Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio MODULE 1: GENERAL CHEMISTRY & INORGANIC PHARMACEUTICAL CHEMISTRY Chemistry - Physical science - Study of the composition, structure, properties, and behavior of matter - “The Central Science” - The ABC of Pharmacy Practice” Matter - Anything that has mass and volume - Made up of particles - Exist in 4 fundamental states o Solid o Liquid o Gas o Plasma - Mass – amount of matter present in the material - Weight = mass x pull of gravity - Units of Measurement: o Length – Meter (m) o Mass – Kilogram (kg) o Time – Seconds (sec) o Temperature – Kelvin (K) - Plasma o Colorless fluid part of blood, lymph, or milk, in which corpuscles or fat globules are suspended o Serum § Amber-colored protein-rich liquid that separates out when blood coagulates § Used to provide immunity § Diagnostic agent Classifications of Matter - Element o Simplest form of matter o 1 kind of material or atom - Compound o Substances composed of two or more elements united chemically in definite proportion - Mixture o Composed of 2 or more substances chemically combined States of Matter Solid Liquid Shape Definite Indefinite Volume Definite Definite IFA Strength Strongest Strong Molecular Motion Vibration Gliding that are not Gas Indefinite Indefinite Weakest Constant Random Motion Changes that <atter undergoes - Physical Change – change in phase - 1 Chemical Change – change in both intrinsic and extrinsic properties o Evidences of Chemical Change § Evolution of gas § Formation of precipitate § Emission of light § Generation of Electricity § Production of Mechanical Energy § Absorption/Liberation of Heat o Processes Involved in Chemical Change § Oxidation • (+O) § Reduction • (-O or +H) § Neutralization • acid + base à salt + water § Hydrolysis • water + salt à acid + base Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Saponification • alkali + fats à soap + glycerol § Fermentation • Organic substances + microbes à alcohol Nuclear Change – △ in structure, properties, composition of the nucleus à in the transmutation of the element o Nuclear Fission – splitting of a heavy atom o Nuclear Fusion – union of 2 light atoms to form a bigger molecule § - Atom - Basic unit of matter - Greek – “atomos” – indivisible o Proton – (+) charge o Neutron – no charge o Electron – (-) charge Element - Pure chemical substance - Contains only 1 type of atom - Currently, there are 118 elements - Atomic number = # of protons = # of electrons Mass number = # of protons + # of neutrons Isotope – same number of protons (so same element), but different number of neutrons - Isotone – same number of neutrons - Isobar – same mass number - Ion – charged atom - 3 Most Abundant Elements o Oxygen o Silicon o Aluminum - 1st produced artificially o Technetium - Rarest Element o Astatine - Liquid at Room Temperature o Mercury o Bromine Allotropism - Allotrope – atoms of different elements can link together in different ways to form substances with different properties - Allotropes of Ca: o Diamond, Graphite - Allotropes of O: o [O] nascent, O2 molecular, O3 ozone - Orbitals – region in space where the probability of finding an election is greatest Mixtures - Composed of two or more elements or substances which are not chemically combined - Heterogenous – two or more distinct phases - Homogenous – only one phase or single phase Solutions o Uniform mixture o Composed of solute and solvent o Atoms, molecules, or ions of the substance become dispersed 2 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Suspension o Homogenous dispersion insoluble in a liquid o Coarse mixture o Finely divided solid materials distributed in a liquid Colloids o Contain particles bigger than those in solutions but smaller than those in suspension o Particle of solute are not broken down to the size of the molecules but are small dispersed throughout the medium o Exhibit the light scattering effect o Dividing line between solution and homogeneous mixture o 4 Properties of Colloids: (always remember T-BAC) Tyndall effect § Light scattering effect Brownian movement § Zigzag movement of colloidal particles Adsorption Charged electrically § Electrophoresis – gel electrophoresis à SHSPAGE (used to separate protein and nucleic acids) § Cathode (-) – reduction takes place § Anode (+) – oxidation takes place - Homogeneous mixture o True Solution o Colloid Metals vs Non-Metals - Metallic Property – capability of an element to lose an electron Metals Non-Metals Good conductors of heat and Poor conductors electricity Form BASIC oxides From ACIDIC oxides Lustrous, Ductile, Malleable Dull & Brittle if Solid High Density Low Density High Melting point Low Melting point Tends to lose electron Tends to accept electron - How to remember Metalloids? Mnemonic: “SIGE PO, SABI NI ATE BABY” o Silicon, Germanium, Polonium, Antimony, Arsenic, Telurium, Boron Properties of Elements - Electronegativity – ability of an element to attract electrons to itself - Electron Affinity – energy gained by an atom when an electron is added to it - Ionization Energy/Ionization Potential – amount of energy required to remove an electron from a neutral atom Properties Used to Identify Substances Intensive/Intrinsic vs Extensive/Extrinsic - Intensive/Intrinsic – independent of mass or amount - Extensive/Extrinsic – dependent on mass - Physical Properties – observed or measured without changing the identity of matter o Example: MP, BP, Solubility, p, malleability, ductility - Chemical Properties – describe the change or the reaction a substance undergoes o Flammability, Reactivity, Inertness Laws of Stoichiometry - Law of Definite Proportions (Proust’s Law) Elements (sameàratio) Same Compound - Law of Multiple Proportions Elements (diffàratio) Different Compound Note: Ratio must be a whole number Chemical Reactions - Direct Union/Synthesis/Composition Simple Subs à Complex Subs MgO + H2O à Hg(OH)2 - Decomposition/Analysis Complex Subs △à Simple Subs H2CO3 △à H2O + CO2 - Single Replacement Reaction A + BC à B + AC 3 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Electrochemistry - Separation of particles based on e- charge Making it simpler - Double Displacement Reaction/Metathesis AB + CD à AD + BC Example: Neutralization Reaction Reduction-Oxidation Reaction (REDOX) o GEROA – gain electron reduction oxidizing agent § In this process of reduction, there is/are gain of electron/s, and the one responsible