Intro to Pharmacokinetics: Absorption and Distribution

What is pharmacokinetics? what the body does to the drug What is pharmacodynamics? what the drug does to the body What is drug disposition? all processes by which the body handles drugs What is ADME? absorption, distribution, metabolism, elimination Describe what it means when substance has crossed the boundary of inside/outside the body crossed the epithelial barrier into the blood stream. What are the routes of administration? intravitreal inhalation intranasal transmucosal sublingual oral intravenous intraarterial What prevents the entry of xenobiotics into the body? the intestinal wall and the liver function Define absoroption extent drug is absorbed from the gut lumen into the portal vein (fg) Define first pass effect extent the drug is removed by liver during first passage into the portal vein through the liver (fh) What is bioavailability? fraction of drug that reaches bloodstream as intact drug. What is the equation for bioavailability? What does it mean that cell membranes barriers between compartments in the are barriers? body gastrointestinal epithelial barrier (gut to bloodstream) What are some cell membrane barriers? vascular epithelial( blood to target) bilary tract and renal tubule (circulation to bile/urine) lipids proteins carbs What are some components of the cell membrane? 1/3 Describe cholesterol in the cell membranes intercalates between lipid bilayer. affects memb fluidity and stability. lateral diffusion of molecules within bilayer What are the routes in which molecules can cross cell membrane? diffusion through lipid memb. diffusion through aqueous channel. carrier What is the permeability of lipophilic molecules dependent on? conc gradient of molecules (diffusion) partition coefficient (lipid solubility) How is permeability measured? logP=log (drug)octanol/(drug)water What does a high logP indicate? higher lipophiicity and higher permeability. What is the principle of minimum hydrophilicity? to reduce toxicity always design drugs with the lowest hydrophobicity possible. Avoid CNS penetration and adverse drug reactions and minimise protein binding only partially ionised inn water. fraction What does it mean when most drugs are will exist in an ionised form and a fraction weak acids/bases? exists in an unionised form What defines the extent of the ionisation pKa of the compound and the pH of the vs unionisation? enviro Define the pKa the pH where ionised and unionised forms of the weak acid or base are equal. What is the Henderson-Hasselbalch equation? pKa= pH + log AH/A-lower then stronger acid higher than weaker acid. weak acids are well absorbed from the acidic enviro of the intestine as a largDescribe the relationship between ab- er fraction exists as the unionised form sorption and weak acids and bases? and generally weak bases are absorbed more slowly from acidic intestine as a larger fraction exists in ionised formed Which type of proteins can readily diffuse between compartments to exert a pharmacological effect? 2/3 free non-protein bound drug What is distribution refer to? movement of drug molecules from the circulating blood to other areas of the body: site of action and site of elimination Where are drugs distributed? systematic circulation or tissues of distribution How is drug equilibrium achieved? when the rate of drug entering a tissue or organ is equal to the rate of removal of drug from tissue or organ What is distribution dependent on? blood flow conc gradient permeability of cell memb between compartments drug binding to plasma proteins to tissue components. What is drug-molecule binding? drugs binding to macromolecules in tissue and plasma. proteins bind to drugs and transport them to site of action. What can drugs bind to? proteins in plasma tissue components RBC What are the non-covalent forces? van der waals forces ionic bonding hydrogen bonding What does albumin bind to? acidic drugs drugs dissolve into the memb lipid soluble drug partitions in the lipid biWhat are the properties of lipoproteins? layer, rather than remain in plasma water. binding to other cellular components 3/3