Test Bank for Oral Pharmacology for the Dental Hygienist, 2nd Edition

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Test Bank Answer Key CHAPTER 1 Multiple Choice 1. a,d, e. Until the end of the 19th century, medicines were natural organic or inorganic products. Morphine is obtained from the poppy plant and digitalis for heart conditions is obtained from the foxglove plant. Insulin is developed from gene technology. 2. a,b,c,d. The trade name or brand name (or proprietary name) for a drug is a registered trademark belonging to a particular drug manufacturer and used to designate a drug product marketed by that manufacturer. The chemical name is a long name and refers to the chemical makeup of the drug. Generic name is the โ€œofficialโ€ preferred name and comes from the United States Adopted Names (USAN) designations. 3. d. Category D drugs (e.g., tetracycline) have been shown through medical studies to cause harm to the fetus and/or pregnant woman and should not be given to a pregnant woman or a child under the age of 8 because it causes enamel hypoplasia and permanent tooth discoloration. 4. b. This definition of an adverse drug reaction (ADR) has been created by the World Health Organization (WHO). This term is restrictive because it only considers incidents where use of the drug is appropriate, excluding many adverse events caused by medication errors. Adverse drug reactions are unpredictable and unintentional because it is not known that a reaction will occur. 5. b. Antihistamines cause secretions to dry up; thus, dry mouth (xerostomia). 6. a. Acetaminophen is the generic name for Tylenol, which is the brand or trade name. 7. b. Adverse effect is an undesirable effect not looked for. 8. a. All adverse drug effects are reported to the FDAโ€™s MedWatch program (www.fda.gov/medwatch). 9. a. The FDA determines what drugs can be marketed in the United States. 10.a,b,c. Prescriptions are written to tell the patient what drug to take. Most importantly, it is the law. 11. d,e. The name and dosage of the drug are included in the body of a prescripton. 12. b,e. The patientโ€™s name, address and age are in the heading of a prescription. 13. b,c. Number of refills, label box, and generic substitution signatures and the DEA (Drug Enforcement Administration) number of the prescriber are part of the closing of a prescription. 14. b. In the United States, the FDA can require a pharmaceutical company to place a black box warning on the labeling of a prescription drug or in the PI, at the start of the labeling. A black box warning means that medical studies have shown that the drug causes a significant risk of serious or even lifethreatening adverse effects. A black border is placed around the text of the warning. 15. a, c, d. Liter, gram, and milligram are examples of units of measure in the metric system. 16. b: Grain is a unit of measure in the apothecary system. Some practitioners still use the apothecary system when writing prescriptions (Figure 2โ€“2). 17. b,c . Prescribing by generic name allows the pharmacist flexibility in selecting the particular drug product to filled in the prescription. The patient can also save money and some health insurance providers require use of generics where possible. 18. a,b,c,d. A prescription for a C-III drug may be refilled up to five times by the pharmacist. 19. a,e,f. The best way to avoid prescribing errors is to write in ink and clearly on the prescription. 20. a. Writing โ€œacโ€ on a prescription indicates to take the medicine before eating. 21. d. At the bottom or closing of the prescription is the signature of the prescriber. 22. b. Electronic transmission of prescriptions is increasingly being used and helps reduce errors in reading and filling prescriptions by the pharmacist. 23. b. Taking the medicine 3 times a day for 7 days = 21. The first dose is 2 tabs (1 more than the usual dose of 1)which equals 22 doses. 24. a. The desired plasma concentration of a drug is achieved rapidly and is called the loading dose. 25. c. โ€œSig: 1 qid pc and hsโ€ is translated to mean โ€œTake one 4 times a day after meals and at bedtime.โ€ 26. d. The age, name, and address of the patient are required to be on a prescription. 27. a. โ€œprnโ€ on a prescription indicates to take the medicine as needed. It is usually written for medicine for pain control. 28. a, b. The pharmacist MUST substitute the brand name for a cheaper generic name drug. The pharmacist can ask the patient which is preferred. True or False 1. T: Trade, brand, and proprietary name refer to the same name. 2. F: Clarithromycin is listed as โ€œC.โ€ 3. T: The Harrison Narcotics Act was introduced due to the high incidence of heroin abuse. Habitforming drugs are classified according to their abuse potential and placed in Schedules by the Federal Drug Enforcement Administration (DEA). 4. T: Posology is the science or study of drugs, their preparation, properties uses, and effects. 