Body as a Reservoir for Drugs
The body can act as a reservoir for drugs due to the tendency of some drugs to accumulate in specific tissues or compartments. This process is influenced by factors such as tissue affinity, blood flow, and drug properties, including lipophilicity.
Common Drug Reservoirs in the Body
Adipose (Fat) Tissue
Description: Lipophilic (fat-soluble) drugs often accumulate in adipose tissue due to its high fat content and low blood flow.
Examples
- Thiopental: An anesthetic that initially distributes to the brain but later accumulates in fat, prolonging its effects.
- Diazepam: An anxiolytic that accumulates in fat, leading to extended effects with repeated dosing.
Clinical Importance
Drugs stored in fat may be cleared slowly, affecting dosing in patients with higher fat levels. Lipophilic drugs in adipose tissue may prolong effects or increase toxicity risk in obese patients.
Bone
Description: Certain drugs and heavy metals accumulate in bone by binding with the bone mineral matrix.
Examples
- Tetracycline: An antibiotic that binds to calcium in bone, leading to retention and potential discoloration of developing teeth.
- Lead: Accumulates in bone and is released slowly, potentially leading to toxicity over time.
Clinical Importance
Accumulation in bone can pose risks, particularly during childhood when bones are developing. Slow release from bones can lead to prolonged effects or toxicity.
Muscle
Description: Muscle tissue can serve as a reservoir for drugs binding to muscle proteins or lipids.
Examples
- Digoxin: A cardiac glycoside used for heart conditions, binds to muscle tissue, which can result in prolonged release.
Clinical Importance
Drugs stored in muscle may have prolonged effects, particularly in individuals with high muscle mass, which may help maintain therapeutic levels but also raises toxicity risk with cumulative doses.
Plasma Proteins (Blood)
Description: Many drugs bind to plasma proteins like albumin, creating a reservoir in the bloodstream, where only the unbound portion is active.
Examples
- Warfarin: An anticoagulant with high protein binding, where changes in protein levels can influence its effect.
- Phenytoin: An anticonvulsant with high affinity for albumin, leading to varying levels of active drug based on protein availability.
Clinical Importance
High protein binding extends the half-life of drugs. Conditions like low albumin levels can increase active drug availability, requiring dose adjustments to prevent toxicity.
Liver
Description: The liver serves as a reservoir for drugs undergoing hepatic metabolism or with high affinity for liver tissue.
Examples
- Chloroquine: An antimalarial stored in high concentrations in the liver, prolonging effects but raising hepatotoxicity risks with prolonged use.
Clinical Importance
Liver-stored drugs can have prolonged effects, but accumulation raises the risk of hepatotoxicity, particularly in patients with liver impairments or chronic use.
Clinical Importance of Drug Reservoirs
- Prolonged Drug Action: Reservoirs can provide slow drug release, maintaining steady levels but potentially delaying elimination.
- Toxicity and Overdose Risks: Accumulation may cause toxicity, as stored drugs can release slowly even after stopping the drug.
- Drug Interactions: Competition for the same reservoir, like plasma proteins, can increase the active portion of one or both drugs, raising toxicity risks.
- Individual Variability: Factors like body fat, muscle mass, and protein levels affect drug storage, leading to varying responses between individuals.
- Delayed Clearance in Renal or Hepatic Impairment: Impaired liver or kidney function can slow drug clearance, necessitating dose adjustments to prevent toxicity.