PHARMACY Module 1 Summary

Module 1 Pharmaceutical Chemistry Inorganic and Organic Pharmaceutical and Medicinal Chemistry Kathreen Mae D. Cascabel BSPharmacy

General Chemistry Chemistry – study of matter Matter – anything that occupies space and has mass UNITS OF MEASUREMENT 1. 2. 3. 4.

Composition Structure Changes that matter undergoes Energy involved in such changes or interactions

Length Mass Time Temperature

Meter (m) Kilogram (kg) Seconds (sec) Kelvin (K)

Mass – refers to the amount of matter present in the material Weight = Mass x Pull of gravity Classification of Matter  Element - simplest form of matter, 1 kind of material or atom  Compound - substances composed of two or more elements united chemically in definite proportion  Mixture - composed of 2 or more substances that are not chemically combined

Plasma  Colorless fluid part of blood, lymph, or milk in which corpuscles or fat globules are suspended Serum  Amber- colored protein-rich liquid that separates out when blood coagulates  Used to provide immunity  Diagnostic agent

Classification of Mixture A. According to the Nature of Particles a. Homogenous b. Heterogenous B. According to the Size of Particles a. Solution - uniform mixture (homogenous), composed of solute and solvent where solute is soluble b. Suspension - Coarse Mixture, finely divided solid materials distributed in a liquid where solid is insol. c. Colloid - particles of solute not broken down to the size of the molecules but are small enough to remain suspended and evenly dispersed throughout the medium Process of Separating Components of Mixtures 1. Decantation - difference in specific gravity or density 2. Distillation - evaporation and then condensation 3. Evaporation 4. Magnetic Separation 5. Filtration 6. Sorting 7. Centrifugation - speeding up of settling process of a precipitate 8. Fractional Crystallization - lowering of temp so that the more insoluble comp crystallizes out first 9. Chromatography - difference in solvent affinity

Properties of Matter 1. Intrinsic/Intensive 2. Extrinsic/Extensive

- INDEPENDENT of mass or amount (density, specific gravity, melting point) - DEPENDENT on mass (weight, volume, pressure, heat content)

Changes that matter undergoes 1. Physical Change - change in phase

2. Chemical Change - change in both intrinsic and extrinsic properties Evidences of Chemical Change  Evolution of gas  Formation of precipitate  Emission of light  Generation of electricity  Production of mechanical energy  Absorption/liberation of heat Types of Chemical Reactions A. Direct Union B. Decomposition/Analysis C. Single Replacement D. Double Displacement

Fe + S  FeS (all sulfides are BLACK) Na2CO3  Na2O + CO2 Na + HCl  NaCl + H2 NaCl + AgNO3  NaNO3 + AgCl

Processes Involved in Chemical Change 1. Oxidation +𝑂 2. Reduction −𝑂 𝑜𝑟 + 𝐻 3. Neutralization 𝑎𝑐𝑖𝑑 + 𝑏𝑎𝑠𝑒  𝑠𝑎𝑙𝑡 + 𝑤𝑎𝑡𝑒𝑟 4. Hydrolysis 𝑤𝑎𝑡𝑒𝑟 + 𝑠𝑎𝑙𝑡  𝑎𝑐𝑖𝑑 + 𝑏𝑎𝑠𝑒 5. Saponification 𝑎𝑙𝑘𝑎𝑙𝑖 + 𝑓𝑎𝑡𝑠  𝑠𝑜𝑎𝑝 + 𝑔𝑙𝑦𝑐𝑒𝑟𝑜𝑙 6. Fermentation 𝑜𝑟𝑔𝑎𝑛𝑖𝑐 𝑠𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒𝑠 + 𝑚𝑖𝑐𝑟𝑜𝑏𝑒𝑠  𝑎𝑙𝑐𝑜𝑕𝑜𝑙

3. Nuclear Change – ∆ in structure, properties, composition of the nucleus  in the transmutation of the element  Nuclear Fission - splitting of a heavy atom  Nuclear Fusion - union of 2 light atoms to form a bigger molecule Oxidation state computations: 1. KMnO4 K = +1 (1) = +1 Mn = x O4 = -2 (4) = -8 1+x–8=0 X = +7 2. Na2Cr2O7 Na2 = +1 (2) = +2 Cr2 = x (2) = 2x O7 = -2 (7) = -14 +2 + 2x – 14 = 0 2x = 14 – 2 2x = 12 X = +6 3. AsO3-3 As = x O4 = -2 (4) X – 8 = -3 X=8–3 X = +5

+1 H Li Na K Rb Cs Fr

+2 Be Mg Ca Sr Ba Ra

+3 Al

-2 O S

-1 F Cl Br I At

ATOMIC STRUCTURE Protons Neutrons Mass no. Electrons

Isotopes Isotones Isobars Isomers

Similarities Element Neutrons Mass number Molecule

= Electrons = Atomic number = Mass number – Atomic number = Protons + Neutrons = Protons - Charge

Difference Mass number Protons Element Structure

P =6

ION Cation =

12

+ N = Mass no. – P = 12-6 =6 Anion = E = P – charge =6–0 =6

Democritus John Dalton

J.J Thompson Rutherford Niel Bohr Model Erwin Schrodinger James Chadwick

+1

6

C

12

-

-1

C

6

E = P - Charge = 6 – (+1) =5

E = P -Charge = 6 – (-1) =7

Matter is made up of small indivisible particles | Coined “atomos” “Billiard Ball Model” – atom is a hard indestructible sphere Dalton’s Atomic Theory  Matter is made up of atoms  All atoms of a given element are alike  Atoms enter into a combination with other atoms to form compounds but remain unchanged during ordinary chemical rxn Atom can combine into simple numerical ratios Disproved: subatomic particles “Raisin Bread” model Proton; Gold Film Experiment: Atom is mostly an empty space (99% passed) Planetary model Quantum Mechanic Model; “Electron Cloud” – electrons move in 3D structure (Orbitals) Neutron

ION – charged atom  Atomic Number - number of protons  Mass number - protons + neutrons

ALLOTROPISM  Allotrope – atoms of different elements can link together in different ways to form substances with diff properties  Allotropes of Carbon : Diamond and Graphite  Allotropes of Oxygen o *O+ nascent o O2 molecular o O3 ozone Orbitals – region in space where the probability of finding an electron is greatest

QUANTUM NUMBERS Symbol

Values

Function

Principal Quantum Number  Main energy level

n

1, 2, 3 (+ integer)

Determine the size of the particle

Azimuthal or Angular Momentum

l

0 to (n-1)

Subshell or sublevel, determines the shape (s, p, d, f)

Magnetic Quantum Number

m or ml

-l to +l

Orbitals, determine the orientation

Spin Quantum Number

s or ms

- ½ or + ½

Direction of the spin or rotation

Law of Conservation of Mass - The total mass of all products of a chemical reaction is equal to the total mass of all reactants of that reaction Law of Definite Proportions/Proust’s Law - Inorganic compounds - A chemical compound always contains exactly the same proportion of elements by mass Law of Multiple Proportion - Organic compounds - When chemical elements combine, they do so in a ratio of small whole numbers

GENERAL PRINCIPLES IN ELECTRON CONFIGURATION Pauli’s Exclusion Principle – No two electrons can have the same set of 4 quantum numbers Each atomic orbital can only accommodate 2 electrons (Ex: 1s2) Heisenberg’s Uncertainty Principle – Impossible to determine simultaneously the e- momentum & position Aufbau Building Up Principle – Lower energy levels are filled up first Hund’s Rule of Maximun Multiplicity – Orbitals are filled up singly before pairing up

PERIODIC TABLE OF ELEMENTS Antoine-Laurent Lavoisier Johann Dobereiner Newlands Meyer and Mendeleev Henry Mosley

- Hydrogen, First true periodic table - Triads (Li, Na, K | Ba, Ca, Sr | S, Se, Te | Cl, Br, I) - Octaves - Physical and chemical properties are periodic functions of their atomic weights - Elements are arranged based on atomic numbers (present)

Family A  Representative Elements  Occupy: o S block  Group IA – Alkali Metals  Group IIA – Alkaline Earth o P Block  Group IIIA to VIIIA Family B  Transition elements  Occupy: o D block: Transition Metals o F block: Lanthanide or Lanthanoid series – Rare Earth Metals

PERIODIC TRENDS (noble gases not included)

Atomic Radius (½ the distance bet 2 nuclei) Metallic Property

Ionization potential (energy to remove an e-) Electron affinity (energy when e- is added) Electronegativity (ability to attract e-) *Arrows indicate increasing values

Kinematic Molecular Theory – explains phases of matter based on movement (exclu. direction) of molecules/ions/atoms  SOLID - definite shape and size, definite volume  LIQUID - follows the shape of container, definite volume  GAS - indefinite shape and volume SOLUTIONS – homogenous mixture single phase system of two of more substances  Saturated Solution - maximum amount of solute  Unsaturated Solution - less solute  Supersaturated Solution - more solute than the solvent can dissolve Factors Affecting Solubility 1. Nature of Solute and Solvent  “Like dissolves like” Solubility – maximum amount of solute expressed in grams that can be dissolved in 100 g of water Miscibility – ability of one substance to mix with another substance 2. Temperature  ↑ temperature = ↓ solubility of a gas Exothermic – solubility decreases with increase in temp (Mg citrate) Endothermic – solubility increases with increase in temp 3. Pressure ( for gases only) Henry’s Law – the solubility of a gas increases as pressure increases 4. Particle Size/Surface Area  Decreased particle size = Increased surface area = Increased solubility 5. Presence of Salts  Salting Out  Salting In

– presence of salt decreases solubility – presence of salt increases solubility

Methods of Expressing Concentration of Solutions Percent Solution  % by mass  % by volume  % mass/volume  ppm (parts per million)  proof

Mole fraction (x) = moles of the substance total moles of solution Molarity (M) – moles of solute per L of solution Molality (m) – moles of solute per kg of solvent Normality (N) – no. of equivalents of solute per L of solution

Mole (n) = grams/MW

FORCES OF ATTRACTION INTRAMOLECULAR FORCES – within molecules 1. Ionic Bond - transfer 2. Covalent Bond - sharing a. Polar (unequal) b. Nonpolar (equal) INTERMOLECULAR FORCES – between molecules; physical attraction 1. Van der Waals a. Keesom (Dipole-dipole) o Orientation/Alignment effect o 1-7 kcal/mole b. Debye (Dipole-Induced Dipole) o Induction o 1-3 kcal/mole c. London Dispersion (Induced dipole-Induced dipole) o Very close proximity  internal vibration will cause dispersion of charges o 0.5-1 kcal/mole 2. Ion-Dipole - charged ion + polar molecule (salt & water) 3. Ion-Induced Dipole - charged ion + nonpolar molecule (I2 + KI) 4. Hydrogen Bond - between H and electronegative atom (F, O, N, Cl, S) ; can be intramolecular (A=T) Physical Properties of Systems 1. Additive Property 2. Constitutive Property 3. Colligative Property

- depends on sum - type and arrangement - number of solute

| molecular weight | optical rotation, refractive index | VPL, BPE, FPD, OP

Density = mass per unit volume (M/V) Specific gravity = density of sample/density of standard Specific volume = reciprocal of specific gravity, opposite of density

COLLIGATIVE PROPERTIES – property of solution depend on the number of solute particles dissolved in a solvent Colligative Property Vapor Pressure Lowering

Notes   

Boiling Point Elevation

The 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

BP – temp at which liquid pressure is equal to atmospheric pressure (1 atm = 760 mmHg) The boiling point of a solution containing a nonvolatile solute would be higher than the pure solvent because the solute would lower the vapour pressure of the solvent

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:  Salt is spread on roads to melt ice  Ethylene glycol as “anti-freeze”

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 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 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 – 𝜟𝑷 = 𝑷° 𝒙 𝒎𝒐𝒍𝒆 𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏

∆𝑇𝑏 = 𝐾𝑏 𝑚 ∆𝑻𝒃 = 𝑲𝒃

𝟏𝟎𝟎𝟎 𝒘𝟐 𝒘𝟏 𝑴𝑾𝟐

Kb = ebullioscopic/molal BPE constant (0.52 °C/m) m = molality w1 = weight of solvent w2 = weight of solute MW2 = molecular wt of solute ∆𝑇𝑓 = 𝐾𝑓 𝑚 ∆𝑻𝒇 = 𝑲𝒇

𝟏𝟎𝟎𝟎 𝒘𝟐 𝒘𝟏 𝑴𝑾𝟐

Kf = cryoscopic/FPD constant (Kf = 1.86°C/m)

𝝅𝑽 = 𝒏𝑹𝑻 𝑜𝑟

𝝅 = 𝑴𝑹𝑻

π = osmotic pressure in atm V = volume in L n = no of moles of solute

𝐿.𝑎𝑡𝑚

R = gas constant (0.08205 𝑚𝑜𝑙.𝐾) T = absolute temperature

GAS LAW Boyle's/Mariotte

Charles'

Gay-Lussac's

FORMULA 𝑷₁𝑽₁ = 𝑷₂𝑽₂ 𝑽₁ 𝑻₁

=

𝑽₂ 𝑻₂

𝑷₁ 𝑷₂ = 𝑻₁ 𝑻₂

CONSTANT 𝟏

𝑜𝑟

𝑷 ∝𝑽

Temperature

𝑜𝑟

𝑽∝𝑻

Pressure

𝑜𝑟

𝑷∝𝑻

Volume

𝑷₁𝑽₁ 𝑷₂𝑽₂ = 𝑻₁ 𝑻₂

Combined

R = 0.08206

𝑷𝑽 = 𝒏𝑹𝑻

Ideal

(𝑷 +

𝒂𝒏𝟐 ) (𝑽 − 𝒏𝒃) = 𝒏𝑹𝑻 𝒗𝟐

𝐿.𝑎𝑡𝑚 𝑚𝑜𝑙.𝐾

At STP: T = 273.15 K P = 1 atm V = 22.4 L

Real/Van der Waals

an2 = internal pressure per mole nb = incompressibility Rauolt’s Henry’s Law of Gas Solubility Dalton’s Law of Partial Pressures

Avogadro’s

𝑷𝒔𝒐𝒍𝒖𝒕𝒊𝒐𝒏 = 𝑿𝒔𝒐𝒍𝒗𝒆𝒏𝒕 𝑷𝒔𝒐𝒍𝒗𝒆𝒏𝒕 X = mole fraction

𝑷𝒓𝒆𝒔𝒔𝒖𝒓𝒆 ∝ 𝑺𝒐𝒍𝒖𝒃𝒊𝒍𝒊𝒕𝒚 Total pressure in a mixture is equal to the sum of the partial pressures of each gas 𝑃𝑡 = 𝑃1 + 𝑃2 + 𝑃3 … …. Volume of gas at STP is directly proportional to the number of moles 𝑽₁ 𝑽₂ = 𝒏₁ 𝒏₂

𝑜𝑟 𝑽 ∝ 𝒏 𝑜𝑟

𝑽 =𝒌 𝒏

Temperature

Temperature

k = 6.022 X 1023

Rate of diffusion and speed gas are inversely proportional to the square root of their density Graham’s

𝑅𝑎𝑡𝑒𝑑𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 ∝

1 √𝑑𝑒𝑛𝑠𝑖𝑡𝑦

Diffusion – gradual mixing of molecules of one gas with molecules of another gas by virtue of kinetic properties Effusion – passage of a gas under pressure through a small opening

ACIDS AND BASES Electrolytes – conductors  Weak Electrolytes: incomplete dissolution  Strong Electrolytes: strong acids and bases, complete dissolution Non-Electrolytes – will not dissociate, will not conduct electricity Acid-Base Theories Theory Arrhenius Bronsted-Lowry Theory Lewis Theory Pearson’s HSAB

ACIDS       

Acid Base + Yields H or H3O OH Proton donor Proton acceptor E acceptor E- donor Hard acids are e- acceptor with high positive charges and relatively small sizes while soft acids have positive charges and relatively small +

BASES      

Sour taste Litmus: blue to red + metals  H gas + carbonate and bicarbonate  CO2 Phenolphthalein: colorless Methyl orange: pink/red HCl, HClO3, HClO4, HBr, HI, HNO3, H2SO4, H3PO4

Bitter taste Litmus: red to blue Feel slippery Phenolphthalein: Pink to violet Methyl orange: Yellow NaOH, KOH, Ca(OH)2

NEUTRALIZATION – Acid + Base  Salt and Water Titration – progressive addition of a sol’n of known concentration to a substance of unknown conc 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

𝒑𝑯 = −𝒍𝒐𝒈 [𝑯+]

Sorensen’s pH scale Neutral = 7 Acidic < 7 Basic > 7

𝐻𝐴 + 𝐻2 𝑂 ↔ 𝐻3 𝑂+ + 𝐴− 𝐵 + 𝐻2 𝑂 ↔ 𝑂𝐻 − + 𝐵𝐻 + 𝐻2 𝑂 + 𝐻2 𝑂 ↔ 𝐻3 𝑂+ + 𝑂𝐻 −

pH Calculations Strong Acids Strong Bases

For weak acids For weak bases Water Ionization

𝒑𝑯 = −𝒍𝒐𝒈 [𝑯+] 𝑝𝐻 = −𝑙𝑜𝑔 [𝑂𝐻 −]

or

𝒑𝑯 = 𝟏𝟒 − (−𝒍𝒐𝒈 [𝑶𝑯− ])

1

Weak Acids

𝑝𝐻 = 2 𝑝𝐾𝑎 − 𝑙𝑜𝑔𝐶𝑎

Weak Bases

𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + 𝑙𝑜𝑔

𝑏𝑎𝑠𝑒 𝑠𝑎𝑙𝑡

or

1

𝑝𝐻 = 𝑝𝐾𝑤 − 2 (𝑝𝐾𝑏 − 𝑙𝑜𝑔𝐶𝑏)

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: - Weak acid and some salt of a weak acid or its conjugate base - Weak base and some salt of a weak base or its conjugate acid Henderson-Hasselbach Equation 𝑠𝑎𝑙𝑡

Weak acids

𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔 𝑎𝑐𝑖𝑑

Weak bases

𝑝𝐻 = 𝑝𝐾𝑏 + 𝑙𝑜𝑔 𝑠𝑎𝑙𝑡

𝑏𝑎𝑠𝑒

Buffer Capacity (Buffer action/Buffer efficiency/Buffer index/Buffer value)  Ability of a buffer solution to resist changes in pH Approximate formula

[𝒔𝒂𝒍𝒕]+[𝒃𝒂𝒔𝒆]

𝒑𝑯 = 𝒑𝑲𝒂 + 𝒍𝒐𝒈 [𝒂𝒄𝒊𝒅]−[𝒃𝒂𝒔𝒆] Exact formula/Koppel-Spiro Van Slyke’s Equation 𝑲𝒂 [𝑯𝟑 𝑶+] + 𝟐 𝒂 +[𝑯𝟑 𝑶 ])

𝜷 = 𝟐. 𝟑𝑪 (𝑲

Where C = total buffer concentration, that is, the sum of the molar concentrations of the acid and the salt.

Maximum Buffer Capacity - occurs when pH = pKa - 𝜷𝒎𝒂𝒙 = 𝟎. 𝟓𝟕𝟔 𝑪

THERMOCHEMISTRY Heat (q)

- an energy transfer due to temperature difference

Work (w)

- form of energy transfer between a system and its surroundings in the form of compression or expansion of gas

Internal Energy (U)

- total energy attributed to the particles of matter and their interactions within a system, composed of thermal energy and chemical energy

Enthalpy (H)

- energy of a reaction

Entropy (S)

- degree of disorderliness

Heat Capacity (c)

- amount of heat required to raise the temperature of an object or substance by 1 degree

Specific Heat

- amount of heat required to raise the temperature of an object per gram

Chemical Reactions 1. Endothermic Process 2. Exothermic Process

Hesse’s Law – the total energy is the sum of all energies in all steps of a reaction

- reaction wherein heat is absorbed by the system, indicated by a (+) change in enthalpy - reaction wherein heat is released by the system, indicated by a (-) change in enthalpy Spontaneous

Non-Spontaneous

Enthalpy

-H

+H

Entropy

+S

-S

Reaction

Exothermic

Endothermic

Le Chatelier’s Principle  When a stress is applied to a system in equilibrium, the equilibrium shifts to relieve the stress

Laws of Thermodynamics 1. Law of Conservation of Energy, states that energy cannot be created or destroyed; it can only be redistributed or changed from one form to another. 2. The second law of thermodynamics says that the entropy of any isolated system not in thermal equilibrium almost always increases. 3. The third law of thermodynamics states that the entropy of a system approaches a constant value as the temperature approaches zero.

GROUP IA: ALKALI METALS  

Most reactive metals Valence = 1

A. HYDROGEN (inflammable air) o Lightest and most reactive element o Isotopes: a. Protium - most abundant b. Deuterium - heavy hydrogen (D2O) c. Tritium - radioactive Hardness of water Temporary – Ca or Mg bicarbonates (removed by boiling/ addition of OH source) Permanent – sulfates, chlorides, or hydroxides of Ca or Mg Water Purified Water Water for Injection SWFI BWFI

- official solutions, tinctures and extracts - extemporaneous compounding test reagents - solvent for parenterals; must pass pyrogen test - extemporaneous compounding of parenterals - has one or more antimicrobial agents (e.g. Benzyl alcohol) small volumes of IM injection, not for IV administration

B. LITHIUM (earth) o Lightest metal o Depressant and Diuretic (SE: hyponatremia) 1. Lithium Bromide 2. Lithium Carbonate (Lithase®, Eskalith®)

- Depressant - DOC for mania

Lithium Toxicity (LMNOP)  Lithium Side effects  Movement (tremor)  Nephrogenic diabetes insipidus (ADH antagonist  polyuria)  Hypothyroidism  Pregnancy problems (teratogenic) IP3 – Inositol triphosphate (affected by Lithium) Mania 1. 2. 3. 4. 5. 6. 7.

