Pharmacology 2060A/B Lecture Notes - Lecture 3: Hydrophile, Malnutrition, Bile Canaliculus

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Pharmacokinetics- Distribution
Body Compartments
Drugs distribute into compartments in the body where they may be stored, metabolized, excreted or exert
their pharmacological effect
The body’s compartments include:
1. Interstitial space- the extracellular fluid that surrounds the cells. Low molecular weight, water soluble
drugs distribute in the interstitial space
2. Total body water- includes the fluid in the interstitial space, intracellular fluid and the plasma
3. Plasma- the non-cell containing component of blood. Drugs strongly bound to plasma protein and high
molecular weight drugs typically distribute in plasma
4. Adipose tissue- the body’s fat. Lipid soluble (lipophilic) drugs distribute into adipose tissue
5. Muscle- some drugs bind tightly to muscle tissue
6. Bone- some drugs absorb onto the crystal surface of bone with eventful incorporation into the crystal
lattice. Bone can be a reservoir for the slow release of some drugs
7. Other tissues
Drug Distribution
Determined by:
1. Blood flow to tissues
2. Ability of drug to move out of capillaries
3. Ability of drug to move into cells
The more drug that distributes out of the blood, the lower the concentration of drug in the blood
1. Blood Flow to Tissues
Is a key determinant of drug distribution
In well perfused tissues such as the liver, kidney and brain, drug distribution is rapid
Distribution to tissues with lower blood flow such as skin, fat and bone is much slower
Implications for Altered Blood Flow
Neonates have limited blood flow and therefore may have limited drug distribution
Poor blood flow rarely limits drug distribution in adult patients however some exceptions do exist
oPatients with heart failure or shock may have reduced blood flow and therefore altered drug
distribution
oSolid tumors have low regional blood flow. The outer portion of tumors has a high blood flow but
the blood flow progressively decreases towards the middle. Therefore, it is difficult to attain high
drug concentrations within solid tumors
oAbscesses (infection filled with pus) have no blood supply and are therefore difficult to treat with
antibiotics. They are often drained prior to drug therapy
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