Pharmacology 2060A/B Lecture Notes - Lecture 3: Extracellular Fluid, Lipophilicity, Glycoprotein
15 Jul 2016
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Drugs& distribute& into& compartments& in& the& body& where& they& may& be& stored,& metabolized,& excreted&or&exert&their&pharmacological&effect. & & the& extracellular& fluid& that& surrounds& cells. & & low& molecular& weight,& water&soluble&drugs&distribute&in&the&interstitial&space. & Drug&distribution&is&determined&by:: blood&flow&to&tissues. , ability&of&drug&to&move&out&of&capillaries. , 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. &, blood&flow&to&tissues, blood&flow&to&tissues&is&a&key&determinant&of&drug&distribution. & Therefore& it& is& difficult& to& attain& high& drug& concentrations& within& solid& tumours. & (important*in*module*17*when*we*look*at*chemotherapy): abscesses&(infection&filled&with&pus)&have&no&blood&supply&and&are&therefore&difficult& to&treat&with&antibiotics. &&they&are&often&drained&prior&to&drug&therapy. &(important*in* &&&&&ability&of&drug&to&move&out&of&capillaries: with&the&exception&of&the&brain,&drug&movement&out&of&the&capillaries&into&the&interstitial&space& occurs&rapidly&due&to&the&permeable&nature&of&the&capillary&wall. &, drugs&move&out&of&the&capillary&through&fenestrations. , ability&of&drug&to&move&into&cells, once&drugs&leave&the&vasculature&they&must&enter&their&target&organ/cells&to&have&an&effect. &&, the&cell&membrane&is&a&significant&barrier&to&drugs&reaching&their&targets. &&& 1. acid. glycoprotein& & binds& primarily& cationic& (i. e. & weakly& basic)& and& very& hydrophilic& drugs. &&& Plasma&protein&binding&is&reversible: the& binding& of& drugs& to& plasma&proteins&is&reversible. & In& the& diagram& to& the& right,& the&free&drug&(yellow&dot)&is&in& equilibrium& with& plasma& protein. & & if& some& of& the& free& drug&is&removed,&some&of&the& protein& bound& drug& will& dissociate& from& the& protein& and&become&free. & 3. 5. volume. of. distribution. (vd): represents&the&apparent&volume&that&a&drug&distributes&into. , vd& is& the& ratio& of& the& total& amount& of& drug& in& the& body& (d)& to& the& plasma& concentration& of& the& drug&(c),&therefore:&