5. F: The FDA stands for the Food and Drug Administration, the agency that is responsible for approving new drugs before they go out into the public. 6. F: Pharmacokinetics is the study of what the body does to the drug, while pharmacodynamics is the study of drug action. 7. F: Prescriptions should be written in ink (printed) or submitted to the pharmacist by electronic transmission. 8. F:Theapothecarysystemusesoldmeasuresofweightsandvolumessuchasgrains(gr). 9. F: Children and infants have different absorption, distribution, and metabolism kinetics than adults and usually the dosage is less. 10. F: Over-the-counter drugs do not require a prescription to purchase. 11. T: C-II prescriptions are not refillable and only one prescription can be used. 12. T: The FDA approves a drug to be used for specific purposes. These approved or labeled uses are found in the package insert (PI) in the box that the drug came in. These labeled uses may not include all medical conditions where the drug may be used. Thus, federal laws allow the prescriber to prescribe a drug for an โ€œoff-labeled use.โ€ For example, diflunisal (Dolobid) is an analgesic that is indicated for use in mild to moderate pain, osteoarthritis, and rheumatoid arthritis. Although dental pain is not an indication, it still can be prescribed for that purpose. 13. F: The prescriber is required by law to write for drugs that pertain to his or her profession. 14. F: It is required to state the dose and frequency of taking the medication. 15. F: Open-ended statements such as โ€œtake as directedโ€ or โ€œas neededโ€ should not be written. 16. T: 1 gram is equivalent to 1000 milligrams. Fill in the Blank 1. Mutagenic effects: The display of damage is evident in the children from these parents. Essentially, it is a heritable genetic defect. 2. Toxicity: toxic doses. Acute toxicity results in an overdose when an individual dose is too large and is taken at one time. Chronic toxicity occurs when the dose effects accumulate over time. 3. trade name or brand name (or proprietary name): Used to designate a drug product marketed by that manufacturer. 4. Idiosyncrasy: Unexplained, uncharacteristic response to a drug. Usually drug idiosyncrasies are caused by hereditary factors or genetic differences that are unknown or not yet understood. 5. B: Penicillin has a pregnancy category of B and is safe to give to pregnant women. 6. errors: Minimizing prescription and dispensing errors will help to avoid drug complications. 7. controlled: Controlled drugs are usually narcotics or stimulants that can be abused by people. 8. dispense as written: DAW is signed by the prescriber so that the pharmacist dispenses the drug that as written. 9. gm: The abbreviation of a gram is gm. 10. ml: The abbreviation of a milliliter is ml. 11. doxycycline: The generic doxycycline has many brand name equivalences such as Vibramycin or Doryx. 12. bid: Twice a day is abbreviated on prescriptions as bid. 13. tid: Three times a day is written on prescriptions as id. 14. qid: Four times a day is written on prescriptions as qid. 15. stat: When a drug has to be taken immediately, it is written on a prescription as stat. 16. qh: When a drug has to be taken every hour it is abbreviated as qh. 17. write on label: SIG on the prescription actually means to write on the label of the bottle. 18. orally: When โ€œPOโ€ is written on a prescription it means to take the medicine orally. 19. DEA: Every prescriber requires a DEA number in order to write prescriptions for controlled drugs. 20. bedtime: Writing โ€œhsโ€ on a prescription means for the patient to take the medicine at bedtime. 21. every day: Writing โ€œqdโ€ on a prescription means for the patient to take the medicine every day. 22. heading: The body contains the symbol Rx (which means โ€œtake thouโ€). The heading contains the prescriberโ€™s name, address, telephone number, the date when the prescription was written, the patientโ€™s name, address, and age. 23. cheaper: The generic drug is usually cheaper to the patient than the equivalent brand name. 24. No refill: The number of refills must be written on the prescription. NR means no refills are allowed. 25. 5: C-III narcotics may not be refilled more than 5 times within 6 months. EXTENDED MATCHING 1. 1. d 2.b 3. a 4.c 2, 1. e 2, a 3.b, f 4. c 5.d Case Study 1. The development of the allergic state requires a foreign substance called an antigen to enter the body, which causes the body to produce antibodies in response to the antigen. The allergic response will only be seen on the second, subsequent exposure to the antigen. In this case, penicillin allergy will be evident by rashes in the mild form and anaphylaxis in severe forms where the airway can close up. This is in contrast to the patient reporting that he had gastrointestinal upset and was nauseated. This is an adverse effect of the drug. This information should be noted in red on the patientโ€™s chart. 