122. (D) Originally Ex-Lax and several other OTC laxatives contained phenolphthalein, a stimulant laxative, as the active ingredient. However, because of some evidence that phe-nolphthalein may be carcinogenic, many companies have reformulated by using other laxatives. The sennosides are active components from senna and stimulate the GI tract. (2a:234; 3:1169)

123. (B) Searle's Covera-HS is formulated into a COFR-24 delivery system. The 180- or 240-mg tablets are intended for bedtime dosing to ensure maximum plasma levels in the early morning. This time-factor design is intended to take advantage of the body's circadian rhythm because blood pressures tend to be higher when the patient rises in the morning. (10)

124. (B) Products such as Potassium Chloride Enseals are enteric-coated to protect the stomach from irritating substances or to prevent drug decomposition in the stomach. En-durets are sustained-release tablets. Preludin is an example. Extentabs are prolonged-action tablets (for example, Dimetapp Extentabs). Filmtabs are tablets coated with a transparent protective coating (for example, Eutron Filmtabs). (1:1653; 10)

125. (D) Mannitol possesses characteristics that make it an almost ideal sweetener for chew-able tablets. Although not as sweet as sucrose, it has "good body," leaves a cool taste in the mouth, and is not hygroscopic. Mannitol is also easily compressed by wet granulation. (24:217)

126. (B) Sterile powders of water-unstable drugs are often prepared by lyophilization (freeze-drying). Mannitol may be included in the formula to build up the dry powder, known as the cake. The larger, more visible cake is helpful in that the pharmacist can more readily ascertain when dissolution is completed. (13:36)

127. (A) Benzyl alcohol is used in many parenterals, especially in Bacteriostatic Sterile Water for Injection, as an antimicrobial agent. Although its relative toxicity is low, there are a few reports of hypersensitivity Also, it is contraindicated for use in premature infants because of incidences of fetal toxic syndrome. (13:17)

128. (D) Thickening a suspension will slow its sedimentation, but it is still necessary to get the product out of the bottle. A pseudoplastic flow is desirable because it is characterized by a greater flow rate after the system has been agitated. Thixotropy refers to a reversible sol-gel system; it is characterized by a gel that forms a flowable sol when shaken. On standing, the reformation of the gel will slow particle settling. Caking is undesirable because settling particles form a dense pack in the bottom of the container. It is very difficult to break this cake and to reconstitute the original suspension. (1:295, 298)

129. (C) Inhalation aerosol products may be intended for either localized activity (bron-chodilators for asthma) or systemic action (ergotamine for migraine). In either situation, the onset of action will be rapid. When the drug is absorbed through the alveolar-capillary membrane, the first-pass metabolism in the liver is avoided. Because of the limited capacity of aerosol units, especially in the small-chamber metered valves, only a limited amount of drug can be administered. (1:1676)

130. (A) The acronym MDI refers to "metered-dose inhaler," which are the pressurized aerosol units that dispense accurate metered doses. Epinephrine is the active bronchodila-tor in such OTC products as Bronkaid Mist and Primatene Mist. Ephedrine is available OTC only in tablet and syrup dosage forms. Metaproterenol aerosol products are by prescription only (2a:167-68; 2b:148; 11:254)

131. (B) An ileostomy results when the entire colon (large intestine) and a portion of the small intestine is removed and the remaining end of the small intestine is attached to the abdominal wall. Because of the narrow diameter of the small intestine, the wall opening

(stoma) is not as large when compared to colostomy stomas. The fecal discharge is watery because there has been limited opportunity for water reabsorption. Also, there are higher concentrations of enzymes present that may irritate the skin. (1:1864; 22:208)

132. (A) Diacetylmorphine is commonly known as heroin. It is a Class I controlled substance; this means that it may be used only for experimental work by special permit. (1:401)

133. (A) The first-degree burn is the mildest injury because only the epidermis is affected. Blisters and pain are characteristics of a second-degree burn, which affects the epidermis and portions of the dermis. The skin will regenerate. A third-degree burn penetrates through the entire skin. Damage may be permanent. Blackened skin is characteristic of a fourth-degree or char burn. Both the skin and underlying tissues are affected. There is a danger of deep infection. (2a:635)

134. (C) Benzocaine is widely used for surface anesthesia of the skin and mucous membranes. It remains on the skin for a long period of time because of its poor water solubility and because it is poorly absorbed. Systemic toxicity is rare. Although the possibility of local sensitization should be considered, the incidence is low considering the frequent use of benzocaine. Although the incidence of hypersensitivity to lidocaine is lower than that of benzocaine, prolonged administration of lidocaine to a large skin area may result in systemic side effects. Lidocaine is present in Medi-Quik Aerosol, Bactine, and Unguentine Plus. Although phenol (carbolic acid) possesses both antiseptic and local anesthetic effects, there is the possibility that it may accentuate tissue damage because of its caustic properties. (1:1412,1151; 2a:641)