for this is the oxidizing agent o LEORA – loss electron oxidation reducing agent § In this process of oxidation there is/are loss of electron/s and the one responsible for this is the reducing agent Atomic Structure - Democritus – Atomos - Dalton – Billiard Ball Model - Thomson – Raisin Bread Model / Electron - Rutherford – Gold Foil Experiment / Proton in the Nucleus - James Chadwick – Neutron - Bohr – Planetary Model - Schrodinger – Quantum Mechanic Model / 3D Model Quantum Numbers - Principal Quantum Number (n) o Describes the Main Electron Shell and the Size of the electron cloud § Value: 1, 2, 3, 4… 4 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio - Angular/Azimuthal Quantum Number (l) o Describes the subshell and the shape of the electron cloud § Value 0 up to n-1 - Magnetic Quantum Number (Ml) o Describes the orbital or orientation in space § Values: -l, 0, l - Spin (Ms or s) o Values: +1/2 or -1/2 Rules/Principles - Pauli’s Exclusion Principle o No 2 e- can have the same set of quantum numbers - Aufbau’s Principle o Building up Principle o Electrons are placed first on the subshell with lowest energy level - Hund’s Rule o Electrons are spread singly before pairing up Periodic Table of Elements - There are 118 Elements, 18 Groups/Families, 7 periods/series - Lavoisier – 1st to set up the table (33 elements) - Dobereiner – Triads - Newland – law of octaves o 8 elements are grouped before another set of 8 elements - Meyer & Mendeleev – 1st Periodic Law o Properties are periodic functions of atomic weight - Moseley – First modern Periodic Table - Family A o Representative elements o Occupies § S block – IA & IIA § P block – IIIA & VIIIA - Family B o Transition elements o Occupies § D block – transition metals § F block – Lanthanide or Lanthanoid series – Rare Periodic Trends - Atomic Radius o ½ the distance between 2 nuclei o Right to Left increases o Top to Bottom increases - Electronegativity o Ability to attract electrons o Left to Right increases o Going up increases - Ionization Energy or Potential o Ability to remove an electron from a positively charged atom o Left to Right increases o Going up increases - Electron Affinity o Property to accept an electron o Right to Left increases o Top to Bottom Increases Chemical Bonding - Forces that hold atoms together - All elements try to achieve the configuration of the Noble Gases - Octet Rule – atoms become stable when the valence electron will complement fully the valence shell 5 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Types of Chemical Bonding - Complete Electron Transfer (Ionic Bond) o Bond formed by a metal and a non-metal o Electrostatic Bond - Sharing of Electrons (Covalent Bond) o 2 nonpolar (similar atoms) à equal electron sharing o 2 polar (dissimilar atoms) à unequal electron sharing VSEPR theory - Valence Shell Electron Pair Repulsion - model used to predict 3D molecular geometry based on the number of valence shell electron bond pairs among the atoms in a molecule IMF (Intermolecular Forces of Attraction) - Dipole-Dipole (Keesom Forces) - Dipole-Induced Dipole (Debye Forces) - London Forces (Dispersion/Van der Waals) - Hydrogen Bonds (hydrogen attached to a highly electronegative atom) STP (Standard Temperature and Pressure) - Conditions: o 1 atm / 760 mmHg (torr) o 0oC / 273 K (Kelvin) - Note: At STP – 1 mole of a substance occupies 22.4 L Physical Properties of Systems - Additive Property – depends on sum o Molecular weight - Constitutive property – type and arrangement o Optical rotation, refractive index - Colligative Property – number of solute o VPL, BPE, FPD, OP - Density = mass per unit volume (m/v) - Specific Gravity = # of sample/ # of standard - Specific volume = reciprocal of spgr Colligative Properties Vapor Pressure Lowering - Addition of a non-volatile solute lowers the VP of a liquid - A liquid in a closed container will establish an equilibrium with its vapor - When equilibrium is reached, vapor exerts a pressure (vapor pressure) - Volatile – exhibits VP - Nonvolatile – no measurable VP - Raoult’s Law – lowering of a vapor pressure of a solvent is equal to the product of the mole fraction of the solute and vapor pressure of the solvent - Formula: 6 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Boiling Point Elevation - BP – temp at which liquid pressure is equal to atmospheric pressure (1 atm = 760 mmHg) - The boiling point of a solution containing a non-volatile solute would be higher than the pure solvent because the solute would lower the vapor pressure of the solvent - Formula: - Kb = ebullioscopic/molal BPE constant (0.52oC/m) - M = molality - w1 = weight of solvent - w2 = weight of solute - MW2 = molecular wt of solute Freezing Point Depression - FP – temp at which the solid and liquid phases are in equilibrium under an external pressure - In general, solutions have a lower freezing point than the pure solvent - Applications: o Salt is spread on roads to melt ice o Ethylene glycol as “anti-freeze” - Formula: - Also defined as the pressure required to prevent osmosis in solutions. Hypertonic – causes crenation Hypotonic – causes swelling/lysis Isotonic – 0.9% (w/v) NaCl Formula: - π = osmotic pressure in atm - V = volume in L - n = no. of moles of solute - R = gas constant (0.08205 L·atm/mol·K) - T = absolute temperature Gas Laws - Boyle’s Law – volume is inversely proportional to pressure o Formula: P1V1 = P2V2 - Charles’ Law – volume is directly proportional to temperature (Kelvin) o Formula: V1/T1 = V2/T2 - Avogadro’s Law – volume is directly proportional to moles o Formula: V1/n1 = V2/n2 - Dalton’s Law of Partial Pressure – the pressure exerted by a mixture of gases is the sum of the partial pressures that each gas in the mixture exert individually o Formula - - Kf = cryoscopic/FPD constant (Kf = 1.86oC/m) Osmotic Pressure - Osmosis – movement of water across a semipermeable membrane from low to high concentration - This is the pressure required to offset the movement of solvent thru a s. membrane 7 Ideal Gas Law o Formula: PV=nRT Graham’s Law – rate of the effusion of two gases (and diffusion) are inversely proportional to the square roots of their densities providing the temperature and pressure are the same for the two gases o Formula: Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o o Diffusion – gradual mixing of molecules of one gas with the molecules of another gas by virtue of their kinetic