Intro Pharmacology, Pharmacokinetics/ADME I, II, and III
What percentage of Aspirin would be ionized in the blood compartment (pH = 7.4) assuming pH is 7.5 and Aspirin pKa is 3.5? a) (10,000 - 1) / 1 = 99.99% b) (100 - 1) / 1 = 99% c) None d) 1 / (100 - 1) = 0.9% e) 1 / (10,000 - 1) = 0.009%
*The answer is A.* A majority of aspirin would be in its ionized and unprotonated form.
A weak base drug has a pKa of 6.5. If the pH of the medium is 7.5, the drug is A) mainly neutral B) mainly positively charged
*The answer is A.* A weak base drug has a pKa of 6.5. If the pH of the medium is 7.5, the drug is mainly neutral.
If the pH - pka = 2, what percentage of weak acid is nonionized? a) 99 b) 90 c) 50 d) 10 e) 1
*The answer E.* Based on the information given, the pKa of the weak acid is two units lower than the pH. The pKa can be 2 while the pH is 4. Therefore, at a pH of 4, about 99% of the weak acid will be unprotonated and ionized while about 1% will be protonated and unionized.
A 12-year-old child has bacterial pharyngitis and is to receive an oral antibiotic. Ampicillin is a weak organic acid with a pKa of 2.5. What percentage of a given dose will be in the lipid-soluble form in the duodenum at a pH of 4.5? (A) About 1% (B) About 10% (C) About 50% (D) About 90% (E) About 99%
*The answer is A.* Ampicillin is an acid, so it is more ionized at alkaline pH and less ionized at acidic pH. The Henderson-Hasselbalch equation predicts that the ratio changes from 50/50 at the pH equal to the pKa to 1/10 (protonated/unprotonated) at 1 pH unit more alkaline than the pKa and 1/100 at 2 pH units more alkaline. For acids, the protonated form is the nonionized, more lipid-soluble form.
Aspirin readily donates a proton in aqueous solutions and pyrimethamine readily accepts a proton in aqueous solution. Thus, aspirin is a(b) ____ and pyrimethamine is a(n) ____. a) Acid; Base b) Base; Acid c) Acid; Acid d) Base; Base
*The answer is A.* Aspirin is an acid and pyrimethamine is a base.
Bioavailability of drug refers to (a) Percentage of administered dose that reaches systemic circulation in the unchanged form (b) Ratio of oral to parental dose (c) Ratio of orally administered drug to that excreted in the faeces (d) Ratio of drug excreted unchanged in urine to that excreted as metabolites
*The answer is A.* Bioavailability refers to the percentage of administered dose that reaches systemic circulation in the unchanged form.
Which of the following describes the amount of drug absorbed by the body and distributed systemically? a) bioavailability b) first- pass metabolism c) biotransformation d) pharmacokinetics
*The answer is A.* Bioavailability refers to the quantity of the administered drug that is absorbed into the body and distributed by the systemic blood circulation. Bioavailability is affected by incomplete absorption and first- pass metabolism, so the route of administration is signifi cant in determining the bioavailability of a drug. For example, drugs that are administered orally may not be fully absorbed from the stomach or intestinal tract (if there is a lot of food present or there is GI disturbance), which will reduce the amount of drug entering the bloodstream. Some drugs are signifi cantly metabolized in their fi rst transit through the liver (first- pass metabolism), which also reduces bioavailability (see Answer 32). Drugs administered intravenously are considered to have 100% absorption (because they are delivered directly into the bloodstream) and so the blood plasma concentration of orally administered drugs is compared against the concentration of IV-administered drugs to determine the bioavailability of the oral dosage. Biotransformation describes the metabolism of drugs in the body. It mainly occurs in the liver. Pharmacokinetics describes what the body does to drugs from administration to excretion
For the calculation of the volume of distribution (Vd) one must take into account: a) Concentration of a substance in plasma b) Concentration of substance in urine c) Therapeutical width of drug action d) A daily dose of drug
*The answer is A.* For the calculation of the volume of distribution (Vd) one must take into account the concentration of substance in plasma.