2. All medications that the patient is taking should be reviewed, including drug-drug interactions. There are many reference books, online sources, and hand-held computer devices to look up drugs including www.rxlist.com, www.medscape.com, Delmarโ€™s Dental Drug Reference, Lippincott Williams & Wilkins Dental Drug Reference and LEXi-COMPโ€™S Drug Information Handbook. 3. Since nitroglycerin is used to control angina attacks, which can be precipitated by stress, the patient should have the nitroglycerin bottle within easy availability. The patient should be asked when the last angina attack was. Blood pressure and pulse should be recorded prior to treatment for baseline measurements in case of emergency. 4. Nitroglycerin is administered sublingually and ibuprofen is given orally. Ask the patient why he is taking ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug used to control pain. Ask the patient if he is taking it for arthritis or other painful conditions. Also, ask if he is taking aspirin. Many patients are taking aspirin to prevent strokes. There are drug interactions even with over-thecounter drugs. The only way to learn about drug interactions with the drugs the patient is taking and the drugs the dentist will prescribe is to refer to a reference source including LEXI-COMP which is for dentistry and epocrates. 5. Use references to look up any information before discussing with the patient. Therapeutic effect is the desired and beneficial pharmaceutical effect that a drug exerts at the site of action. This occurs whether the result was expected, unexpected, or an unintended consequence of the treatment. The therapeutic effect of ibuprofen is analgesia and anti-inflammatory. Side effects of a drug are additional drug actions at therapeutic levels, and they can be good or bad. Adverse effects of ibuprofen include headache, bleeding, and dizziness. Case Study 1. a. Do not use the statement โ€œTake as directed.โ€ b. Write out the word โ€œtenโ€ after โ€œ10 tabs.โ€ c. Write out the exact age of the patient instead of just writing โ€œA,โ€ which indicates โ€œadult.โ€ d. Write the number of refills allowable, and if no refills than write โ€œNR.โ€ 2. A heading B Body C Closing 3. Take one tab po q4-6h prn for dental pain. 4. The patient should not take the pain reliever more than one tablet every 4 to 6 hours. The medicine may make you sleepy, sedated, or constipated. Do not drive while taking this medication. 5. Explain to the patient that Vicodin is the brand name for hydrocodone/acetaminophen. A generic drug is identical or bioequivalent to a brand name drug in dosage form, strength, route of administration, quality, performance characteristics, and intended use. The generic drug is usually cheaper than the brand name drug and/or required by your insurance company. CHAPTER 2 Multiple Choice 1. b. Placement of medications used in periodontics (such as a Atridox or Arestin) into the gingival crevice is an example of topical administration (referred to as subgingival) because they are medications applied to the epithelium. 2. c. Pharmacodynamics refers to the actions a drug has on the body, including the drugโ€™s mechanism of action, receptor interactions, dose-response relationship, and therapeutic and toxic reactions. Pharmacokinetics describes what the body does to drugs. 3. a. Pharmacokinetics describes how the drug is handled by the body, including absorption, distribution, metabolism, and elimination. 4. b. Solutions are a clinically and physically homogenous mixture of two or more substances. Solutions are generally liquid: chlorhexidine gluconate + alcohol. 5. a,b,e. Oral, sublingual and rectal routes of drug administration involve the drug being absorbed from the GI tract. There other routes of drug administration are parenteral and avoid the GI tract. 6. a, b,c. Adverse drug reaction is a noxious and unintended response to a drug or medical device or product as long as the drug was properly prescribed regarding normal dose, route. Medical errors are not included in the definition of adverse drug reaction. An adverse drug event includes medical errors. 7. b. Administration of a drug involves the injection of liquid into the connective tissue under the skin. This route cannot be used for irritating drugs or if a large volume of the drug (solution) must be administered. 8. c. Transdermal administration is the application of drugs to the skin that will be absorbed into the bloodstream. Dosage forms include a skin patch or ointment. Common patches include nitroglycerin for angina, oral contraceptives, and nicotine patches for smoking cessation. 9. a. Nitroglycerin tablets to relieve acute angina pain are placed under the tongue (sublingually) for quick absorption and relief. 10. c. Oraqix, a topical anesthetic, is applied directly into the gingival crevice. 