Distribution Flashcards
refers to the reversible transfer of drug from one location to another within the body.
Distribution
Factors Affecting Distribution (5)
- Regional blood flow
- Capillary permeability
- Physicochemical properties of the drug
- Protein binding
- Volume of distribution
Regional blood flow
(Rate of distribution)
- Give 4 highly perfused organ that increases the drug distribution
Brain
Heart
Liver
Kidney
Regional blood flow
(Rate of distribution)
Give 3 slow perfused organ that decreases the drug distribution
Fat
Tissue
Skin
(Factor) It is the ability to pass through capillary and enter to tissues
Capillary permeability (volume of blood )
What are the 2 junction types or capillary permeability
Discontinuous
Continuous
junction type of capillary permeability that:
β- has spaces in between
β- easily pass through
Discontinuous
Ex. Organ that has discontinuous type
Liver
ββ fast distribution (1st factor)
ββ easily pass through (2nd factor)
Ex. Organ that has discontinuous type
Liver
Ex. Organ that has continuous type
Brain (BBB - walls of capillary)
ββ fast distribution (factor 1)
ββ not easily pass through (factor 2)
junction type of capillary permeability that:
β- w/o spaces in between
β- do not easily pass through
Continuous
Ex. Of drugs that passes through continuous type
LUNA - passes through BBB
Super lipophilic
Ex. 1st gen. Antihistamines
Effect: sedative
What are the 2 factors under physicochemical properties of drug.
Molecular weight
Solubility
Physicochemical factors (molecular weight)
- give ex. Of VERY large molecule (upto 2000kDa)
- it stays at_____
Dextran
- Plasma
Physicochemical factors (molecular weight)
- give ex. Of large molecule (5-30 kDa)
- it stays at_____
Heparin
- extracellular space
Why High MW - X Pass through cell membrane ?
Because of large structure
(Solubility)
Hydrophilic, ionized drug stays at_____
Extracellular fluid(space)
(Solubility)
Lipophilic compounds is readily diffuse into_____
Tissues
Extremely lipid soluble compounds accumulate in the _______
adipose tissue
(Factor) Indicator of the extent of drug distribution into body fluids and tissues
β’ Relates the amount of drug in the body to the measured concentration in the plasma
ππππ’ππ ππ πππ π‘ππππ’π‘πππ (πd ) = ππππ’ππ‘ ππ πππ’π /ππππ ππ πππππππ‘πππ‘πππ (πΆβ)
β’ Important for the calculation of loading dose
total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.
Volume of Distribution or apparent volume of distribution
Correlation of Vd with body fluids
β’ Total body fluids =___% of BW (males); ____% of BW (females)
Intracellular fluids = ____% of BW o Extracellular fluids =____% of BW
β Interstitial compartment =___% BW β Intravascularcompartment=__%BW
TBF male: 60%
TBF female: 50-55%
ICF: 40%
EXF: 20%
ISC: 15%
IVC: 5%
Volume of Distribution of Warfarin
8
Volume of Distribution of Gentamicin
18
Volume of Distribution of Digoxin
440
Volume of Distribution of Diazepam
80
Volume of Distribution of Diazepam
80
Volume of Distribution of Nortriptyline
1700
Volume of Distribution of Chloroquine
> 15000
SIGNIFICANCE of determining drug__________:
β’ Provides slow release form of a drug (repository, resulting to extended effect)
β’ Limit access to certain body compartments
β’ Can make the drug prone to drug-drug interaction
Protein binding
(3) SIGNIFICANCE of determining drug protein binding:
1.Provides slow release form of a drug (repository, resulting to extended effect)
2.Limit access to certain body compartments
3.Can make the drug prone to drug-drug interaction
Protein binding of Gentamicin
3
Protein binding of Gentamicin
3
Protein binding of Digoxin
25
Protein binding of Vancomycin
30
Protein binding of Lidocaine
51
Protein binding of phenytoin
89
Protein binding of warfarin
99
2 types of plasma protein
Albumin
Alpha 1 acid glycoprotein
Types of plasma protein that bind to drug w/ neutral and acidic pH ( low pH)
Albumin
Give 3 example of drug with neutral pH
Chloramphenicol
Dexamethasone
Diazepam
Give 4 example of drug with acidic/weak acid
Barbiturates
Penicillins
Salicylates (Aspirin)
Gentamicin
Types of plasma protein that bind to weak bases
Alpha 1 acid glycoprotein
Give 3 example of drug with weak base
Lidocaine (Xylocaine)
Saquinavir
Propranolol
Significance of determining drug protein binding
Protein displacement