properties Effusion – passage of a gas under pressure through a small opening Solutions - Solute + Solvent - Factors affecting solubility: o Nature of Solute and Solvent o Temperature: ⬆ Temp = ⬆ Solubility (Most of the time) o Pressure: ⬆ Pressure = ⬆ Solubility of gas in liquid (Henry’s Law) - Exceptions: o Exothermic - ⬆ Temp = ⬇ Solubility o Solution of gas in liquid: ⬆ Temp = ⬇ Solubility Chemical Thermodynamics - Thermodynamic System – part of the universe isolated from the rest by a boundary - Surrounding = everything outside Type of System Allows Exchange of Open (Non-conservative) Matter and Energy Closed (Conservative) Energy ONLY Isolated (Adiabatic) No Matter, No Energy Law of Thermodynamics - 1st Law of Thermodynamics - Heat and work are forms of energy transfer. Energy is invariably conserved, however the internal energy of a closed system may change as heat is transferred into or out of the system or work is done on or by the system o Remember: Conservation of Energy & Energy of the Universe if Constant - 2nd Law of Thermodynamics - An isolated system, if not already in its state of thermodynamic equilibrium, spontaneously evolves towards it. Thermodynamic equilibrium has the greatest entropy among the states accessible to the system. o Remember: Entropy, Gibbs Free Energy, GFE – expendable amount of energy o △G(-) = Spontaneous, △G(+) = Non-Spontaneous, △G(0) = Equilibrium 3rd Law of Thermodynamics - The entropy of a system approaches a constant value as the temperature approaches zero. The entropy of a system at absolute zero is typically zero, and in all cases is determined only by the number of different ground states it has. Specifically, the entropy of a pure crystalline substance at absolute zero temperature is zero Chemical Equilibrium - State at which the amount of reactant and products present are constant - Le Chatelier’s Principle o If a system is subjected to stress, the system will adjust to relieve the stress o Stress: § Concentration § Pressure and Volume § Temperature § Catalyst – causes NO SHIFT in Equilibrium Ionic Equilibrium - Electrolytes dissociates into ions - Acids and Bases Acids Bases Sour taste Bitter taste Litmus: blue to red Litmus: red to blue + metals à H gas Feel slippery + carbonate & bicarbonate à Phenolphthalein: pink to violet CO2 Phenolphthalein: colorless Methyl orange: yellow Methyl orange: pink/red NaOH, KOH, Ca(OH)2 HCl, HClO3, HClO4, HBr, HI, HNO3, H2SO4, H3PO4 - Electrolytes – conductors o Weak § incomplete dissolution o Strong § strong acids and bases, complete dissolution - 8 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio - Non-Electrolytes – will not dissociate, will not conduct electricity Acid-base Theories Theory Acid Base Arrhenius H+ in H2O OH- in H2O Bronsted-Lowry H+ donor Accepts H+ Lewis Accepts e pair e- pair donor Neutralization - Acid + Base à Salt and Water - Titration – progressive addition of a solution of known concentration to a substance of unknown concentration - Indicator – Substance that changes color at the end point - Neutralization point (Stoichiometric point/Equivalence Point/Theoretical Point) – point when equal amounts of acid and base have reacted; non-observable - Endpoint – Experimental approximate of neutralization point; observable - pH – the negative logarithm of the H+ concentration Basic Principles of Analysis pH - number of grams equivalent of H per liter of solution - pH = -log[H+] - pOH = -log[OH-] - pH + pOH = 14 - (–) value of pH is possible - >14 value is also possible - Protolysis – process whereby a proton is transferred from one molecule to another - Autoprotolysis – process whereby there is a transfer of proton from one molecule to another identical molecule - Amphoteric – property where a substance can act either as acid or base - Isohydric – a solution having the same pH as the standard solution Salts - Neutral Salt = SA + SB - Acidic Salt = SA + WB - Basic Salt = WA + SB - Strong Acid – ionizing more completely o H-CBNIPS § HCl, HBr, HNO3, HI, HClO4, H2SO4 Strong Base – releasing more hydrogen ions o Hydroxides of Group IA/IIA Ka – acid dissociation constant Kb – base dissociation constant Ksp – solubility product constant pH7 – neutral pH<7 – acidic pH>7 – basic pH Calculations Buffers - Solutions that have the property of resisting changes in pH when acids or bases are added to them - This property results from the presence of a buffer pair which consists of either: o Weak acid and some salt of a weak acid or its conjugate base o Weak base and some salt of a weak base or its conjugate acid - Henderson-Hasselbach Equation o Weak acids o - 9 Weak bases Buffer Capacity o Ability of a buffer solution to resist changes in pH Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Depends on the amount of the acid and the base from which the buffer can neutralize before pH begins to change to an appreciable degree o Van Slyke § Was responsible for a quantitative expression § Amount of g/l of strong acid or strong base required to be added to a solution to change its pH by 1 unit § Higher buffer capacity, lower change in pH o Pearson’s HSAB Principle § Hard acids are electron acceptor with high positive charges and relatively small sizes while soft acids have low positive charges and relatively large sizes Nuclear Chemistry - Radioactivity – decomposition process of unstable nuclei to more stable ones - Radiation – energy and particles released during the decomposition process 3 Types of Natural Radioactivity - ɑ-radiation - ɑ-particle o Mass number decrease by 4 and atomic number by 2 - β-radiation – e- (neutron à proton) o mass number stays the same but the atomic number increases by 1 o - γ-radiation – γ-rays are high energy photons o no change in mass number and atomic number Units of Radioactivity - Non-SI – Curie (Ci) – 1Ci = 3.7 x 1010 decays/sec - SI: Bequerel (Bq) – 1Bq = 1 decay/sex - Unit of Radiation Damage – R.E.M. - Unit of amount of exposure to Radiation – rad or gray MODULE 1: INORGANIC MEDICINAL & PHARMACEUTICAL CHEMISTRY Alkali Metals - Group IA: Alkali Metals - Most Reactive Metals - Valence = 1 Hydrogen (H) - Inflammable air - Lightest element - Isotopes: o Protium – most abundant o Deuterium – heavy hydrogen o Tritium – radioactive Lithium (Li) - Earth - Lightest Metal - Pharmacologic Action: o Depressant o Diuretic - Non-Pharmacologic Action o Heat exchanger in aircon - Important Compounds o