11. a,b,c,d. Absorption, distribution, metabolism, and elimination are all involved in the actions of the body to the administered drug. Protein binding is what the drug does in the body and is not part of pharmacokinetics. 12. a. Biotransformation refers to the metabolism or changing/altering the drug so that it can be eliminated from the body. 13. b. Bioavailability of a drug refers to how much of a drug is absorbed or appears in the bloodstream after a dose is administered. 14. c. A drug given IV directly goes into the bloodstream. 15. b. A more lipid-soluble, nonionized drug will pass through the biphospholid layer of the cell membrane. 16. c. Half-life (t1/2) of elimination is the time it takes for the concentration of the drug in the blood to fall to half (50%) of its original value. It is an indicator of how long a drug will produce its effect in the body and defines the time interval between doses. It takes about 4โ€“5-lives for a drug to be โ€œconsideredโ€ eliminated from the body. At this point, steady-state is reached. 17. a. Sublingually or buccally administered drugs must be able to go through the epithelium of the oral mucosa (tongue or buccal mucosa) before they can enter the blood and be distributed to the site of action. This barrier is referred to as the tissue/blood barrier. 18. a. During passive diffusion, the drug penetrates the membrane exclusively by diffusion in which the rate of transport is solely proportional to the concentration gradient. 19. d. The surface area of the small intestine is of concern for absorption. The drug just passes down the esophagus, which is not involved in absorption. 20. b. Drugs are absorbed from the gut but may be biotransformed by enzymes in the gut and liver before reaching the systemic circulation. This process lowers their degree of bioavailability. 21. c. Distribution is the process by which the effective concentration of the drug is reached at the site of action. 22. a. Many drugs are excreted in the bile. After the bile empties into the intestines, part of the drug may be reabsorbed back into the blood (circulation) and eventually return to the liver. This process reduces the elimination of drugs and prolongs their half-life and duration of action in the body. 23. d. The liver is the primary site where drugs are biotransformed or changed in order to prepare them for elimination from the body. 24. b. CYP enzymes are involved in oxidative or reductive metabolism. For example, CYP3A4 is responsible for the biotransformation of cholesterol-lowering statin drugs, and if taken with erythromycin/clarithromycin, will inhibit the metabolism of these drugs because CYP3A4 is an enzyme inhibitor. 25. a. Drugs with a first-order elimination exhibit a half-life (t1/2) of elimination, which is the time it takes for the drug to eliminate half (50%) of the amount of its concentration in the plasma or body. For example, if the elimination t1/2 of a drug is 20 minutes, 50% of it remains in the blood 20 minutes after IV administration. This is a mathematical calculation that is important for adequate drug dosing. 26. a. Total body clearance is a more accurate measure of the efficiency with which a drug is eliminated by the body than the half-life (tยฝ). 27. b. Pharmacodynamics describes the actions a drug has on the body; the drugโ€™s mechanism of action. Additionally, pharmacodynamics involves drug-receptor interactions, drug response, and doseresponse relationship. 28. a. Agonist is a drug that rapidly combines with a receptor to initiate a response and rapidly dissociates or releases from the receptor. It has a high efficacy. Most drugs used today are agonists. An antagonist is a drug that binds to the receptor but does not dissociate and has no positive response and no efficacy. A ligand is a molecule or drug that binds to a receptor to form a larger complex. 29. a. Effective dose is the dose that produces 50% of the maximal response. The potency of a drug varies inversely with a drugโ€™s ED50. For example, a drug whose ED50 is 4 mg is ten times more potent than a drug whose ED50 is 40 mg. 30. a. Tachyphylaxis, a very rapid development of tolerance, is defined as a rapid decreasing response (within hours/days) with repeated administration of the same dose of drug at short intervals. In dental practice, tachyphylaxis to local anesthetics may develop. For example, a local anesthetic is administered to a dental patient. Once the nerve function returns to its preinjection state and the patient requires more anesthetic because of pain, the duration and intensity of anesthesia with reinjection is greatly diminished. Thus, successive doses of the anesthetic will be less effective than those given previously. 31. d. Tolerance is defined as the need for increasing amounts of drug to obtain the same therapeutic effect. 32. a. Receptors are usually macromolecules composed of proteins, carbohydrates, and glycoproteins. 