Distractability Irresponsibility Grandiosity Flight of ideas Increase in goal directed activity/ Psychomotor agitation Decrease need for sleep Talkativeness or pressured speech

C. SODIUM (natrium) o Primary extracellular fluid cation o Action: fluid retention Acetate

Acetate of Soda

Diuretic, Urinary and systemic acidifier, Antacid

Bicarbonate

Soda Saleratus Sal de Vichy Soda acid Carbonate

Systemic antacid, Carbonating agent SE: Alkalosis, Rebound hyperacidity, Edema

Fleet Enema

Cathartic, Source of P or phosphate, Urinary acidifier(+ methenamine)  HCHO (formaldehyde), NH3  urinary antiseptic

Dihydrogen Phosphate/ Biphosphate NaH2PO4

Leucogen Sodium Hydrogen Sulfite Sodium Acid Sulfate Washing Soda, Sal soda Soda Ash Monohydrate Na carbonate

Bisulfite

Carbonate

Chloride Citrate

Rock/Table/Solar salt Na3C6H5O7

Fluoride Caustic soda, sosa, lye

Phosphite

Electrolyte replenisher, Tonicity adjuster, Condiments, Preservative Alkalizer, Buffer, Diuretic, Expectorant Shorten the coagulation time (parenterally)

Saponifying agent (hard soap) Reducing agent

Dakin’s solution Chlorox

Hypochlorite Iodide

All iodides are for cough

Lactate

Na3C3H5O3

Nitrite

NaNO2

Natrium, Nitrosum Chile salt peter

Sulfate

Glauber’s salt C4H4O6

Expectorant, Antifungal, Iodine solubilizer

Cyanide poisoning, Meat preservative

Cathartic Primary standard for KFR (Karl Fischer Reagent)

Thiocyanate Thiosulfate Na2S2O3 • 5H2O

Oxidizing agent, bleaching agent Disinfectant (Labarraque’s solution)

Antacid, Diuretic

Nitrate

Tartrate

Antacid, Carbonating agent

Anticariogenic (2% solution)

Hydroxide

nitrites, nitrates, thiosulfates, thiocyanates are vasodilators

Anti-oxidant

Hypotensive agent (vasodilator) Antichlor Hypochlor

Cyanide poisoning with Na nitrite VS in iodometry and permanganometry

D. POTASSIUM (kalium) o Most abundant and predominant intracellular cation o Deficiency: hypokalemia Manifestation: muscle paralysis (Barker’s syndrome) o Diuretic, Important in muscle contraction Acetate Bicarbonate Bitartrate

Diuretic salts

Antacid, Diuretic, Urinary and systemic alkalizer

Potassium Acid Carbonate Salaeratus Cream of tartar Creamor, Argol

Systemic antacid, carbonating agent, bicarbonate source

Bromide Carbonate

Depressant Potash Salt of peter Perlash, Salt of Wormwood

Kalium Chloratum Kali Chloridum

Citrate

Electrolyte replenisher (Note: SLOW push) Diuretic, Expectorant, Diaphoretic

Caustic potash Lye potash Potassa

Saponifying agent (soft soap)

Kalium Jodatum

Expectorant, antifungal, iodine solubilizer

Nitrate

Saltpeter Salitre, Niter Salt prunelle

Diuretic, meat preservative

Permanganate

Mineral chameleon

Oxidizing agent, Antiseptic, VS in permanganometry

Hydroxide Iodide Oxalic acid removes stains of

Antacid, carbonating agent, carbonate source Oxidizing agent Component in toothpaste, gargle & mouthwash

Chlorate Chloride

Laxative

Dihydrogen Phosphate Na K Tartrate

Cathartic Rochelle salt Sal signette

Thiocyanate

Cathartic, sequestering agent Hypotensive

K2Sx • K2S2O3

Sulfurated potash Liver of sulfur

K arsenite

Fowler’s Solution

Antileukemic

Sb K Tartrate

Tartar emetic

Schistosomiasis

E. Ammonium (NH4) o Hypothetical alkali metal o Pcol action: a. Diuretic b. Buffer c. Expectorant (like Iodide) d. Anti-cariogenic (like Fluoride)

Ammonium Bromide

Household ammonia – contains 10% NH4; is known as 16° ammonia

Depressant/Sedative

(NH4)2CO3 Ammonium carbonate

Sal volatile Hartshorn Preston Salt Baker's Ammonia Ammonium Sesquicarbonate

Expectorant (ammonium) Antacid (carbonate) Basis of smelling salts (aromatic spirit of ammonia)

Aromatic NH4 Spirit

Spirit of Hartshorn Spirit sal volatile

Respiratory stimulant

NH4Cl

Muriate of hartshorn Ammonium Muriate Sal Ammoniac Salmiac

Expectorant, Diuretic, Urinary acidifier CI: Impaired hepatic function Treatment for Brominism

HgNH2Cl

Mercuric Ammonium Cl Ammoniated mercury White precipitate

NH4I

Ammonium Iodide

Source of iodide, expectorant, antifungal

NH4CH3COO Ammonium acetate

Spirit of minderesus

Styptic

Strong Ammonia Solution

Ammonia Hydroxide Stronger Ammonia Water

Diluted Ammonia Solution circulatory stimulant by inhalation

Ammoniacal AgNO3

Howe’s solution

F. CESIUM o Catalyst in polymerization of resin forming material

Topical anti-infective

GROUP IB: COINAGE METAL – can occur in free metal state, Complexes/chelates A. COPPER (Cuprum) o Only reddish metal, 3rd most malleable, 3rd best conductor o Protein precipitant, Enhances physiological utilization of iron o Component of hemocyanin and cytochrome oxidase (Deficiency: Hypochromic anemia) o Alloys: Brass (+ Zn), Bronze (+ Sn) o Wilson’s disease | D-Penicillamine CuSO4 • 5 H2O

*Cu3(AsO3)2 • Cu(C2H3O2)2+ (Cu)3(C6H5O7)8

Blue vitriol Blue stone Caparrosa Azul Piedra Lipiz Paris green Copper acetoarsenate

Component of Benedict’s, Barfoed’s, and Fehling’s Antidote for P poisoning Increase hematinic activity of Fe Ingredient of Bordeux mixture  algaecide in pool Insecticide (suicidal drug in the past) Astringent in 8% concentration

B. SILVER (argentum, shining, bright) o Oligodynamic property (germicidal action) o Argyria | NSS or PNSS Soluble

AgNO3

Ag(NH3)2NO3 Insoluble AgI Ag proteinate

Lapiz infernulariz Lunar caustic Indelible ink Caustic pencil, Azotas

Warts and Opthalmia neonatorum (1% drops) – Crede’s prophylaxis

Howe’s solution

Dental protective, Desensitizing agent Poisonous, Disinfectant Antiseptic for eye (nlt 19 nmt 23%) Ear and throat (nlt 7.5 nmt 8.5%) General germicide

Mild (Argyrol) Strong (Protargol) Colloidal (Collargol)

Present: Erythromycin (for N. gonorrhea and Chlamydia trachomatis – no. 1 cause of blindness)

C. GOLD (Aurum”, Shining dawn, King of all metals, Purple of Cassibis) o Most malleable and ductile, Best conductor of electricity o Dimercaprol o Dissolved by: Aqua regia (3 part HCl + 1 part HNO3) Selenic acid 1. Aurothioglucose (IM) 2. Gold Na Thiomalate (IM) 3. Auranofin (PO)

- treatment of gout and R.A - treatment of gout and R.A - AE: glossitis

Gold preparations are used as Disease Modifying AntiRheumatic Drugs (DMARDs) for Rheumatoid arthritis.

GROUP IIA: ALKALINE EARTH METALS A. BERYLLIUM o Never employed in medicine because it is the most toxic metal B. MAGNESIUM o Lightest of all structurally important metal o 2nd most abundant intracellular cation o Chlorophyll component o Compound of Grignard’s reagent o Natural Sources: 1. As silicates (talc, asbestos) 2. As CO3 (magnesite, dolomite) 3. As SO4 (kieserite) o Pcol action: 1. Laxative (PO) 2. Depressant 3. Natural Ca-channel blocker (anticonvulsant – IM) o Antidote: Ca gluconate

MgCO3

Magnesium carbonate Magnesia

Antacid, Laxative

Mg(OH)2

Milk of magnesia Magnesia magma

Antacid, Laxative

MgO

Calcined magnesia

Antacid, Laxative Component of universal antidote

2MgO • 3SiO2

Mg trisilicate

Antacid (Adv: prolonged action)

MgSO4

Epsom salt Bitter salt (Ref or dissolve in cold water)

Cathartic (PO) Anticonvulsant (IM) Antidote for Ba and barbiturate toxicity

Mg3(C6H5O7)2

Lemonade purganti Purgative lemon

Hydrated Mg Silicate

Talc Soapstone French chalk

Mg3(Si2O5)(OH)4

Asbestos

Filtering agent Clarifying agent Dusting powder

C. CALCIUM o 2nd most abundant cation in extracellular fluid o Vit. D is needed for its maximum absorption Hyperpara  HyperCa Hypophos o PTH controls Ca levels in the blood o Pcol action: 1. Coagulation 2. Contraction 3. Release of neurotransmitter 4. Bones and teeth (98-99%) o Deficiency states: Osteoporosis (density) Osteomalacia (resorption) Rickets (mineralization) Hypocalcemia CaBr2

CaCO3

CaCl2

Sedative/depressant Precipitated Chalk Carbonic Acid Calcium Salt Creta Praecipitata Muriate of lime Fosforo de Homberg

Ca gluconate

Antacid, Ingredient of toothpaste, dentrifices

Ca replenisher Ca supplement and replenisher, Heart failure

Ca(OH)2

Slaked lime Milk of lime Calcium hydrate

Antacid, Saponifying agent

Ca(C3H5O3)2

Ca lactate

Ca supplement

CaHPO4 • 2H2O

Source of Ca and PO4

CaO

lime, quicklime, calx

Component of Bordeux mixture, Insecticide

Ca3(PO4)2

Bone ash

Antacid

CaClO

CaSO4 • ½ H2O or 2 H2O

D. STRONTIUM 1. SrCl2

Chlorinated lime Chloride of lime Gypsum Terra alba Satin Spar Alabaster Light

Disinfectant, Bleaching agent Rodenticide, Prep of surgical casts and dental impressions Plaster of Paris – calcium sulfate hemihydrate

- Temperature desensitizing agent (Sensodyne®)

E. BARIUM (Heavy) o Baritosis | Epsom salt 1. BaSO4 Ba meal, Esophotrast 2. Ba(OH)2 Baryte

- radiopaque for GIT imaging (non-toxic since not soluble) - CO2 absorbent

F. RADIUM o Radioactive element used for cancer radiotherapy & diagnostic purpose

GROUP IIB: VOLATILE METAL A. ZINC o o o o

Present in inZulin and carbonic anhydraZe Astringent, Antiseptic, Antiperspirant, Protectant Parakeratosis Metal Fume Fever | NaHCO3 Butter of Zinc Burnette’s disinfectant liquid Zinc white Lassar’s paste Flores de Zinc Lana o Algodon Flioficos

ZnCl2

ZnO

ZnO2

Disinfectant/antiseptic, Dentin desensitizer, Corrosive Escharotic, more caustic than astringent Antiseptic, astringent, topical protectant

Antiseptic

ZnS

White lotion White sulfide

Parasiticide, topical protectant, antiseptic

ZnSO4 • 7 H2O

White Vitriol

Emetic, ophthalmic astringent in 0.25% sol’n Pharmaceutical necessity in white lotion

Hydrated Zn Silicate

Natural Calamine

Topical protectant

Zinc-Eugenol cement

Dental protective

B. CADMIUM o Astringent, manufacture of stink bomb o Itai-Itai | BAL 1. CdCl2 - emetic, treatment of Tinea infection 2. CdS (yellow sulfide) - anti-seborrheic 3. CdSO4 - ophthalmic antiseptic

C. MERCURY (Quicksilver, Messenger of the Gods) o Diuretic, Antiseptic, Treatment of syphilis, Cathartic, Parasiticidal/fungicidal o Thermometer, amalgams (dental cement) o Minamata | EDTA 1. 2. 3. 4. 5. 6. 7.

