Pharmacokinetics, Clinical Applications of Pharmacokinetics, Pharmacodynamics
Vignettes & Practice Questions
Don’t hesitat...
# 2
Vignettes in your handouts
Answer: _____, modifying urine pH can help.
Aspirin is a weak acid. So to help its eliminat...
# 3
Vignettes in your handouts
HA H+ A-+
[1]
HA H+ A-+
Cell Membrane
Plasma pH=7.4
Urine pH=4-8
[1]
100 -
-
-
-
-
50 -
-
-...
# 4
Vignettes in your handouts
Dr. S, a middle aged man, has always suffered of mild hypertension accompanied by fluid ret...
# 5
Vignettes in your handouts
><
Cindy, 52-yr-old woman is used to taking midazolam (a benzodiazepine) when she travels a...
# 6
Vignettes in your handouts
><
Charles a 32-yr-old man weighing 80 kg (for Q1) or 60 kg (for Q2), has received a cardia...
# 7
Transport of drugs across membranes
Influence of pH
Which drug would you predict would be absorbed most readily
from t...
# 8
Transport of drugs across membranes
Influence of pH
Which drug would you predict would be absorbed most readily
from t...
# 9
Transport of drugs across membranes
Influence of pH
Which drug would you predict would be absorbed most readily
from t...
# 10
Transport of drugs across membranes
Influence of pH
Which drug would you predict would be absorbed most readily
from ...
# 11
Transport of drugs across membranes
Influence of pH
Which drug would you predict would be absorbed most readily
from ...
# 12
Transport of drugs across membranes
Influence of pH
B + H+ BH+
Lipid Mucosal Barrier
Plasma pH=7.4
Large Intestine pH...
# 13
Transport of drugs across membranes
Influence of pH
Which weakly acidic drug is distributed more readily
from the sto...
# 14
Transport of drugs across membranes
Influence of pH
Which weakly acidic drug is distributed more readily
from the blo...
# 15
Transport of drugs across membranes
Influence of pH
Which weakly acidic drug is distributed more readily
from the cer...
# 16
Transport of drugs across membranes
Influence of pH
Which weakly acidic drug is distributed more readily
from the lar...
# 17
Transport of drugs across membranes
Influence of pH
Which weakly basic drug is distributed more readily
from the bloo...
# 18
Transport of drugs across membranes
Influence of pH
What is the ratio of ionized to unionized drug (I/UI) for a weak ...
# 19
Transport of drugs across membranes
Influence of pH
A nursing mother is taking penicillin V (a weak acid, pKa = 2.4)....
# 20
Transport of drugs across membranes
Influence of pH
><
A drug that is a weak acid is best absorbed in an environment ...
# 21
Transport of drugs across membranes
Influence of pH
Assuming the passive diffusion hypothesis for the passage of drug...
# 22
Transport of drugs across membranes
Influence of pH
Assuming the passive diffusion hypothesis for the passage of drug...
# 23
Transport of drugs across membranes
Influence of pH AND l/w partition coefficient
Which of the following weakly acidi...
# 24
Transport of drugs across membranes
Influence of pH AND l/w partition coefficient
The pKa values for three drugs are ...
# 25
Transport of drugs across membranes
Influence of pH AND l/w partition coefficient
Which of the following weakly acidi...
# 26
Transport of drugs across membranes
Influence of pH AND l/w partition coefficient
Which of the following weakly basic...
# 27
Transport of drugs across membranes
Factors affecting passive transport of drugs
You are developing a new drug, to be...
# 28
Drug Absorption
Drug X is administered intramuscularly (curve A) or orally (curve B).
Which of the following statemen...
# 29
Drug Absorption
First pass effect (or first pass metabolism) can be reduced if drugs are:
a. Very lipophilic
b. Very ...
# 30
Drug Absorption
A patient enters the emergency room with severe signs of angina pectoris and clear signs of imminent
...
# 31
Drug Distribution
A 50-yr-old woman with atrial fibrillation has been taking 5mg of warfarin daily for the past year....
# 32
Drug Distribution
A patient with cardiac failure due to a previous myocardial infarction has been taking daily digoxi...
# 33
Drug Distribution
A highly lipid soluble drug has been injected into a patient who dies after 10 minutes.
Which of th...
# 34
Drug Metabolism
Which of the following best describes phase I metabolism?
a. It involves hydrolysis reactions and req...
# 35
Drug Metabolism
Which of the following descriptions best describes phase II metabolism of a drug?
a. It often conjuga...
# 36
Drug Metabolism & Excretion
To facilitate sleep induction a young woman has the habit of taking one pill of alprazola...
# 37
Clinical applications of pharmacokinetics
><
A new drug that follows first order kinetics and whose half life is 8h i...
# 38
Clinical applications of pharmacokinetics
><
Patient G is admitted to the emergency room with a severe infection. She...
# 39
Clinical applications of pharmacokinetics
><
Drug X follows first order kinetics, and its Kel (constant of eliminatio...
# 40
Clinical applications of pharmacokinetics
><
Toby is a tiny teenager who weighs 35 kg, and takes 10 mg of a drug whos...
# 41
Clinical applications of pharmacokinetics
><
Mr. Blue, a 29-year-old man weighing 140 kg and 1.95 m tall (6.4 feet) i...
# 42
Clinical applications of pharmacokinetics
><
Mr. Blue, a 29-year-old man weighing 140 kg and 1.95 m tall (6.4 feet) i...
# 43
Clinical applications of pharmacokinetics
><
Graham Negative is a very tall individual; he weighs 140kg (given his he...
# 44
Clinical applications of pharmacokinetics
><
The plasma level of an antibiotic is to be maintained at 20 µg/mL in a 6...
# 45
Clinical applications of pharmacokinetics
><
Dee Vourer is an overweight young lady who weighs 140kg and who tends to...