33. a. Drugs binding to plasma proteins is a reversible action. A highly protein-bound drug has a longer duration of action. Only a free drug, not bound to plasma proteins, is active. One drug may displace another form its binding site on the protein, elevating the free concentration of the displaced drug. This is a type of drug interaction. An example of a highly protein-bound drug is warfarin (a blood thinner). 34. d. Tablets and capsules are easier to administer than an injectable drug form. 35. b. Before plasma levels can drop back toward zero, intermittent maintenance doses are administered to keep blood concentrations in the therapeutic range. True or False 1. F: Once a drug is taken orally, it initially passes down the esophagus and into the small intestine before it is absorbed into the blood. 2. F: Cell membranes or tissue barriers are composed of two layers of lipids (fat), referred to as the biphospholipid layers with small aqueous (water) holes, channels or pores throughout the layers with proteins on the outside. 3. F: A drug that is soluble in fat is called lipophilic and hydrophilic when soluble in water. 4. T: The rate of absorption increases as long as the concentration outside the cell (circulatory system; blood) is greater than the concentration inside the cell (target tissue; where the drug acts). No energy is used by the cell. 5. F: A hydrophilic drug is more water soluble and easier to be excreted. 6. T: Drugs that are weak acids will be mostly nonionized at the acid pH of the stomach (pH 1), allowing them to be readily absorbed. 7. T: Drugs that are weak will be more nonionized (nonpolar) at the pH of the basic small intestine (pH 6-7) and ionized, more polar, and more water soluble in the stomach. The nonionized portion of the drug shows great lipid solubility and therefore greater absorption in the small intestine. 8. T: Drugs that have a high first-pass effect are biotransformed in the liver with less of the drug being available to get to the site of drug action. 9. T: Water-soluble drugs are easily excreted in the urine and do not have to be biotransformed as do lipid-soluble drugs. 10. T: The dose of a drug refers to the amount of drug given. 11. T: Intravenous administration (IV) of a drug is made directly into the circulation (vein) so it is used for emergency situations when it is critical to get the drug into the blood as quickly as possible. 12. F: All dental anesthetic injections are subcutaneous injections. 13. T: Topical administration refers to the application of drugs to the surface of the body (e.g., skin, mucous membranes of the gingiva, eyes, gingival crevice of teeth, mouth, and throat). 14. F: Local delivery of antibiotics (Arestin, Atridox) used in periodontics are administered topically into the gingival crevice. Fill in the Blank 1. absorbed: Drugs must be absorbed from the GI tract into the blood before they can get to the site of action and exert a pharmacologic response. 2. Bioavailability: Once a drug is administered, it must be absorbed into the blood. This is referred to as bioavailability. 3. 100%: A drug that is administered IV goes directly into the bloodstream and does not have to go through any barriers to get into the blood. Thus, it is 100% absorbed. 4. small intestine: The small intestine has a larger surface area for absorption than the stomach. 5. tissue barriers: Drugs must pass through tissue barriers or cell membranes from the GI tract to the blood and then from the blood to the site of action. 6. blood/tissue: Once the drug enters the blood, it is transported to the various tissues in the body through body fluids until it passes through blood (capillary) cell membranes to get to the site of action where the drug will exert its pharmacological effect(s). Thus, the drug must go through another barrier. This barrier membrane between the blood and the tissue is called the blood/tissue barrier. 7. passive: This is the most common route of drug passage into the blood. 8. parenteral: Orally administered drugs must go through the GI tract before being absorbed into the blood, whereas parenteral (injectable) drugs bypass the GI tract. 9. stratum corneum: The stratum corneum is the most superficial layer of skin and a topically applied drug must pass through it. 10. metabolite: Drugs are eliminated either as the original parent compound (referred to as โ€œunchangedโ€) or as a drug metabolite where the drug molecule must be changed or metabolized in the body for it to be eliminated 11. water: To be readily eliminated from the body, a drug must be in a water-soluble/polar form. Thus, many drugs must be changed (biotransformed) before elimination, and the liver is the primary site of drug biotransformation. 12. prodrug: A prodrug is only active once it reaches the liver. 13. cytochrome P450: These enzymes are responsible for biotransforming many drugs and are involved in many drug/drug interactions. 