Q

What are some common exposure metrics used in pharmacokinetics?

A
  1. AUC (Area under the curve). This value can give pharmacists some idea about cumulative exposure to drug
  2. Cp or Css (average stady state plasma concentration)
  3. Cmax (Maximum plasma concentration)
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12
Q

Review slide 15 for review of key pharmacokinetic parameters

A
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13
Q

What are the primary pharmacokinetic parameters?

A

They are determined only by the physiological system

  1. Ka (absorption rate constant)
  2. F (bioavailibility)
  3. Vd (Volume of Distribution
  4. Cl s (Systemic Clearance)
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14
Q

What are the secondary pharmacokinetic parameters?

A

They are determined by the primary pharmacokinetic parameters

  1. t1/2 (Half-life)
  2. k (Elimination rate constant)
  3. fe (fraction excreted)
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15
Q

What are Derived pharmacokinetic parameters?

A

Determined by the primary pharmacokinetics or can be gleaned from the Cp vs Time curve

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16
Q

What is the difference between Linear and Non-linear pharmacokinetics?

A

Linear PK: Predictable relationship between dose and Cp

Non-linear: No predictable relationshipp between dose and Cp (wild changes in Cp can resilt in negative clinincal outcomes)

17
Q

Is plasma drug concentration consistent between two patients recieving the same treatment?

A

No, there is considerable interindividual variation. This variation is due to individual differences in ADME

18
Q

What is the definition of Absorption in the context of pharmacokinetics?

A

PAssage of intact drug from administration site into systemic circulation (F, ka)

19
Q

What are the Disposition Processes?

A

It is a combination of distribution, metabolism, and excretion

They are all related because they are all observed in the systemic circulation

20
Q

What is the definiton of Distribution in the context of pharmacokinetics?

A

Reversible movement of drug between systemic circulation and the tissues (Vd and fub)

21
Q

What is the definition of Metabolism in the context of pharmacokinetics?

A

Irreversible enzymatic alteration of the drug (Phase I/II enzymes)

It is a component of Cls (systemic clearance)

22
Q

What is the definition of Excretion in the context of pharmacokinetics?

A

Irreversible passage of drug/metabolite out of body (renal, biliary)

Excretion is a component of Cls (systemic clearance)

23
Q

What are the two main routes of administration?

A

Extravascular (oral, sublingual, subQ, derma, intranasal, etc.)

Intravasular (IV)

24
Q

What factors govern the shape of Cp (plasma concentration) vs. time curves?

A
  1. Adjustable elements of dose (amount, route, dosing interval, formulation)
  2. ADME
25
Q

What factors are related to drug effect?

A
  1. Cmax (max drug concentration)
  2. tmax (time of max concentration)
  3. AUC or Css
  4. t1/2 (half-life)
  5. Therapeutic Window
26
Q

What can pharmacists observe to ensure a given dosing regimen is appropriate?

A
  1. Clinical response (most commonly measured dosing metric)
  2. Therapeutic Range (used when administering drugs with narrow therapeutic index)
27
Q

Refer to page 24 for therapeutic range

A
28
Q

What is therapeutic index?

A

The ratio of toxic Cp to effective Cp values

Wide TI (safe drug)

Narrow TI (toxicity can occur in some patients at usual doses)

29
Q

What are the components of the LADMER system?

A
  1. Liberation (dissolution of drug in solution)
  2. Absorption (drug crosses membrane barriers into systemic circulation)
  3. Distribution (free unbound drug crosses between systemic circulation and the tissues/organs)
  4. Metabolism (break down of drug into more readily excreted forms)
  5. Excretion (release of drug from body)
  6. Response (when drug binds to receptor and induces effect)
30
Q

What are the two types of transport across polarized epithelia?

A
  1. Paracellular Transport
  2. Transcellular Transport
    a. Passive Diffusion
    b. Endo-/Exocytosis
    c. Carrier-mediated
    i. Active (efflux or uptake)
    ii. Facilitated Diffusion
31
Q

What is passive diffusion?

A

Transport through a semipermeable membrane without an expenditure of energy

Drug must have hydrophobic and hydrophillic components to cross the cell membrane

32
Q

What equation describes passive diffusion?

A

Fick’s Law (see page 9 in LADMER for more details)

33
Q

What are the optimal physiochemical characteristic for a drug that is intended to be passively diffused?

A
  1. Small molecular size
  2. Lipophillic
  3. Less H-bonding
  4. Unionized
  5. Unbound drug
34
Q

What is the pH partition hypothesis?

A

Increased accumulation of drug on side of membrane where pH favours ionization

35
Q

What is the limiting factor in carrier-mediated transport?

A

Saturation of carrier proteins. Once all carriers are occupied, no amount of additional drug will increase rate of transport

36
Q

What is facilitated diffusion?

A

This process is faster than passive diffusion and it is driven by the electrochemical gradient

37
Q

What is active transport?

A

Transport occurs against the concentration gradient

This form of cellular transport requires ATP and it is unidirectional

PHAR 226 (11 decks)

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