Hg2Cl2 HgCl2 HgI HgI2 K2HgI4 HgNH2Cl HgO

Mercurous chloride (Calomel) - cathartic, local antiseptic Mercuric chloride (Corrosive sublimate) - disinfectant - treatment of syphilis - stimulant of indolent ulcers Potassium Mercuric Iodide - antiseptic, component of Mayer’s reagent White precipitate - topical antiseptic Yellow Precipitate - ophthalmic and anti-infective

GROUP IIIA A. BORON o Industrial use: In vulcanizing rubber 1. H3BO3 (Sal sativum, Boracic acid, Hydrogen borate, orthoboric acid)  Lobster appearance  1. Buffer (ophthalmic solution 2%) 2. Antiseptic 3. Tonicity adjusting agent (isotonic can still cause hemolysis) 2. Na2B4O7 • 10H2O (Borax, Na tetraborate, Dobell solution, Na pyroborate, Tinkal)  Antiseptic, Eye wash, Wet dressing for wounds B. ALUMINUM o Most abundant metal o 3rd most abundant element o Astringent, Aluminum foils used for burn patients AlCl3 • 6 H2O

Astringent, Antiseptic, Antiperspirant

AlNH4(SO4)2 •12H2O AlK(SO4)2 •12H2O

Alum

Al(OH)3

Amphogel, Cremalin gel

AlPO4

Phosphagel

Al2(CO3)3 Alumina

Al2(SO4)3

Cake/Pickle/Pearl/Papermaker's Alum

Al Acetate

Burrow's Solution

Bentonite Pumice

Antacid, Protectant (D/A: Constipation and PO4 deficiency) Antacid, astringent, demulcent (A: doesn’t inferfere PO4 abs.) Treatment of phosphatic calculi

Al2O3

Kaolin

Astringent, Antiperspirant

China clay Native hydrated aluminum silicate Soap clay, Mineral Soap Native colloidal hydrated aluminum silicate Pumice stone, Piedra Pomez

Treatment of silicosis

Adsorbent in diarrhea Suspending agent Dental abrasive

C. GALLIUM o Pcol use: treatment of cancer-related hypercalcemia by binding with transferring o Nonpharma: substitute for mercury in manufacture of arc lamps; Galvanized iron

GROUP IVA A. CARBON o Crystalline: Diamond (purest native form) and Graphite (lead pencil) o Amorphous: Coal and Anthracite 1. CO2 - acne, warts, corns, calluses, eczema, persistent hiccups (most potent resp. stimulant) 2. CO3 - Antacid, pharmaceutical for effervescent tablet 3. CO - 210x greater affinity to hemoglobin than oxygen leading to asphyxia then death - Targets cytochrome oxidase - Pathogonomic of CO poisoning: Cherry red color of blood and mucous membranes Treatment: 1. 100% O2 2. Artificial air (He 80%, O2 20%) 3. Hyperbaric O2 B. SILICON o 2nd most abundant element, Component of glass 1. SiO2 2. Glass Sodium silicate, Na4SiO4 3. Purified Siliceous Earth Silicates of: 4. Kaolin Native hydrated aluminum silicate 5. Bentonite Native colloidal hydrated aluminum silicate Mg (talc, asb) Al (k, b, p) 6. Talc French Chalk, Piedra Grasa, Soapstone, Creta Gallica Zn (calamine) 7. Attapulgite Polymagma, Diatabs, Quintess 8. Simethicone Polymeric dimethyl siloxane 9. Asbestos C. TIN (Stannum) 1. SnF2 2. SnO2

- anticariogenic 8% solution - germicide for Staph infection

- Toxicity: silicosis - Na2CO3 + pure silica - Adsorbent - Adsorbent - Suspending agent - Clarifying, dusting - Adsorbent - Antiflatulent

I II III NP

– borosilicate – treated SL – soda lime – gen. SL

B

– coeff of expansion – brown – ↑refractive index

K D. LEAD (Plumbum) Pb o Astringent, Protein Precipitant o Plumbism | EDTA , Ca Versenate (adults) , Succimer (kids) 1. Pb(CH3COO)2 Sugar of Lead, Burrow’s sol’n - astringent 2. Pb2(CH3COO) Goulard’s extract - astringent, antiseptic 3. PbO Litharge® - cans (toxic)

GROUP IVB A. TITANIUM (Titan, Sons of the Earth) o Powerful reducing agent 1. TiO2 - Opacifying agent (Ocusert®) and UV ray protectant B. ZIRCONIUM o antiperspirant but banned due to granuloma formation

Cyanide (CN) - MOA: inhibits cytochrome oxidase (ETC) Source: cassava, Na nitroprusside Treatment: 1. NaNO2/Amylnitrite MOA: methemoglobinemia 2. Sodium thiosulfate MOA: CN to thiocyanate 3. Methylene blue MOA: methemoglobinemia

GROUP VA

A. NITROGEN (Mephitic air, azote, without life) o Most abundant gas in air: 71% N2, 29% O2 N2 Azote Cont: BLACK N2O Laughing Gas, Nitrogen monoxide, Cont: BLUE Dinitrogen monoxide NO2 Nitrite NO3 Nitrate HNO3 Spirit of Nitre, Aqua Fortis/Fuerte/Eau Forte B. PHOSPHORUS (light carrier, St. Elmo’s Fire) o White/yellow (poisonous), Red (non-poisonous) o CuSO4 1. PO4 - antacid, cathartic 2. H3PO4 (Orthophosphoric Acid) 3. HPH2O2 - antioxidant

INERT ATMOSPHERE Liquid nitrogen – refrigerant Inhalational anesthetic (general) SE: diffusion hypoxia Vasodilator, For CN poisoning Preservative

Allotropes of P:  Scarlet  Violet  Metallic/Black  Red

- tribromide ∆240°C with Hg - white ∆200°C with Na - 530° with Pb - white + chromic acid

C. ARSENIC (Lewisite Metal) o Protoplasmic poison o Insecticide: Copper Aceto Arsenate (Paris green) o Mee’s Line | BAL (British Anti Lewisite) o First anti-syphilis (Paul Ehrlich) – Arsphenamine/Salvarsan/Magic bullet/Compound 606 1. As2O3 2. AsI3 3. K arsenite D. ANTIMONY 1. Na stibogluconate 2. SbKOC4H4O6

Fowler’s solution

- Insecticide, Anti-leukemic - Primary standard in the preparation of cerric sulfate - antileukemic

Tartar emetic, Brown mixture

- Leishmaniasis - Schistosomiasis; emetic

E. BISMUTH (Beautiful Meadow) o Astringent, Antiseptic, Internal protective for ulcer, Used in silvering of mirror o Dark stool, Blue-black gums | Dimercaprol 1. Bi Subcarbonate, Subgallate, Subnitrate 2. Milk of Bi (Bismuth Cream) Bi subnitrate + Bi OH

- Antacid, Astringent, Antiseptic - Antacid, Internal protective, Inhibits H. pylori

GROUP VB A. TANTALUM o Not affected by any body fluid, Sheet form used in repair of bones, nerve and tissue

GROUP VIA: CHALCOGENS A. OXYGEN (Empyreal air, Dephlogisticated air, Yne, Aire Vital, Fire Air, Aire Puro) o Most abundant element, discovered by Scheele o Uses: Oxygen Requirement: 1. Treatment of hypoxia/asphyxia 1. Anoxic - inadequate O2 tension in air 2. Oxidative metabolism for the production of energy 2. Anemic - lack of O2 carrier in heme 3. Final e- acceptor in ETC 3. Stagnant - blood circulation is retarded o Container: GREEN 4. Histotoxic - cell defect interference of cell metabolism

Carbon Dioxide (Carbonic Acid Gas, Carbonic Anhydride)  Container: GRAY  Solid Carbon Dioxide or “Dry Ice” - refrigerant

B. SULFUR (Brimstone, Shubari, Enemy of Copper) o Antifungal, Parasiticide, Scabicide, Depilatory agent

H2SO4

Oil of Vitriol Vitrilic Acid Aceitede de Vitriolo

Dehydrating agent in Pyroxylin Nordhausen acid – Fuming H2SO4

Sulfur Dioxide

Sulfurous Anhydride

Antioxidant

Sublimed Sulfur (condensed sulfur vapors)

Flower of Sulfur Asufre, Rhombic S

Cathartic + Lime  Vleminckx’s solution

Precipitated Sulfur (sulfur + metal hydroxides)

Milk of Sulfur

Prepared by mixing

Sulfurated Potash (K polysulfides + K thiosulfate)

Liver of Sulfur

Psoriasis, Parasiticide White lotion (ZnS)

C. SELENIUM (Selena, Moon)

- Promotes Vit. E absorption, Antioxidant (SeS2 /Selsun blue – anti-dandruff)

GROUP VIB A. CHROMIUM (Glucose tolerance factor) B. MOLYBDENUM C. URANIUM

- hyperglycemia (K2Cr2O7- powerful oxidizing agent) - Co-factor enzyme (Molybdenum Oxide + FeSO4 – hematinic) - Becquerel, Atomic bombs

GROUP VIIA: HALOGENS (Salt-forming group) A. FLUORINE o Strongest oxidizing agent o Fluorosis (Mottled enamel, Abnormal bone growth) 1. 2. 3. 4.

NaF SnF2 Na2FPO3 CCl2F2

- anticariogenic at 2% solution - anticariogenic at 8% solution - anticariogenic - refrigerant, aerosol propellant (Freon®)

B. CHLORINE (Dephlogisticated muriatic acid) o Most abundant extracellular anion, green gas o Used as water disinfectant 1. Hypochlorite (Na, K) - bleaching agent 2. HCl (Muriatic acid, Spirit of Sea Salt, Marine Acid, Espiritu de Sal Marine) - treatment of achlorhydria

C. BROMINE o Dark reddish brown fuming liquid with suffocating odor o Sedative/depressant o Brominism (Skin eruption, Psychosis, Weakness, Headache) | NaCl and NH4Cl

D. IODINE o o o o o

Oldest known germicide Expectorant, Antifungal Preparation of T3 and T4 Deficiency: Goiter Elemental Iodine preparation: 1. Strong Iodine Solution (Lugol’s Solution) 2. Iodine Solution 3. Iodine Tincture 4. Povidone-Iodine (Betadine®)

E. ASTATINE o Only metallic o Only synthetic halogen o Only radioactive halogen

- 5% - 2% - 2% with 50% alcohol - PVP (nonionic surfactant)

GROUP VIIB A. MANGANESE o Co-factor in: 1. Protein synthesis 2. Phosphorylation 3. Fatty acid and cholesterol synthesis o Poisoning: Parkinson-like symptoms (resting tremors) 1. KMnO4 (Mineral Chameleon)

- oxidizing agent, antiseptic

B. TECHNETIUM (Technetos) o 1st element produced artificially o Used in preparation of radiopharmaceuticals

RADIOPHARMACEUTICALS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Tc99m-Phytate Tc99m-heptagluconate Tc99m-IDA Tc99m-Etidronate I-131-Human Serum Albumin NaI-125 Sodium Phosphate Serum Sodium Chromate Cr 51 Gold Au 198 Chlormerodin Hg 197/203

Liver imaging & potency studies Kidney imaging, determine renal function Hepatobiliary studies Bone imaging Blood plasma volume/cardiac output determination Thyroid function Localization of ocular tumors, polycythemia vera RBC mass, volume, survival time, scanning of spleen Scintillation scanning of the liver Scintillation scanning of the kidneys or the brain

1

Alpha particles (a 42He )  heaviest and slowest of all radioactive emissions (0.1 the speed of light)  penetrating power is very low and can be stopped by a sheet of paper or a very thin sheet of Al  usually emitted only from elements having atomic numbers greater than 82

2

Beta particles (B or B )  negatively charged species having a mass of an electron  move at a faster velocity (0.9 the speed of light)  their emissions from elements do not alter the mass number but do alter the atomic number  more penetrating power and able to travel 10 to 15 cm in water or penetrate almost 1 inch thickness of Al  sometimes called negatrons  emitted by unstable nuclei having neutrons in excess of protons

3

Gamma Radiation (t)  photon of electromagnetic radiation  demonstrates both wave and particle properties as do electrons and beta particles  short wavelength similar to x-rays and travel at the speed of light  no mass and no charge  excellent penetrating power (very thick lead is required to protect against it)

2+

+

GROUP VIIIA: NOBLE GASES A. HELIUM o 2nd lightest gas o Donald-duck-like sound o Use: 1. Carrier/diluents of medically important gases 2. Component of artificial gas o Container: BROWN B. NEON o For advertising C. ARGON o Most Abundant noble gas o Substitute for N2 in providing inert atmosphere; Container: RED (Argon methane) o By-product of fractionalization of liquid air D. KRYPTON o Least abundant of all noble gases o Have inhalational anesthetic activity E. XENON o Investigational with inhalatory anesthetic activity F. RADON (Niton) o Synthetic noble gas o Used for treatment of CA (cervical CA)

GROUP VIIIB A. IRON o

o

o o o

o

Present in proteins: 1. Hemoglobin 2. Transferrin 3. Ferritin – storage form of iron 4. Cytochrome oxidase Enhance absorption of 1. Vit C 2. Copper Most important element in engineering Use: hematinic Toxicity: 1. GIT distress 2. Cardiac collapse Antidote: Dexferroxamine 1. 2. 3. 4. 5. 6. 7. 8.