# 46
Clinical applications of pharmacokinetics
><
Ann Orexia is a young patient weighing 50Kg. She is treated with drug X,...
# 47
Clinical applications of pharmacokinetics
><
Ann Orexia is a young patient weighing 50Kg. She is treated with drug X,...
# 48
Clinical applications of pharmacokinetics
><
In the patient above, you stop treatment and then measure blood [drug] a...
# 49
Clinical applications of pharmacokinetics
><
Time (hours)
0 4 8 12 16 20 24 28 32 36 40
PlasmaConcentration(mg/L)
0.0...
# 50
Clinical applications of pharmacokinetics
><
The plasma conc. of an oral hypoglycemic drug is 20 mg/100mL when measur...
# 51
Clinical applications of pharmacokinetics
><
If 50% of a drug is eliminated by 1h, what is the half life of this drug...
# 52
Clinical applications of pharmacokinetics
><
If 50% of a drug is absorbed by 1h, what is the half life of this drug?
...
# 53
Clinical applications of pharmacokinetics
><
If ~88% of a drug is eliminated by 3h, what is the half life of this dru...
# 54
Clinical applications of pharmacokinetics
><
If ~88% of a drug is absorbed by 3h, what is the half life of this drug?...
# 55
Clinical applications of pharmacokinetics
><
A patient (70 kg) is to be administered an experimental drug. Its pharma...
# 56
Clinical applications of pharmacokinetics
><
Time (h)
plasmadrugconc(mg/L)
32 -
-
16 -
-
8 -
-
4 -
-
2 -
-
1 -
I I I ...
# 57
Clinical applications of pharmacokinetics
><
The clearance for drug X prior to sodium bicarbonate administration is a...
# 58
Clinical applications of pharmacokinetics
><
The clearance for drug X after to sodium bicarbonate administration is a...
# 59
Clinical applications of pharmacokinetics
>
Time (h)
0 1 2 3 4 5 6 7 8 9 10 11 12
Plasmaconcentration(mg/L)
2048
1024...
# 60
Pharmacodynamics
><
Mr. Pink agrees to pet-sit his neighbor’s cat for a few days. The morning after having spent the ...
# 61
Pharmacodynamics
><
Which of the following is true about metabotropic receptors?
a. When activated, they metabolize d...
# 62
Pharmacodynamics
><
In the figure below, drugs X, Y and Z have been developed to reduce pharmacology-associated heada...
# 63
Pharmacodynamics
><
In the figure below, the graded dose-response curve for a drug is presented for the drug alone (D...
# 64
Pharmacodynamics
><
In the figure below, the graded dose-response curve for a drug is presented for the drug alone (D...
# 65
Pharmacodynamics
><Dose (mg)
0 1 10 100 1000 10000
%MaxiumumResponse
10
20
30
40
50
60
70
80
90
100
Patient 1
Patient...
# 66
Pharmacodynamics
<
Dose (mg)
0 1 10 100 1000 10000
%MaxiumumResponse
10
20
30
40
50
60
70
80
90
100
Blood pressure re...
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Pharm a 01-04_vignettes_&_practice_questions_no_answers

  1. 1. Pharmacokinetics, Clinical Applications of Pharmacokinetics, Pharmacodynamics Vignettes & Practice Questions Don’t hesitate to email me: Micky.Marinelli@RosalindFranklin.edu (do NOT use D2L email to contact me) or to come to my office (room 2.124) if any of these are unclear. > These vignettes and practice questions should help you “work through” sample problems. We will go over some of these in class, and you can go over the rest on your own. Answers are not provided in this file. This will give you a chance at solving the questions yourself. You can print this file (recommended format of 2/page) and work your way through them on your own or in class as we go through some of them. If you have trouble finding the answer, you can go to the file “Vignettes & Practice Questions”, which contains all the answers and the reasoning behind most answers.
  2. 2. # 2 Vignettes in your handouts Answer: _____, modifying urine pH can help. Aspirin is a weak acid. So to help its elimination, you want to make urine more _______. If you make urine more ______, aspirin (a weak acid) becomes more ionized and thus remains “trapped” into the urine, without being reabsorbed into the blood stream. To make urine more ______, you can give ___________________. I.W., a 30-yr old male student, is studying for his pharmacology exam. He has only eaten two bags of beef jerky in the past day and a half (no time to leave home!) but he constantly drinks plenty of coke and orange juice. He has a terrible headache, and decides to take some aspirin to alleviate the pain. The drug does not seem to work too well, so he takes several more pills. He does not realize that, instead of the usual dosage (325mg/tablet) he is taking the extra-strength formula (500mg/tablet). He ingests a total of 10 tablets in 3 hours. Soon after, he experiences heart racing, ringing in the ears, nausea, agitation and confusion. At the hospital he is diagnosed with aspirin overdose. Q: Given that aspirin is a weak acid with pKa=3.5, could modifying urine pH help I.W. eliminate the drug faster, and if so, how? (give both theoretical reasons, and practical approach). >< Now try to graph what would happen to elimination if your drug were a weak acid or a weak base (see next slide)
  3. 3. # 3 Vignettes in your handouts HA H+ A-+ [1] HA H+ A-+ Cell Membrane Plasma pH=7.4 Urine pH=4-8 [1] 100 - - - - - 50 - - - - - 0 - - - - - - - - - - - [PlasmaDrug] 1 2 3 4 5 6 Time (h) Sodium bicarbonate (makes urine more basic) Drug: weak acid Orange juice (makes urine more acidic) 100 - - - - - 50 - - - - - 0 - - - - - - - - - - - [PlasmaDrug] 1 2 3 4 5 6 Time (h) Sodium bicarbonate (makes urine more basic) Drug: weak base Orange juice (makes urine more acidic) B + H+ BH+ [1] B + H+ BH+ Cell Membrane Plasma pH=7.4 Urine pH=4-8 [1] Making urine more basic (with sodium bicarbonate) or more acidic (with orange juice) will change the manner in which acids and bases are eliminated. The slope of elimination curves changes when the pH of the urine changes. ><
