I.

TOPICAL AGENTS a. protective b. astringents c. antimicrobials a. heterogeneous effect on epithelial surfaces non-selective action limited chemical activity physical basis in action Protectives: isolate exposed surface(skin/membrane) from harmful stimuli properties: insolubility chemical inertness adsorbent example 1. Boric acid dusting powder + diluted with inert material 2. Magnesium stearate emollient 3. Talc native hydrous magnesium silicate (Mg3Si4O10(OH)2); dusting powder 4. Titanium Dioxide high reflectance 5. Zinc Oxide -mild astringent -weak antimicrobial -Zinc Oxide Ointment -Zinc Oxide Paste 6. Zinc Stearate--> -dusting powder -component of water repellant ointments 7. Calamine ZnO + Fe2O3 8. Zinc Carbonate -drying agent -lubricating agent

5.

6.

-polymeric compounds -less acidic than AlCl3 -hydrates of Al(OH)2Cl Aluminum Sulfate -powerful astringent -buffered with sodium aluminum lactate -alum flocculation process Zinc Chloride -Butter of Zinc -deliquescent

c.

Antimicrobials types 1. Antiseptic kill microorganism in living tissue 2. Disinfectant at inanimate objects 3. Germicide fungicicide, amoebicide mechanism of action a. Oxidation b. Halogenation c. Protein Precipitation (Astringent) Examples: 1. Hydrogen Peroxide o 2.5-3.5g H2O2 o deteriorates on standing o decomposed rapidly with OA or RA o act as OA or RA (depending on environment) o mild oxidizing antiseptic (due to catalase) 2. Sodium Perborate o Official in NF XII o Composite of H2O2, NaBO2, NaOH o Bleaching agent in non-chlorine bleaches 3. Potassium Permanganate o Odorless, dark purple crystalline compound o strong OA (dry and aqueous) o acidic solution: Mn7+ to Mn2+ o neutral/alkaline: Mn7+ to Mn4+ 4. Sodium Hypochlorite Solution, USP o Dakins solution o 4-6% NaClO o Labaraqques solution: 2.5% NaClO o Diluted Sodium Hypochlorite Solution (Modified Dakins solution): 450-500mg NaClO; w/ bicarbonate o Sodium Hypochlorite Topical Solution, USP: 0.2-0.32 g NaClO; w/ biphosphates 5. Other Chlorine Containing Compounds o Chlorinated Lime bleaching lime chloride of lime by passing Cl gas over slaked lime w/ Calcium Hypochlorite, Calcium Hydroxide, Chlorine ions o Chloramines organic amines w/ 1 or 2 chlorine atoms bonded to N example: Chloramine-T (Na ptoluensulfonchloramide) and Halazone (pdichlorosulfamoyl benzoic acid) 6. Iodine Preparations and Compounds: o antimicrobial due to oxidation and iodination o iodophores: enhance solubility of I2 (iodides or PVP) o compounds a. Iodine Topical Solution b. Strong Solution c. Iodine Tincture d. Strong Iodine Tincture 7. Silver Compounds:

Astringents and Antiperspirants locally-applied protein precipitants low cell penetrability uses: o Promote healing o Antidiarrheal o Reduce inflammation of mucous membranes o Decrease sweating o Stypic types: 1. Salts of cations (Al, Zn, Mn, Fe, Bi) 2. Salts with MnO43. Tannins or related polyphenolic compounds example 1. Alum astringent in acidic solutions; stypic 2. Aluminum acetate Topical Solution -Burrows Solution -tx for athletes foot dermatitis diaper rash dry skin poison ivy poisoning inflammation of ear 3. Aluminum Chloride astringent anhidrotic 4. Aluminum Chlorohydrates

b.

antimicrobial due to protein precipitant action Silver Nitrate Topical Solution: prophylaxis against infection by gonoccocal microorganisms o Silver Sulfadiazene: -antimicrobial -effective against Pseudomonas aeruginosa -adjunct in prevention treatment of wound sepsis in 2nd and 3rd degree burns -Argyria: gra-black staining of the skin due to silver deposition 8. Sulfur and Sulfur Compounds o Exist in different allotropic forms o Used as fungicide, parasiticide, keratolytic agent, depilatory agent o Sublimed Sulfur--> -Flowers of sulfur -rhombic sulfur -formed from condensing sulfur vapor o Precipitated Sulfur -Milk of sulfur -prepared from reactions of sulfides and HCl o Sulfur Ointment prepared from Precipitated Sulfur, Mineral Oil and White Ointment o Sulfurated Potash -liver of sulfur -mixture of potassium polysulfides and potassium thiosulfate; -prepared by heating potassium carbonate and sulfur at 185 degrees C o Selenium Sulfide -tx for seborrhea dermatitis; -has cytostatic effects -Cadmium Sulfide 9. Antimony compounds o Antimony Potassium Tartrate -Tartar Emetic -emetic property due to irritant action on GI mucosa o Stibophen: tx for schistosomiasis o o 10. Arsenic compounds o Melarsoprol: organic asrsenical; tx for African Sleeping Sickness o Tryparsamide o Carbarsone: tx for Trichomonas vaginalis o Glycobiarsol: -bismuthyl-containing -pentavalent -tx for intestinal amebiasis II. GASTROINTESTINAL AGENTS a. antacids b. protective c. cathartics o Gastric Acid Release -parietal cell -gastric pit -chief cell -mucous neck cell Gastric Mucosal Barrier -special type of epithelial cells that has high lipid, protein, carbohydrate content -hydrophobic properties preventing back diffusion off acid Acid peptic Disease Excessive secretion of acid and pepsin Weakened stomach mucosal defense Ulceration aka acid peptic disease Drugs:

1. o

2. Antacids -neutralize acid and decrease pepsin activity -Acid neutralizing Capacity: # of mEq of HCl required to maintain 1ml of antacid suspension at pH 3 for 2 hr in vitro. Side effects 1. Soluble antacids (NaHCO3) systemic effects such as electrolyte imbalance and systemic alkalosis 2. Hypercalcemia and Milk-Alkali Syndrome 3. Rebound Hyperacidity 4. Constipation; Laxation Examples 1. Sodium Bicarbonate Baking Soda, Sodium Acid Carbonate Disadvantages: a. reacts with HCl to form CO2 gas causing epigastric distress and eructation b. rapid onset of action but short duration c. absorbed systemically 2. Basic Aluminum Carbonate Gel (Basaljel) tx for hyperacidity adjunct in treatment of peptic ulcer excreted as aluminum phosphate phosphate urinary stones 3. Aluminum Hydroxide Gel Colloidal Aluminum Hydroxide, Amphojel, Alternagel Management of peptic ulcer, gastritis and esophagitis Weak antacid Does not elevate gastric pH sufficiently to inhibit pepsin activity Not absorbed by the body Causes hypophosphatemia 4. Dihydroxyaluminum Sodium Carbonate tx for dispepsia and heartburn adjunct for management of peptic ulcer, gastritis and esophagitis partial systteic antacid rapid onset of action due to sodium carbonate less intense due to aluminum hydroxide 5. Dihydroxyaluminum Aminoacetate rapid onset due to protonation of amine group sutained buffering effect due to 2 hydroxyls and glycine carboxyl group causes constipation and hypophosphatemia 6. Calcium Carbonate rapid onset of action cause constipation Calcium supplement 7. Tribasic Calcium Phosphate antacid due to H+ accepting property of phosphate anions production of OH- upon hydrolysis of phosphate anions 8. Magnesium Carbonate (Magnesium Carbonate Hydroxide) 9. Magnesium Hydroxide (Milk of Magnesia) 10. Magnesium Oxide o Light and Heavy Magnesium Oxide o Light and Heavy Magnesia o Calcined and Heavy Calcined Magnesia 11. Magnesium phosphate (tribasic Magnesium phosphate) 12. Magnesium Trisilicate (2MgO.3SiO2.xH20)

Drugs that decrease acid (ex. antacids, H2receptor antagonists, proton-pump inhibitors) Drugs that enhance mucosal protection

Antacid Mixtures (combined) 1. Combined fast and slow-reacting antacids: rapid onset and even sustained action 2. lower the dose of each component and minimize adverse events 3. one component antagonize side effects of the other (ex laxation vs. constipation) Antacids (protectives) 1. Bismuth Subnitrate [Bi(OH)2NO3]4. BiO(OH) 2. Bismuth Subcarbonate [(BiO)2CO3]2.H2O 3. Bismuth Subsalicylate 4. Milk of Bismuth -soluble salt: in gastric acid -hydrolyzes: to orm insoluble bismuthyl salts (BiO+) -does not neutralize gastric acid -mechanical protective: coats the gastric walls -forms complex with the glycoprotein component of mucus that creates the protective barrier 5. Simethicone Antifoaming agent Decrease the tendency of gastroesophageal reflux 6. Sucralfate sucrose sulfate-aluminum complex forms ulcer-adherent complex with proteinaceous exudate @ulcer site complex covers ulcer site and protects it from further attack by pepsin and acid 7. Catharthics/ Laxatives Accelerate fecal passage or decrease its consistency Ex. a. Stimulant -stimulate water secretion @ GIT - inhibit water absorption - inc motility b. Saline/ Hyperosmotic osmotic effect; inc volume of water and stool c. Lubricant easier passage to to oil cating; inhibit colonic water absorption d. Bulk-forming absorb water; inc volume of stool e.