Metals present in cytochrome oxidase: 1. Fe 2. Cu

Iron toxicity: Hemochromatosis/Hemosiderosis (Prussian blue stain of the heart)

FeSO4 (Iron Sulfate, Copperas, Green Vitriol, Iron Vitriol) Ferrous gluconate Ferrous fumarate FeCO3 (Chalybeate pills, Ferruginous pills) FeCl3 Basham’s Mixture (Iron + NH4 acetate) Fe4*Fe(CN)6+3 (Ferriferrocyanide or Prussian blue) Fe3*Fe(CN)6+2 (Ferroferricyanide or Turnbull’s blue)

B. COBALT o Essential in development of erythrocyte and hemoglobin o Component of Vit. B12 (cyanocobalamin) o Deficiency: Megaloblastic anemia and Pernicious anemia 1. CoCl2 2. Cobalt zincate 3. Cobalt meta-aluminate

Lover’s ink, sympathetic ink Rinmann’s Green Thenard’s blue

- Hematinic, SE: constipation, tarry stool - Fergon®, Advantage: less irritating - Toleron® - Hematinic - Astringent, Styptic, tannin detection - Astringent, Styptic

Schilling’s test - dessicator indicator - test for Zn ion - test for Al ion

C. NICKEL (Old nick’s copper) o Fossil fuel, fancy jewelries D. OSMIUM o Heaviest/densest metal 1. Osmic acid and Osmium tetroxide Both used in staining microorganism for microscopic study especially electron microscopy. E. PLATINUM F. PALLADIUM

- Catalyst in finely divided steel - Catalyst in finely divided steel

BUFFERS o o

pair or related chemical compounds capable of resisting large change in the pH of a solution composed of a weak acid & its salt (conjugate base) or a weak base & its salt (conjugate acid)

Phosphate Buffer System  𝐷𝑖𝑕𝑦𝑑𝑟𝑜𝑔𝑒𝑛 + 𝑚𝑜𝑛𝑜𝑕𝑦𝑑𝑟𝑜𝑔𝑒𝑛 𝑝𝑕𝑜𝑠𝑝𝑕𝑎𝑡𝑒  D/A; insolubility of the phosphate salts of metals such as Ag, Zn, and Al and phosphate salt of growth  Sorensen Phosphate buffer system – for ophthalmic (isotonic with body fluids) Borate Buffer System  used in preparations containing metals that would otherwise precipitate in the presence of phosphate  CI in parenterals bec of toxicity of borates 3 Primary Borate Buffer System presently recognized: 1 Feldman’s Buffer System (pH 7-8.2) - boric acid + NaCl, sodium borate 2 Gifford Buffer System (6-7.8) - boric acid + KCl, sodium borate 3 Atkins and Pantin Buffer System (7.6-11) - boric acid + NaCl, sodium carbonate __________________________________________________________________________________________________ (a) Intracellular fluid (K, Mg, PO4) (b) Extracellular fluid: (Na, Cl)  interstitial fluid  plasma and vascular fluid __________________________________________________________________________________________________ Buffer systems that the body utilize: 1. Bicarbonate/Carbonic Acid (HCO3-/H2Co3) - plasma and kidneys 22. Monohydrogen phosphate (HPO4 /H2PO4 ) - cells and kidneys 3. Hemoglobin and proteins - red blood cells Acidosis – below 7.38 Alkalosis – above 7.42 COMPENSATORY MECHANISM OF THE BODY Conditions

Causes

Buffer System

Metabolic Acidosis

HCO3 deficit (diabetic acidosis, diarrhea, renal failure)

HCO3-/H2Co3

Metabolic Alkalosis

HCO3 excess (administration of excess alkali, vomiting)

HCO3-/H2Co3

Respiratory Acidosis

H2Co3 excess (cardiac disease, lung damage, drowing)

Hemoglobin and protein

Respiratory Alkalosis

H2CO3 deficit (fever, anoxia, hysteria, salicylate poisoning)

HCO3-/H2Co3

Metabolic acidosis – treated with the sodium salts of bicarbonate, lactate, acetate, and citrate Metabolic alkalosis – treated with ammonium salts (action is in the kidneys where it retards the Na-hydrogen exchange)

Electrolyte Combination Therapy 1. Fluid Maintenance  to supply normal regrement for water and electrolytes to those who cannot take them orally  should contain at least 5% dextrose to minimize the build-up of metabolites associated with starvation (urea, phosphate and ketone bodies)  general electrolyte composition: Na, Cl, HCO3, Mg & P ions 2. Electrolyte Replacement  needed when there is a heavy loss of water and electrolyte Official Combination Electrolyte Infusions Ringer’s Injection Lactated Ringer’s Injection Oral electrolyte solutions

– 8.6 g NaCl, 0.3 g KCl and 0.33 g Ca Chloride per liter – 600 mg NaCl, 30 mg KCl & 20 mg Ca and 310 mg Na lactate per 100 ml – to supply water and electrolyte in amount needed for maintenance – given to replace mild to moderate fluid loss __________________________________________________________________________________________________ ESSENTIAL AND TRACE IONS Essential – not synthesized by the body and must be included in the diet Trace – required for normal functioning but does not need to be included in the diet Ions Iron (Fe or Fe3+)

Principal Metabolic Functions Constituent of hemoglobin

Iodine (I-)

Constituent of thyroxin and triiodothyronine

Cobalt (Co2+)

Constituent of Vit. B12 (cyanocobalamin)

Zinc (Zn2+)

Constituent of insulin and carbonic anhydrase

2+

Copper (Cu2+) Sulfur (S2-)

Formation of hemoglobin (increases iron utilization) Constituent of oxidase enzymes Constituent of proteins mucopolsaccharides, heparin, biotin, detoxication

Clinical Manifestations of Deficiency Anemia Endemic (simple) goiter Cretinism Deficiency of Vit. B12 Pernicious anemia Polycythemia Anemia Stunted growth Hypogonadism Hypochromic anemia Wilson’s disease Cystinuria Cystine renal calculi

Iron – electron carrier in respiration chain; responsible for transport of molecular oxygen Body Components Containing Iron Occurrence Iron bound as Blood System 1 hemoglobin 2 plasma Tissues 1 Functional Iron (myoglobin, cell hemes 2 Storage Iron

Mode of Linkage Heme Transferrin Heme a. ferritin b. hemosiderin

Functions Oxygen Transport Iron Transport Cell respiration Iron pool detoxication

GASTROINTESTINAL AGENTS Inorganic agents used to treat gastrointestinal disorders include: 1 antacids - products for altering gastric pH 2 protectives for intestinal inflammation 3 adsorbents for intestinal toxins 4 cathartics or laxatives for constipation Stomach pH: 1 when empty to 7 when food is present Gastritis – specified circumscribed erosion Peptic ulcer or Esophageal ulcer (heartburn) occurs when the esophageal sphincter is defective due to gastric food entering the esophagus during a belch or upon lying in bed; emotional makeup is also a factor. Malignancy and hemorrhage are common with gastric ulcers. Perforation is more common with duodenal ulcers.

Antacids - alkaline bases used to neutralize the excess gastric HCl associated with gastritis and peptic ulcers a. b. c. d. e. f.

should not be absorbable or cause systemic alkalosis should not be a laxative or cause constipation should exert the effect rapidly and over a long period of time reaction with gastric HCl should not cause a large evolution of gas should buffer in the pH 4-6 range should probably inhibit pepsin

COMBINATION ANTACID PREPARATIONS a. Aluminum Hydroxide Gel-Magnesium Hydroxide (Aludrox, Wingel, Maalox, Creamalin) b. Aluminum Hydroxide Gel-Magnesium Trisilicate (Gelusil, Tricreamalate, Triosgel) c. Magaldrate – Aluminum Hydroxide & Magnesium Hydroxide (Riopan) d. Simethicone-Containing Antacids (Di-gel, Mylanta, Kremil-S) – simethicone - defoaming agent e. Aliginic Acid-Sodium Bicarbonate-Containing Antacids (Gaviscon, Fomtab) PROTECTIVES AND ADSORBENTS – mild diarrhea Diarrhea - when some factor impairs digestion and/or adsoprtion, thereby increasing bulk of intestinal tract Acute Diarrhea - caused by bacterial toxins, chemical poisons, drugs, allergy and disease Chronic Diarrhea - from GI surgery, carcinomas, chronic inflammatory conditions & various adsorptive defects).

BISMUTH-CONTAINING PRODUCTS  intestinal hydrogen sulfate acts upon bismuth salts to form bismuth sulfate (result: black stools) SALINE CATHARTICS (purgatives) o Laxatives – mild cathartics, prolonged use causes “Laxative habit” 1. Stimulant Laxatives – act by local irritation 2. Bulk-forming Laxatives – from cellulose and other non-digestible polysaccharides which swell when wet 3. Emollient Laxatives – lubricants or stool softeners (e.g. Mineral Oil) 4. Saline Cathartics – increase osmotic load of GI tract NON-OFFICIAL SALINE CATHARTICS Sodium Sulfate (Glauber's Salt) Potassium Phosphate (Dibasic Potassium Phosphate, Dipotassium Hydrogen Phosphate, DKP) Potassium Bitartrate (Cream of Tartar, Potassium Acid Tartrate, Potassium Hydrogen Tartrate) Calomel (Mercurous Chloride, Mild Mercury Chloride)

FLAME TEST METALS

Non-luminous flame

Under cobalt glass

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, Tl, P

green

Pb, As, Sb, Bi, Cu

blue

Ammonium

colorless

yellow

GROUPS OF ANION Group No. - Member

Precipitate Formed and Visual Result with 1 M AgNO3 + 6 M HNO3

with 1 M BaCl2 + HNO3

I – Cl, Br I

AgCl *white+ AgBr *cream+ AgI *yellow+ insoluble in HNO3

No ppt

II – NO2-, S-2, C2H3O4- (acetate)

AgS *black+ soluble in HNO3, NO2 and C2H3O2 *no ppt+

No ppt

III – SO3, CO3-2, C2O4-2

White ppt soluble in HNO3

White ppt of BaSO4, CaSO4, BaC2O4 soluble in HNO3

IV – PO3-3, AsO4-3, CrO4-2

Ag3PO4 *yellow+ Ag3AsO4 *brown+ Ag2CrO4 *red+ all ppt soluble in HNO3

BaCrO4 *yellow+ Ba3(AsO4)2 *white+ all ppt soluble in HNO3

V – NO3-, ClO-

No ppt

No ppt

VI – SO4 -2

No ppt

White ppt soluble in HNO3

GROUPS OF CATION

GROUP OF CATION I (Insoluble chloride)

CATION Pb+2 Hg+2

COLOR OF PPT White White

Ag+2

White

Hg+ Bi+3 Cu+2

Black Brown Black

Cd+2 As+3 As+5 Sb+

Yellow Yellow Yellow Orange

Sn

Yellow

Fe Al Cr Ni Co Mn Zn

Brown White Gray green Black Black Pink white

IV (Sulfate insoluble groups)

Ba Ca Sr

White White White

V (Soluble group/Alkali metals)

Mg Na K NH4

II (Acid insoluble sulfide) A. Insoluble in acid and base

B. Insoluble in acid

III (Base insoluble sulfides)

ADD’TL Yellow ppt with K2Cr2O7 Black ppt with NH3 Mercuric ion: Yellow ppt with NaOH Scarlet ppt with excess KI White ppt with HNO3, soluble in NH4OH

Reddish brown ppt with K ferroCN Blue in solution

In the presence of HCl, gives a violet ppt with rhodamine B (a pink dye)