135. (D) A topical preparation should contain a minimum of 5% benzocaine. Some studies have indicated that 10 to 20% of the drug is needed. (2a:641; 11:456)

136. (D) Debrisan is not useful in the treatment of nonsecreting wounds. Its action appears to be absorption of fluids and particles that impede tissue repair. The product is available as 0.1- to 0.3-mm spherical beads (4-g packets) that are sprinkled onto secreting wounds. The hydrophilic nature of the beads creates a strong suction force; each gram absorbs about 4 mL of fluid. The beads become grayish yellow when they are saturated with fluid; they should then be washed away by irrigating with sterile water or saline. (1:881)

137. (A) The rectal thermometer bulb has a strong, blunt shape that facilitates insertion into the rectum and retention by sphincter muscles. The oral bulb is cylindrical, elongated, and thin-walled for quick registration of temperature. Rectal thermometers can be used orally The oral bulb is too easily broken and is not suitable for rectal use. The short, sturdy, security bulb represents a compromise intermediate shape. (1:1860)

138. (B) Because fertilization can occur within only a few hours (perhaps 24) after ovulation, accurate knowledge of this event could permit timing of intercourse to either increase or decrease the possibility of conception. Basal temperature (the lowest temperature of the body during waking hours) typically passes through a biphasic cycle over the course of the menstrual cycle. From an initially low temperature, a midcycle thermal shift occurs to a high level, where it remains until it again becomes low premenstrually. The temperature rise roughly corresponds with the time of ovulation. The thermometer is used orally or rectally once daily, immediately on awakening in the morning and before getting out of bed. The scale may be either Fahrenheit or Celsius. The temperature rise is only about 0.5° F, which would be difficult to measure on the usual clinical thermometer. The basal thermometer scale ranges only from 96 to 100° F and is graduated to 0.1°. (1:1860)

139. (C) The French system is used for designating sizes of both urinary catheters and tubing used for enteral feedings. One French unit equals 1 mm on the outside circumference.

Answers: 132-148 105

Thus, a catheter with an outside circumference of 20 mm is identified as a 20F or 20Fr size. Syringe needles are sized by another system—the Stubbs numbers. (1:1867)

140. (D) Although the venoms of some insects are potent, the amounts injected are too small to be toxic. The severity of the sting reaction in some individuals is due to their hypersensitivity to certain proteins in the venom. This results in the anaphylactic shock. (2a:661; 11:446-50)

141. (D) Persons who experience severe anaphylactic reactions to insect sting or bites should carry emergency kits. These kits usually contain antiseptic pads (to clean and disinfect the area), both an antihistamine and epinephrine injection (to counteract the anaphylactic reaction), and tweezers (to remove the stingers). A tourniquet would be of little value because the amount of venom is very small. Self-injectable units of epinephrine, such as EpiPen, are also available for individuals known to be susceptible to stings. (2 a:664)

which a topical drug product has been applied will often enhance the rate of drug absorption. Sweat accumulation at the skin-vehicle interface induces hydration of the skin, a condition that facilitates penetration of drugs. Poorer solubility of the drug in PEG ointment than in white ointment may lead to faster diffusion. This is the converse of choice E. The thicker epidermis of the palms results in slower drug penetration than that which occurs on the backs of the hands. Higher drug concentrations will increase the rate of diffusion and penetration. (1:713; 24:363-64)

145. (A) Benzocaine is included in some dietary aid products at levels of 3 to 15 mg. The products are formulated as lozenges, gum, or candies. The benzocaine is believed to decrease the person's ability to detect sweetness, thus reducing appetite. (2b:313; 11:330)

146. (B) Melatonin is an endogenous hormone produced by the human pineal gland. It appears to shift the circadian rhythm and serves as a sleep aid when taken 1 to 2 hours before bedtime. (2a:184)

142. (B) Pamabrom, a xanthine derivative is present in several OTC products for the prevention of premenstrual syndrome (PMS), specifically bloating. Its diuretic activity is obtained with a dose of 25 to 50 mg four times a day. Examples of products containing pamabrom include Midol PMS and Pamprin. (2b:73; 11:290)

143. (A) The carbamide peroxide will effervesce, thereby softening the waxy material. An example of an OTC product is Debrox, which also contains glycerin and propylene glycol that acts as solvents. (2b:334; 11:418)