Lithium Bromide – LiBr § Depressant o Lithium Carbonate – Li2CO3 § DOC for Mania § BN: Lithase Sodium (Na) - Natrium - Extracellular fluid - Pharmacologic Action: o Fluid Retention - Important Compounds: o Sodium Acetate (C2H3NaO2) § Diuretic § Urinary and systemic alkalizer § Antacid 10 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o o o o o o o o o Sodium Bicarbonate (NaHCO3) § Baking Soda § Systemic Antacid § Carbonating Agent § Side Effects: • Systemic alkalosis • Rebound hyperacidity Na Dihydrogen Phosphate (NaH2PO4) § Feet enema § Cathartic Sodium Metabisulfite (Na2S2O5) § Water soluble antioxidant Sodium Carbonate (Na2CO3) § Antacid § Carbonating agent Sodium Chloride (NaCl) § Rock salt, table salt, soler salt § Electrolyte replenisher § Tonicity adjusting agent § Condiments § Preservative Sodium Citrate (Na3C6H5O7) § Alkalizer § Buffer § Diuretic § Expectorant § Shorten the Coagulation time Sodium Fluoride (NaF) § Anticariogenic (2% solution) Sodium Hydroxide (NaOH) § Caustic soda § Sosa § Lye § Saponifying agent Sodium Phosphite (Na2HPO3) § Reducing agent o o o o o o o o Sodium Hypochlorite (NaClO) § Dakin’s solution, chlorox § Oxidizing agent § Disinfectant § Bleaching agent Sodium Iodide (NaI) § Expectorant § Antifungal § Iodine Solubilizer Sodium Lactate (NaC3H5O3) § Antacid § Diuretic Sodium Nitrate (NaNO3) § Chile Salt Peter § Vasodilator § Meat preservation § Treatment in Cyanide Poisoning Sodium Sulfate (Na2SO4) § Glauber’s salt § Cathartic Sodium Tartrate (C4H4Na2O6) § Primary standard of KFR for water content determination Sodium Thiocyanate (NaSCN) § Hypotensive agent Sodium Thiosulfate (Na2S2O3) § Hypochlor, Photographer’s hypo § Treatment of cyanide poisoning with sodium nitrate § VS in iodometry and permanganometry Potassium (K) - Kalium - Most abundant and predominant intracellular cation - Deficiency: Hypokalemia - Pharmacologic Action: o Diuretic o Important in Muscle Contraction - Important Compounds 11 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o o o o o o o o o o o Potassium Acetate (CH3CO2K) § Antacid § Diuretic § Urinary and systemic alkalizer Potassium Bicarbonate (KHCO3) § Systemic antacid § Carbonating agent § Source of bicarbonate ion Potassium Bitartrate (KC4H5O6) § Cream of tartar, creamor § Laxative Potassium Bromide (KBr) § Antidepressant Potassium Carbonate (K2CO3) § Potash, salt of peter, perlash § Antacid § Carbonating agent § Carbonate source Potassium Chlorate (KClO3) § Oxidizing agent § Component in: • Toothpaste, gargle and mouthwash Potassium Chloride (KCl) § Electrolyte replenisher § Take note: SLOW push Potassium Citrate (C6H5K3O7) § Diuretic § Expectorant § Diaphoretic Potassium Hydroxide (KOH) § Caustic potash, lye potash § Saponifying agent (SOFT soap) Potassium Iodide (KI) § Expectorant § Antifungal § Iodine solubilizer Potassium Nitrate (KNO3) § Salt peter, salitre, salt prunella § Diuretic § Meat preservative o Potassium Permanganate (KMnO4) § Mineral chameleon § Oxidizing agent § VS in permanganometry o Potassium Dihydrogen Phosphate (KH2PO4) § Cathartic o Potassium Sodium Tartrate (KNaC4H4O6·4H2O) § Rochelle Salt, Sal Signette § Cathartic § Sequestering agent o Potassium Thiocyanate (KSCN) § Hypotensive agent o K2Sx·K2S2O3 § Sulfurated potash, liver of sulfur Ammonium (NH4) - Hypothetical alkali metal - Pharmacologic Action o Diuretic o Buffer o Expectorant (like iodide) o Anti-Cariogenic (like fluoride) - Important Compounds o NH4Br § Depressant § Sedative o (NH4)2CO3 § Sal volatile, hartshorn § Expectorant (ammonium) § Antacid (carbonate) § Respiratory stimulant o NH4Cl § Muriate of hartshorn § Expectorant § Diuretic § Urinary acidifier 12 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio HgNH2Cl § White precipitate § Topical anti-infective o NH4I § Source of iodide § Expectorant § Antifungal o NH4CH3COO § Spirit of Mendererus § Styptic Coinage Metals - Can occur in free metal state - Complexes/chelates Copper (Cu) - Cuprum - Only reddish metal - Component of hemocyanin and cytochrome oxidase - Important Alloys: o Brass – Cu + Zn o Bronze – Cu + Sn - Pharmacologic Actions o Protein precipitant o Enhances physiological utilization of iron o Toxicity: Wilson’s Disease § Antidote: Penicillamine - Important Compounds o CUSO4·5H2O § Blue vitriol, blue stone § Component of Benedict’s, Barfoed’s Fehling’s Ingredient § Antidote for Phosphorus poisoning § Ingredient of Bordeaux mixture o [Cu3(AsO3)2·Cu(C2H3O2)2] § Paris green § Insecticide o (Cu)3(C6H5O7)3 § Astringent in 8% concentration Silver (Ag) - Argentum, shining, bright - Pharmacologic Action: o Oligodynamic Property (germicidal action) - Toxicity: Argyria - Antidote: Normal Saline Solution (NSS) - Important Compounds Soluble Compounds o AgNO3 § Lapiz infernulariz, lunar caustic, indelible ink, caustic pencil § Treatment of warts § Eye antiseptic for newborn babies of mother with gonorrhea o Ag(NH3)2NO3 § Howe’s solution § Dental protective § Desensitizing agent Insoluble Compounds o AgI § Poisonous § Disinfectant o Ag Proteinate § Mild Ag Proteinate • Argyrol • Antiseptic for the eye o § and § Strong Ag Proteinate • Protargol • Stronger germicide for ear and throat Colloidal Ag Proteinate • Collargol • General germicide Gold (Au) - Aurum, shining dawn, king of all metals - Most malleable and ductile - Best conductor of electricity 13 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio - Dissolved by: o Aqua Regia (3 part HCl + 1 part HNO3) o Selenic Acid - Important Compounds o Aurothioglucose (IM) § Treatment of gout and RA o Gold Na Thiomalate (IM) § Treatment of gout and RA o Auranofin (PO) § Treatment of gout and RA Alkaline Earth Metals Beryllium (Be) - Never employed in medicine because it is the most toxic metal - Fluorescent lamp Magnesium (Mg) - Lightest of all structurally important metal - Chlorophyll component - Compound of Gringnard’s reagent - Natural Sources: o As Silicates (talc, asbestos) o As CO3 (magnesite, dolomite) o As SO4 (keisrite) - Pharmacologic Action o Laxative o Depressant o Natural Calcium Channel Blocker - Antidote: Ca Gluconate - Important Compounds o MgCO3 § Magnesia § Antacid § Laxative o Mg(OH)2 § Milk of magnesia, magnesia magma § Antacid § Laxative o MgO § Calcined Magnesia o o o o § Laxative § Antacid § Component of Universal Antidote 2MgO·3SiO2·nH2O § Antacid § Advantage: • Prolonged antacid action MgSO4 § Epsom Salt § Cathartic (PO) § Anticonvulsant (IM) § Antidote for Ba toxicity Hydrated Mg Silicate § Talc, soapstone, French chalk § Softest mineral § Filtering agent § Clarifying agent § Dusting powder Mg3(C6H5O7)2 § Magnesium Citrate § Lemonade purgante, purgative lemon Calcium (Ca) - 2nd most abundant cat ion in extracellular fluid - Vitamin D is needed for its maximum absorption - Pharmacologic Action o Blood coagulation factor o Important muscle contraction o Important release of neurotransmitter o Primary element of bones and teeth - Deficiency state o Osteoporosis o Osteomalacia (adults) o Rickets (immature mamals) o Hypocalcemia - Important Compounds o CaBr2 § Sedative 14 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o o o o o o o o o o § Depressant CaCO3 § Precipitated chalk, prepared chalk § Antacid § Ingredient of toothpaste, dentifrices CaCl2 § Muriate of lime § Ca replenisher Ca Gluconate § Ca supplement and replenisher Ca(OH)2 -solid-liquid § Slaked lime, milk of lime, calcium hydrate § Antacid § Saponifying agent Ca(C3H5O3)2 § Ca supplement CaHPO4·2H2O § Source of Ca and PO4 CaO § Lime, quicklime, calx § Component of Bordeaux mixture § Insecticide Ca3(PO4)2 § Bone ash § Antacid CaClO or CaOCl § Chlorinated lime, chloride of lime § Disinfectant bleaching agent CaSO4·½ H2O or 2H2O W § GPlaster of paris, gypsum, terra alba § Rodenticide § Prep of surgical casts and dental impressions Strontium (Sr) - Manufacture of flares - Important Compound o SrCl2 § Temperature de sensitizing agent (Sensodyne) Barium (Ba) - Heavy - Toxicity: Baritosis - Antidote: Epsom Salt - Important Compounds o BaSO4 § Radiopaque substance used for GIT imaging o BA(OH)2 § CO2 absorbent Radium (Ra) - Marie Curie - Radioactive element used for: o Cancer radiotherapy o Diagnostic purpose Volatile Metals Zinc - Present in insulin - Pharmacologic Action o Astringent o Antiseptic o Antiperspirant o Protectant - Container of batteries - Protective coating of galvanized iron - Deficiency: Parakeratosis - Antidote: NaHCO3 - Important Compounds o ZnCl2 § Burnett’s disinfectant fluid § Disinfectant/antiseptic § Dentin desensitizer § Corrosive o ZnO § Zinc white, Lassar’s paste § Antiseptic § Astringent § Topical protectant 15 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o o o o o ZnO2 § Antiseptic ZnS § White lotion, while sulfide § Parasiticide, topical protectant, antiseptic ZnSO4·7H2O § White vitriol § Emetic § Astringent § Prep of white lotion Hydrated Zinc Silicate § Natural calamine § Topical protectant Zinc-Eugenol Cement § Dental protective Cadmium (Cd) - Pharmacologic Action o Astringent - Manufacture of stink bomb - Poisoning – Itai-itai (ouch-ouch) - Antidote – BAL (British Anti-Lewesite) or Dimercaprol - Important Compound o CdCl2 § Emetic § Treatment of Tinea infection o CdS § Yellow sulfide § Anti-seborrheic o CdSO4 § Ophthalmic antiseptic Mercury (Hg) - Quicksilver, messenger of Gods - Diuretic - Antiseptic - Treatment of Syphilis - Cathartic - Parasiticidal/Fungicidal - Industrial Use: o Thermometer o Amalgams (dental cement) - Disease: Minamata - Antidote: EDTA - Important Compounds o Hg2Cl2 § Calomel § Cathartic § Local antiseptic o HgCl2 § Corrosive sublimate § Disinfectant o HgI § Treatment of syphilis o HgI2 § Stimulant of indolent ulcers o K2HgI4 § Antiseptic § Component of Mayer’s reagent o HgNH2Cl § White precipitate § Topical antiseptic o HgO § Yellow precipitate § Ophthalmic anti-infective Boron (B) - Industrial use: o Vulcanizing rubber - Important Compounds o H3BO3 § Sal sativum § Toxicity: lobster appearance § Buffer (ophthalmic solution 2%) § Antiseptic § Tonicity adjusting agent o Na2B4O7·10H2O § Borax 16 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio § § § § § Aluminum (Al) - Most abundant metal - 3rd most abundant element - Pharmacological Uses: o Astringent o Aluminum foils used for burn patients - Important Compounds o AlCL3·6H2O § Astringent § Antiseptic § Antiperspirant/deodorant o o o o o o • Na Tetraborate Dobelle’s solution Antiseptic Eye wash Wet dressing for wounds Alum § [AlNH4(SO4)2·12H2O] – NH4 salt § [AlK(SO4)2·12H2O] – K salt § Astringent Al(OH)3 § Amphojel, Cremalin Gel § Antacid § Protectant § Disadvantage: constipation AlPO4 § Phosphagel § Antacid § Astringent § Demulcent Al2(CO3)3 § Treatment of phosphatic calculci Al2O3 § Alumina § Treatment of silicosis Aluminum Silicate § Kaolin § § China clay, native hydrated aluminum silicate • Adsorbent in diarrhea Bentonite • Soap clay, mineral soap, native colloidal hydrated magnesium silicate • Suspending agent Pumice • Volcanic origin and used as dental abrasive Gallium (Ga) - Substitute for mercury in manufacture of arc lamps Carbon Group Carbon (C) - Manifestation o Crystalline – graphite, diamond o Amorphous – coal, anthracite - Important Compounds o CO2 § Treatment of acne, warts, corns, calluses, eczema o CO3-2 § Antacid § For effervescent tablets o CO § 210x greater affinity to hemoglobin than oxygen leading to asphyxia then death § Treatment: • 100% O2 • Artificial air (He 80%, O2 20%) • Hyperbaric O2 Silicon (Si) - 2nd most abundant element - Important Compounds o SiO2 § Toxicity: Silicosis 17 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o o o o o o o Glass § Na2CO3 + pure silica Kaolin § Adsorbent Purified Siliceous Earth § Absorbent Bentonite § Suspending agent Talc § Clarifying agent § Dusting agent Attapulgite § Polymagma, diatabs, quintess § Adsorbent Simethicone § Polymeric Dimethyl Siloxane § Antiflatulent Tin (Sn) - Stannum - Preparation of tin cans - Important Compounds o SnF2 § Anticariogenic o SnO2 § Germicide Lead (Pb) - Plumbum - Astringent - Protein precipitant - Poisoning: Plumbism - Antidote: EDTA - Sources of Poisoning o Lead pipes o Paints o Batteries - Important Compounds o Pb(CH3COO)2 § Sugar of lead § Astringent Pb2(CH3COO) § Goulard’s extract § Astringent § Antiseptic o PbO § Litharge Titanium/Zirconium Titanium (Ti) - Titan, sons of the earth - Powerful reducing agent - Important Compound o TiO2 § Opacifying agent • Ocusert § UV Ray Protectant • TiO2 reflects UV Zirconium (Zr) - Use: same with aluminum but banned due to granuloma formation - Former Official Compounds o Oxide o CO3 § Both used as antiperspirant and for athlete’s foot Nitrogen Group Nitrogen (N) - Mephitic air, azote, without life - Most abundant gas in air: 71% N2, 29% O2 - Important Compounds o N2 – very stable § Used as INERT atmosphere for readily oxidizable substance § Liquid N2 • Used as refrigerant • Container: Black o N2O § Laughing gas o 18 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio § § § o o NO2 § § NO3§ Inhalation anesthetic S/E: Diffusion hypoxia Container: Blue Vasodilator For cyanide poisoning Preservative Aromatic Ammonia spirit § Spirit of Hartshorn, spirit of sal volatile § Respiratory stimulant Phosphorus (P) - Light carrier, St. Elmo’s fire - 2 forms: o White – poisonous o Red – non-poisonous - Important Compound o PO4 § Antacid § Cathartic Arsenic (As) - Lewisite metal - Insecticide o Copper aceto arsenate (Paris green) - Antidote: BAL - Important Compounds o As2O3 § Insecticide § Anti-leukemic o AsI3 § Primary standard in the preparation of ceric sulfate Antimony (Sb) - Pharmacologic use: o Expectorant o Emetic o o Anti-helminthic Important Compound o SbKOC4H4O6 § Tartar emetic, brown mixture § Emetic § Tx of schistosomiasis Bismuth (Bi) - Beautiful meadow - Pharmacologic Action o Astringent o Antiseptic o Internal Protective for ulcer - Causes o Dark stool & Blue-black gums - Antidote: BAL/ Dimercaprol Tantalum (Ta) - Not affected by any body fluid, therefore inert in our body - Sheet form use in repair of bones, nerve, and tissue Chalcogens Oxygen (O) - Empyreal air, dephlogisticated air, “yne” - Most abundant element - Treatment of hypoxia/asphyxia - Container: Green Sulfur (S) - Brimstone, shubari, enemy of copper - Used in preparation of scabicidal and keratolytic ointment or lotion - Stimulant cathartic - Depilatory agent - Anti-dandruff Selenium (Se) - Selena, moon - Essential trace element - Promotes absorption of Vitamin E - Antioxidant - 19 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio - Important Compound o SeS2 (Selsun blue) § Anti-dandruff Chromium, Molybdenum, Uranium Chromium - Essential trace element - Glucose tolerance factor - Deficiency: Hyperglycemia - Important Compound o K2Cr2O7 § Oxidizing agent Molybdenum (Mo) - Essential trace element - Co-factor enzyme - Important compound o Molybdenum Oxide + FeSO4 § Hematinic § BN: Mol-Iron Uranium (U) - Discovered by Becquerel - Radioactive element used for manufacture of atomic bombs - No pharmaceutical use Halogens Fluorine - Strongest oxidizing agent - Poisoning: Fluorosis - Principal Manifestation: o Motted Enamel o Abnormal bone growth - Important Compounds o NaF § Anticariogenic at 2% solution o SnF2 § Anticariogenic at 8% solution Chlorine (Cl) - Dephlogisticated muriatic acid - Most Abundant Extracellular anion - Used as Water disinfectant - Important Compounds o Hypochlorite (Na, K) § Bleaching agent o HCl § Tx of achlorhydria Bromine (Br) - Dark reddish brown fuming liquid with suffocating odor - Pharmacologic Action o Sedative o Depressant - Poisoning: Bromism - Principal Manifestation o Skin Eruption o Psychosis o Weakness o Headache - Antidote: NaCl and NH4Cl Iodine (I) - Expectorant - Anti-fungal - Deficiency: Goiter - Elemental Iodine preparation o Strong Iodine Solution – Lugol’s soln o Iodine Tincture – disinfectant o Povidone-Iodine – Betadine Astatine (At) - Only metallic - Only synthetic halogen - Only radioactive halogen Manganese/Technecium Manganese (Mn) - Co-factor in: o Protein synthesis o Phosphorylation o Fatty acid and cholesterol synthesis - Poisoning: Parkinson-like - Important Compound 20 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio KMnO4 § Mineral chameleon § Oxidizing agent § Antiseptic Technecium (Tc) - 1st element produced artificially - Used in preparation of radiopharmaceuticals Noble Gases Helium (He) - 2nd lightest gas - Toxicity (Inhalation) – Donald duck-like sound - Container: Brown Neon (Ne) - For advertising Argon (Ar) - Most abundant noble gas - Substitute for N2 in providing inert atmosphere Krypton (Kr) - Least abundant of all noble gases - Have inhalational anesthetic activity Xenon (Xe) - Investigational with inhalational anesthetic activity Radon (Rn) - Niton - Synthetic noble gas - Used for treatment of Cervical CA Iron (Fe) - Present in proteins: o Hemogloin o Transferrin o Ferritin o Cytochrome oxidase - Enhance absorption of: o Vitamin C o Copper - Hematinic o - Toxicity: o GIT Distress o Cardiac Collapse - Antidote: Deferoxamine - Important Compounds o FeSO4 § Green vitriol § Hematinic § S/E: constipation o Ferrous Gluconate § BN: Fergon § Adv: less irritating o Ferrous Fumarate § BN: Toleron o FeCO3 § Chalybeate pills, Ferrunginous pills § Hematinic o FeCl3 § Astringent § Styptic § Detection of tannins o Fe4[Fe(CN)6]3 § Ferric ferrocyanide § Prussian blue o Fe3[Fe(CN)6]2 § Ferrous ferricyanide § Turnbull’s blue Other Metals Cobalt (Co) - Essential in development of erythrocyte and hemoglobin - Component of Vitamin B12 - Deficiency: Megaloblastic Anemia - Important Compound o CoCl2 § Lover’s ink, sympathetic ink § Desiccator indicator 21 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Nickel (Ni) - Old Nick’s copper - Fossil fuel Osmium (Os) - Heaviest - Densest metal - Important Compounds o Osmic acid o Osmium tetroxide § Both used in staining microorganism for microscopic study specially in electron microscopy Platinum (Pt) & Palladium (Pd) - Catalyst in finely divided steel Flame Test Metals Non-luminous flame Under cobalt gas Sodium Persistent Golden Yellow Nil Potassium Violet Crimson Lithium Carmine Red Purple Calcium Brick Red Light Green Strontium Crimson Purple Barium Yellowish Green Bluish-Green Borate, Cu, Green Tl, P Pb, As, Sb, Blue Yellow Bi, Cu Ammonium colorless MODULE 1: ORGANIC CHEMISTRY & ORGANIC MEDICINAL CHEMISTRY Organic Chemistry - Branch of chemistry that deals with carbon-containing compounds with: o H, O, P, N, S, X - Isomerism o Existence of two or more compounds having the same molecular formula, but different structure - Isomer o Compounds having the same molecular formula, but different structure Stereochemistry o Branch of organic chemistry that is solely dedicated to the study of isomers Carbon - Contains 4 binding sites for other atoms to attach to it - These four binding sites, when bonded with atoms/molecules form a tetrahedron - Group 4, Period 2 - Atomic No. 6 o 1s2 2s2 2p2 22 other Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio o Needs 4 more electrons to complete its octet o Valence: 4 o Can only share: covalence Hydrocarbon - Contains C, H - Hydrocarbon Derivatives – hydrocarbons that bear other carbon & hydrogen atoms & other elements such as Oxygen, Nitrogen, Sulfur, Halogen, Phosphorus, etc