If the pKa of Aspirin (acetylsalicylic acid) is 3.5 and the pH of the stomach is 2.5, how much Aspirin is in the protonated species in the stomach and is this the amount available for absorption? a) ≈ 91%; Yes b) ≈ 91%; No c) ≈ 9%; Yes d) ≈ 9%; No
*The answer is A.* If the pKa of Aspirin (acetylsalicylic acid) is 3.5 and the pH of the stomach is 2.5, about 91% of aspirin is in its protonated form. This protonated form is unionized, making it available for absorption.
Which route of drug administration is most likely to lead to the first-pass effect? a) Sublingual b) Oral c) Intravenous d) Intramuscular
*The answer is B.* Oral and rectal drug administration are more likely to lead to the first-pass effect.
Following IV administration, the initial rates of drug distribution to different tissues depend primarily on which of the following parameters? (A) Blood flow to the tissues (B) Fat content of the tissues (C) Degree of ionization of the drug in the tissues (D) Active transport of the drug out of different cell types (E) Specific organ clearances
*The answer is A.* The initial rate of distribution of a drug to a tissue depends primarily on the rate of blood flow to that tissue. At longer times, however, a drug may undergo redistribution among various tissues, e.g., a very lipophilic drug may become concentrated in adipose tissue with time.
Which of the following routers of administration is the most convenient, although may have a bioavailability anywhere from 5-100%? a) PO (oral) b) IV (intravenous) c) IM (intramuscular) d) SQ (subcutaneous) e) Transdermal
*The answer is A.* The oral route is the most convenient, although may have a bioavailability anywhere from 5-100%.
The pKa of a weak acid drug is 6.5. If the pH of the medium is 5.5, the drug will be: A) mainly neutral B) mainly ionized and negatively charged
*The answer is A.* The pKa of a weak acid drug is 6.5. If the pH of the medium is 5.5, the drug will be mainly neutral.
What is a feature of the sublingual route? a) Pretty fast absorption b) A drug is exposed to gastric secretion c) A drug is exposed more prominent liver metabolism d) A drug can be administrated in a variety of doses
*The answer is A.* The sublingual route has a fast absorption because of venous drainage from the mouth is to the superior vena cava, avoiding first-pass effect.
You want to estimate, following drug administration, some measure that reliably reflects the total amount of drug reaching target tissue(s) over time. The drug is being given orally. What would you assess to get the desired information? a. Area under the blood concentration-time curve (AUC) b. Peak (maximum) blood concentration c. Product of the apparent volume of distribution (Vd) and the first-order rate constant d. Time-to-peak blood concentration e. Vd
*The answer is A.* We obtain the AUC orally, by measuring drug concentrations measured in sequential blood samples . However, we must compare those data to measurements of AUC obtained with giving the same drug intravenously (where bioavailability is, by definition, 1.0). The fraction of a drug dose absorbed after oral administration is affected by a variety of factors that can strongly influence the peak blood levels and the time-to-peak blood concentration. The Vd and the total body clearance also are important in determining the amount of drug that reaches a target tissue. Only the area under the blood concentration-time curve, however, reflects absorption, distribution, metabolism, and excretion factors, and their interactions; it is the most reliable method of evaluating bioavailability overall.
A 'toxic effect' differs from a 'side effect' in that (a) It is not a pharmacological effect of the drug (b) It is a more intense pharmacological effect that occurs at high dose or after prolonged medication (c) It must involve drug induced cellular injury (d) It involves host defense mechanisms
*The answer is B.* A 'toxic effect' differs from a 'side effect' in that It is a more intense pharmacological effect that occurs at high dose or after prolonged medication.
The earliest evidence that a drug is stored in tissue is (a) An increase in plasma protein binding (b) A large apparent volume of distribution (VD) (c) A decrease in the rate of formation of metabolites by the liver (d) An increase in the number of side effects produced by the drug (e) A decrease in the amount of free drug excreted in the urine
*The answer is B.* A large apparent volume of distribution is an indicator that a drug is stored in the tissue.