144. (E) Diffusion of a drug from a vehicle into the skin is often related to the solubility of the drug in the vehicle relative to the solubility in the skin, ie, the partition coefficient. Drugs that are very soluble in a vehicle will tend to remain in the vehicle and will penetrate more slowly than drugs with poorer solubility in the vehicle. Covering the area to

147. (E) Allantoin is included in many topical formulations as a vulnerary (healing agent), which is a substance that stimulates tissue repair. (1:880)

148. (D) Compazine is available in hard gelatin spansules for sustained release of the drug. It is used to treat anxiety and as an antiemetic. All of the other drugs are formulated into soft gelatin capsules which allow formulation of water insoluble drugs in other solvents such as corn oil, coconut oil, and propylene glycol. Because of the liquid nature of the drug or its formula, the solid dosage form has faster disintegration/dissolution rates. All of the other choices consist of drug in soft gelatin capsules. Cyclosporine (Sandimmune) is an immunosuppressive agent. Eth-chlorvynol (Placidyl) is used as an hypnotic. Ethosuximide (Zerontin) is an anticonvulsant, and ranitidine (Zantac GELdose) helps prevent peptic ulcers. Another example of a soft gelatin capsule is Lanoxicaps which is a liquid form of digoxin. Less drug is required for the same activity as the solid tablet dosage form. (10; 24:196)

149. (D) The extent of drug release and absorption will vary depending upon the properties of the drug, the suppository base, and the condition of the colon. Oil-soluble drugs will be poorly released from a cocoa-butter base because of their high lipid/water solubility. The rectal fluid pH is essentially neutral and has a low buffer capacity. Therefore, drugs that can be destroyed by the acidity of the stomach may be successfully administered rectally. Drugs that are absorbed through the colon pass into the lower hemorrhoidal veins and into the general systematic circulation. Avoidance of first-pass exposure to the liver may enhance the effect of those drugs inactivated by the liver. Drugs that are absorbed from the upper intestinal tract pass directly through the portal vein into the liver, where metabolism may occur. The lesser dose frequency and lower propensity for irritation are the reasons certain drugs can be administered rectally but not orally. (24:281)

150. (E) Selected combinations of the polyethylene glycols (PEGs) can be formulated into water-miscible suppositories with a range of consistency. They are easy to insert and do not require refrigeration. (24:293)

151. (A) Lactose is a readily compressible and water-soluble inert ingredient. It also encourages the growth of Doderlein's bacilli, a microorganism present in the healthy vagina.

starch in the form of a paste will bind powders during the formation of granules suitable for compression into tablets. (1:1618-19)

154. (E) Carbomers (Goodrich's Carbopols) are polymers with a number of carboxy groups present. When the pH of a solution containing the carbomer is increased, there will be a significant increase in viscosity. (1:1396,1518)

155. (D) Excessive tablet compression may hinder tablet disintegration into aggregates, thus slowing the dissolution process. Other factors that affect dissolution include drug solubility, particle size, and crystalline structure; however, these factors may not influence the disintegration rate. However, there is usually fairly good correlation between tablet disintegration characteristics and dissolution, and disintegration times are a convenient in-house manufacturing control. Increasing drug particle surface area by micronization of drugs such as griseofulvin, chloramphenicol, and sulfadiazine have increased their dissolution rates (decreased dissolution times) and improved absorption. (1:594-5)

156. (E) The disintegration times for uncoated tablets may vary and will be specified in the official monographs. The usual time is 30 minutes. For sugar-coated tablets, the time may be as much as 2 hours. Enteric-coated tablets are first placed in gastric fluid, then transferred to a simulated intestinal fluid. Buccal tablets may need four hours to disintegrate while sublingual tablets such as nitroglycerin have a limit of only a few minutes. (1:1641: 24:206-9)

152. (B) Semicid inserts contain 100 mg of the spermicide nonoxynol-9. The active ingredient in Norforms vaginal suppositories is the quaternary ammonium germicide benzetho-nium chloride, which decreases odor-producing microorganisms. Terazole contains ter-conazole for the treatment of moniliasis. (2b:70; 24:293)

153. (C) When moistened, starch will swell, thus aiding in the disintegration of a tablet. Corn

157. (A) Properties of a solution that depend on the number of particles of the solute and are independent of the chemical nature of the solute are termed colligative properties. The magnitude of vapor pressure, freezing-point reduction, boiling-point elevation, and osmotic pressure are all related to the number of particles in solution. (1:206)

158. (A) Solutions with equal osmotic pressure are isoosmotic; they also will be isotonic if