Aliphatic - Single chain, no ring/s - Saturated – single bonds only o Alkane (parafins) o CnH2n+2 - Unsaturated – has multiple bonds o Alkenes – double bond § CnH2n o Alkynes – triple bonds § CnH2n-2 Aromatic - Presence of ring/s, specifically benzene ring & its derivatives - Examples Alicyclic or Carbocyclic - Chains that form a ring and behave like aliphatic (single bonds) - Examples o Cyclopropane o Cyclobutene o Cyclopropane o Cyclobutene - Cycloalkanes: o CnH2n Oxygen-Containing - Aldehydes (RCHO) o Ketones (RCOR) - Ethers (ROR) o Formed during dehydration of alcohol o CnH2n+20 - Alcohols (Phenol) - Carboxylic Acid o Carboxyl, -COOH o Organic acid (RCOOH) Carboxylic Acid Derivatives o Acid acyl o Anhydrides o Ester (RCOOR) o Amides Nitrogen Containing - Amines (amino group, –NH) o Primary Amines: RNH2 o Secondary Amines: R2NH o Tertiary Amines: R3N - Heterocyclic - Nitrogen-compounds Halogen-containing - Alkyl halides - Aryl halides Phosphorus-containing - Phosphate groups - Organophosphate - - 23 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Sulfur-containing - Thiols (–SH) o Sulfur analogue of alcohols o Sulfhydryls - Thioethers (R-S-R) Systems of Nomenclature - Common o Uses the name given when it was discovered o Formic acid – ants o Butyric acid – butter o Prefixes: n-, iso-, neo- Derived o Derived from parent compound - IUPAC o Most SYSTEMATIC Based on § Longest continuous C chain or parent chain § Use of numbers § Use of C # prefixes o QSAR – Quantitative Structure & Activity Relationship IUPAC Rules: o Name by considering the longest carbon chain o Number C atoms consecutively from one end so that the branches or substituents are given the lowest position numbers o Modify the Suffix based on the type of formula or the functional group § ROH (-ol) § RCHO (-al) § RCOR (-one) § RCOOH (-oic acid) o Identify the substituents & indicate the positions by using numbers § CH3 (methyl) § R (alkyl) § OCH3 (methoxy) § OR (Alkoxy) o ↑ § Cl (Chloro) § Br (Bromo) § NH2 (Amino) o If there is more than one of the same substituent/ alkyl group on the chain, indicate the number of groups by using prefixes; di- two; tri-three; tetra-four; & so on. Saturated Hydrocarbons - Alkanes: CnH2n+2 (-ane) # of C Prefix + -ane Molecular Formula atoms 1 MethMethane CH4 2 EthEthane C2H6 3 PropPropane C3H8 4 ButButane C4H10 5 PentPentane C5H12 6 HexHexane C6H14 7 HeptHeptane C7H16 8 OctOctane C8H18 9 NonNonane C9H20 10 DecDecane C10H22 (separate pdf for examples) - Alkyl groups o Can participate in Van der Waals interaction and hydrophobic bonding o Metabolism: Oxidation o Aryl Groups (Ar) – aromatic (benzene ring) with a hydrogen atom removed - Reactions to Consider o Combustion – chemical reaction in which HC burns (rapid oxidation) & produces CO2 and H2O - Cycloalkanes – alkanes that exist in the shape of a ring o Cyclopropane/Trimethylene o Cyclobutane o Cyclopentane Unsaturated Hydrocarbons – have multiple bonds in their molecules - Alkenes: CnH2n (-ene) o Double bond 24 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Ex: Propene: CH3-CH=CH2 Reactive site occur in C=C – double bond (e- rich) o Electrophile (E!) – e- poor/ e- loving reagents (+) o Nucleophile (N !) – e- rich reagent (-) o Electrophilic Addition – alkene react with electrophiles - Alkynes: CnH2n-2 (-yne) o Triple bond (one or more) - Aromatics – contain benzene ring that have multiple double bonds o Benzene: C6H6 (subject to substitution electrophilic) o Toluene – methyl derivative of benzene o Xylene – dimethyl benzene Aromaticity (Criteria) o Cyclic o Flat/Planar – (sp2C = double bond) o Conjugated double bonds – having alternating double bonds o Huckel’s Rule – 4n+2 rule Stereochemistry (Reasons) Order of Bonding - Structurally isomer - Chain – branching o Exhibited by alkanes o Differ in the arrangement of C atoms o C4H10 (butane/isobutane) o o - - C5H12 (pentane/ isopentane/ neopentane) Position – position of multiple bond or differ in the position of substituent or functional group o Differ in position of the substituent or unsaturated bonds o C4H8 – alkene with 1 double bond o C3H7Br o Prefixes that designate positions in the benzene: § Ortho – indicate substances on the benzene ring in positions next to each other § Meta – substituents on the benzene ring separated by one carbon atom § Para – substituents separated by two carbon atoms Functional Isomer – functional group o Differ in their functional groups Spatial Orientation - Arrangement of atom in space - Stereoisomer o Geometric Isomers – double bond (alkene), cyclic – CisTrans 25 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio § § o Cis (means on the same side) Trans (means across or on opposite sides) Cyclobutane Planar – not a stable conformation, all are eclipsing Conformational Isomers § Open chain/acyclic – can be obtained in rotation along a single bond § Cyclic-ring flipping Ethane Saw horse projection Butterfly conformation – more Stable Cyclopentane Planar – not stable Perspective formula (dash – back, wedge – front) Envelope conformation Cyclohexane Chair – most stable Newman projection eclipse conformation & staggered conformation (more stable) Planar – not stable Boat conformation – more stable 26 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Optical Activity - Ability of a compound to rotate a polarized light either to right or to the left - Can only be determined by POLARIMETER - Dextrorotatory = d/(+) - Levorotatory = l/(-) Chiral Center/Chiral Carbon/Asymmetric Chiral Carbon - Stereocenter - Carbon to which four different atoms or group of atoms are attached No symmetry element - Enantiomers – mirror images but not superimposable o Optical Isomer since they rotate light in the opposite direction - Diastereomers – non-mirror images, not superimposable - Mesocompounds – mirror images, superimposable o Same compounds - Epimer – special type of diastereomers o Identical in all except in one chiral center o Differ only in configuration at one asymmetry carbon atom § D-glucose/D-mannose – epimers at 2 § D-glucose/D-galactose – epimers at 4 - Anomer – differ only in configuration at Carbon 1 (carbonyl C or anomeric C) o Fischer Projection Formula - - - Tartaric Acid = # stereoisomers = 2n (n = chiral center) = 22 =4 27 I-II - mirror images o Superimposable § Meso compounds (compounds with stereocenters but are chiral) § Optically inactive II-III – non mirror images o Non