Physiochemical Properties of Drugs

The ability of a chemical compound to elicit a pharmacological/therapeutic efwhat is the definition of physiochemical fect is related to the influence of various properties? physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with. 1)Physical Properties Physical property of drug is responsible for its action what do physiochemical properties depend on? 2)Chemical Properties The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc. Solubility Partition Coefficient - LogP Ionization Hydrogen Bonding Chelation Surface activity Isosterism what are some examples of physiochemical properties? The choice of appropriate route in a given situation depends upon both drug as what does the choice of the route of adwell as patient related factors. ministration depend on? Drugs administered locally or systematically. how can drugs be administered? if a drug is administered systemically what is the intention? The drugs administered through systemic routes is intended to be absorbed into blood & distributed all over. what are the different routes of administration? 1 / 13 The process by which the drug is released in the body from its dosage form is known as absorption. What is absorption? what is drug absorption? Drug absorption is the movement of a drug into the bloodstream. The factors which effect the rate of absorption are what are the factors that effect the rate of æConcentration of the drug absorption? æRoute of administration æSolubility of the drug æDissolution rate for solid dosage form what does the drug have to cross to get to the site of action? one or more membrane barriers The main process by which a drug molecule cross the neutral barrier is, æSimple diffusion what are the processes of which a drug æFacilitated diffusion crosses the barrier? æPore transport æDiffusion of the ion across the membrane æActive transport æphagocytosis Once the drug has been absorbed into the blood ,it distributed around the body. what happens during distribution? It get distributed throughout the blood supply , with in a minute. As the blood recirculates, the drug moves from the bloodstream into the body's tissues. Drug is evenly distributed through out the blood supply, this does not mean the drug is evenly distributed through the the drug is evenly distributed around the blood supply, what does this mean? body . Since he blood supply is rich in some areas of the body than the other. 2 / 13 Drugs penetrate different tissues at different speeds, depending on the drug's ability to cross membranes. what properties depend on how fast a drug can penetrate the membrane? In general, fat-soluble drugs can cross cell membranes more quickly than water-soluble drugs can. For example, the anesthetic thiopental, a highly fat-soluble drug, rapidly enters the brain, but the antibiotic penicillin, a water-soluble drug, does not. Distribution of a given drug may also vary from person to person. For instance, obese people may store large amounts of fat-soluble drugs, how may distribution also differ in differ- whereas very thin people may store relent people? atively little. Older people, even when thin, may store large amounts of fat-soluble drugs because the proportion of body fat increases with aging. Drug metabolism is the chemical alteration of a drug by the body. what is drug metabolism? metabolism is what the body does to the drug what are prodrugs? Some drugs, called prodrugs, are administered in an inactive form, which is metabolized into an active form. The substances that result from metabwhat are metabolites? what may be difolism (metabolites) may be inactive, or ferent about them? they may be similar to or different from 3 / 13 the original drug in therapeutic activity or toxicity. what do the resulting metabolites produce? The resulting metabolites produce the desired therapeutic effects. The subsequent metabolites are then excreted. The termination of the drug effect is caused by bio transformation and excretion. what happens to the metabolites after this? All the substance in the circulatory system , including drugs ,metabolites ,and nutrients will pass through the liver. A significant portion of the drug metabolised by hepatic enzyme to inactive chemical. Plasma proteins, certain tissues, neutral fat, bone and transcellular fluids (gastro intestinal tract) are found to act as a drug reservoirs or storage sites for drugs. what are storage sites for drugs? Plasma proteins: approximately 6.5% of the blood constitute the proteins, of which 50% is albumin. The drug can also be stored in the tissue depots. Neutral fat constitutes some 20% to 50% of body weight and constitutes a depot of considerable importance. what is the drug is lipophillic what is protein binding? }The reversible binding of protein with non-specific and non- functional site on the body protein with out showing any biological effect is called as protein binding. 4 / 13 Depending on the whether the drug is a weak or strong acid ,base or is neutral. It what is the most significant protein? can bind to single blood proteins to multiple proteins. The most significant protein what is the factor that depends on if a drug can bind to a single protein or mul- involved in the binding of drug is albumin, which comprises more than half of blood tiple? volume. what is a protein binding value? protein binding values are normally given as the percentage of total plasma concentration of drug that is bound to all plasma protein. It serves as a main storage site for drugs having a high partition coefficient what does neutral fat act as for drugs? (lipid/water system) or a high lipid solubility (thiobarbiturates). A macromolecular component of the organism that binds the drug and initiates its effect. what is a receptor? Traditional model was a rigid "Lock and Key" -Lock - Receptor surface -Key - Drug or Ligand what is the lock and key model? 5 / 13 Ligand-gated ion channels G-protein (Guanine nucleotide-regulatory protein) coupled receptors. Tyrosine Kinase-linked Receptors what are the 4 primary receptor types? Intracellular receptors regulating gene transcription what are the different types of drug receptor interactions? what is solubility? The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equilibrium with the solid solute. Sufficient solubility and membrane permeability is an important factor for oral absorption. 