PICA risk factor Can be inhaled Tetraethyl lead (skin) Mobilization childhood: blood levels reflect environmental lead level (exogenous lead) adults: release of endogenous lead from bone protection: a. prevention of exposure b. preservation of bone density Acute Lead Poisoning infrequent ingestion of acid soluble lead compounds inhalation of vapors local actions: thirst, metallic taste, nausea, abdominal pain, vomiting black stool due to lead sulfide acute CNS symptoms: paresthesias, pain, muscle weakness acute hemolytic crisis: severe anemia and hemoglobinuria

Acute Lead Poisoning GI, neuromuscular, CNS, hematological, renal (may be in combination) Children: CNS syndrome or lead encephalopathy Adults: GI syndrome Early signs of lead encephalopathy: clumsiness, vertigo, ataxia, falling, headache, insomnia, restlessness and irritability; delirium with repetitive tonic-clonic convulsions or lethargy and coma flow MECHANISM OF TOXICITY: please READ at slide 50!!! Konti nalang te.matatapos na.push push push Mechanism of toxicity lead disrupts processes regulated by calcium affinity to SH- groups

Emollient -surfactant -mixture of water and lipid-soluble substances to soften stool -stimulate water secretion @ GIT 8. Saline Cathatics Sodium Phosphate Sodium Phosphate and Sodium Biphosphate Enema Sodium Phosphate and Sodium Phosphate Oral Solution Potassium Sodium Tartrate (Rochelle salt) Magnesium Sulfate (Epsom salt) Magnesium Oxide III. ELEMENTS 1. LEAD o example -obiquitous -paint -petrol (tetraethyl lead) -Household dust -solder -ceramic glazes -pesticides (lead arsenate) -cigarettes -mines, smelters o absorption children (50%) orally adults (10%) poorly enhanced if diet is poor in iron and calcium

2. CADMIUM o characteristics minor element metallic component in the earths crust and oceans by-product from extraction, smelting and refining of nonferrous metals such as Zn, Pb, Cu used as pigments, coatings, specialty alloys, electronic compounds > 80% reachargeable Ni-Ca batteries o exposure absorbed orally non-oral(dermal and respiratory) Cd accumulates in liver and kidneys Acute toxicity: resembles flu o Itai-itai Disease: The Ouch-ouch Disease symptoms: osteomalacia, osteoporosis, renal failure similar radium with Ca2+ compete with cellular transporters renal damage disrupt vitamin D activation causes anemia, teeth discoloration, olfactory toxicity (anosmia) 3. MERCURY types: a. elemental Hg b. inorganic Hg (salts) c. Organic Hg (methyl-, ethyl-, phenylmercury) =Elemental HG= o Sources:

1. 2. o

liquid form measuring devices, batteries vapor form >burning fossil fuels; mining o

Exposure: a. Inhalation easily absorbed b. Dermalminimal c. Placentalaccumulate in fetus d. Oralminimal

Garlic odor of breath, excessive salivation and sweaing, stomatitis, itching, sore throat, coryza, lacrimation, numbness, tingling extremeties, dermatitis, alopecia Treatment of Leukemia: TRISENOX -Arsenic trioxide in water with NaOH and dil. HCl to adjust pH (7.5-8.5)

= Inorganic Hg= o Sources: mercurous or mercuric salts protein precipitants, disinfectants, parasiticide (petrucci and Harwood, 1997, p766) o Exposure: oral: gastric irritant but low systemic absorption dermal: poor absorption unless exposed to large amounts =organic Hg= o sources: Hg converted to organic compounds by organisms Organic Hg: fungicide o Exposure Oral: completely absorbed: lipid soluble CNS: easily crosses BBB Placenta and breast milk: easily crosses placenta and accumulates in milk Chemistry and toxicity forms covalent bonds with sulfur divalent Hg replaces H of Sulfhydryl groups (sulfur form) forms mercaptides (X-Hg-SR) and Hg(SR)2 X EN radical R protein @ low conc: mercurals inactivate SH groups of enzymes interfere with metabolism and function

IV. RADIOPHARMACEUTICALS Radioactivity: spontaneous transformation of one nuclide to another; emission of energy (radiation) Types: a. Alpha particles identical to He2+ nucleus heaviest emission: atomic numbers > 82 b. Beta Particles negatron or positron same mass as electron lower mass negatron = positron (except charge) Gamma Radiation NO mass and charge Very high energy Photon/ quanta of energy travelling at speed of light Emission: nuclear DEEXCITATION K-capture/ Electron Capture from isotopes with unstable proton: neutron ratio but can emit positron electron (from K-Shell) + proton neutron X-rays: rearrangement of orbital electrons

c.

d.