  4. 4. # 4 Vignettes in your handouts Dr. S, a middle aged man, has always suffered of mild hypertension accompanied by fluid retention. He never paid much attention to it, so he has never taken any medications, despite the discomfort and bloating caused by the fluid retention. In addition to this, he has an inguinal hernia, that produces intermittent pain (when he coughs, laughs, goes skating etc…). He takes tylenol (acetaminophen) to reduce the pain, and only one pill/day is sufficient. He finally decides to see a doctor concerning his hernia. The doctor immediately detects hypertension, which is confirmed upon a second visit. The doctor prescribes demadex (a long-lasting sulfonamide), and says that the hernia is of little concern at the moment. Dr. S starts taking the diuretic, and feels much better, however, every time the hernia bothers him, he realizes that he can no longer suppress the pain with tylenol. Q: Did the hernia condition get worse? What could have happened? What should he do? ><
  5. 5. # 5 Vignettes in your handouts >< Cindy, 52-yr-old woman is used to taking midazolam (a benzodiazepine) when she travels abroad. She claims that it helps us relive the stress of being in a new country and reduces jet-lag-induced insomnia. Prior to leaving abroad (Italy), she develops a moderate cough, so she goes to the doctor, who detects mild bronchitis and prescribes erythromycin, to be taken in the event that the cough worsens. For “safety” reasons, Cindy decides to take the antibiotic all the same, so as to be sure that her symptoms will not worsen during her trip. Once she reaches Rome, she has a large meal, a couple of glasses of Chianti, and then takes her midazolam pill. She develops strong hypotension and respiratory depression, unlike what she has ever experienced before. Q: How could this have been avoided?
  6. 6. # 6 Vignettes in your handouts >< Charles a 32-yr-old man weighing 80 kg (for Q1) or 60 kg (for Q2), has received a cardiac drug orally every day for the past 4 weeks (0.4 mg/day, in tablet form). Recently, symptoms of appreciable toxicity appeared. Blood tests indicate that plasma concentrations of the drug are 6.4 ng/mL. These levels are in the toxic range, whereas ideal therapeutic levels are about 1.6 ng/mL. You stop drug treatment for 1 day, and now [drug]=3.2 ng/mL. Q1: What new dosing regimen should Charles use; how long will it take to reach the new plateau? Q1: What if Charles weighed 60 kg?
  7. 7. # 7 Transport of drugs across membranes Influence of pH Which drug would you predict would be absorbed most readily from the stomach (pH 1)? a. Weak acid b. Weak base >< Which drug would you predict would be absorbed most readily from the intestine (pH 8)? a. Weak acid b. Weak base HA H+ + A- Acid HB+ H+ + B Base By making the arrows thicker point to the direction of the reaction if you place an acid or a base in an acidic environment (pH 1 is acidic; you add H+) By making the arrows thicker point to the direction of the reaction if you place an acid or a base in a basic environment (pH 8 is basic; you add OH-) HA H+ + A- Acid HB+ H+ + B Base Note, this is not the “typical” type of question I will be asking, but it helps us “work through” each step that is necessary for the understanding of the influence of pH on drug absorption
  8. 8. # 8 Transport of drugs across membranes Influence of pH Which drug would you predict would be absorbed most readily from the stomach (pH 1)? a. Strong acid b. Weak acid c. Strong base d. Weak base >< Which drug would you predict would be absorbed most readily from the intestine (pH 8)? a. Strong acid b. Weak acid c. Strong base d. Weak base HA H+ + A- Weak Acid HA H+ + A- Strong Acid HB+ H+ + B Strong Base HB+ H+ + B Weak Base By making the arrows thicker point to the direction of the reaction for strong and weak acids By making the arrows thicker point to the direction of the reaction for strong and weak acids Note, this is not the “typical” type of question I will be asking, but it helps us “work through” each step that is necessary for the understanding of the influence of pH on drug absorption
  9. 9. # 9 Transport of drugs across membranes Influence of pH Which drug would you predict would be absorbed most readily from the stomach (pH 1)? a. Weak acid b. Very weak acid c. Weak base d. Very weak base >< Which drug would you predict would be absorbed most readily from the intestine (pH 8)? a. Weak acid b. Very weak acid c. Weak base d. Very weak base Note, this is not the “typical” type of question I will be asking, but it helps us “work through” each step that is necessary for the understanding of the influence of pH on drug absorption
  10. 10. # 10 Transport of drugs across membranes Influence of pH Which drug would you predict would be absorbed most readily from the stomach (pH 1)? a. Weak acid, pKa = 2.0 b. Weak acid, pKa = 3.5 c. Weak base, pKa = 3.0 d. Weak base, pKa = 9.0 e. There would be no difference HA H+ A-+ HA H+ A-+ Lipid Mucosal Barrier Plasma pH=7.4 Gastric Juice pH=1 >< Strength pKa 1 pKa 2 pKa 3 pKa 4 pKa 5 pKa 6 pKa 7 pKa 8 pKa 9 pKa 1 pKa 2 pKa 3 pKa 4 pKa 5 pKa 6 pKa 7 pKa 8 pKa 9 Strength Weak Acids Weak Bases