Superimposable § Diastereomers III-IV – mirror images o Non Superimposable § Enantiomers Meso Compounds – compounds with stereocenters but are chiral o Characterized by the presence of a plane of symmetry and are superimposable Racemic Mixtures (racemates) o Produced with mixtures of equimolar concentrations of dextro & levo isomers o Contain equal amounts of § D & L isomers § R & S isomers – determine by Cahn-IngoldPrelog o Example: Thalidomide § exist 2 chiral center § r-thalidomide – sedative/ hypnotic § s-thalidomide – teratogenic § Thalidomide syndrome – because of the presence of s-thalidomide • Phocomelia (short limb) • Amelia (no limb) Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio Haworth Projection - Presents a cyclic sugar structure - Bioisostere - substituents or groups w/ similar physical or chemical properties that in impart similar biological properties to a chemical compounds Purpose: o Enhance the desired biological or physical properties of a compound without making significant changes in chemical structure o Increase Potency o Decrease Side effects o Increase duration of action by altering metabolism o Isosteric analogs may act antagnonistically w/ the parent molecule Example of Bioisosteric replacements: o Fluorine vs Hydrogen o Hydroxyl vs Amino Acids o Hydroxyl vs Thiol Groups o Methyl, Methoxyl, Hydroxyl, Amino groups vs Hydrogen o Fluoro, Chloro, and Bromo, thiol vs Methyl and other small alkyl groups Types of Organic Reactions: o Addition o Substitution o Elimination o Re-arrangement o Propagation, Initiation, Termination o Oxidation o Reduction Organic Medicinal Chemistry - Deals with the physicochemical properties of drugs that affect its biological action - Practice of medicinal chemistry is devoted to the discovery and development of new drugs Anti-Infective Agents - Joseph Lister – introduced phenol (carbolic acid) - Paul Ehrlich – Salvarsan (compound 606), selective toxicity - Atoxyl (sodium arsanilate and arsphenamine) – for sleeping sickness - Germicides – anti-infective agents that are used locally - Antisepsis – apply to living tissue - Decontamination – destruction or marked reduction in the number or activity of microorganisms - Disinfection – on inanimate objects - Sanitation – reduction to a level acceptable for public health - Sterilization – kills all types including spores - Pasteurization – nonsporulating microorganisms (65o-100oC) Local Anti-Infectives or Germicides Alcohols and Related Compounds - activity ↑with MW until C8 (octanol), Branching ↓ antibacterial potency - As primary alcohol chain ↑, Van der Waals interactions ↑, ability to penetrate microbial membranes ↑ - As water solubility ↓, potency ↓ with MW Alcohol, USP (Spiritus vini rectificatus, wine spirit, Grain alcohol) - Fermentation product from grain and many other carbs, or sulfuric-acid-catalyzed hydration of ethylene - Most widely abused of all recreational drugs - Commercial: 95% ethanol (forms an azeotrope in water that distills at 78.2:C) - Antidote: disulfiram blocks aldehyde dehydrogenase à acetaldehyde (nausea, vomiting, flushing) - Denatured - Completely denatured alcohol contains added methanol (wood alcohol) and benzene - Rubbing (70%) - Astringent, rubefacient, refrigerant, mild local anesthetic - Dehydrated/Absolute - nlt 99% ethanol; obtained by azeotropic distillation - Isopropyl - Rapidly bactericidal (50% to 95%), 40% equal antiseptic power to a 60% ethanol Ethylene Oxide - Used to sterilize temp-sensitive medical equipment and those that could not be autoclaved 28 Pharmacy Board Exam Reviewer Reviewer by: camila kim vertucio - Carboxide – 10% ethylene oxide + 90% CO2 (to prevent explosion) - MOA: alkylation of functional groups in nucleic acids and proteins Formaldehyde Solution (Formalin) - nlt 37% of formaldehyde + methanol (retard polymerization to formic acid and paraformaldehyde) - MOA: direct, nonspecific alkylation of nucleophilic functional groups Glutarol/Glutaraldehyde (Cidex) - components: glutaraldehyde and buffer Phenols and their Derivatives - standard for germicides - phenol coefficient – ratio of a dilution of a given test disinfectant to the solution of phenol that is required to kill a strain of S.typhi under carefully controlled time and temperature - straight-chain and substitution with alkyl, aryl, and halogen ↑ bactericidal activity - low concentrations: denature bacterial proteins, high concentrations: lysis of cell membranes Phenol (Carbolic Acid) - Introduced as surgical antiseptic by Joseph Lister; its use is now obsolete - Exhibits germicidal activity (general protoplasmic poison), caustic, local anesthetic - Liquefied Phenol – Phenol with 10% water - p-Chlorophenol – used in combination with camphor in liquid petrolatum - p-Chloro-m-xylenol – 2% (shampoo), for athlete’s foot and jock itch - Hexachlorophene – easily adsorbed onto skin and enters sebaceous glands (neurotoxicity) Cresol - mixture of three isomeric methylphenols; obtained from coal tar or petroleum - Chlorocresol – preservative Thymol - m-cresol; from Thymus vulgaris; mild fungicidal (tinea) Eugenol - from clove oil; applied on cotton to relieve toothaches, ingredient in mouthwashes Resorcinol - weak antiseptic, keratolytic - Hexylresorcinol - produces numbness when applied to tongue; ingred in lozenges Oxidizing Agents - MOA: Oxidation (peroxides) and protein denaturation (permanganates) - Poor penetrability to infected tissues and organic matter - Hydrogen Peroxide - active against anaerobic bacteria, wound cleansing - Carbamide Peroxide (urea + H2O2) - releases hydrogen peroxide when mixed with water - Hydrous Benzoyl Peroxide (2.5%, 5%, 10%) - most effective topical OTC agent for the control of acne Halogen-Containing Compounds Iodine (oldest known germicide) - Iodine tincture (2% solution of iodine in 50% alcohol with NaI) - Lugol’s sol’n/Strong Iodine Sol’n (5% iodine in water with KI) - Iodine Solution (2% iodine in water with KI) Iodophors (Iodine + nonionic surfactants) - Povidone-Iodine (Betadine)— complex with the nonionic surfactant polymer, polyvinylpyrrolidone Chlorine-Containing Compounds - Disinfection of water supplies - Forms Hypochlorous acid (HClO) when dissolved in water - Halazone - disinfects drinking water - Chloroazodin - a glyceryltriacetate solution is used as wound dressing - Oxychlorosene Sodium - complex of sodium salt of dodecylbenzesulfonic acid and hypochlorous acid 29