Pharmacokinetics 2 Flashcards
Drug Distribution Factors
Passive diffusion, tissue blood flow, macromolecule binding (more binding = less distribution (can’t bind to cells = no biological effect)), p-glycoproteins (more glycoproteins = less distribution) and ion trapping (gets stuck in 1 location, poor distribution)
Relationship between blood flow and distribution
better blood flow to area = better perfusion = better distribution
Binding To Macromolecules Outline
Bind to drug in blood for transport, there is competition for drug binding. Drugs can bind and dissociate indefinetly Multiple types: albumin, alpha1 acid glycoprotein, lipoproteins and beta glycoproteins
Albumin Outline
69,000 daltons. Bind anionic (mainly acidic) drugs (eg NSAIDs and diuretics). Multiple high capacity, low affinity binding sites (2 main ones). 40% in plasma and 60% extravascular
Alpha1 Acid glycoproteins
40,000 daltons. Binds cation (alkaline) and neutral drugs. Present in acute reactions
Lipoproteins/Globulins Outline
Macromolecules. Binds lipophilic weak bases (cations)
Plasma Protein Binding Outline
Hypoalbuminemia, uremia, age and binding displacement
Hypoalbuminemia Outline
low albumin levels = increase unbound substances = faster distribution = more unsustained metabolism. Eg liver cirrousis
Uremia Outline
Excess urea in blood = decrease in drug binding. Result of kidney binding
Age relationship to binding proteins
fetuses and neonatals (newborns a few weeks old) don’t have as many binding proteins
Displacement from binding outline
When a drug is outcompeted from a binding site by another drug
Clinical importance of protein binding
Free drug conc, therapeutic window (more free drug = narrower therapeutic window = more tissue-drug interactions) and drug displacement from binding sites
Narrow Therapeutic Window Outline
1 microgram - 50 micrograms
Wide Therapeutic Window Outline
1 microgram - 1,000 micrograms
Warfarin Binding relation to aspirin
Warfarin has a high % bound to protein (98%), in 5gs there’s 0.1g free. When administerd at the same time aspirin competes for the same receptors displacing some of the warfarin doubling the amount free (ie 0.1 to 0.2g)
Location of drug and macromolecule binding
Both in blood (drug-protein) and cell (drug-protein/lipid/nucleic acid)
What state are alkaline drugs in acidic enviorments
Neutralized (non-protenised). Means that alkaline substances don’t get absorbed in stomach (lipid cells are impermeable)
Volume of Distribution Def
Fluid volume a drug would occupy if drug concentration in body (as a solution) was the same as the drug concentration in the plasma. Measure of tendency for drug to leave plasma for another site
3 sites of body’s water
Interstitial (between cells), intracellular and plasma
Evan’s Blue Mode of Distribution Outline
Drug distribution only in plasma
Inulin Mode of Distribution Outline
Drug distribution from plasma to interstitial fluid
Ethanol mode of distribution Outline
Drug distributes to all water (plasma, interstitial and intracellular)
Quinicare Mode of Distribution Outline
Drug distributes to inside of cells
Volume of Distribution Calculation
Volume = Dose/Concentration. SI units: Liters (ensure all units agree)