3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
                      3.1.3.1.1. Pharmacokinetics
 3.1.3.1.1.3. Distribution of drugs 

Distribution of drugs

[SH4:p10]

Perfusion and drug distribution

  • Highly perfused tissues receive a disproportionately large amount of drug
    --> Acts as reservoir
  • When plasma concentration drops below the concentration in these tissues
    --> Drugs redistributes from highly perfused tissues to less well perfused tissues

Lung

  • Highly perfused
  • High uptake, especially for basic lipophilic amine (pK8)
    * e.g. lidocaine, propanolol, meperidine, fentanyl, sufentanil, alfentanil
    * First-pass pulmonary uptake >65% of doses

CNS

Ionised

  • Ionised water-soluble drugs
    --> Entry into CNS restricted due to blood-brain barrier
    * Can be overcome by large dosage
    * BBB may be disrupted by acute head injury or arterial hypoxemia

Non-ionised

  • Nonionised lipid-soluble drugs
    --> Entry into CNS limited only by cerebral blood flow

High dose and redistribution

  • When dosage is high
    --> Less well perfused tissues become saturated
    --> No more redistribution
    * Example: thiopentone, fentanyl

Thus,

  • Metabolism becomes the only mechanism for drug level to decrease
    --> Drug level only falls slowly