0512 Drug distribution in special compartments Flashcards
Name 3 major factors (of the a drug) that will affect the rate at which they leave blood
Lipid solubility, molecular weight, degree of protein binding
List the 3 types of capillaries
Continuous, fenestrated and sinusoidal
Describe continuous capillaries (what it allows through and physical features, where it is found)
IT is characterised by conitnuous basement membrane, tight intercellular clefts and pinocytic vesicles. It allows passage of water and small solutes. It can be found in skeletal and smooth muscle, connective tissues and lungs
Describe fenestrated capillaries (what it allows through and physical features, where it is found)
Similar to continuous capillaries but characterized by fenestrations (pores) in the epithelial cells. It allows rapid exchange of fluids and solutes as large as small peptides. It can be found in the kidneys, small intestines and choroid plexus
Describe sigmoid capillaries (what it allows through and physical features, where it is found)
It is wider and more winding than all other capilarries. It has an incomplete basement membrane, large fenestrations and large intercellular clefts. It allows passage of large proteins. Can be found in the liver and spleen
Describe the 3 methods that a solute may pass through a membrane
Diffusion, transport or carrier mediated
What is the relationship between lipid solubility and permeability of a solute? What is it’s implication in terms of distribution of drugs
As lipid solubility increases, so does permeability. This means that lipid soluble drugs distribute a lot more readily and evenly across different body compartments than non lipid soluble drugs
Describe how the pH of a drug might affect it’s distribution in body compartments. How might a drug get ‘trapped’
Only unbound (no hydrogen ion) forms of a solute can move across a membrane. Usually, bound and unbound forms are in equilibrium. As an unbound form of a drug distributes, differences in pH of compartments mean more or less get ionized. Those that are ionized cannot move back across membranes
In terms of pH, where are weak acidic and weak basic drugs likely to accumulate
Weak acidic drugs are likely to accumulate in compartments that are basic (move into compartment, gets ionized and trapped). Weak basic drugs are likely to accumulate in acidic compartments
Why is a simple pH consideration of drugs distribution ( weak acidic drugs go to basic compartments) unrealistic ?
Because there will always be some diffusion of a charged/bound species and an equilibrium is only rarely reached
When we administer a drug into a patient, there is often a sharp initial decline of the [drug] in plasma. After this drop the reduction in concentration stabilizes. To what is drop attributed to
The distribution of the drug into other compartments
What is the main factor that determines the order/priority distribution of a drug to other compartments
The perfusion of those compartments. Heavily perfused compartments are where the drug goes first
in order, what are the 4 compartments of the model drug distribution (from first concentration spike to last)
Blood, Vessel-rich-group, muscles, fat
The concentration peak of drug in fat is lower than the other 3 compartments. Why is this
Because fat is the last compartment to get a spike, the drug is starting to get eliminated
Although perfusion to the CNS is extremely high, why can’t all drugs readily diffuse into the cerebro - spinal fluid
BEcause the blood brain barrier has a very low permeability