Pharmacokinetics is: a) The study of biological and therapeutic effects of drugs b) The study of absorption, distribution, metabolism and excretion of drugs c) The study of mechanisms of drug action d) The study of methods of new drug development
*The answer is B.* Pharmokinetics is the study of absorption, distribution, metabolism and excretion of drugs.
Which of the following factors will determine the number of drug-receptor complexes formed? (A) Efficacy of the drug (B) Receptor affinity for the drug (C) Therapeutic index of the drug (D) Half-life of the drug (E) Rate of renal secretion
*The answer is B.* Receptor affinity for the drug will determine the number of drug-receptor complexes formed. Efficacy is the ability of the drug to activate the receptor after binding has occurred. Therapeutic index (TI) is related to safety of the drug. Half-life and secretion are properties of elimination and do not influence formation of drug-receptor complexes.
A 64-year-old woman with a history of multiple abdominal surgeries due to Crohn's disease presents to the emergency room with obstipation and feculent emesis. A diagnosis of small bowel obstruction is made, and she is taken to the operating room for lysis of adhesions and resection of stenosed region of small bowel. Postoperatively, the patient is noted to have elevated blood pressure, and oral metoprolol is administered; however, no improvement of hypertension is observed. This is likely due to (A) The first-pass effect (B) Decreased passage of drug through intestine (C) Decreased GI blood flow (D) Destruction of drug by stomach acid (E) Increased protein binding of the drug
*The answer is B.* Adequate passage of drug through the small intestine is required to observe the effects of the drug, because most of the absorption takes place in the small intestine. After extensive abdominal surgery, especially that involving a resection of a portion of small bowel, the passage may be slowed, or even stopped, for a period of time. Abdominal surgery rarely results in reduced blood flow to the intestine, nor does such an operation influence protein binding, or the first-pass effect. Destruction of drug by stomach acid does not depend on intraabdominal surgery.
You are conducting pharmacokinetic studies on a new drug that we hope will be approved for clinical use. We insert a venous catheter to sample blood at various times after drug administration, and also take a sample for the immediate pre-drug blood concentrations of the drug (which should be zero). After assaying the blood samples for the drug we make a graph that plots plasma drug concentrations over time, continuing until tests reveal undetectable blood levels. What can you calculate or estimate based on the ratio of the area under the curve (AUC) obtained by oral administration versus the AUC for intravenous administration of the same drug? a. Absorption b. Bioavailability c. Clearance d. Elimination rate constant e. Extra ction ratio f. Volume of distribution
*The answer is B.* Among other things, knowing the AUC of a drug given intravenously (which, by definition, is associated with a bioavailability of 1.0, or 100%) is a prerequisite for determining the bioavailability of the same drug give n by any other route; bioavailability is calculated as the ratio of AUC for any non-IV route and the AUCV.
Bioavailability (F) is the fraction or percentage of administered drug that reaches the systemic circulation via a given route as compared to what route? a) Oral b) IV (intravenous) c) IO (intraosseous) d) CSF (cerebrospinal fluid)
*The answer is B.* Bioavailability (F) is the fraction or percentage of administered drug that reaches the systemic circulation via a given route as compared to intravenous (IV).
The route of drug administration that gives the most rapid onset of the pharmacological effect is (a) Intramuscular injection (b) Intravenous injection (c) Intradermal injection (d) Peroral administration (e) Subcutaneous injection
*The answer is B.* The route of drug administration that gives the most rapid onset of the pharmacological effect is intravenous injection.
Using the Fick Law of Diffusion, how will flux change if the permeability coefficient is quadrupled? a) It will double b) It will quadruple c) It will halve d) It will quarter e) It will not change
*The answer is B.* Using Fick's law of diffusion, if the permeability coefficient is quadrupled, flux will also quadruple.
Volume of distribution describes: a) How successful is the commercial distribution of a new drug in the market. b) The volume that would be needed to dilute the drug for it to reach the concentration observed in the serum. c) The ability of the drug to make it successfully through the first pass elimination so it can spread in the full volume of the patient. d) The volume of fluids in the body of the patient. e) The volume of the serum in the specific patient.
