Pharmacokinetics Flashcards
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Chapter 2
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Pharmacokinetics is the quantitative study of drug
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movement in
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through and out of the body. The
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overall scheme of pharmacokinetic processes is
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depicted in Fig. 2.1. The intensity of response
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is related to concentration of the drug at the site
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of action
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which in turn is dependent on its
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pharmacokinetic properties. Pharmacokinetic
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considerations
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therefore
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of administration
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dose
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of peak action
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duration of action and frequency
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of administration of a drug.
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All pharmacokinetic processes involve trans-
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port of the drug across biological membranes.
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Biological membrane This is a bilayer (about
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100 Ả thick) of phospholipid and cholesterol
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molecules
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the polar groups (glyceryl phosphate
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attached to ethanolamine/choline or hydroxyl
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ABSORPTION
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Drug in
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dosage
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form
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Pharmacokinetics: Membrane
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Transport
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Absorption and
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Distribution of Drugs
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Release
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Drug in
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solution
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DISTRIBUTION - STORAGE
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Site of action
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Bound Free
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Blood
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group of cholesterol) of these are oriented at the
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two surfaces and the nonpolar hydrocarbon chain
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are embedded in the matrix to form a continuou
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sheet. This imparts high electrical resistance
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and relative impermeability to the membrane
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ExtrinsiC and intrinsic protein molecules are
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adsorbed on the lipid bilayer (Fig. 2.2). GIlyco
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proteins or glycolipids are formed on the surface
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by attachment to polymeric sugars
aminosugar
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or sialic acids. The specific lipid and protein
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Composition of different membranes differ
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according to the cell _or the organelle type. The
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proteins are able to freely float through the
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membrane: associate and organize or vice versaY
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Some of the intrinsic ones
which extend through (Dru
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(a)
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the full thickness of the membrane
surround fit.
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(b)
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aqueous pores. Paracellular spaces or channel
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also exist between certain epithelial/endothelia
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→ FREE DRUG
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Protein bound
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Storage tissue
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Free Bound
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Metabolites
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BIOTRANSFORMATION
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Fig. 2.1: Schematic depictlon of pharmacokinetic processes
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Urine
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Bile
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Int
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pr
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Hyd
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Sweat
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Saliva
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Hy
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Fi
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cell
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cart
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EXCRETION dire
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Lip
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mer
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Pas
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he
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mer
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Thi
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of
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(xe
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dev
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met
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the
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the
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lipie
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Faeces tion
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mor
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gre
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dru
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Infl
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lyte
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stro
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What is the effect of a change in pH on ionization?
A change in pH causes a 10-fold change in ionization.
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What type of drugs form salts with ions?
Weakly basic drugs such as atropine sulfate, ephedrine HCl, and chloroquine phosphate.
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At what pH do weakly basic drugs become more ionized?
At acidic pH.
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What is the consequence of a pH difference across a membrane?
It can cause differential distribution of weakly acidic and weakly basic drugs on the two sides.
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How does the ionization of acidic drugs like aspirin occur in the stomach?
Aspirin (pKa 3.5) is largely unionized at acidic gastric pH and is absorbed from the stomach.
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Why are basic drugs like atropine absorbed only in the intestines?
They are largely ionized at gastric pH and require the intestinal environment for absorption.
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What is ion trapping?
A weak electrolyte crosses a membrane to encounter a pH from which it cannot escape easily.
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What happens to the unionized form of acidic drugs in gastric mucosal cells?
It reverts to the ionized form within the cell (pH 7.0) and passes slowly to the extracellular fluid.
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What is a consequence of acidic drugs being ionized more in alkaline urine?
They do not back diffuse in the kidney tubules and are excreted faster.
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How does urine pH affect the excretion of basic drugs?
Basic drugs are excreted faster if urine is acidified.
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What type of substances can readily cross biological membranes regardless of pH?
Lipid-soluble nonelectrolytes such as ethyl ether.
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What is filtration in pharmacology?
The passage of drugs through aqueous pores in the membrane or through paracellular spaces.
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What accelerates the filtration of drugs?
Hydrodynamic flow of the solvent under hydrostatic or osmotic pressure gradient.
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What is required for lipid-insoluble drugs to cross biological membranes?
Their molecular size must be smaller than the diameter of the pores.
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What is the maximum molecular weight of drugs that can penetrate the majority of cell pores?
Drugs with molecular weight > 100 or 200 cannot penetrate.
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What type of spaces do capillaries (except in the brain) have?
Large paracellular spaces of 40 Å.
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What does diffusion of drugs across capillaries depend on?
The rate of blood flow through them rather than on lipid solubility or pH.
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What are the two types of specialized transport?
Carrier mediated and pinocytosis.
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What do all cell membranes express for transport?
Transmembrane proteins that serve as carriers or transporters.
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What is the nature of carrier transport?
It involves transient binding and conformational change to transport substrates across the membrane.
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How is carrier transport different from channels?
Carrier transport is slower, specific for the substrate, and can be competitively inhibited.