  11. 11. # 11 Transport of drugs across membranes Influence of pH Which drug would you predict would be absorbed most readily from an environment of pH 2.0? a. Weak acid, pKa = 2.0 b. Weak acid, pKa = 3.5 c. Weak base, pKa = 3.0 d. Weak base, pKa = 9.0 e. There would be no difference HA H+ A-+ HA H+ A-+ Lipid Mucosal Barrier Plasma pH=7.4 Gastric Juice pH=2 >< Strength pKa 1 pKa 2 pKa 3 pKa 4 pKa 5 pKa 6 pKa 7 pKa 8 pKa 9 pKa 1 pKa 2 pKa 3 pKa 4 pKa 5 pKa 6 pKa 7 pKa 8 pKa 9 Strength Weak Acids Weak Bases
  12. 12. # 12 Transport of drugs across membranes Influence of pH B + H+ BH+ Lipid Mucosal Barrier Plasma pH=7.4 Large Intestine pH=8 Which drug would you predict would be absorbed most readily from the large intestine (pH 8)? a. Weak acid, pKa = 4 b. Weak acid, pKa = 8 c. Weak base, pKa = 4 d. Weak base, pKa = 8 e. There would be no difference B + H+ BH+ >< Strength pKa 1 pKa 2 pKa 3 pKa 4 pKa 5 pKa 6 pKa 7 pKa 8 pKa 9 pKa 1 pKa 2 pKa 3 pKa 4 pKa 5 pKa 6 pKa 7 pKa 8 pKa 9 Strength Weak Acids Weak Bases
  13. 13. # 13 Transport of drugs across membranes Influence of pH Which weakly acidic drug is distributed more readily from the stomach (pH 1) to the blood (pH 7.4)? a. Drug A; pKa = 7.2 b. Drug B; pKa = 7.3 c. Drug C; pKa = 7.4 d. Drug D; pKa = 7.5 e. Drug E; pKa = 7.6 ><
  14. 14. # 14 Transport of drugs across membranes Influence of pH Which weakly acidic drug is distributed more readily from the blood (pH 7.4) to the cerebrospinal fluid (pH 7.2)? a. Drug A; pKa = 7.2 b. Drug B; pKa = 7.3 c. Drug C; pKa = 7.4 d. Drug D; pKa = 7.5 e. Drug E; pKa = 7.6 ><
  15. 15. # 15 Transport of drugs across membranes Influence of pH Which weakly acidic drug is distributed more readily from the cerebrospinal fluid (pH 7.2) to the blood (pH 7.4)? a. Drug A; pKa = 7.2 b. Drug B; pKa = 7.3 c. Drug C; pKa = 7.4 d. Drug D; pKa = 7.5 e. Drug E; pKa = 7.6 ><
  16. 16. # 16 Transport of drugs across membranes Influence of pH Which weakly acidic drug is distributed more readily from the large intestine (pH 8) to the blood (pH 7.4)? a. Drug A; pKa = 7.2 b. Drug B; pKa = 7.3 c. Drug C; pKa = 7.4 d. Drug D; pKa = 7.5 e. Drug E; pKa = 7.6 ><
  17. 17. # 17 Transport of drugs across membranes Influence of pH Which weakly basic drug is distributed more readily from the blood (pH 7.4) to the milk (pH 6.9) of a lactating mother? a. Drug A; pKa = 7.2 b. Drug B; pKa = 7.3 c. Drug C; pKa = 7.4 d. Drug D; pKa = 7.5 e. Drug E; pKa = 7.6 ><
  18. 18. # 18 Transport of drugs across membranes Influence of pH What is the ratio of ionized to unionized drug (I/UI) for a weak acid with pKa of 4.2 in the urine of a patient treated with sodium bicarbonate (pH of urine = 8.2)? a. 100:1 b. 1:1000 c. 1:1 d. 10:1 e. 10,000:1 ><
  19. 19. # 19 Transport of drugs across membranes Influence of pH A nursing mother is taking penicillin V (a weak acid, pKa = 2.4). The pH of her serum is 7.4, and so is the one of her milk. However, she drinks orange juice, which acidifies her milk to pH 6.4 (quite an unlikely scenario, but let’s assume it is true). Will this change in pH modify the retention of penicillin V in the milk and by how much? a. Facilitate the retention of penicillin V in the milk by a factor of 100,000 b. Facilitate the retention of penicillin V in the milk by a factor of 10,000 c. Facilitate the retention of penicillin V in the milk by a factor of 10 d. Reduce the retention of penicillin V in the milk by a factor of 100,000 e. Reduce the retention of penicillin V in the milk by a factor of 10,000 f. Reduce the retention of penicillin V in the milk by a factor of 10 ><
  20. 20. # 20 Transport of drugs across membranes Influence of pH >< A drug that is a weak acid is best absorbed in an environment that is: a. Acidic b. Basic A drug that is a weak base is best absorbed in an environment that is: a. Acidic b. Basic Note, this is not the “typical” type of question I will be asking, but it helps us “work through” each step that is necessary for the understanding of the influence of pH on drug absorption HA H+ + A- HA H+ + A- Acidic environment Basic environment HB+HB+ H+ + B H+ + B Acidic environment Basic environment By making the arrows thicker point to the direction of the reaction if you place an acid (HA) in an acidic (add H+) or basic (add OH-) By making the arrows thicker point to the direction of the reaction if you place a base (B) in an acidic (add H+) or basic (add OH-)
  21. 21. # 21 Transport of drugs across membranes Influence of pH Assuming the passive diffusion hypothesis for the passage of drugs across membranes, the transport of a weakly acidic drug (pKa = 8.5) will be expected to be greater from a medium of: a. pH 2.5 b. pH 4.5 c. pH 5.5 d. pH 8.5 e. pH 9.5 ><
  22. 22. # 22 Transport of drugs across membranes Influence of pH Assuming the passive diffusion hypothesis for the passage of drugs across membranes, the transport of a weakly basic drug (pKa = 8.5) will be expected to be greater from a medium of: a. pH 4.2 b. pH 5.2 c. pH 6.2 d. pH 8.5 e. pH 9.5 ><
  23. 23. # 23 Transport of drugs across membranes Influence of pH AND l/w partition coefficient Which of the following weakly acidic drugs is absorbed more readily from the large intestine? a. Drug A; pKa=6, l/w=1000000000000 b. Drug B; pKa=6, l/w=100 c. Drug C; pKa=7, l/w=1 d. Drug D; pKa=7, l/w=100 e. Drug E; pKa=8, l/w=1 >< Note: this is an “extreme situation”, and it is unlikely to represent the types of questions you will be getting. However, it helps work-through the rationale behind these types of questions and prepares you for more “likely scenarios” (see next question).