*The answer is B.* Volume of distribution describes the volume that would be needed to dilute the drug for it to reach the concentration observed in the serum.
The volume of distribution of gentamicin, a highly polar water-soluble drug, is 14 L per 70 kg. This reflects the distribution of gentamicin into: a. Plasma b. Plasma and Blood c. Plasma, blood, and interstitial fluid (extracellular water) d. Total body water e. Adipose tissue
*The answer is C.* A low Vd indicates that the drug does not tend to enter the tissues.
After peroral administration, drugs generally are absorbed best from the (a) Buccal cavity (b) Stomach (c) Duodenum (d) Ileum (e) Rectum
*The answer is C.* After peroral administration, drugs generally are absorbed best from the duodenum.
The reasons determing bioavailability are: a) Rheological parameters of blood b) Amount of a substance obtained orally and quantity of intakes c) Extent of absorption and hepatic first-pass effect d) Glomerular filtration rate
*The answer is C.* Bioavailability is dependent on the extent of absorption and hepatic first-pass effect.
Which statement about the distribution of drugs to specific tissues is most correct? (A) Distribution to an organ is independent of blood flow (B) Distribution is independent of the solubility of the drug in that tissue (C) Distribution depends on the unbound drug concentration gradient between blood and the tissue (D) Distribution is increased for drugs that are strongly bound to plasma proteins (E) Distribution has no effect on the half-life of the drug
*The answer is C.* Distribution of drugs to specific tissues in dependent on the size of the organ, the blood flow, solubility, and binding of the drug to macromolecules.
Botulinum toxin is a large protein molecule. Its action on cholinergic transmission depends on an intracellular action within nerve endings. Which one of the following processes is best suited for permeation of very large protein molecules into cells? (A) Aqueous diffusion (B) Aqueous hydrolysis (C) Endocytosis (D) Lipid diffusion (E) Special carrier transport
*The answer is C.* Endocytosis is an important mechanism for transport of very large molecules across membranes. Aqueous diffusion is not involved in transport across the lipid barrier of cell membranes. Lipid diffusion and special carrier transport are common for smaller molecules. Hydrolysis has nothing to do with the mechanisms of permeation; rather, hydrolysis is one mechanism of drug metabolism.
You receive a call from a frantic mother whose 3-year-old son ate a handful of her amitriptyline (a weak acid). You instruct the mother to take her son to the emergency department where he is given bicarbonate (in addition to other measures). What is the most likely explanation for bicarbonate administration in this case? (A) Bicarbonate should not have been given; a weak acid such as ammonium chloride should have been given instead (B) Bicarbonate traps amitriptyline in the blood to keep it from reaching its active site (C) Ion trapping the amitriptyline in the urine to hasten elimination is accomplished by giving bicarbonate (D) Weak acids such as amitriptyline are chemically inactivated by bicarbonate
*The answer is C.* Excess bicarbonate is rapidly excreted in the urine, raising the urine pH. Any weak acid, such as amitriptyline, that enters this basic urine will become ionized. Once ionized, it is not reabsorbed and so is effectively trapped for excretion in the urine. The reaction is RCOOH (in blood) → RCOO⁻ + H⁺ (in the urine). (A) A weak acid lead to acidic urine. Acidic urine would cause amitriptyline to be less ionized and therefore more effectively reabsorbed. (B) Bicarbonate is rapidly excreted in the urine to maintain physiologic pH in the blood. It is not therapeutically reasonable to manipulate the blood pH for the purpose of ion trapping. (D) Weakly acidic medications are not generally inactivated by bases
Saturable transport systems (Select all that apply): A) passive diffusion B) aqueous diffusion C) lipid diffusion D) active transport -- carrier mediated E) facilitated diffusion -- carrier mediated
*The answer is D and E.* Facilitated transport and active transport are saturable transport systems.