Answers: 149-168 107

separated by a membrane permeable to the solvent but impermeable to the solute. Any of the colligative properties can be used to determine tonicity of solutions. Freezing-point depression values are used most frequently. The freezing point of a 0.9% sodium chloride aqueous solution is -0.52° C; the same as that of human blood and tears. Saline solutions of this concentration are isotonic with these body fluids. More concentrated solutions are hypertonic; less concentrated are hypotonic. (1:207)

159. (D) Solutions with the same osmotic pressure as blood are usually isotonic with blood. Solutions that have a higher osmotic pressure (ie, hypertonic) will cause water to pass out of the red blood cells. Solutions that have a lower osmotic pressure (ie, hypotonic) will allow water to pass into the cells. This causes them to swell and rupture with a release of hemoglobin (hemolysis). (1:207; 112:180)

160. (C) A hypertonic solution will draw water from within the cell until an equilibrium is reached with equal pressure on each side of the cell membrane. Because of the loss of volume, the cell will shrink and take on a wrinkled appearance (crenation). (1:207; 24:472)

161. (A) A sodium chloride equivalent is the weight of sodium chloride that will produce the same osmotic effect as 1 g of the specified chemical. For example, morphine hydrochloride has an E value of 0.15. This indicates that 1 g of morphine hydrochloride produces the same osmotic pressure (and depression of freezing point) in solutions as 0.15 g of sodium chloride. (1:620; 12:182)

162. (C) Any two solutions that have the same freezing points will have the same osmotic pressure and should be isotonic. Because blood freezes at -0.52° C, any aqueous solution that freezes at this temperature will be isoosmotic. The use of freezing-point data for isotonicity adjustment for both ophthalmic and parenteral solutions is common in the pharmaceutical industry because freezing points can be measured easily. (1:620; 12:181)

163. (D) Aqueous solutions that freeze at the same temperature as blood have the same osmotic pressure as blood (ie, are isoosmotic with blood and each other). However, to be isotonic a solution must maintain a certain pressure, or "tone," with the red blood cells. If the chemical in a solution passes freely through the red blood cell membrane, equalized pressure on both sides of the membrane is not possible without changes in the cell volume. Tone will not be maintained, and the solution will not be isotonic, though it might be isoosmotic with blood. (1:619; 12:180)

164. (C) The Remington: The Science and Practice of Pharmacy presents extensive tables of sodium chloride equivalents (E) and freezing point depression (D) values. (1:622)

165. (E) In spite of its name, Veegum is not an organic gum but is an inorganic clay. It is water-insoluble and would probably be unsuitable for ophthalmic administration since insoluble particles could be deposited in the ocular areas. (1:1571)

166. (B) Increasing the contact time between a drug and the cornea will often increase the amount of drug absorption that will occur.

167. (B) Fluorescein sodium is an ophthalmic diagnostic agent. It is instilled into the eye to delineate scratches and corneal lesions. It would be very dangerous to place a contaminated solution on a damaged cornea through which microorganisms may easily pass. If Pseudomonas aeruginosa enters the interior of the eyeball, blindness may occur quickly. Pharmacists should not prepare fluorescein sodium solutions extemporaneously unless sterility can be guaranteed. Pharmaceutical manufacturers supply fluorescein as unit-dose solutions or individual paper strips. (1:1569)

168. (A) Acanthamoeba keratitis has been identified in solutions used by contact lens wearers. These solutions were either home-made or commercial solutions that were recycled.

Thermal disinfection is effective in eliminating microbial contamination including Acan-thamoeba. (2a:482)

169. (A) The combination of benzalkonium chloride and edetate (0.01% of each) is effective against those microorganisms likely to contaminate ophthalmic solutions. These include some strains of Pseudomonas aeruginosa that are resistant to benzalkonium chloride alone. (4:15.9; 24:472)

170. (A) Epinal contains epinephrine borate while the other two products (Epifrin and Glaucon) contain the hydrochloride salt of epinephrine. There may be a distinct advantage in using the borate salt since the pH of the solution will be higher, thus causing less irritation when placed in the eye. (3:1729)

171. (D) Papain and subtilisin are proteolytic enzymes that aid in the removal of proteina-ceous residues that slowly build up on soft lenses during wear. Allergan markets Enzymatic Contact Lens Cleaner as tablets containing papain. Subtilisin is present in Bausch & Lomb's ReNu series of products. A third enzyme that has been used is pancreatin. Once weekly, the soft lenses are soaked overnight in solutions prepared from the previously mentioned products. Hydrogen peroxide is the active ingredient in a number of soft lens disinfecting products. (2a:142; 2b:329)