(+) Thenard’s blue Green in solution (+) Vogel test (+) Rinmann’s Green

Yellow ppt with cobalt uranyl acetate White ppt with Na bitartrate Alkalinized vapour turns red litmus paper to blue Brown ppt with Nessler’s reagent

METAL OR ANION Acetate (CH3COO- or C2H3O2-) Aluminum (Al) Ammonium thiocyanate (NH4SCN) Arsenate (AsO43-) Arsenites (AsO33-) Borates (BO33-) Bromine (Br) Carbonate (CO32-) Chloride (Cl) Citrate (C6H5O73-)

Chromium Cobalt

Copper Iodide

Nickel Phosphate (PO43-) Potassium (K)

Saccharin Salicylate Silver (Ag) Tartrate Thiosulfate (S2O32-) Zinc

H2SO4 + Ethanol (CH3C2OH)

COLOR REACTIONS  fruity odor (ethyl acetate)

+ Ammonium TS  gelatinous ppt that dissolves in excess Ammonium TS + Aluminon reagent red lake + cobalt solution (acidic) intense blue colored complex at interface + Ferric salts blood red Fe(SCN)3 (ferric thiocyanate) + Silver nitrate TS chocolate brown soluble in HNO3 + Ammonium molybdate test yellow ppt + Silver nitrate TS yellow ppt soluble in HNO3 + Magnesia mixture differentiating test for arsenates & arsenites + H2SO4 + methanol (CH3OH) green bordered flame + Turmeric paper orange +NaOH  olive green + CCl4 (carbon tetrachloride) Orange color + acidic aqueous solution effervescence + Phenolphthalein red + AgNO3 white curdy ppt, soluble in NH3, insol in HNO3 +pyridine + acetic anhydride carmine red (3:1)/Denige’s reagent *Denige’s test is the differentiating test between citrates and tartrates + NaOH grayish green slug, which dissolves with excess reagent + NaOH blue ppt of Co(OH)2 (boiling) olive green rose green + potassium nitrate (KNO2) + acetic acid yellow ppt + α-nitro-β-naphthol brown ppt soluble in HCl + Fe + HCl deposit of red film on iron + potassium ferrocyanide green ppt forming a blue solution with ammonia + Chlorine water or KMnO4 solution violet color + H2SO4 + sodium bisulfite(cold) decolorized + H2SO4 + oxalic acid (hot) decolorized + dimethylglyoxime bright red crystalline ppt insoluble in NH3 + α-nitro-β-naphthol reddish brown ppt soluble in HCl + Silver nitrate yellow ppt + Ammonium molybdate yellow ppt in HNO3 and NH3 + Tartaric acid white crystals of potassium bitartrate insoluble in ethanol and glacial acetic acid but soluble in NaOH *Potassium bitartrate is the only insoluble compound of potassium Fluorescin test: Resorcinol + H2SO4 + fluorescent green liquid excess NaOH + Ferric chloride (FeCl3) violet color + Acids white ppt of salicylic acid + HCl white curdy ppt insoluble in HNO3 but soluble in NH3 + Pyridine + acetic anhydride (3:1) emerald green + HCl white ppt turning yellow + FeCl3 dark violet which quickly disappears H2S white ppt of ZnS (only white sulfide)

COMMON NAMES

CHEMICAL NAME

FORMULA

Alcohol, grain

ethyl alcohol or ethanol

C2H5OH

Alcohol, wood

methyl alcohol or methanol

CH3OH

Alum

potassium aluminum sulfate

K2SO4 · Al(SO4)3 · 24H2O

Ammonia water

ammonium hydroxide solution

NH4OH

Agua Fortis

concentrated nitric acid

HNO3

Agua Regia

conc. nitric acid and conc. hydrochloric acid

HNO3 / 3HCl

Baking soda

sodium bicarbonate

NaHCO3

Baryte

barium hydroxide

Ba(OH)2

Bauxite

impure aluminum oxide

Al2O3

Benzol

benzene

C6H6

Bleaching powder

calcium oxychloride or chloride of lime

CaOCl2

Blue vitriol

copper sulfate

CuSO4 · 5 H2O

Borax

sodium tetraborate

Na2B4O7 · 10 H2O

Brimstone

sulfur

S

Brine

sodium chloride solution

NaCl

Calomel

mercurous chloride

Hg2Cl2

Cane sugar

sucrose

C12H22O11

Carbolic acid

phenol

C6H5OH

Carbona

carbon tetrachloride

CCl4

Carborundum

silicon carbide

SiC

Caustic potash

potassium hydroxide

KOH

Chalk

calcium carbonate

CaCO3

Chile saltpeter

sodium nitrate

NaNO3

Chloroform

trichloromethane

CHCl3

Cinnabar

impure merciruc sulfide

HgS

Corrosive sublimate

mercuric chloride

HgCl2

Cream of tartar

potassium bitartrate

KHC4H4O6

Cryolite

sodium aluminum fluoride

Na3AlF6

Deuterium oxide

heavy water

D2O

Dry ice

solid carbon dioxide

CO2

Epsom salts

magnesium sulfate

MgSO4 · 7 H2O

Flourspar

calcium fluoride

CaF2

COMMON NAMES

CHEMICAL NAME

FORMULA

Galena

lead sulfide

PbS

Glauber's salt

sodium sulfate decahydrate

Na2SO4 · 10 H2O

Gypsum

dihydrated calcium sulfate

CaSO4 · 2 H2O

Hematite

ferric oxide

Fe2O3

Iodoform

triiodomethane

CHI3

Laughing gas

nitrous oxide

N2O

Limestone

calcium carbonate

CaCO3

Limewater

calcium hydroxide solution

Ca(OH)2

Litharge

lead oxide

PbO

Lunar caustic

silver nitrate

AgNO3

Lye

sodium hydroxide

NaOH

Marsh gas

methane

CH4

Milk of Magnesia

magnesium hydroxide

Mg(OH)2

Muriatic acid

hydrochloric acid

HCl

Nitroglycerine

glyceryl nitrate or glyceryl trinitrate

C3H5(NO3)3

Oil of vitriol

conc. sulfuric acid

H2SO4

Phosgene

carbonyl chloride

COCl2

Plaster of Paris

hydrated calcium sulfate

(CaSO4)2 · H2O

Prussian blue

ferric ferrocyanide

Fe4*Fe(CN)6+3

Prussic acid

hydrocyanic acid

HCN

Pyrite

iron sulfide

FeS2

Quicklime

calcium oxide

CaO

Quicksilver

mercury

Hg

Rochelle salt

sodium potassium tartrate

NaKC4H4O6

Sal ammoniac

ammonium chloride

NH4Cl

Salt (table)

sodium chloride

NaCl

Saltpeter

potassium nitrate

KNO3

Sand

silicon dioxide

SiO2

Slaked lime

calcium hydroxide

Ca(OH)2

Turnbull's blue

ferrous ferricyanide

Fe3*Fe(CN)6+2

Vinegar

dilute acetic acid

CH3COOH

Washing soda (sal soda)

sodium carbonate

Na2CO3 · 10 H2O

Water glass

sodium silicate

Na2SiO3

Zinc blende

impure zinc sulfide

ZnS

o

ORGANIC CHEMISTRY branch of chemistry that deals with carbon-containing compounds with: H, O, P, N, S, X

Organic Compounds

Simple Hydrocarbons

Aliphatic

Alkanes

Alkenes

Aromatic

Hydrocarbon Derivatives Alicyclic/ Carbocyclic

X

N

RX

ArX

Amines

O

S ROH

1° RNH2

1° RCH2OH

2° R2NH

2° R2CHOH

3° R3N

3° R3COH

RSH

RSR

4° R4N+ ArOH

Alkynes ROCNH2

ROR

RCHO

RCOR

RCOOH

RCOOR

RCONH2

RCOOOCR

Acid/Acyl Chloride

ArSH

Carbon  Contains 4 binding sites for other atoms to attach to it  These four binding sites, when bonded with other atoms/molecules form a tetrahedron  Group 4, Period 2  Atomic No. 6 o 1s2 2s2 2p2 o Needs 4 more electrons to complete its octet o Valence: 4 o Can only share: covalence SYSTEMS OF NOMENCLATURE 1. Common  Uses the name given when it was discovered  Formic acid – ants  Butyric acid – butter  Prefixes: n-, iso-, neo2.

Derived  Derived from parent compound

3.

IUPAC 

Most systematic No. of C atoms 1 2 3 4 5

Prefix Meth Eth Prop But Pent

No. of C atoms 6 7 8 9 10

Prefix Hex Hept Oct Non Undec

ORGANIC MEDICINAL CHEMISTRY • •

deals with the physicochemical properties of drugs that affect its biological action the 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 Decontamination Disinfection Sanitation Sterilization Pasteurization

• Apply to living tissue • Destruction or marked reduction in the number or activity of microorganisms • On inanimate objects • Reduction to a level acceptable for public health • Kills all types including spores • Nonsporulating microorganisms (65:-100:C)

LOCAL ANTI-INFECTIVES OR GERMICIDES ALCOHOLS AND RELATED COMPOUNDS o o o

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

1. 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  acetaldehyde (nausea, vomiting, flushing) Denatured Rubbing (70%) Dehydrated/Absolute Isopropyl

- Completely denatured alcohol contains added methanol (wood alcohol) and benzene - Astringent, rubefacient, refrigerant, mild local anesthetic - nlt 99% ethanol; obtained by azeotropic distillation - Rapidly bactericidal (50% to 95%), 40% equal antiseptic power to a 60% ethanol

2. Ethylene Oxide  Used to sterilize temp-sensitive medical equipment and those that could not be autoclaved  Carboxide – 10% ethylene oxide + 90% CO2 (to prevent explosion)  MOA : alkylation of functional groups in nucleic acids and proteins 3. Formaldehyde Solution (Formalin)  nlt 37% of formaldehyde + methanol (retard polymerization to formic acid and paraformaldehyde)  MOA : direct, nonspecific alkylation of nucleophilic functional groups 4. Glutarol/Glutaraldehyde (Cidex)  components: glutaraldehyde and buffer

PHENOLS AND THEIR DERIVATIVES (standard for germicides) o o o

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

1. 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) 2. Cresol Chlorocresol 3. Thymol 4. Eugenol 5. Resorcinol Hexylresorcinol

- mixture of three isomeric methylphenols; obtained from coal tar or petroleum - preservative - m-cresol; from Thymus vulgaris; mild fungicidal (tinea) - from clove oil; applied on cotton to relieve toothaches, ingredient in mouthwashes - weak antiseptic, keratolytic - produces nubness when applied to tongue; ingred in lozenges

OXIDIZING AGENTS o o

MOA: Oxidation (peroxides) and protein denaturation (permanganates) poor penetrability to infected tissues and organic matter

1. Hydrogen Peroxide 2. Carbamide Peroxide (urea + H2O2) 3. Hydrous Benzoyl Peroxide (2.5%, 5%, 10%)

- active against anaerobic bacteria, wound cleansing - releases hydrogen peroxide when mixed with water - most effective topical OTC agent for the control of acne

HALOGEN-CONTAINING COMPOUNDS 1. Iodine (oldest known germicide) Iodine tincture Lugol’s sol’n/Strong Iodine Sol’n Iodine Solution

(2% solution of iodine in 50% alcohol with NaI) (5% iodine in water with KI) (2% iodine in water with KI)

2. Iodophors (Iodine + nonionic surfactants) Povidone-Iodine (Betadine)— complex with the nonionic surfactant polymer, polyvinylpyrrolidone

CHLORINE-CONTAINING COMPOUNDS o o

disinfection of water supplies forms Hypochlorous acid (HClO) when dissolved in water 1. Halazone 2. Chloroazodin 3. Oxychlorosene Sodium

- disinfects drinking water - a glyceryltriacetate solution is used as wound dressing - complex of sodium salt of dodecylbenzesulfonic acid and hypochlorous acid

CATIONIC SURFACTANTS o o o o o o o

Quaternary ammonium compounds that ionize with water and exhibit surface-active properties MOA: adsorb onto the surface of bacterial cell, causing lysis Compounds with polar head group and nonpolar hydrocarbon chain form micelles critical micelle concentration – right concentration Gerhard Domagk – pioneer inactivated by soaps and other detergents, also adsorbed on glass, talc, and kaolin to reduce action tissue constituents, blood, serum, and pus tend to reduce effectiveness of these substances solutions are intended for disinfecting surgical instruments, gloves, etc. (NEVER REUSE – can harbor pathogens) 1. 2. 3. 4. 5.