Azithromycin, an antibiotic, has an apparent volume of distribution (Vd) of approximately 30 L/kg. What is the main interpretation of this a. Effective only when given intravenously b. Eliminated mainly by renal excretion, without prior metabolism c. Extensively distributed to sites outside the vascular and interstitial spaces d. Not extensively bound to plasma proteins e. Unable to cross the blood-brain or placental "barriers"
*The answer is C.* For a 70-kg individual, total body water is about 40 L (0.6 L/kg); interstitial plus plasma water occupies about 12 L (0.17 L/kg) Azithromycin, with a Vd of 30 L/kg, would be distributed in an apparent volume of about 2100 L in a typical 70-kg person. Even if you don't remember what total body water is (about 40 L or 0.6 L/kg), or the approximate value for interstitial plus plasma water (about 12 L or 0.17 L/kg), do the quick math. If you take the stated 30 L/kg and compute the total (and very hypothetical) apparent volume for a 70-kg individual, you would arrive at 2100 L. That number not only reflects distribution into a hypothetical volume far in excess of vascular and interstitial volumes, but is also far beyond what could be physically real. After all, 2100 L of water equal 2100 kg; you won't find human beings weighing that much!
Correct statements listing characteristics of a particular route of drug administration include all of the following EXCEPT: a) Intravenous administration provides a rapid response b) Intramuscular administration requires a sterile technique c) Inhalation provides slow access to the general circulation d) Subcutaneous administration may cause local irritation
*The answer is C.* Inhalation provides a fast access to the general circulation.
Which of the following parameters is used to indicate the ability of a drug to produce the desired therapeutic effect relative to a toxic effect? (A) Potency (B) Intrinsic activity (C) Therapeutic index (D) Efficacy (E) Bioavailability
*The answer is C.* Lithium is an example of drug with a very low therapeutic index, which requires frequent monitoring of the plasma level to achieve the balance between the desired effect and untoward toxicity. Potency of the drug is the amount of drug needed to produce a given response. Intrinsic activity of the drug is the ability to elicit a response. Efficacy of the drug is the maximal drug effect that can be achieved in a patient under a given set of conditions. Bioavailability of the drug is the fraction of the drug that reaches the bloodstream unaltered.
Parenteral administration: a) Cannot be used with unconsciousness patients b) Generally results in a less accurate dosage than oral administration c) Usually produces a more rapid response than oral administration d) Is too slow for emergency use
*The answer is C.* Parenteral administration usually produces a more rapid response than oral administration.
The set of properties that characterize the effects of a drug on the body is called (A) Distribution (B) Permeation (C) Pharmacodynamics (D) Pharmacokinetics (E) Protonation
*The answer is C.* Pharmacodynamics is the term given to drug actions on the body.
A 60-year-old patient with severe cancer pain is given 10 mg of morphine by mouth. The plasma concentration is found to be only 30% of that found after intravenous administration of the same dose. Which of the following terms describes the process by which the amount of active drug in the body is reduced after administration but before entering the systemic circulation? (A) Excretion (B) First-order elimination (C) First-pass effect (D) Metabolism (E) Pharmacokinetics
*The answer is C.* U.S. Medical Licensing Examination (USMLE)-type questions often contain a lengthy clinical description in the stem. One can often determine the relevance of the clinical data by scanning the list of answers. In this question, the emphasis is clearly on pharmacokinetic principles. "First-pass effect" is the term given to elimination of a drugbefore it enters the systemic circulation (ie, on its first pass through the portal circulation and liver). The first-pass effect is usually, but not always, due to metabolism in the gut, the portal blood, or the liver.
What form of a drug is more lipid-soluble, and thus would remain trapped within a compartment where the pH does not favor the lipid-soluble form? a) Strong acid (A-) b) Weak acid (A-) c) Neutral (AH and B) d) Weak base (BH+) e) Strong base (BH+)
*The answer is C.* Unionized, or neutral drugs, are more lipid soluble.
Using the Fick Law of Diffusion, how will flux change if membrane thickness is doubled? a) It will double b) It will quadruple c) It will halve d) It will quarter e) It will not change
*The answer is C.* Using Fick's law of diffusion, if membrane thickness is doubled, flux will halve.