  24. 24. # 24 Transport of drugs across membranes Influence of pH AND l/w partition coefficient The pKa values for three drugs are Drug A: 8.5, Drug B: 7.7, Drug C: 7.5. These drugs are all weak ACIDS. Their l/w partition coefficients are 0.005, 0.005, and 50 respectively. According to these properties, which of the following is the likely correct order of rate of absorption from the stomach? a. Drug A>Drug B>Drug C b. Drug A=Drug B>Drug C c. Drug C>Drug B>Drug A d. Drug C>Drug A>Drug B e. Drug C>Drug B=Drug A ><
  25. 25. # 25 Transport of drugs across membranes Influence of pH AND l/w partition coefficient Which of the following weakly acidic drugs is absorbed more readily from the large intestine? a. Drug A; pKa=9, l/w=1 b. Drug B; pKa=9, l/w=100 c. Drug C; pKa=7, l/w=1 d. Drug D; pKa=7, l/w=100 e. Drug E; pKa=1, l/w=1 ><
  26. 26. # 26 Transport of drugs across membranes Influence of pH AND l/w partition coefficient Which of the following weakly basic drugs is absorbed more readily from the large intestine? a. Drug A; pKa=9, l/w=1 b. Drug B; pKa=9, l/w=100 c. Drug C; pKa=7, l/w=1 d. Drug D; pKa=7, l/w=100 e. Drug E; pKa=1, l/w=1 ><
  27. 27. # 27 Transport of drugs across membranes Factors affecting passive transport of drugs You are developing a new drug, to be applied as transdermal patch. Ideally drug should be: a. Large lipophilic compound, with low polarity b. Small lipophilic compound, with high polarity and protein binding c. Low degree of ionization, small molecular size, high lipophilicity d. High lipid solubility and lipid/water partition coefficient and high polarity e. Low lipid/water partition coefficient and low polarity ><
  28. 28. # 28 Drug Absorption Drug X is administered intramuscularly (curve A) or orally (curve B). Which of the following statements is NOT correct? a. Curve A shows shorter half life than curve B b. Curve B shows less bioavailability than curve A c. For curve B, elimination has started before absorption is complete d. For curve A, biovailability is high e. Curve A follows zero order kinetics; curve B follows first order kinetics Logplasma[Drug] - - - - - - - - Time (min) - - - - - - - - - A B ><
  29. 29. # 29 Drug Absorption First pass effect (or first pass metabolism) can be reduced if drugs are: a. Very lipophilic b. Very hydrophilic c. Administered rectally d. Administered orally e. Administered in a buffered solution ><
  30. 30. # 30 Drug Absorption A patient enters the emergency room with severe signs of angina pectoris and clear signs of imminent myocardial infarction. To prevent full myocardial infarction, you immediately prescribe a sublingual tablet of nitroglycerin. One of the main reasons for the sublingual vs. oral route of administration in this situation is: a. To have rapid drug absorption (by sublingual vasculature) b. To have slow but safe drug absorption, without risking stomach damage c. To reduce rapid renal and intestinal clearance and increase duration of effect d. To have prolonged duration of action of the drug e. To reduce first pass metabolism from the stomach ><
  31. 31. # 31 Drug Distribution A 50-yr-old woman with atrial fibrillation has been taking 5mg of warfarin daily for the past year. She develops a urinary tract infection and, instead of visiting the doctor, she decides to take some left-over pills of ciprofloxacin acid that were previously prescribed to her daughter. Warfarin is an anticoagulant drug that is 97% bound to plasma proteins, and ciprofloxacin is an antibacterial drug that binds 90% to plasma proteins. Which adverse effect(s) is(are) most likely to occur after one week combined warfarin + ciprofloxacin acid treatment? a. Atrial fibrillation b. Blood clotting in the extremities c. Hematomas in the extremities and or/hematuria d. Accelerated recovery from the urinary tract infection e. No recovery at all from the urinary tract infection ><
  32. 32. # 32 Drug Distribution A patient with cardiac failure due to a previous myocardial infarction has been taking daily digoxin (a cardiotonic drug) for the past 2 months. She develops mild bacteria-induced bronchitis. She has previously suffered of bacteria-induced bronchitis and has been successfully treated with erythromycin (an aminoglycoside antibiotic). She has some left-over pills from the year before, which she decides to take to treat the bronchitis. Given that erythromycin inhibits PGP transport, and that digoxin binds to PGP, which of the following adverse effects are likely to occur? a. Blurred vision, heart palpitations and nausea b. Respiratory depression and vomiting c. Decreased cardiac output, decreased blood pressure and heart rate d. Increased state of alertness, difficulty to fall asleep e. Rapid recovery from bronchitis ><
  33. 33. # 33 Drug Distribution A highly lipid soluble drug has been injected into a patient who dies after 10 minutes. Which of the following tissues/organs will have the least amount of drug recovered? a. Liver b. Blood c. Skin d. Kidneys e. Heart ><
  34. 34. # 34 Drug Metabolism Which of the following best describes phase I metabolism? a. It involves hydrolysis reactions and requires the presence of NADP+ b. It involves hydrolysis reactions and requires the presence of NADPH c. It involves functionalization reactions, which expose or introduce functional groups d. Pharmacological activity changes and polarity decreases e. Always preceded Phase II metabolism ><
  35. 35. # 35 Drug Metabolism Which of the following descriptions best describes phase II metabolism of a drug? a. It often conjugates endogenous glucuronic acid with the drug or its metabolites b. It can only occur after phase I metabolism has occurred in the cytosol c. It occurs on the endoplasmic reticulum or in microsomes and requires cytochrome P450 d. It decreases the hydrophilic properties of drugs, which increases glomerular filtration e. It often refers to hydrolysis and/or oxidation reactions ><