1)Buffer & Ionic strength 2)Polymorphism & Purity of the sample what does the measurement of aqueous 3)pH solubility depend on? 4)Super saturation 5)Thermodynamic Vs Kinetic solubility Why is solubility important? (1) Formulation of the drug in an appropriate dosage form and (2) Bio-disposition: Disposition of OMAs in the living system after administration (absorption, distribution, metabolism, and excretion). 6 / 13 In ascending homologous series, the Physicochemical properties like boiling point, viscosity, surface activity and partition coefficient increases then the aqueous solubility decreases. how can the solubility of a drug be increased or decreased? The solubility characteristics of a drug can be increased or decreased by derivatisation. 1)Structural modification 2)Use of co solvents 3)Employing surfactants 4)Complexation what are the 4 methods to increase solubility? Partition co-efficient is one of the Physico chemical parameter which influencing what is the partition co efficient? (log p) the drug transport & drug distribution., the way in which the drug reaches the site of action from the site of application Partition co-efficient is defined as equilibwhat is the partition co efficient defined rium constant of drug concentration for a as? molecule in two phases. eq to learn what are the factors effecting the partition co efficient? pH Cosolvents Surfactant Complexation Partition Co-efficient are difficult to measure in living system. They are usually determined in vitro 7 / 13 1-octanol as a lipid phase and phosphate buffer of pH 7.4 as the aqueous phase. The Partition co-efficient, P is dimensionless and its logarithm, log P is widely used as the measure of lipophilicity. what is log p widely used as? The log P is measured by the following methods. 1)Shake flask method 2)Chromatographic method 3)Spectroscopy method how is log p measured? Phenobarbitone has a high lipid/water partition coefficient of 5.9. Thiopentone sodium has a chloroform/water partition coefficient of about 100, so it is highly soluble in lipid. surfactant is defined as a material that can reduce the surface tension of water at low concentration. what is a surfactant? Surface active agents affect the drug absorption which depends on: what is a hydrogen bond? 1.The chemical nature of surfactant 2.Its concentration 3.Its affect on biological membrane and the micelle formation. At lower concentration the surfactant enhances the absorption rate, the same in higher concentration reduce the absorption rate. The hydrogen bond is a special dipole-dipole interaction between non bonding electron pairs of hetero atoms like N, S, O and electron deficient hydrogen atom in polar bonds such as OH, NH, F These are weak bonds and denoted as dotted lines. O-H.......O, HN-H.......O, 8 / 13 The compounds that are capable, of forming hydrogen bonding is only soluble in water. what are the 2 types of hydrogen bonding? intermolecular hydrogen bonding intramolecular hydrogen bonding intermolecular hydrogen bonding intramolecular hydrogen bonding h bonding and biologicalaction examples '' what is the definition of chelation The compounds that are obtained by donating electrons to a metal Ion with the formation of a ring structure are called chelates. what is a ligand The compounds capable of forming a ring structure with a metal are termed as ligands. 9 / 13 a)Antidote for metal poisoning b)8-Hydroxyquinoline and its analogs acts as antibacterial and anti fungal agent by complexing with iron or copper. what is the importance of chelates in medicine? c) Undesirable side effects caused by drugs, which chelates with metals . what is a redox potential and what is the eq? The oxidation-reduction potential may be defined as a quantitative expression of the tendency that a compound has to give or receive electrons. The redox potential of a system may be calculated from the following equation. E=E0+0.0592/n log[conc. of reductant /conc.of oxidant] examples of interfering with natural redox system in biological conditions: Riboflavin analogues ionisation and pka Acids are two typesUnionized acid - HA Ionized acid - BH + By using drug pKa, the formulation can be adusted to pH to ensure maximum solubility in water or maximum solubility 10 / 13 in non-polar solvent. The pH of a substance can be adjusted to maintain water solubility and complete ionisation. e.g what are steric featrues of a drug? why do drugs show stereo selectivity? Different arrangement of atoms that can be converted into one another by rotation about single bonds are called conformations. what are conformational isomers? Rotation about bonds allows inter conversion of conformers. example of conformational isomers (ach) Stereochemistry, enantiomers, symmetry and chirality are impotant concept in therapeutic and toxic effect of drug. what are optical isomers? what is a chiral compound? A chiral compound containing one asymmetric centre has two enantiomers. Although each enantiomer has identical chemical & physical properties, they may have different physiological activity like interaction with receptor, metabolism & protein binding. A optical isomers in biological action is due to one isomer being able to achieve a three point attachment with its receptor molecule while its enantiomer would only 11 / 13 be able to achieve a two point attachment with the same molecule what is geometric isomerism? What is isosterism? Geometric isomerism is represented by cis/trans isomerism resulting from restricted rotation due to carbon carbon double bond or in rigid ring system. which postulated that two molecules or molecular fragments containing an identical number and arrangament of electron should have similar properties and termed as isosteres. Isosteres should be isoelectric i.e. they should possess same total charge. what is bioisosterism? what are the 2 types? compounds or groups that possess near or equal molecular shapes and volumes, approximately the same distribution of electron and which exhibit similar physical properties. i)Classical biososteres ii)Non classical bioisosters They have similarities of shape and electronic configuration of atoms, groups and molecules which they replace. Classical Bioisosteres Trivalent atoms and groups 12 / 13 Application of Classical Bioisosteres in in drug design They do not obey the stearic and electronic definition of classical isosteres. Non classical Bioisosteres These isosteres retain activity by the retention of their properties such as pKa, electrostatic potentials, which can alter selective enzyme processes. examples 13 / 13