14. first-order: Most drugs undergo first-order kinetics of elimination, whereby drug elimination is proportional to drug concentration. That is to say, after a drug is given orally, it will be absorbed by passive diffusion, and the blood levels attained will be proportional to the dose administered. Thus, the greater the dose administered, the larger will be the blood level concentration. As the drug is eliminated from the body, the concentration of the drug in the plasma will decrease equally over time. 15. loading: A loading dose establishes initial therapeutic plasma drug concentrations. 16. receptor: The site where such drug attachment takes place is termed the receptor and is regarded as being specific cell molecules. 17. maximum: A maximum response is the dose of drug that will give the maximum response, and increasing the dose will not increase the response. The minimal effective dose is the dose below which no response is elicited. 18. potency: Potency is the dose required to produce a defined magnitude of drug effect. Potency of a drug varies inversely with a drugโ€™s ED50. 19. Adaptation: The body adjusts itself and minimizes the affects of the drug. 20. placebo: An individual given a placebo will report experiencing effects that would have been expected when receiving the active drug. This is called the placebo effect. Placebos are usually required as control in FDA clinical trials. 21. solid dosage form 22. intradermal. An intradermal injection is made directly into the dermis layer of the skin, which is below the epidermis. Intradermal injections are given to test for allergery reactions and for tuberculin skin test. 23. topical route: Oraqix is administered into the gingival crevice, which is a type of topical administration. Oraqix (lidocaine and prilocaine) periodontal gel is a needless application of local anesthetic in periodontal pockets. 24. gingival crevice: Arestin is applied by topical administration directly into the periodontal pocket. EXTENDED MATCHING 1. 1. 2. 3. 4. c a, e b d, f 2. 1. b 2. c 3. a 4. f, g, h 5. e 6. d Case Study 1. The patient should be questioned regarding allergies to medications before the prescription for penicillin is given. Ask the patient directly if he is allergic to penicillin. Taking a drug that someone is allergic to can result in a mild rash or a severe anaphylatic shock resulting in death. 2. This is called a loading dose. The purpose of giving a loading dose is to rapidly establish a therapeutic plasma drug concentration. A large loading dose may be required initially in order to achieve a rapid response in situations that are life-threatening. A maintenance dose (500 mg four times a day) maintains a desired drug concentration in the plasma. Steady-state plasma concentration refers to the point at which the rate of drug administration is equal to the rate of drug elimination. 3. The patientโ€™s drug history should be reviewed before giving a prescription. Any drug-drug, drugdisease, or drug-food interactions should be noted before the prescription is given to the patient. For instance, if the patient were allergic to penicillin and erythromycin or clarithromycin (Biaxin) were prescribed instead, then there would be a drug interaction because simvastatin is biotransformed by CYP3A4 enzymes in the liver. Erythromycin/clarithromycin are potent inhibitors of this enzyme, which would result in elevated simvastatin blood levels. Thus, erythromycin/clarithromycin is contraindicated in this patient. 4. Consider factors that affect the absorption of the drug. Penicillin V should be taken on an empty stomach (one hour before or two hours after eating) for more complete absorption from the GI tract into the blood. Elimination of the drug is delayed in patients with renal disease, thus the dose would have to be adjusted. 5. The infected tooth and surrounding tissues are the site of action where the penicillin will exert its antibiotic effect. The following are steps involved in the actions of the antibiotic: a. The penicillin is swallowed in the mouth. b. It goes down the esophagus into the stomach and then into the small intestine. c. Since penicillin is a weak acid, it is readily absorbed from the upper regions of the GI tract (stomach), where it is primarily in an unionized form. d. Food in the GI tract will reduce the absorption of penicillin. e. Before the penicillin enters the general circulation, it goes through the portal vein into the liver where it undergoes first-pass effectโ€”biotransformation by enzymes in the liverโ€”then the penicillin enters the general circulation. f. Penicillin is fairly well distributed to most body fluids and bone and appears in breast milk. g. Now the molecule undergoes biotransformation and excretion in order to reduce the plasma drug concentration. h. Penicillin is not metabolized much in the body so that it is excreted rapidly unchanged in the urine.

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