  36. 36. # 36 Drug Metabolism & Excretion To facilitate sleep induction a young woman has the habit of taking one pill of alprazolam (a short- acting benzodiazepine, weak acid, pKa = 5.0) prior to going to bed. She realizes that the pill works well, however she wakes up too early in the morning, and would like to prolong drug effect. Which of the following things would be more effective? a. eat food to reduce gastric emptying b. drink several glasses of water to accelerate gastric emptying c. drink some wine, to modify drug effect d. drink grapefruit juice to acidify urine and to reduce drug metabolism e. exercise to modify metabolism and blood flow ><
  37. 37. # 37 Clinical applications of pharmacokinetics >< A new drug that follows first order kinetics and whose half life is 8h is administered intravenously in a patient, as a bolus infusion of 320 mg. Plasma levels of the drug are measured early-on, during the distribution phase (α phase) and then at 8 h, during the elimination phase (β phase). Complete the graph below by adding what plasma levels would look like at 12h, 16h, 20h, and 24h [PlasmaDrug(ng/L] t ½ 320 160 80 40 20 0 Time (h) 4 8 12 16 20 24 28 α phase phase
  38. 38. # 38 Clinical applications of pharmacokinetics >< Patient G is admitted to the emergency room with a severe infection. She requires immediate treatment with an antibiotic whose half life is 10h and whose therapeutic window is about 20 mg/L. If the clearance rate for this antibiotic is about 0.693 L/h, what would be an appropriate first dose (loading dose) one should administer? a. 20 mg b. 40 mg c. 50 mg d. 200 mg e. 300 mg
  39. 39. # 39 Clinical applications of pharmacokinetics >< Drug X follows first order kinetics, and its Kel (constant of elimination) is 0.693/h. If this drug is to be given as constant IV infusion, approximately how long will it take for the drug to reach Css (steady state plasma concentrations)? a. 0.7h b. 1.0h c. 1.7h d. 4.7h e. 6.9h
  40. 40. # 40 Clinical applications of pharmacokinetics >< Toby is a tiny teenager who weighs 35 kg, and takes 10 mg of a drug whose elimination rate follows zero order kinetics. If Toby’s Ke for this drug=1mg/h, how long will it take for 50% of the drug to be eliminated? a. 0.5h b. 1.0h c. 2.5h d. 5.0h e. 10.0h
  41. 41. # 41 Clinical applications of pharmacokinetics >< Mr. Blue, a 29-year-old man weighing 140 kg and 1.95 m tall (6.4 feet) is admitted to the hospital with symptoms of arrhythmias. The doctors prescribe immediate intravenous procainamide. The pharmacokinetic values for procainamide in a 70 kg person are: Vd 100L, CL 40L/h, therapeutic concentration 5 mg/L. Which of the following doses would be most appropriate as an initial (loading) dose? a. 10 mg b. 50 mg c. 100 mg d. 500 mg e. 1000 mg
  42. 42. # 42 Clinical applications of pharmacokinetics >< Mr. Blue, a 29-year-old man weighing 140 kg and 1.95 m tall (6.4 feet) is admitted to the hospital with symptoms of arrhythmias. The doctors prescribe immediate intravenous procainamide. The pharmacokinetic values for procainamide in a 70 kg person are: Vd 100L, CL 40L/h, therapeutic concentration 5 mg/L. What constant intravenous infusion rate should be used to maintain the therapeutic concentration? a. 80 mg/h b. 100 mg/h c. 200 mg/h d. 400 mg/h e. 800 mg/h
  43. 43. # 43 Clinical applications of pharmacokinetics >< Graham Negative is a very tall individual; he weighs 140kg (given his height he is not overweight). He is admitted to the hospital with pneumonia. He is treated with an intravenous antibiotic. In this individual, the clearance rate of the antibiotic is 4 L/h. If you decide to administer the antibiotic every 4h, what would be a good maintenance dose to administer so as to achieve a steady-state concentration of 4mg/L? a. 8 mg b. 16 mg c. 32 mg d. 64 mg e. 128 mg
  44. 44. # 44 Clinical applications of pharmacokinetics >< The plasma level of an antibiotic is to be maintained at 20 µg/mL in a 60 kg patient. The drug is 95% bound to plasma proteins, and is moderately lipid soluble. It has CL = 15mL/min. What rate of IV infusion is needed to maintain this concentration? a. 2 mg/hour b. 6 mg/hour c. 12 mg/hour d. 18 mg/hour e. 30 mg/hour
  45. 45. # 45 Clinical applications of pharmacokinetics >< Dee Vourer is an overweight young lady who weighs 140kg and who tends to eat everything in sight. She arrives to the emegency room, showing internal and nose bleeding. She claims to have inadvertently eaten rat poison containing rodenticide the day before. Rodenticide is an anticoagulant that is very lipid- soluble. Blood levels of rodenticide are 30 mg/L (24h post ingestion). How many mg of rodenticide did Dee Vourer ingest 24h before? Note that rodenticide follows first-order kinetics with t½ of 12h and with Vd=4L in normal adults. a. 60 mg b. 120 mg c. 240 mg d. 480 mg e. 960 mg
  46. 46. # 46 Clinical applications of pharmacokinetics >< Ann Orexia is a young patient weighing 50Kg. She is treated with drug X, where target blood levels are 20 micrograms/L. The pharmacokinetics parameters for this drug in this patient are Vd = 10L/Kg CL = 1L/h Half life = 7h What is a good LOADING for this patient? A. 10 micrograms B. 50 micrograms C. 100 micrograms D. 500 micrograms E. 1 milligram F. 5 milligrams
