Flashcards in 0512 - Drug distribution into different compartments - EG Deck (20):
List potential body areas for the distribution of drugs.
plasma proteins, body compartments such as fat and muscle, special compartments such as breast milk, CNS, foetus, teeth and bone.
What factors affect the distribution of a drug? (4)
(1) permeability across tissue barriers (2) binding within the compartments (3) pH partitioning (4) fat:water partitioning.
List factors that affect the rate at which drugs leave the blood. (3)
(1) lipid solubility (2) molecular weight (3) degree of protein binding
List the 3 types of capillaries, tissue in which they can be found, and what they permit the diffusion/exchange of.
(1) continuous capillaries; in skeletal, muscle, lung; permit diffusion of water and small solutes. (2) fenestrated capillaries; kidneys, intestinal villi, choroid plexus; permit exchange of fluid and solutes as large as small peptides. (3) sinusoids; in liver, spleen; permit large proteins.
What are the four compartments in the four compartment model of drug distribution? Which compartments have the fastest drug accumulation time? Which have the greatest capacity to accumulate a drug?
(1) blood, vessel-rich group, muscle and fat. (2) Speed of drug perfusion:blood>VRG>muscle>fat ; dependent on blood supply to tissue. (3) capacity for drug accumulation:fat>muscle>VRG>blood
List some organs in the vessel-rich group..
brain, heart, liver, kidney, endocrine glands
What type of molecules are likely to distribute in total body water? Example?
small water-soluble molecules, e.g. ethanol.
What type of molecules are likely to distribute in extracellular water? Example?
large water-soluble molecules, e.g. mannitol
What type of molecules are likely to distribute in blood plasma? Example?
strongly plasma protein-bound molecules, highly charged molecules, e.g. heparin
What type of molecules are likely to distribute in fat? Example?
highly lipid-soluble molecules, e.g. diazepam
What type of molecules are likely to distribute in bone? Example?
certain ions, e.g. fluoride
What are the features of the blood brain barrier (BBB) that prevent passage of many drugs from the blood to the brain?
tight endothelial junctions, absence of fenestration, diminished trans-endothelial vesicle movement, enables the exclusion of >98% of small molecule drugs and polar compounds. Diffusion only if lipid soluble and small molecular weight or if able to hijack already present transporters.
Why can antibiotics be given intravenously to treat bacterial meningitis (instead of intrathecally?
because meningitis and encephalic inflammation can increase blood brain barrier permeability.
What are the properties of drugs that tend to concentrate in breast milk?
they are weak bases, have low plasma protein bindings, and are highly lipid soluble.
What is the milk to plasma (M:P) ratio and when is it used?
describes the ratio of [drug in breast milk] to [drug in maternal plasma]. used to calculate dose to infant = [maternal plasma] x M:P x volume of milk
How can drugs cross into the placenta?
simple diffusion (depended on molecular weight as must be <500Da, pKa, lipid solubility and protein binding), active transport, pinocytosis, filtration
Are weak acids absorbed typically in the stomach or the small intestine?
Are weak bases absorbed typically in the stomach or the small intestine?
will a weak acid be excreted (cleared) more in acidic or alkaline urine?