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09 - ICPP > 11 - Pharmacokinetics Drug In > Flashcards

11 - Pharmacokinetics Drug In Flashcards

1
Q

What is pharmacokinetics?

A

What the body does to the drug

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2
Q

What is

  • Pharmaceutical process?
  • Pharmacokinetic process?
  • Pharmacodynamic process?
  • Therapeutic process?
A
  • Is the drug getting into the patient
  • Is the drug getting to the site of action
  • Is drug producing the desired effect
  • Is this translated to a therapeutic effect
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3
Q

What are the main factors affecting rate of drug in and drug out?

A
  • Absorption
  • Distribution
  • Metabolism
  • Excretion
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4
Q

What are the different sites of administration of drugs?

A
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5
Q

What are the advantages of focal administration?

A
  • Concentrates drug at site
  • Prevents side effects
    e. g local steroids
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6
Q

What are the different ways of administering a drug orally?

A
  • Tablet (rate of action depends on rate of dissolution)
  • Liquid (faster)

BEST WAY TO ADMINISTER DRUGS IS ORALLY

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7
Q

How do drugs get absorbed via the enteral route?

A

SI: 6-7m length, 2.5 diameter

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8
Q

What ways can drugs be absorbed when they are in the body?

A
  • Passive Diffusion (lipophilic uncharged)
  • Facilitated Diffusion
  • Pinocytosis
  • Primary/Secondary active transport
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9
Q

What is valproate and how is it absorbed?

A
  • Antiepileptic drug
  • pKa = 5 so slightly protonated (10%)
  • Lipophilic so absorbed
  • As long transit time more chance to become protonated and absorbed
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10
Q

How are charged drugs absorbed by faciltated diffusion?

A

Solute carrier family (SLC) (OCT and OAT’s)

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11
Q

What are the properties of SLC’s?

A
  • Large family
  • Important for drug absorption and elimination
  • Larged expressed in GI, renal and hepatic epithelia
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12
Q

What drugs are absorbed by SLC secondary active transport?

A

- Prozac: antidepressant co-transported with Na+

- Penicillin: antibiotic co-transported with H+

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13
Q

What factors affect drug absorption?

A
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14
Q

Give examples of a drug absorbed by OAT and OCT?

A

OCT - Metformin (diabetes)

OAT - Methotrexate (cancer)

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15
Q

What is first pass metabolism?

A

Concentration of a drug is largely reduced before it reaches systemic circulation

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16
Q

How do you avoid first pass metabolism?

A
  • Different route of administration if large concentration of drug lost e.g parenteral, rectal, sublingual (glyceryl trinitrate)
17
Q

What is oral bioavailability of a drug?

A

Proportion of drug given orally that reaches the systemic circulation unchanged

Measured by amount and rate

18
Q

How do you calculate oral bioavailability and what does this determine?

A

Determines route of administration

19
Q

What factors affect drug distribution?

A
  • Drug lipophilicity
  • Capillary permeability
  • OAT/OLC Expression
  • Drug pKa and local pH
  • Drug binding to proteins and lipids (albumin and LDL)
20
Q

What is the importance of drugs binding to plasma proteins?

A
  • Bind in equillibrium
  • Only free drug can bind to receptors
  • Protein bound drug acts as a reservoir
21
Q

What is therapeutic index?

A
  • Got to keep drug concentration between therapeutic window

(Median Lethal Dose/Median Effective Dose)

22
Q

What is the volume of distribution?

A
  • Theoretical volume into which drug is distributed if this occurred instantaneously
  • Extrapolate back to zero
23
Q

Why do you need to look at the therapeutic ratio when deciding what concentration to give for different administation purposes?

A

If fast release preparation was same concentration of slow release preparation then the dose may go over the therapeutic window

24
Q

How do you interpret the volume of distribution and what are the units?

A
  • Small Vd, lots in blood, little distribution
  • Large Vd, little in blood, lots of distribution
  • Litres or L/Kg (standard)
25
Q

What is the volume of distribution of warfarin?

A

8L, low because lots bound to albumin

26
Q

What can Vd be affected by?

A
  • Change in regional blood flow, e.g pregnancy
  • Hypoalbuminimea, e.g neonates
  • Changes in body weight, e.g elderly
  • Drug interactions
  • Renal failure
  • Drugs with narrow therapeutic ratio
27
Q

If something has high protein binding drug interactions what is the outcome?

A

Lowered therapeutic effect

28
Q

When is protein binding interactions important?

A
  • When drug is highly bound to albumin
  • When something has a low therapeutic index
  • Has a small volume of distribution
29
Q

What is a class I and class II drug?

A

I = object

II = precipitant

30
Q

What is the issue with using a class II drug?

A
  • Will displace class I drug if administered simultaneously so concentration of class I in blood could be dangerous
  • Elimination rate of Class I will rise
  • Steady state restored in few days
31
Q

What are some precipitant drugs for warfatin and tolbutamide?

A

09 - ICPP (12 decks)

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