Benzalkonium Chloride Methylbenzethonium Chloride Benzethonium Chloride Cetylpyridinum Chloride Chlorhexidine (Bactidol)

- Detergent, emulsifier, wetting agt, antiseptic, preservative (+Na nitrate) - for diaper rash (Bacterium ammoniagenes which produces NH4 in urine) - Antisepsis, irrigation of mucous membranes - General antiseptic, tx of gingivitis (Forms: lozenges, mouthwash) - Best antiseptic based on antibacterial effect, no systemic toxicity

DYES o o o

Used before discovery of sulfonamides and antibiotics Forms colorless leucobase forms in alkaline conditions Active against G+ bacteria and many fungi; Gram negative bacteria are generally resistant 1. Gentian Voilet (Crystal v) 2. Basic Fuchsin 3. Methylene Blue

- vaginal suppositories (yeast infections), topical (cutaneous candidiasis) - carbol-fuchsin solution (Castellani’s paint) – used topically for fungal infections - Antidote for cyanide poisoning High conc: promotes the conversion of hemoglobin to methemoglobin Low conc: treat drug-induced methemoglobinemia

MERCURY COMPOUNDS (MERCURIALS) o o o

2 classes:

a. compounds with at least one carbon-mercury bond (does not ionize readily) b. mercury bonded to heteroatoms (ionize partially or completely) MOA : reaction with sulfhydryl (-SH) groups in enzymes and other proteins (reversible by treatment with thiolcontaining compds such as cysteine and dimercaprol *BAL+) antibacterial activity greatly reduced in the serum because of presence of proteins that inactivate Hg compds 1. 2. 3. 4. 5.

Nitromersol Thimerosal Mercuric Chloride (corrosive sublimate) Mercurous Chloride (calomel) Ammoniated Mercury (white precipitate)

— was a very popular antiseptic for skin & ocular infections — topical bacteriostatic antiseptic — were used as antiseptic —used for skin infections

PRESERVATIVES o o

prevent microbial contamination, maintain sterility in the event of accidental contamination Effective at low concentrations against all possible microbes, nontoxic, compatible, stable for the shelf life

PARABENS (p-hydroxybenzoic acid) o

Useful for liquid dosage forms, Antifungal, Preservative effect tends to increase with molecular weight 1. Methylparaben - more effective against molds 2. Propylparaben - more effective against yeast, more oil soluble so it is preffered for oils and fats 3. Butylparaben 4. Ethylparaben

OTHER PRESERVATIVES 1. 2. 3. 4. 5. 6. 7. 8. 9.

Chlorobutanol - bacteriostatic in pharmaceuticals for injection, opthalmic, and intranasal Benzyl Alcohol - common in vials of injectables with 1%to 4% concentrations in water or saline Phenylethyl Alcohol - occurs primarily in rose oil ans pine-needle oil; used in perfumery Benzoic Acid - preservatives in foods and pharmaceuticals at low pH Sodium Benzoate - preservative in acidic liquid preparations in which benzoic acid is released Sodium Propionate - antifungal preservative Sorbic Acid - antifungal preservative; preserve preparations containing sugars Potassium Sorbate Phenylmercuric Nitrate and Acetate

ANTIFUNGAL AGENTS FATTY ACIDS (All fatty acids and their salts have fungicidal properties) 1. Propionic Acid – present in perspiration (0.01%) 2. Undecylenic Acid – from destructive distillation of castor oil 3. Sodium Caprylate – from caprylic acid (in coconut and palm oil)

Ketoconazole, Itraconazole, Fluconazole -

For SC and systemic mycoses

Clotrimazole, Miconazole, Econazole -

For superficial mycoses

AZOLES (MOA: interacts with C-14 α-demethylase to block demethylation of lanosterol to ergosterol in membranes) 1. Ketoconazole - Only topically, Inhibits androgen and adrenal steroid synthesis (AE: gynecomastia) 2. Itraconazole - Lacks the endocrinologic effects of ketoconazole 3. Fluconazole (PO, IV) - Excellent penetrability into the CSF DOC for cryptococcal meningitis POLYENES (MOA: Pore formation; binds to ergosterol  disrupts membrane function  cell death) 1. Amphotericin B (Streptomyces nodosus) - DOC for systemic mycoses 2. Nystatin (Streptomyces noursei) - Candida infections 3. Natamycin (Streptomyces natalensis) NUCLEOSIDES (MOA: Inhibits DNA and RNA synthesis) 1. Flucytosine - pyrimidine, + Amphotericin B (systemic mycoses & meningitis - Cryptococcus & Candida) ALLYLAMINE 1. Terbinafine

- inhibits squalene epoxidase

GRISEOFULVIN (Penicillum griseofulvum) o MOA: Interacts with the microtubule within the fungus and inhibit mitosis (metaphase) o Absorption is increased with fatty acids

ANTITUBERCULAR AGENTS MOA Isoniazid (Isonicotinic acid hydrazide) Pyrazinamide (Pyrazinecarboxamide) Pyrazinoic acid (active)

Notes

(-) cell wall synthesis

Adverse Effects

First line

Hepatotoxicity Peripheral neuritis (TX: pyridoxine)

Combined with other agents (resistance develops rapidly) First line drug for short term tx

Hepatotoxicity Optic neuritis (red- green color blindness)

Ethambutol Ethionamide Para-Aminosalicylic Acid

Structural analogue of isoniazid Competitive inhibitor for PABA

Clofazimine Rifampin (S. mediterranei)

(-) RNA polymerase

For isoniazid-resistant TB

Severe GI irritation Basic red dye for leprosy, including dapsone-resistant forms

Hyperpigmentation

Most active agent Enzyme inducer

Reddish secretions + INH or ethambutol  higher hepatotoxicity

Cycloserine

Streptomyces: S. orchidaceus, S. garyphalus, S. Lavendulus

Capreomycin

Streptomyces capreolus

Streptomycin

(-) CHON synthesis

Hepatotoxicity, Peripheral neuritis

First antibiotic for TB

Ototoxicity, nephrotoxicity

ANTISCABIES AND ANTIPEDICULAR AGENTS SCABICIDES (to control the mite Sarcoptes scabei) 1. Benzyl Benzoate 2. Crotaminon

- DOC for scabies; from Peru balsam and other resins

PEDICULOSIDES (head, body, and crab lice) 1. 2. 3. 4.

Pyrethrin Piperonyl Butoxide Permethrin Lindane

- from chrysanthemum plants (MOA: nerve poisoning) - enhances the pediculicide effects of pyrethrins - for head lice only - Gamma-benzene hexachloride, AE: neurotoxicity (Kwell, Scabene, Kwindane)

ANTIBACTERIAL ANTIBIOTICS CELL WALL BETA-LACTAM ANTIBIOTICS 1. Penicillins (Penicillum notatum)- Interfere with last step of cell wall synthesis (transpeptidation or crosslinking) o Beta lactam attached to thiazolidine ring, Nucleus: 6-aminopenicillanic acid I.

Natural Penicillins Penicillin G (Benzylpenicillin) – PO, IV, IM(Procaine and Benzathine) Use: RHD and Syphilis Penicillin V (Phenoxymethylpenicillin) – PO

II.

Penicillinase-Resistant/Antistaphylococcal Penicillins/Narrow Spectrum Methicillin (2,6-dimethoxyphenylpenicillin) - Prototype; off the market (interstitial nephritis) Nafcillin (2-ethocy-1-phenylpenicillin) Isoxazolyl Penicillins (Oxacillin, Cloxacillin,Dicloxacillin – best absorbed orally)

III.

Aminopenicillins/Broad Spectrum Ampicillin (Parenteral, poor GI absorption) - Prodrugs: Hetacillin, Bacampicillin, Cyclacillin Amoxicillin (PO)

IV.

Extended Spectrum/Anti-Pseudomonal Penicillins Carboxypenicillins (Carbenicillin, Ticarcillin) Ureidopenicillins (Piperacillin – most potent, Azlocillin, Mezlocillin)

2. Beta-lactamase Inhibitors (Clavulanic acid, sulbactam, tazobactam) o No antibacterial activity. They inactivate beta-lactamases 3. Cephalosporins o Beta-lactam ring attached to dihydrothiazine ring; Nucleus: 7-aminocephalosporanic acid Generation Gram + Gram First fa, pha, Cephradine +++ + Second fo, fu, fp, Cefaclor, Cefamandole, Loracarbef +++ ++ Third t/d, pera, tax, Moxolactam + +++ Fourth Cefepime, Cefpirome ++ ++++ Fifth Ceftaroline, Ceftobipole ++++ ++++ 4. Carbapenems Thienamycin, Meropenem, Imipenem (cleaved by dihydropeptidase; cilastatin) 5. Monobactam (Aztreonam – magic bullet for Pseudomonas) o The beta-lactam ring is not fused to another ring, no cross sensitivity with penicillin POLYPEPTIDES Vancomycin (S. Orientalis)  DOC for Pseudomembranous colitis and MPSA  Only IV (not orally absorbed); AE: Flushing (Red Man Syndrome) Bacitracin (B. Subtilis) – nephrotoxic (not for IV) Polymyxin (B. Polymyxa) – only for G+ ; MOA: Alter cell membrane permeability; Polymixin B and Colostin (Polymixin E) Gramicidin (S. Brevis) – only for G-

PROTEIN SYNTHESIS Binds to 30s (AT) AMINOGLYCOSIDES (Streptomycin, Gentamicin, Netilmicin, Neomycin, Tobramycin, Amikacin – from Kanamycin A) o Streptomyces (mycin) | Micromonospora (micin) o Allergic reactions, Muscle relaxation, Incompatile with B-lactams, Nephrotoxic (neomycin) Ototoxic (streptomycin), G- cocci only o IV (not absorbed orally) except neomycin (topical and oral only) TETRACYCLINES (Doxycycline, Minocycline, Tetracycline, Demeclocycline) o Broadest spectrum antibiotic o AE: Gastric discomfort, deposition in the bones and primary dentition causing discoloration and hypoplasia of the teeth and a temporary stunting of growth, hepatotoxicity, phototoxicity (demeclocycline), vestibular problems (minocycline) o Fanconi-like syndrome – ingestion of expired tertacycline Binds to 50s MACROLIDES o Common chemical characteristics 1. A large lactone ring 2. A ketone group 3. A glycosidically linked amino sugar Erythromycin (Ilotycin) - S. erythreus  Alternative/DOC for Pen G allergy and Legionnaire’s disease  Esters (eg. stearate, estolate, and ethylsuccinate) have improved acid stability  AE: epigastric distress, cholestatic jaundice (estolate form of erythromycin) Clarithromycin  Used with Omeprazole or Lansoprazole (H.pylori eradication), more potent for strep and staph Azithromycin, OD  For nongonococcal urethritis (Chlamydia, LRTI, PID, pharyngitis, Legionnaire’s)  40 to 68 hours half life is prolonged because of extensive tissue sequestration and binding (↑Vd)

LINCOSAMIDES (Clindamycin) - Streptomyces lincolnensis o Sulfur-containing; Resemble sulfonamides in antibacterial spectrum and biochemical MOA o For abdominal and female genitourinary tract infections caused by B. fragilis o AE: Pseudomembranous colitis, rash, (DOC: Vancomycin) CHLORAMPHENICOL (S. venezuelae) o For typhoid fever (Ceftriaxone-new DOC), meningococcal infections and H.influenza infections in cephalosporin-allergic patients, anaerobic infections o Precautions and monitoring:  Bone marrow suppression (dose-related)  Aplastic anemia (non-dose related)  Gray Baby Syndrome (neonates)

INHIBITION OF NUCLEIC ACID SYNTHESIS MUPIROCIN (Pseudomonas fluorescens) o Used topically for impetigo, eczema, staphylococcal and beta-hemolytic streptococcal infections o MOA: Inhibition of RNA and DNA synthesis QUINOLONES o Patterned after nalidixic acid (introduced for the treatment of UTI and URTI) o 1,4-dihydro-4-oxo-3-pyridinecarboxylic acid moiety (essential for antibacterial activity) o Fluoroquinolones have enhanced antibacterial activity  Ciprofloxacin – most potent  Norfloxacin – anti-pseudomonal o Chelates with metals o MOA: Inhibits DNA gyrase (topoisomerase II) o AE: Diarrhea, nausea, headache, dizziness, nephrotoxicity, phototoxicity

NITROFURAN AND NITROHETEROCYCLIC COMPOUNDS 1. 2. 3. 4.