Identical doses of a drug are given orally and intravenously. We sample blood at various times, measure blood concentrations of the drug, and plot the data (shown in the image). Further analysis of only these data will allow you to determine which of the following? a. Elimination route (s) b. Extent of plasma protein binding c. Oral bioavailability d. Potency e. Therapeutic effectiveness
*The answer is C.* We are making these data comparison to determine the drug's bioavailability. We define the bioavailability of a drug given intravenously as 1.0 (100%), since with IV administration we avoid all the applicable barriers to drug absorption But, of course, it's important to know how much total drug, over a period of time, gets into the bloodstream with other administration routes that we might want to use clinically. Drugs given by routes other than IV must be absorbed (and be exposed to all the barriers that limit or slow or otherwise affect absorption); and because they might not be absorbed from their administration site, or might be susceptible to such processes as hepatic first-pass metabolism, they usually have a bioavailability <1.0 The calculation of bioavailability is based on the ratio of the area under the concentration-time curve (AUC) for the administration route being considered (oral, IM, etc) and the AUC obtained with IV administration.
Which of the following is an action of a noncompetitive antagonist? (A) Alters the mechanism of action of an agonist (B) Alters the potency of an agonist (C) Shifts the dose-response curve of an agonist to the right (D) Decreases the maximum response to an agonist (E) Binds to the same site on the receptor as the agonist
*The answer is D.* A noncompetitive antagonist decreases the magnitude of the response to an agonist but does not alter the agonist's potency (i.e., the ED50 remains unchanged). A competitive antagonist interacts at the agonist binding site.
Factors that influence the passive movement of drugs down a concentration gradient: A) drug concentration differences on either side of the barrier (e.g. membrane) B) thickness of the diffusion pathway C) mobility of the drug molecule in the medium of the diffusion path (permeability) D) all of the above
*The answer is D.* All of these factors influence the passive movement of drugs down the concentration gradient.
If the pH - pKa = -1, what percentage of weak base is nonionized? a) 99 b) 90 c) 50 d) 10 e) 1
*The answer is D.* Based on the information given, the pKa of the weak base is one unit higher than the pH. The pKa can be 8 while the pH is 7. Therefore, at a pH of 7, about 90% of the weak base will be protonated and ionized while about 10% will be unprotonated and unionized.
Referring to the following figure regarding the pharmacokinetics of prototype Drug X-100A, a novel chemotherapeutic agent to treat breast cancer, which of the following letters represents the process of elimination? (A) Letter A (B) Letter B (C) Letter C (D) Letter D
*The answer is D.* Elimination is represented by letter D. The drug and its metabolites are eliminated from the body in urine, bile, or feces. (A) Letter A represents the process of drug absorption from the site of administration. (B) Letter B represents the pro-cess of drug distribution ultimately into the interstitial and intracellular fluids. (C) Letter C represents the metabolism of the drug in the liver or other tissues.
What kind of substances can't permeate membranes by passive diffusion? a) Lipid-soluble b) Non-ionized substances c) Hydrophobic substances d) Hydrophilic substances
*The answer is D.* Hydrophilic substances cannot permeate the membrane by passive diffusion.
Pick out the parenteral route of medicinal agent administration: a) Rectal b) Oral c) Sublingual d) Inhalation
*The answer is D.* Inhalation is the parenteral route of medicinal agent administration.
A classmate is doing summer research, in your school's clinical pharmacology division, between her first and second years of medical school Her topic involves new investigations into the roles of P-glycoprotein. Which statement accurately summarizes the biologic role of P-glycoproteins, particularly as it affects drugs and their actions? a. Conjugates a variety of drugs, or their metabolites, to facilitate their ultimate renal elimination from the body b. Maintains structural integrity of cell membranes and the surface receptors found on them c. Phosphorylates certain substances, such as in the conversion fo adenosine monophosphate (AMP) into the diphosphate and triphosphate forms (ADP, ATP) d. Transports certain drugs and xenobiotics across cell membranes e. Works, in conjunction with various G-proteins, to transduce (convert) interactions between drugs and their receptors into biologic responses
*The answer is D.* P-glycoprotein (PGP; the P stands for "permeability") is part of a super-family of transmembrane transporter proteins, substrates for which include many xenobiotics (chemicals not found naturally in the body), including many therapeutic agents. An important member of the P-glycoprotein family is involved in an ATP-dependent (ie, active transport; this is part of the ABC ATP-binding cassette-family) mechanism that pumps drugs and other chemically diverse xenobiotics out of certain cells, against the usual concentration gradient. That is, PGP serves an ATP-driven efflux pump. PGP does not form drug conjugates (a) or participate in other Phase lI reactions; maintain membrane/receptor structure and function (b); phosphorylate any substrates (c); or play a role in signal transduction (e).