5. ARSENIC o environmental toxicant o insecticide, parasiticide, herbicide o toxicity: organic < As5+ As3+ < arsine (AsH3) o Arsenate PENTAVALENT: -uncouples mitochondrial oxidative phosphorylation - arsenate substitute for inorganic phosphate in ATP formation -formation of unstable arsenate hydrolyzed rapidly ARSENOLYSIS o Arsenate TRIVALENT: and inorganic arsenite -SH reagent inhibit enzymes by reacting with ligands o arsine poisoning: rapid hemolysis; arsine combines with hemoglobin then oxygen o Acute Poisoning GI discomfort, burning lips, constriction of throat, difficulty in swallowing, projectile vomiting, severe diarrhea Oliguria with proteinuria and hematuria, severe thirst Shock; coma and death o Severe poisoning death within an hour o Chronic poisoning signs: muscle weakness, aching, skin pigmentation, hyperkeratosis, edema GI involvement less prominent in long term

Energy and kinetics Electron Volt: E acquired by electron when accelerated through potential of 1 volt 1 volt (1 J/ Coulomb) X 1.602 X 10-19 C Decay rate: time rate of atom disintegration Half-life: time required for of given number of atoms to decay t1/2 = ln 2/ (= disintegration/decay constant) Units: Radioactivity a. Curie: dps of 1 g of Ra (3.7x10^10) b. Becquerel: 1 dps (1Bq=2.7x10^-11 Curie) Units: Dosimetry 1. Roentgen (R) x-ray or gamma radiation to produce 1 esu 2. Radiation Absorbed Dose (Rad) measures amt of Energy transferred to medium; 100 ergs absorbed per 1 g 3. Roentgen Equivalent Man (REM) determine doses received by workers RAD x RBE (Relative Biological Effectiveness) a particle: 10-20 B-particle, Y radiation: 1 4. Gray (Gy): adsorbed radiation dose by 1 Joule 5. Sievert: equivalent dose of radiation; -a particle: 20 -B-particle, Y: 1 Biological Effects interaction of radiation with molecules formation of abnormal amt of ions and free radicals Production of Radionuclides 1. Fission heavy nucleus splits into 2 nuclei (equal size) w/ simultaneous emission of 2 or 3 neutrons

2. 3.

Neutron Reaction neutron activation (n, ) transmutation (n, p) Accelator/ Cyclotron bombard nucleus with accelerated particles

V.

Diagnostics 1. Contrast Media enhance contrast between structure or fluids in the body examples: -X-rays atoms with large number of e-MRI(magnetic resonance imaging) alter relaxation times of atoms -SPECT and PET gamma and beta emitters for visualization 2. Radiopharmacueticals -SPECT and PET gamma and beta emitters for visualization

MISCELLANEOUS INORGANIC PHARMACEUTICAL AGENTS 1. Inhalants a. Oxygen: oxidative phosphorylation O2 requirement: Anoxic Anemic Stagnant Histotoxic b. CO2: respiratory stimulant; tx for CO poisoning c. He: diluent for O2 d. Nitrogen: diluent for O2 e. Nitrous Oxide: anesthetic 2. Respiratory Stimulants a. Ammonium carbonate examples: -Sal volatile -Prestons salt -hartshorn varying NH4NHCO3 and NH2CO2NH4 preparation of Aromatic Ammonia Spirit Antidotes a. Physiological antidote: counteract effects by producing other effects b. Chemical antidote: changes chemical nature of poison c. Mechanical antidote: prevents absorption examples 1. Sodium Nitrite and Sodium Thiosulfate CN poisoning: CN- combines w/ Fe3+ of cytochrome oxidase electron transfer stops

Therapeutics a. External beam Co-60 b. Internal Beam Co-60, Ir-192, Au-198, Ta-182 c. Radioisotope Therapy NaI I-131 Diagnostics 1. Barium Sulfate a.Barium Sulfate Paste b. Barium Sulfate Suspension c. Barium Sulfate Tablets 2. Diatrizoate Meglumine

3.

4.

2. 3. Iodopamide 3.

adsorbents a. Kaolin b. Activated Charcoal precipitants a. Cupric Sulfate: Phosphorus poisoning b. Sodium Phosphate: Fe poisoning c. Magnesium Sulfate: Ba and Pb poisoning

4.

Gadopentate Dimeglumine

5. 6. 7. 8. 9.

Ferumoxidase: sterile colloidal superparamagnetic iron oxide associated with dextran in water for injection Chromium Cr-51 Edetate injection: determination of GFR Cyanocobalamine (Co-57 or Co-58): diagnosis of pernicious anemia Ferrous Fe-59 Citrate: iron metabolism and RBC formation Fludeoxyglucose

10. Sodium pertechnetate Tc-99m: brain, salivary glands, thyroid glands, stomach, heart, joints 11. Technetium Tc-99 biciromab-deep vein thrombosis