I - Basic Principles Flashcards
Any substance that brings about a change in biologic function through its chemical actions
drugs
Actions of a drug on the body
Pharmacodynamics
Actions of the body on a drug
Pharmacokinetics
Molecular Weight of most drugs
100-1000
MW of Lithium
7
MW of Altepase
50,000
MW: rarely selective in their actions
< 100
MW: poorly absorbed and poorly distributed
> 1000
Bonds According to Strength
covalent > electrostatic > hydrophobic
Movement of drug molecules into and within biologic environments
Permeation
Passive movement of non-protein-bound drugs between the blood and extravascular space through small water-filled pores
Aqueous Diffusion
Aqueous Diffusion happens in all organs except
brain, testes, eye, placenta
Aqueus Diffusion is governed by
Fick’s Law of Diffusion
Movement of drugs through lipid membranes separating body compartments and the ECF from the ICF
Lipid Diffusion
Most important limiting factor for permeation
Lipid Diffusion
Lipid Diffusion is governed by
Fick’s Law of Diffusion
Lipid Diffusion is very important for the diffusion of
weak acids and weak bases
Drugs that do not readily cross through membranes may be transported across barriers by mechanisms that carry
similar endogenous substances
Transport by special carriers is _____ by Fick’s Law of Diffusion and is _____-limited
not governed by Fick’s Law of Diffusion, capacity-limited
For large drugs to be endocytosed, they have to
bind with receptors
Large drugs are internalized and released after
vesicle breakdown
Small polar drugs combine with _____ to form _____ which undergo endocytosis.
special proteins, complexes
Predicts the rate of movement of molecules across a barrier
Fick’s Law of Diffusion
Rate = (C1-C2) x (permeability coefficient/thickness) x area
Fick’s Law of Diffusion
Absorption is faster in organs with _____ surface area and _____ membranes.
larger surface area, thinner membranes
Aqueous solubility is _____ proportional to electrostatic charge.
directly
Lipid solubility is _____ proportional to electrostatic charge.
inversely
Many drugs are _____ acids and bases.
weak
Unprotonated acids are more _____-soluble and undergoes _____ clearance.
water-soluble, better clearance
Protonated acids are more _____-soluble and are _____ to cross biological membranes.
lipid-soluble, more likely to cross biological membranes
Unprotonated bases are more _____-soluble and are _____ to cross biological membranes.
lipid-soluble, more likely to cross biological membranes
Protonated bases are more _____-soluble and undergoes _____ clearance.
water-soluble, better clearance
pH below pKa: protonated __ unprotonated
>
pH at pKa: protonated __ unprotonated
=