  47. 47. # 47 Clinical applications of pharmacokinetics >< Ann Orexia is a young patient weighing 50Kg. She is treated with drug X, where target blood levels are 20 micrograms/L. The pharmacokinetics parameters for this drug in this patient are Vd = 10L/Kg CL = 1L/h Half life = 7h What is a good MAINTENANCE dose ONCE DAILY for this patient? A. 20 micrograms B. 24 micrograms C. 48 micrograms D. 240 micrograms E. 480 micrograms F. 2000 micrograms
  48. 48. # 48 Clinical applications of pharmacokinetics >< In the patient above, you stop treatment and then measure blood [drug] after 11.5 min and find that they are 2.5 mg/L. What is the approximate Vd in this patient? a. 1L b. 10L c. 36L d. 69L e. It cannot be calculated given the information above A patient is administered a continuous drug infusion of 3 mg/min for 70 min. Steady-state blood concentration of the drug are reached by 50 min and are 5 mg/L. The CL rate of this drug is about: a. 3 mL/min b. 60 mL/min c. 600mL/min d. 900 mL/min e. 1000 mL/min If steady state concentrations were reached within 35 min, rather than 50, the clearance rate of this drug would be about: What would be a good loading dose? a. 6 mg b. 9 mg c. 25 mg d. 38 mg e. 50 mg
  49. 49. # 49 Clinical applications of pharmacokinetics >< Time (hours) 0 4 8 12 16 20 24 28 32 36 40 PlasmaConcentration(mg/L) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 1 0.8 a. CL=2 L/h b. Vd=30 L c. T ½ = 4 h d. Css=0.8 mg/L e. Elimination follows zero order kinetics You are developing a new drug for the treatment of breast cancer. Volunteer women are administered the drug intravenously at the rate of 8mg/h. Given the information collected you can conclude that:
  50. 50. # 50 Clinical applications of pharmacokinetics >< The plasma conc. of an oral hypoglycemic drug is 20 mg/100mL when measured at 2h after administration. If disposition of drug is assumed to obey first order kinetics (Ke=0.115/h) what will be the plasma conc. 20h after administration? a. 5 mg/100mL b. 4.0 mg/100mL c. 3.5 mg/100mL d. 2.5 mg/100mL e. 2.0 mg/100mL If you assume that the above drug were to follow zero order kinetics (elimination constant of 1 mg/h) what will be the plasma conc. At 20h after administration? a. 5 mg/100mL b. 4.0 mg/100mL c. 3.5 mg/100mL d. 2.5 mg/100mL e. 2.0 mg/100mL
  51. 51. # 51 Clinical applications of pharmacokinetics >< If 50% of a drug is eliminated by 1h, what is the half life of this drug? (Assume there is no first-pass effect). a. 15 min b. 25 min c. 30 min d. 45 min e. 60 min f. 120 min
  52. 52. # 52 Clinical applications of pharmacokinetics >< If 50% of a drug is absorbed by 1h, what is the half life of this drug? (Assume there is no first-pass effect). a. 15 min b. 25 min c. 30 min d. 45 min e. 60 min f. 120 min
  53. 53. # 53 Clinical applications of pharmacokinetics >< If ~88% of a drug is eliminated by 3h, what is the half life of this drug? (Assume there is no first-pass effect). a. 15 min b. 25 min c. 30 min d. 45 min e. 60 min f. 120 min
  54. 54. # 54 Clinical applications of pharmacokinetics >< If ~88% of a drug is absorbed by 3h, what is the half life of this drug? (Assume there is no first-pass effect). a. 15 min b. 25 min c. 30 min d. 45 min e. 60 min f. 120 min
  55. 55. # 55 Clinical applications of pharmacokinetics >< A patient (70 kg) is to be administered an experimental drug. Its pharmacokinetic properties are the following: pKa=3.4, Vd=140L, bioavailability=100%, protein binding=85%, Ke=0.3/hour. What should be the orally administered loading dose in order to achieve plasma concentrations of 21µg/L? a. 1.45 mg b. 2.94 mg c. 3.94 mg d. 5.50 mg e. 7.25 mg
  56. 56. # 56 Clinical applications of pharmacokinetics >< Time (h) plasmadrugconc(mg/L) 32 - - 16 - - 8 - - 4 - - 2 - - 1 - I I I I I I I I I I I I I I I I I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 If you are given a graph like the one below, and you are given the loading IV dose, how do you calculate Vd, CL, and t½? During the α phase (red circles) the drug concentration in the blood is very high because the drug has not yet distributed, even though clearance already begun. During the β phase (black circles) the drug has distributed and clearance is still ongoing. sodium bicarbonate
  57. 57. # 57 Clinical applications of pharmacokinetics >< The clearance for drug X prior to sodium bicarbonate administration is approximately: a. 0.7 L/h b. 1.0 L/h c. 1.4 L/h d. 3.5 L/h e. 7.0 L/h A new anti-inflammatory drug X is developed and the efficacy and pharmacokinetics are being studied. The drug is administered to healthy male subjects weighing approximately 70 kg. A dose of 480 mg is administered intravenously as a bolus infusion and blood samples are analyzed at the time points shown below (both before and after administration of sodium bicarbonate). Time (h) plasmadrugconc(mg/L) 32 - - 16 - - 8 - - 4 - - 2 - - 1 - I I I I I I I I I I I I I I I I I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 sodium bicarbonate
  58. 58. # 58 Clinical applications of pharmacokinetics >< The clearance for drug X after to sodium bicarbonate administration is approximately: a. 0.7 L/h b. 1.0 L/h c. 1.4 L/h d. 3.5 L/h e. 7.0 L/h A new anti-inflammatory drug X is developed and the efficacy and pharmacokinetics are being studied. The drug is administered to healthy male subjects weighing approximately 70 kg. A dose of 480 mg is administered intravenously as a bolus infusion and blood samples are analyzed at the time points shown below (both before and after administration of sodium bicarbonate). Time (h) plasmadrugconc(mg/L) 32 - - 16 - - 8 - - 4 - - 2 - - 1 - I I I I I I I I I I I I I I I I I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 sodium bicarbonate
