Module 3 Distribution Flashcards
1
Q
Interstitial Space
A
- Extracellular fluid surrounding cells
- Low molecular weight
- Water soluble drugs
2
Q
Plasma
A
- Non-cell component of blood
- High molecular weight
- Drugs bound to plasma protein
3
Q
Adipose Tissue
A
- Lipophilic drugs
4
Q
Muscle
A
- Some drugs bind to muscle tissue
5
Q
Bone
A
- Crystal surface absorption, crystal lattice
- Slow release of drugs
6
Q
Drug Distribution Factors
A
- Blood flow to tissues
- Ability to move out of capillary
- Ability to move into cell
7
Q
Low-Perfused Tissues
A
- Skin
- Fat
- Bone
8
Q
High-Perfused Tissues
A
- Liver
- Brain
- Kidney
9
Q
Implications of Altered Flow
A
- Heart failure/shock slows distribution
- Solid tumours (low flow in centre)
- Abscesses (no flow)
10
Q
Ability to Move out of Capillary
A
- Rapid movement into interstitial space
- Excluding brain
- Uses fenestrations (gaps)
11
Q
Ability to Move into Cell
A
- Cell membrane requires lipophilic component
- Carried by transporter
- Efflux transporters perform removal
12
Q
P-Glycoprotein
A
- Important efflux transporter
- Drug distribution
- Protective/permeability
- Requires ATP to transport against gradient
13
Q
P-GP Protection
A
- Facilitates drug efflux from cells
- Promotes excretion
- Protects against toxin exposure
14
Q
P-GP in Liver
A
- Drugs into bile
- Excretion
15
Q
P-GP in Intestine
A
- Drugs into lumen
- Preventing blood absorption
16
Q
P-GP in Kidney
A
- Drugs into lumen
- Facilitate excretion
17
Q
P-GP in Brain
A
- Drugs into blood
- Limiting brain exposure
18
Q
Plasma Protein Binding
A
- Drugs bound to plasma can’t pass fenestrations
- Can’t elicit a pharmacological response
- Reversible reaction
19
Q
Plasma Protein Types
A
- Albumin
- Alpha 1 acid glycoprotein
20
Q
Albumin
A
- Lipophilic & anionic (weakly acidic)
- Majority of protein binding
21
Q
Alpha 1 Acid Glycoprotein
A
- Cationic (weakly basic) & hydrophilic
22
Q
Reversible Plasma Binding
A
- Equilibrium between plasma protein & free drug
- Free drug removal = dissociation from plasma
23
Q
Affecting Factors of Albumin Binding
A
- Malnutrition
- Trauma
- Aging
- Liver & kidney disease
- Increase free drug concentration
- Toxicity risk
24
Q
Affecting Factors of Alpha 1 Binding
A
- Aging
- Trauma
- Hepatic inflammation
- Decrease free drug concentration
- Ineffective therapy risk
25
Q
Volume of Distribution (Vd)
A
- Apparent volume that drug distributes into
- Determine relative drug distribution
- Extensive binding increases volume
26
Q
Vd Equation
A
= D/c
- D, total amount of drug in body
- C, plasma concentration of drug
27
Q
Small Vd Drugs
A
- Highly protein bound
- Large molecular weight
- No passage through fenestrations
- Exclusively distributed in plasma (vascular space)
28
Q
Intermediate Vd Drugs
A
- Low molecular weight
- Hydrophilic, no membrane crossing
- Vascular space & interstitial space
- Unable to enter cells
29
Q
Large Vd Drugs
A
- Low molecular weight
- Lipophilic, cross membrane
- Distribute fat, muscle, bone
30
Q
Drug Displacement
A
- Dependant on volume of distribution
- One drug can displace another
31
Q
Small Vd in Displacement
A
- Displaced drug remains in plasma
- Free drug concentration increase
32
Q
Large Vd in Displacement
A
- Displaced drug leaves plasma, distributes into tissue
- Total plasma drug concentration decrease
- Vd increases
33
Q
Muscle Composition Changes
A
- Decreased % of muscle
- Muscle distributing drugs, lower Vd
34
Q
Fat Distributing Drugs
A
- Increased fat proportions in elderly & obese
- Larger Vd
