Karens Cards on Pharmacokinetics Flashcards
What is pharmacokinetics?
What the body does to the drug
How the drug is handled
What are the 4 principles of pharmacokinetics?
ADME
A - Absorption
D - Distribution
M - Metabolism
E - Excretion
Name 4 routes of drug administration?
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
What is first pass metabolism?
- 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
1) What is bioequivalance?
2) What is bioinequivalance?
1) Bioequivalance:
- Role and extent of absorption is the same
- Different companies
2) Bioinequivalance:
- Therapeutic in-equivalence
What is half life? (2)
- 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
What is steady state? (2)
- 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
What is distribution? What is the most important factor influencing distribution? (4)
- 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
What is meant by Volume distribution?
- How far will drugs go
- The further the drug will go the longer it will take to come out
1) What are the characteristics of low volume distribution (Vd)?
2) What are the characteristics of high volume distribution (Vd)?
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
What are the considerations of plasma protein binding? (5)
- 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)
What are the 4 types of permeation?
- 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
Diffusion through cell membrane:
1) What is lipophilic?
2) What is hydrophilic
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
How does PH and ionisation impact diffusion?
- 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
Distribution summery:
Drugs cross cell membrane to produce an effect. This happens easiest with……..(4)
1) Low ionisation - cross blood brain barrier
2) Low molecular weight
3) High lipid concentration
4) High concentration gradient
Where are drugs metabolised?
- Liver is the principle organ - mainly for lipophilic drugs
Other tissues:
-GI tract
-Lung
-Skin
-Kidney
- Metabolism sometimes produce toxic metabolites
What are 8 factors that influence drug metabolism?
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
What are phase 1 and phase 2 of liver metabolism?
- 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
What are phase 1 and phase 2 of the metabolism of paracetamol?
Phase 1 - enzyme P450 (2E1) makes toxic metabolite NAPQ1 & non toxic - sulphate & glucuronide
Phase 2 - NAPQ1 conjugates with glutathione to make it non toxic
1) What are inhibitors?
2) What are inducers?
3) What are blockers?
1) Inhibitors prolong the actions of drugs
2) Inducers shorten the action of drugs
3) Blockers
Where are drugs excreted? (5)
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
1) What is Zero order?
2) What is First order?
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
