Karens Cards on Pharmacokinetics Flashcards

1
Q

What is pharmacokinetics?

A

What the body does to the drug

How the drug is handled

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2
Q

What are the 4 principles of pharmacokinetics?

A

ADME

A - Absorption
D - Distribution
M - Metabolism
E - Excretion

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3
Q

Name 4 routes of drug administration?

A

Oral - convenient, efficient, differences in PH, 1st pass metabolism

Buccal - High blood flow, avoids first pass metabolism

Inhalation - Large surface area, high blood flow

Rectal - reduced 1st pass metabolism

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4
Q

What is first pass metabolism?

A
  • prepares the blood to go back into circulation and filters out foreign bodies
  • gut wall
  • hepatic portal vein
  • liver (metabolised)
  • vena cava
  • What is left in the blood is bioavailability (amount of drug available to the body) NOT how effective the drug is
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5
Q

1) What is bioequivalance?

2) What is bioinequivalance?

A

1) Bioequivalance:
- Role and extent of absorption is the same
- Different companies

2) Bioinequivalance:
- Therapeutic in-equivalence

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6
Q

What is half life? (2)

A
  • Time taken for the concentration of a drug in the blood to fall by 50% of its original value
  • Metabolism and excretion will determine half life
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7
Q

What is steady state? (2)

A
  • When the value of drug input is equal to the rate of elimination
  • It takes 5 half lives to reach steady state in any drug
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8
Q

What is distribution? What is the most important factor influencing distribution? (4)

A
  • The transport of drugs to the target site of action
  • Most important factor in determining distribution is protein binding
  • Most drugs bind to plasma proteins (Albumin - carrier molecules)
  • If Albumin is low then they will have problems with distribution
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9
Q

What is meant by Volume distribution?

A
  • How far will drugs go
  • The further the drug will go the longer it will take to come out
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10
Q

1) What are the characteristics of low volume distribution (Vd)?

2) What are the characteristics of high volume distribution (Vd)?

A

1) Low Vd:
- Drug confined within the plasma, more affinity to plasma proteins, more bound
- Limited distribution

2) High Vd:
- Higher affinity to tissue proteins not present in the plasma, so more distribution in the extravascular space
- Drug goes further

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11
Q

What are the considerations of plasma protein binding? (5)

A
  • Drugs get to the circulatory system bind to proteins - non specific & reversible
  • When a drug is bound to a protein it is inactive. When it is not bound it is active
  • Extensive plasma protein binding will increase the amount of drug that has to be absorbed before effective therapeutic levels of unbound drug are released
  • Elimination of a highly bound drug may be delayed
  • Changes in plasma protein concentration. Low plasma protein means smaller amount will be bound & therefore more free drug (risk of toxicity)
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12
Q

What are the 4 types of permeation?

A
  • Aqueous diffusion (water soluble)
    *Lipid diffusion (fat soluble)
  • Facilitated diffusion (concentrated gradient, small molecules, non charged)
  • Pinocytosis (cell eating)

Flicks 1st law of diffusion - diffusion through lipid of cell membrane

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13
Q

Diffusion through cell membrane:

1) What is lipophilic?

2) What is hydrophilic

A

1) Lipophilic - fat loving, non ionised/uncharged

2) Hydrophilic - water loving, charged/ionised

  • cell membrane fatty acids - lipophilic - fat loving. Lipophilic can get through
  • Drugs in their active form are usually lipophilic
  • Hydrophilic drugs are excreted rapidly from the body
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14
Q

How does PH and ionisation impact diffusion?

A
  • Ionised drugs - can’t get very far - hydrophilic
  • Unionised drugs - can go anywhere - lipophilic
  • Lipid drugs attract non ionised molecules
  • Aqueous drugs attract ionised molecules
  • Acid drugs in acid environment - non ionised
    *Alkali drugs in alkali environment- non ionised
    *Acid drugs in alkali environment- ionised
    *Alkali drugs in acid environment - ionised
  • Non ionised move through lipid membrane, ionised doesn’t
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15
Q

Distribution summery:

Drugs cross cell membrane to produce an effect. This happens easiest with……..(4)

A

1) Low ionisation - cross blood brain barrier
2) Low molecular weight
3) High lipid concentration
4) High concentration gradient

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16
Q

Where are drugs metabolised?

A
  • Liver is the principle organ - mainly for lipophilic drugs

Other tissues:
-GI tract
-Lung
-Skin
-Kidney

  • Metabolism sometimes produce toxic metabolites
17
Q

What are 8 factors that influence drug metabolism?

A

1) Genetics - cytochrome P450 enzyme
2) Gender (males metabolise faster)
3) Age - over 50 or young immature liver
4) Liver size and function - young babies
5) Circadian rhythms
6) Body temp - cold metabolise slower
7) Nutritional state - distribution low Alb
8) Environment - smoking - fast acrlater

18
Q

What are phase 1 and phase 2 of liver metabolism?

A
  • Phase 1:
    -Metabolic reactions caused by enzyme super family P450, located in the endoplasmic reticulum. Makes a toxic metabolite. Usually oxidation
  • Phase 2:
  • Performed by various enzymes located in the endoplasmic reticulum & cytosol. H2O is added to make less toxic and easier to excrete
19
Q

What are phase 1 and phase 2 of the metabolism of paracetamol?

A

Phase 1 - enzyme P450 (2E1) makes toxic metabolite NAPQ1 & non toxic - sulphate & glucuronide

Phase 2 - NAPQ1 conjugates with glutathione to make it non toxic

20
Q

1) What are inhibitors?
2) What are inducers?
3) What are blockers?

A

1) Inhibitors prolong the actions of drugs
2) Inducers shorten the action of drugs
3) Blockers

21
Q

Where are drugs excreted? (5)

A

1) Kidneys
* Glomerula Filtration:
- no control
- driven by BP and MAP
- Anything H2O soluble can go through and come out in urine
* Tubular secretion:
- under control
- some things absorbed or secreted

2) GI tract
3) Lungs
4) breast milk, sweat

5) Liver - some drugs excreted in bile (sedatives). Enterohepatic re uptake - drugs in bile re absorbed in small bowel

22
Q

1) What is Zero order?
2) What is First order?

A

1) Zero order:
- excretion is independent of the concentration
- non linear
- cars roadblock
- ethanol

2) First Order:
- Excretion is generally proportional to its concentration
-linear
- hole in a jug, the more it’s filled the more it flows
- most drugs