  59. 59. # 59 Clinical applications of pharmacokinetics > Time (h) 0 1 2 3 4 5 6 7 8 9 10 11 12 Plasmaconcentration(mg/L) 2048 1024 512 256 128 64 32 16 8 4 2 1 Cranberry juice The figure below represents the plasma concentrations of pharmagood, a new drug developed to promote critical thinking. Pharmagood is given as a bolus intravenous injection of 1024mg in a normal individual (a pharmacology student, weighing 70kg). The empty circles represent plasma concentrations of pharmagood in its alpha phase, whereas the filled circles represents concentrations of pharmagood during its beta phase (before or after the administration of cranberry juice). What is the approximate clearance rate after the administration of cranberry juice? a. 0.1 L/h b. 0.35 L/h c. 0.7 L/h d. 1.4 L/h e. 2.8 L/h <
  60. 60. # 60 Pharmacodynamics >< Mr. Pink agrees to pet-sit his neighbor’s cat for a few days. The morning after having spent the night with the cat, Mr. Pink starts showing signs of mild allergy-induced asthma. He decides to take a tablet of diphenydramine (benadryl), which causes slight drowsiness, but eventually relieves Mr. Pink from the allergy-induced discomfort. The second morning, the allergy-induced asthma becomes so severe that Mr. Pink is required to visit the emergency room for immediate relief of severe asthma. Given the choice between administering an inhalant preparation of norepinephrine or of beclomethasone (B: a glucocorticoid, steroid drug), the doctors will opt for norepinephrine because: a. B will interact with diphenydramine and provoke severe drowsiness b. B would take too long to have an effect, because it acts on intracellular receptors c. B’s effects would only last a very short time, b/c benadryl increases its metabolism d. B cannot be absorbed in inhalant form because it is not lipophilic enough e. B risks being absorbed in the circulation because it is too lipophilic
  61. 61. # 61 Pharmacodynamics >< Which of the following is true about metabotropic receptors? a. When activated, they metabolize drugs b. When activated, they phosphorylate a protein kinase c. They are associated to G proteins d. They are associated to excitatory G proteins e. They need to translocate into the nucleus to have an effect
  62. 62. # 62 Pharmacodynamics >< In the figure below, drugs X, Y and Z have been developed to reduce pharmacology-associated headaches. All three drugs act on a new receptor (pharmidache). Which of the following is true? a. Drug Z is a partial agonist with high affinity for pharmidache receptors b. Drug Z is a full agonist with high affinity for pharmidache receptors c. Drug Z is a full agonist with low affinity for pharmidache receptors d. Drug Y is a partial agonist with high affinity for pharmidache receptors e. Drug Y is a full agonist with low affinity for pharmidache receptors 100 - - - - - 50 - - - - - 0 %ofmaximalresponse - - - - 1 10 100 1000 - - - - 1 10 100 1000 Log [Drug] X Y Z
  63. 63. # 63 Pharmacodynamics >< In the figure below, the graded dose-response curve for a drug is presented for the drug alone (Drug A) and in combination with other drugs (A+B, A+C, A+D). If Drug A is highly bound to plasma proteins, which drug may have displaced Drug A from its protein binding sites on the plasma proteins? a. Drug B b. Drug C c. Drug D d. Drug B and C e. Drug C and D
  64. 64. # 64 Pharmacodynamics >< In the figure below, the graded dose-response curve for a drug is presented for the drug alone (Drug A) and in combination with other drugs (A+B, A+C, A+D). What is drug D? a. It is a non-equilibrium antagonist, which decreases the potency of Drug A b. It is a non-equilibrium antagonist, which decreases the efficacy of Drug A c. It is an equilibrium antagonist, which decreases the potency of Drug A d. It is an equilibrium antagonist, which decreases the efficacy of Drug A e. It is a non-competitive antagonist, which decreases the efficacy of Drug A
  65. 65. # 65 Pharmacodynamics ><Dose (mg) 0 1 10 100 1000 10000 %MaxiumumResponse 10 20 30 40 50 60 70 80 90 100 Patient 1 Patient 2 Patient 3 Based on the graph, which of the following statements is true? (solid lines=therapeutic effect; dotted lines=tachycardia side-effect; max side effect is an increase of 100BPM) a. At the therapeutic ED50 nobody would experience more than a very slight tachycardia b. At the therapeutic ED50 one of the individuals would show moderate (+25BPM) tachycardia c. At the therapeutic ED99 one individual would definitely have major tachycardia (at least +75BPM) d. At the therapeutic ED99 two patients would reveal an increase in heart rate
  66. 66. # 66 Pharmacodynamics < Dose (mg) 0 1 10 100 1000 10000 %MaxiumumResponse 10 20 30 40 50 60 70 80 90 100 Blood pressure reduction (max effect: 40mm/Hg) Increase in heart rate (tachycardia) (max effect: 1 beat/min) Impotence (max effect: 100% impotence) Ankle swelling (max effect: 1mm) a. Tachycardia, impotence, ankle swelling b. Tachycardia and impotence c. Impotence and ankle swelling d. Tachycardia e. Impotence In this figure, the graded dose-response curves represent the effects and side-effects of a novel vasodilator designed as anti-hypertensive medication. For it to be more effective than simple change in life-style, it needs to be administered at the EC90. Eager to try the new drug, you administer it to a set of male patients (ages 25- 40). After a week of treatment, all patients return to your office; they report to be uncomfortable with the side effect(s) they are experiencing. What are they most-likely complaining about? (NOTE: Read the graph carefully, including all the words in the legend. Use your judgment to determine if each side-effect, at the degree it is experienced, would cause discomfort or not).

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