An orally administered medication is eliminated by the kidney. Passive reabsorption of the drug occurs because it is lipid soluble and un ionized. At which of the following locations in the kidney will this reabsorption occur? (A) Letter A (B) Letter B (C) Letter C (D) Letter D (E) Letter E
*The answer is D.* Passive reabsorption occurs at level D, which is the distal tubule/collecting duct. Here, passive reabsorption of lipid-soluble, un-ionized drug can undergo reabsorption. (A) Letter A represents free drug entering the glomerular filtrate. (B) Letter B represents active secretion into the proximal tubule. (C) Letter C represents the loop of Henle. (E) Letter E represents the ionized lipid insoluble drug in the urine
What does "pharmacokinetics" include? a) Pharmacological effects of drugs b) Unwanted effects of drugs c) Chemical structure of a medicinal agent d) Distribution of drugs in the organism
*The answer is D.* Pharmokinetics includes the distribution of drugs in the organism.
Target proteins which a drug molecule binds are: a) Only receptors b) Only ion channels c) Only carriers d) All of the above
*The answer is D.* Target proteins which a drug molecule binds are receptors, ion channels, and carrier proteins.
The main mechanism of most drugs absorption in GI tract is: a) Active transport (carrier-mediated diffusion) b) Filtration (aqueous diffusion) c) Endocytosis and exocytosis d) Passive diffusion (lipid diffusion)
*The answer is D.* The main mechanism of most drugs absorption in GI tract is passive diffusion.
Which of the following enteral administration routes has the largest first-pass effect? a) SL (sublingual) b) Buccal c) Rectal d) Oral
*The answer is D.* The oral route has the largest first-pass effect.
The volume of distribution (Vd) relates: a) Single to a daily dose of an administrated drug b) An administrated dose to a body weight c) An uncharged drug reaching the systemic circulation d) The amount of a drug in the body to the concentration of a drug in plasma
*The answer is D.* The volume of distribution (Vd) relates the amount of a drug in the body to the concentration of a drug in plasma
Which of the following characteristics is most likely to be associated with a high apparent volume of distribution? a. High hepatic extraction ratio b. Penetration across the blood:brain and blood:testes barriers c. Extensive binding to plasma protein d. Distribution into total body water e. Extensive binding to tissue constituents
*The answer is E.* A high apparent volume of distribution is associated with an extensive binding to tissue constituents.
pH affects drug transfer across the membrane because a) A weak acid tends to become ionized in the acidic environment of the stomach and therefore unable to cross into the serum. b) A weak acid tends to become unionized in the acidic environment of the stomach and therefore unable to cross into the serum. c) A weak acid tends to become ionized in the slightly basic environment of the intestine and therefore able to cross into the serum. d) A weak base tends to become ionized in the acidic environment of the stomach and therefore able to cross into the serum. e) A weak acid tends to become unionized in the acidic environment of the stomach and therefore able to cross into the serum.
*The answer is E.* A weak acid tends to become unionized in the acidic environment of the stomach and therefore able to cross into the serum. A weak base tends to become unionized in the basic environment of the intestine and therefore able to cross into the serum.