172. (A) The capacity of the cul-de-sac is estimated to be not more than 0.03 mL, with a normal tear volume of approximately 0.007 mL. Probably less than 0.02 mL of an ophthalmic solution can be placed successfully in an eye at one time. This volume is less than the nominal 0.05 mL (1 drop) usually requested in prescription directions. This implies that a portion of the dose is lost through drainage or overflow onto the cheek. (1:1565)

173. (C) Sodium bisulfite and sodium metabisulfite are included in pharmaceutical solutions as antioxidants. For example, the oxidation of epinephrine may be retarded by the presence of sodium bisulfite, which is preferentially oxidized. Unfortunately, some individuals are sensitive to the bisulfites and must avoid products containing them. The labels of many wines caution about the presence of bisulfites. (1:1381; 4:16.4)

174. (A) One of the first signs of sensitivity to bisulfites is difficulty in breathing. Also, the patient may experience hives, abdominal pain, and wheezing. (24:82-83)

175. (B) LYMErix vaccine develops reasonable titers in approximately 80% of the population. It is injected into the deltoid muscle rather than subcutaneously. The spirochete is carried in ticks which are often found on wild deer. The original tick bite often appears as a small red bull's eye. Recovery rate for humans is fast if treated early with one of the tetracyclines. Otherwise, a severe form of arthritis may develop. (3:1505)

176. (C) Because membrane filtration does not involve heat, it is suitable for drug solutions that either are sensitive to heat or have not been studied sufficiently concerning their heat stability. The pharmacist may purchase presterilized filter units such as Millipore's Millex through which 15 to 100 mL of solution can be filtered. However, autoclaving is still considered the most reliable sterilization procedure. (13:68-70)

178. (C) The Henderson-Hasselbalch equation, or buffer equation, for a weak acid and its corresponding salt, is represented by pH = pKa + log ^

where pKa is the negative log of the dissociation constant of the weak acid and salt/acid is the ratio of the molar concentrations of salt and acid in the system. The volume of the solution is not critical because the chemical concentrations are already expressed in terms of moles. (12:170)

179. (E) According to the Henderson-Hasselbalch equation, pH will equal pKa when the expression i [salt] . , .

log 1S equal to zero.

This can occur only when the salt/acid ratio equals 1, because the log of 1 is 0. The point at which the salt concentration equals the acid concentration is the half-neutralization point. It is also the pH at which a buffer system, based upon the weak acid's pKa, has the best buffering capacity. (12:170)

180. (D) For many years, the curie (Ci) has been the basic unit for expressing radioisotope decay. Now the becquerel is recognized as the "official" unit. One becquerel equals one decay per second (dps).

The rad is a quantitative measure of radioactivity. (24:488)

181. (B) Decay rate is the rate at which atoms undergo radioactive disintegration. The rate of decay (-dn/dt) is proportional to the number of atoms (n) present at any time (t); thus, radioactive decay is a first-order process. (1:368)

182. (C) Gamma radiation, x-rays, and ultraviolet radiation are forms of electromagnetic radiation and are radiated as photons or quanta of energy. These forms of radiation differ only in wave length and are the most penetrating types of radiation. Gamma rays are the most penetrating of all and can easily penetrate more than a foot of tissue and several inches of lead. Alpha radiation is particulate radiation consisting of two protons and two neutrons. The range of alpha particles is about 5 cm in air and less than 100 microns in tissue. Beta radiation is also particulate radiation, but exists as two types, the negative electron (negatron) and the positive electron (positron). Both may have a range of over 10 feet in air and up to about 1 mm in tissue. (1:379)

183. (B) somTc is available commercially as a technetium generator from various manufacturers in which molybdenum "Mo is the parent nuclide. The half-life of technetium (6 hours) is long enough to allow completion of usual diagnostic procedures for which it is used, yet short enough to minimize the radiation dose to the patient. Lack of a beta component in its radiation further decreases the dose delivered to the patient. The gamma energy is weak enough to achieve good collimation, yet strong enough to penetrate tissue sufficiently to permit deep-organ scanning. (1:371)

184. (B) Although it is desirable to use isotopes with short half-lives to minimize the radiation dose received by the patient, it is evident that the shorter the half-life, the greater the problem of supply. Radioisotope generators, or "cows," have been developed to deal with this problem. A radioisotope generator is an ion-exchange column containing a resin of alumina on which a long-lived parent nuclide is absorbed. Radioactive decay of the long-lived parent results in the production of a short-lived daughter nuclide that is eluted or "milked" from the column by means of an appropriate solvent such as sterile, pyrogen-free saline. (1:371)

185. (B) The drug solution lost 0.5 mg of its 2.0 mg/mL concentration in 24 hours. This represents a loss of

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