Nitrofurazone Furazolidone (PO) Nitrofurantoin Nifurtimox

5. Metronidazole

- topical treatment of burns - diarrhea (SPEcKs;) CI: Alcohol - Urinary antiseptic - Treatment of Chagas’ disease/American Sleeping sickness (Trypanosoma cruzi) Vector: reduviid bug/kissing bug - DOC for E. Histolytica, G. Lambia, Trichomonas vaginalis Metallic taste, Disulfiram-like effect

SULFONAMIDES o o o o

Gerard Domagk studied a bright dye, Prontosil (metabolized in vivo to sulfanilamide – active) MOA: Compete with PABA for dihydropteroate synthetase  prevents synthesis of folic acid AE: Crystalluria, Steven-Johnson Syndrome, Kernicterus, Anemia Sulfonamides are usually used with dihydrofolate reductase inhibitors (e.g Trimethoprim) 1. DOC for UTI - Sulfamethoxazole and trimethoprim/Cotrimoxazole (Bactrim®) 2. DOC for Pneumocystis carinii - Bactrim; alternative drug: Pentamidine (aromatic diamide) 3. Burn therapy - Silver sulfadiazine and Mafenide (Flammazine®) 4. Conjunctivitis - Sodium sulfacetamide 5. Chloroquine-resistant malaria - Quinine + pyrimethamine + sulfadoxime (Fansidar®)

SULFONES 1. Dapsone

- DOC for leprosy (Test: G6PD)

ANTIMALARIALS o o

Common structural feature: quinoline ring, or a “quinoline with an additional benzene added” (an acridine ring) None except the cinchona alkaloids has a quinuclidine ring

CINCHONA ALKALOIDS

Reserved for malarial strains resistant to other agents AE: Cinchonism, Abortifacient DOC for erythrocytic falciparum Acute P. vivax attack Anti-inflammatory (RA and discoid lupus) Highly supressive (P. vivax and P. falciparum) Curative (P. falciparum) Only for exoerythrocytic stages of malaria Radical cure of the P. vivax & ovale, Gametocidal for all species Giardiasis, tapeworm and malaria, leishmaniasis CI: primaquine (inc. Toxicity)

Quinine Chloroquine

7-CHLORO-4AMINOQUINOLINES

Amiodaquine 8-AMINOQUINOLINES

Primaquine Quinacrine

9-AMINOACRIDINES Mefloquine

For multi-drug resistant forms of Plasmodium falciparum

CYCLOGUANIL

Both erythrocytic and exoerythrocytic

ANTIVIRAL AGENTS Herpes HIV (Antiretroviral)

DNA Polymerase Inhibitors NRTI NNRTI Protease Inhibitors

Influenza Vidrabine

Acyclovir, Valacyclovir, Ganciclovir Zidovudine, Abacavir, Dideoxynosine, Lamivudine, Stavudine, Tenofovir, Disoproxil, Fumarase, Zalcitabine Delavirdine, Efavirenz, Nevaripine Amprenavir, Indinavir, Lopinavir, Nalfinavir, Ritonavir, Saquinavir Amantadine, Rimantadine, Olsetamivir, Sanamivir

ANTHELMINTHICS CHEMOTHERAPY FOR NEMATODES Albendazole Mebendazole (Antiox ®) Pyrantel Pamoate Piperazine Ivermectin Thiabendazole Diethylcarbamazine

Inhibits microtubule synthesis Inhibits microtubule synthesis, Depletes glucose Depolarizing neuromuscular agent (nicotinic receptors) Flaccid paralysis of helminth (Blocks Ach response) Targets GABA receptors  paralysis Also affects microtubular aggregation AE: Erythema multiforme and SJS (fatal) Unknown

Roundworm (intestinal and muscle) Hookworms (old and new) Whipworm Pinworm Onchocerca volvulus (river blindness) Strongyloidiasis (threadworm) Filariasis

CHEMOTHERAPY FOR TREMATODES Praziquantel

Increases membrane permeability to calcium  contraction  vacuolization  parasite death CHEMOTHERAPY FOR CESTODES

Niclosamide

(-) oxidative phosphorylation

For intestinal cestodes only: T. saginata, D latum, H. nana

CANCER CHEMOTHERAPY Cancer (Latin “crab”) Solid Tumors Carcinomas - epithelial cells Sarcoma - connective tissues o Bone (Osteosarcoma) o Muscles (Leiomyosarcoma) Hematologic malignancies Lymphoma - lymphatic system Leukemia - blood-forming elements



Each cycle of cancer chemotherapy kills a certain percentage of tumor cells

CHEMOTHERAPEUTIC AGENTS 1. Phase-Specific/Narrow Spectrum Antineoplastic 2. Phase-Nonspecific/Broad Spectrum 3. Cell Cycle Nonspecific/Extended Spectrum

Etiology  Viruses – EBV, HBV, HPV  Environmental and occupational exposure o Ionizing and UV radiation o Vinyl chloride, asbestos, benzene  Lifestyle factors  Medications  Genetic factors Warning Signs of Cancer (American Cancer Society) Change in bowel or bladder habits A sore that does not heal Unusual bleeding/discharge Thickening or lump in the breast or elsewhere Indigestion or difficulty swallowing Obvious change in a wart or mole Nagging cough or hoarseness Screening  Mammography  FOBT  Papanicolau smear  DRE Tumor markers 1. Carcinoembryonic antigen (CEA) 2. Alpha-fetoprotein (AFP) 3. Prostate specific antigen (PSA) Tumor Biopsy  Definitive test (read by a pathologist)  Types: FNAB, Incision, Excision Staging: TNM, AJC Tumor cell burden  Number of tumor cells in the body (109)

Chemotherapy Objectives  Cure – eg. Leukemia o Remission induction (maximal cell kill) o Consolidation therapy (10°)  Palliation  Adjuvant chemotherapy  Neoadjuvant chemotherapy Basis for Dosing: Body weight, BSA, AUC Reasons for Combination Therapy  Overcoming or preventing resistance  Cytotoxicity to resting or dividing cells  Biochemical enhancement of effect  Rescue of normal cells  CMF (breast CA) – Cyclophosphamide, Methotrexate, 5-FU

ALKYLATING AGENTS (MOA: Alkylation – Inh DNA replication) Nitrogen Mustards

Examples Mechlorethamine - WWII (vesicant) - Nitrogen Mustard Chlorambucil (DOC for CLL) Cyclophosphamide Ifosfamide Mephalan

Ethylenimenes/ Methylmelamines Alkyl sulfonates Nitrosureas For brain tumors Triazines Platinum Coordination Complex

Thiotepa, Altretamine (hexamethylmelamine) Busulfan Carmustine, Lomustine Streptozotocin Dacarbazine Cisplatin Carboplatin

Substituted Urea Others

Hydroxyurea Procarbazine, Temozolamide

Adverse Effects  

  

Bone Marrow depression Hemorrhagic cystitis (fibrosis of the bladder) o Acrolein (cyclophosphamide) MESNA (sodium 2-mercaptoethane sulfonate) Germ cells – amenorrhea, testicular atrophy, sterility Neurotoxicity (ifosfamide) – chloroacetaldehyde Secondary malignancies

Pulmonary Toxicity Pulmonary Toxicity Toxic to beta cells of islets of Langerhans (Insulinomas) Cisplatin  Severe persistent vomiting  Nephrotoxicity (dose-limiting) Carboplatin  Mild nausea and vomiting  Not nephro-, neuro-, or ototoxic  Myelosuppression (dose-limiting)

ANTITUMOR ANTIBIOTICS (MOA: Intercalation) A. Anthracyclines  Daunorubicin/Daunomycin S. peucetius  Doxorubicin/Adriamycin/Hydroxydaunorubicin  Epirubicin  Idarubicin B. Anthracenediones  Mitoxantrone C. Other Agents  Bleomycin (Pulmonary toxicity)  Dactinomycin/Actinomycin D  Plicamycin/Mithramycin  Mitomycin C

S. verticillus Streptomyces spp. S. plicatus S. caespritosus

CARDIOTOXIC Dexrazoxane

ANTIMETABOLITES (MOA: Inhibit DNA synthesis)  Structural analogs of naturally occurring substrates for biochemical reactions (False substitutes) Adenosine Analogs Purine Analogs

Folic Acid Analog

Pyrimidine Analogs

Cladribine, Fludarabine Mercaptopurine (6MP or thiouric acid) Thioguanine Fludarabine (5’phosphate of 2-Fluoro-adenine arabinoside) Thioguanine Methotrexate o Inhibits dihydrofolate reductase (converts folic acid to tetrahydrofolic acid) Capecitabine, 5-Fluorouracil, Gencitabine Cytarabine (AR-A, cytosine arabinoside)

Stomatitis, myelosuppression, erythema, rash, urticaria, alopecia, vomiting Renal damage, Abortifacient Folinic acid/Leucovorin Ulceration of the GI mucosa, dermopathy (hand foot syndrome)

Indications: Colorectal, breast, ovarian, pancreatic, and gastric CA Topically: Basal cell CA

PLANT ALKALOIDS Vinca Alkaloids

Vinca rosea Camptothecins Podophyllotoxins

Taxanes

Prevent formation of mitotic spindle Inhibit topoisomerase 1 Inhibit topoisomerase II Promote microtubule assembly and stabilization  inhibiting cell division

Vinblastine, Vincristine, Vindesine, Vinorelbine Irinotecan, Topotecan Etoposide, Teniposide (Myelosuppression) Docetaxel (Taxotere), Paclitaxel (Taxol)

HORMONES  Hormone-responsive  Hormone-dependent        

Androgens Antiandrogens Antiestrogens Aromatase inh Corticosteroids Estrogen/N mustard GnRH or LHRH Progestins

- Palliative, Regresses after treatment with the hormone - Removal of a hormone causes tumor regression  Ex. Surgery (orchiectomy for advanced prostate CA); breast CA – Tamoxifen - Fluoxymesterone, testosterone - Flutamide, nilutamide (for prostate CA with Goserelin/Leuprolide) - Toremifene, Tamoxifen (ER + Breast CA | Endometrial CA) - Aminoglutethamide (2nd line for metastatic breast CA) - Dexamethasone, Prednisone (for lymphoma, ALL | Cushing’s: lymphocytopenia) - Diethylestradiol, Ethinyl estradiol (for prostate CA | Gynecomastia, Thromboemboli) - Goserelin, Leuprolide (for prostate CA) - Medroxyprogesterone, megestrol

ENZYMES  L-asparaginase o Source: E. coli o MOA: degrades asparagines o Indication: (+vincristine and prednisone): Childhood ALL