At pH 5.0, the ratio of the protonated to unprotonated forms of morphine (a weak base containing an ionizable amine group, pKa = 7.0) would be: a. 1:100 b. 1:10 c. 1:1 d. 10:1 e. 100:1
*The answer is E.* At pH 5.0, the ratio of the protonated to unprotonated forms of morphine (a weak base containing an ionizable amine group, pKa = 7.0) would be 100:1. pH = pKa + log([B]/[A]) 5.0 = 7.0 + log(B/A) -2 = log (B/A) 10^-2 = B/A 1/100 = B/A 100 = A/B B = Unprotonated A = Protonated
All of the following statements about plasma protein binding of a drug are true except (a) Displacement of a drug from plasma protein binding sites results in a transient increased volume of distribution (VD) (b) Displacement of a drug from plasma protein binding sites makes more free drug available for glomerular filtration (c) Displacement of a potent drug that is normally more than 95% bound may cause toxicity (d) Albumin is the major protein involved in protein binding of drugs (e) Drugs that are highly bound to plasma proteins generally have a greater VD compared with drugs that are highly bound to tissue proteins
*The answer is E.* Drugs that are highly bound to plasma proteins generally have a LOWER Vd compared with drugs that are highyl bound to tissue proteins.
For intravenous (IV) dosages, what is the bioavailability assumed to be? a) 0% b) 25% c) 50% d) 75% e) 100%
*The answer is E.* For intravenous (IV) dosages, the bioavailability is assumed to be 100%.
You orally administer a weak acid drug (A) with a pKa, of 3.4. Gut pH is 1.4 and blood pH is 7.4. Assume the drug crosses membranes by simple passive diffusion (eg, no transporters are involved). Which observation would be true? A. Only the ionized form of the drug, A, will be absorbed from the gut B. The concentration ratio of total drug (A + HA-) would be 10,000:1 (gut: plasma) C. The drug will be hydrolyzed by reaction with HCl, and so cannot be absorbed D. The drug will not be absorbed unless we raise gastric pH to equal pKa as might be done with an antacid E. The drug would be absorbed, and at equilibrium the plasma concentration of the nonionized moiety (HA) would be 10^4 times higher than the plasma concentration of A-.
*The answer is E.* Recall the two Henderson-Hasselbach equations, which apply to how local pH affects the ionization of molecules (eg, of a drug) in an aqueous environment. Assume that membranes are permeable only to nonionized (and more lipid-soluble) forms of a drug. Thus, we are making the assumption that ionized drugs tend to stay, or concentrate, in an environment that favors that pH-dependent ionization; conversely, in an environment that favors formation of nonionized drug molecules, a concentration gradient will favor passive diffusion of nonionized molecules to another locale. For acidic drugs: pH = pK, + log [A-] / [AH] For basic drugs: pH = pK + log [B/BH] Our drug was an acid with pK-3.41 n the stomach (assume pH = 1.4 as noted) the ratio of nonionized to ionized molecules will be about 10.01. The nonionized molecules will diffuse across the membrane. Once in the plasma, pH 7.4, the ratio of HA: A- will become 1:10,000. And the concentration ratio of total drug across the membrane will be 10,000:1, but with the larger amount being in the plasma, not the gut.
A 39-year-old man takes a 100 mg dose of medica-tion X. This drug is taken orally and becomes bio-transformed by metabolism in the liver and secondary metabolism in the kidneys. This defines which of the following processes? (A) Absorption (B) Catabolism (C) Distribution (D) Elimination (E) Metabolism
*The answer is E.* This is the definition of metabolism. Metabolism is the third step in the process of drug delivery and utilization. The drug may be biotransformed by metabolism by the liver or other tissues. (A) Absorption: First, drug absorp-tion from the site of administration permits entry of the therapeutic agent (either directly or indirectly) into plasma. (B) Catabolism involves breakdown of substances by the body. (C) Distribution: Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids (D) Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces.
Which of the following routes of administration has a bioavailability of about 80- 100%, is usually very slow absorbing, and has prolonged duration of action? a) IV (intravenous) b) IM (intramuscular) c) SQ (subcutaneous) d) Rectal e) Transdermal
*The answer is E.* Transdermal has a bioavailability of about 80- 100%, is usually very slow absorbing, and has prolonged duration of action.
