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Pharmacology 2060A/B Lecture Notes - Lecture 3: Heart Failure, Body Water, Glycoprotein

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apricotfly938
3 Mar 2016
School
Western University
Department
Pharmacology
Course
Pharmacology 2060A/B
Professor
Andrea Di Sebastiano

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Document Summary

Module 3 pharmacokinetics distribution. Drugs distribute into compartments in the body where they are stored, metabolized, excreted or exert effect. Bone can be a reservoir for the slow release: other tissue. Determined by: blood flow to tissues, ability of drug to move out of capillaries, ability of drug to move into cells. The more drug that distributes out of the blood, the lower the concentration of drug in the blood. Blood slow to tissue is a key determinant of drug distribution. Rapid distribution liver, kidney, brain. Slower distribution skin, fat, bone. Implications for altered blood flow. Neonates have limited blood flow and therefore low drug distribution. Poor blood flow rarely limits adults except in: heart failure or shock. Usually drained before drug therapy. Ability of drug to move out of capillaries. Drugs move out of the capillary through fenestrations. Ability of drug to move into cells. P- glycoprotein (p- gp) efflux transporter large role in the distribution of drugs.

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Related Questions

1) The neurotransmitters acetylcholine and norepinephrine are digested by enzymes that are located at the axon synapse or within the axon terminal of the neurons.

a)What are the names of these different types of enzymes?

b)Where are they located and what is the result of their enzymatic activity?

2) Explain how the Investigational New Drug process works as well as the four different phases of clinical trials. Why are some drugs still taken off the market after approval by the FDA?

3) A single IV injection of 100 mg drug with a half-life of 4 hours is administered to a young adult.

a) Plot drug concentration versus time on a graph making certain to clearly label.

b) How long will it take to eliminate > 95% of the drug?

c) If the volume of distribution is 4L, what is the clearance of the drug?

4) Many drugs are metabolized in the liver through the microsomal metabolizing system.

a) What specific enzymes are involved in this metabolism?

b) What are the main functions of these enzymes?

c) What are some factors that can contribute to individual drug metabolism variation? Explain.

5) Think of an emergency situation requiring immediate and intense physical exertion.

a) List as many body organs as you can and predict the desired level of activity [increased or decreased].

b) Which neurotransmitter would produce these effects and through what receptors?

6) It is interesting that a drug can produce a therapeutic effect and an undesired side effect in one situation, and that the same drug side effect may be considered a therapeutic effect in another situation. Explain this phenomenon using the drug promethazine as an example.

7) A patient brought into the emergency room is experiencing severe hypotension. Blood pressure reads 90/50.

a) What class of drugs is indicated for treatment and why?

b) What precautions should be observed when these drugs are administered?

c) What would be the first indication that too much drug has been administered?

8) Only certain drugs are capable of crossing the blood brain barrier.

a) How is the blood brain barrier different than barriers found in other areas of the body? Be specific.

b) What properties of drugs will make it more likely to cross the blood brain barrier? Explain your answers.

9) A 32-year-old, presents to the Emergency Department by ambulance with vomiting, confusion, salivation, and respiratory distress. The patient states that he was feeling fine until today when I started getting ill. He then vomits. During a physical exam you record the following information: Heart rate 45; Blood pressure 90/60; Respiratory rate 25; Temperature 36.6C; Pupils constricted. During your exam, 4 more ambulances arrive with patients with similar symptoms. You find out they were all riding in the same care on the Red Line when they began feeling ill.

a) What do you feel is happening and why?

b) Would you expect their symptoms to improve over time? Why or why not?

c) What drug would you prescribe to treat these patients and why?

10) Betty has diabetes and asthma. She also has developed high blood pressure, for which doctor just prescribed propranolol. One of your duties as a physician’s assistant is to make sure patients are not prescribed drugs that are contraindicated because of other health problems.

a) What should you tell the doctor about Betty’s prescription for propranolol and why?

b) Is there a more appropriate drug for Betty? Explain you answer.

1. C6H12O6 + 6O2 Ã 6CO2 + 6H2O Glucose is being _____ to _____ and oxygen is being _____ to _____. a. oxidized; carbon dioxide; reduced; water b. oxidized; water; reduced; carbon dioxide Incorrect c. reduced; water; oxidized; carbon dioxide d. reduced; carbon dioxide; oxidized; water

2. Which of the following stages in the breakdown of the piece of toast you had for breakfast generates the most ATP? a. the citric acid cycle Incorrect b. glycolysis c. the digestion of starch to glucose d. oxidative phosphorylation

3. Which of the following is a catabolic pathway? a. gluconeogenesis b. production of starch Incorrect c. glycolysis d. production of glycogen

4. Per molecule, the oxidation of a fatty acid results in _____ energy storage than the oxidation of glucose. a. the same b. less Incorrect c. more d. None of the above; fatty acids cannot be oxidized.

5. Of the eight reactions in the citric acid cycle, how many are oxidation-reduction reactions? a. one b. two c. three d. four e. five

6. The process of glycolysis transfers the energy in sugar molecules into the stored energy of activated carriers such as ATP and NADH. Which statement is true about glycolysis? a. Only eukaryotic organisms do glycolysis. b. The ten reactions of glycolysis are identical in all eukaryotic cells, but are different in prokaryotic cells due to their diverse metabolic strategies. Incorrect c. The ten reactions of glycolysis are identical in almost all living organisms on the planet. d. There are many ways to oxidize glucose and transfer energy into activated carriers; the diversity of organisms on the planet is reflected in the diversity of their mechanisms of glycolysis.

7. Referring to the sentence completed in #13 above, the purpose of the latter reaction (in active muscle cells) is to _____. a. accumulate lactic acid in the cell, which provides additional energy for the production of ATP Incorrect b. slow down glycolysis until oxygen becomes available again c. accelerate the Krebs cycle, which will restore the oxygen supply d. regenerate NAD+ so that glycolysis can continue in the absence of oxygen

8. What are the products of the citric acid cycle? a. carbon dioxide, NADH, FADH2 and GTP b. carbon dioxide, NAD+, FAD and GTP c. NADH, FADH2, and acetyl CoA Incorrect d. carbon dioxide and water

9. Which statement is true about enzymes? a. Enzymes catalyze chemical reactions because they make inherently endergonic reactions exergonic. b. Each enzyme in a cell can catalyze many different chemical reactions involving chemically different substrates. Incorrect c. Enzymes can only catalyze reactions in one direction. d. After catalyzing a reaction, an enzyme is permanently altered and can no longer bind substrate. e. None of the above is true. 1

10. ∆G measures the change in free energy in a system as it converts reactant (Y) into product (X). When [X] = [Y], ∆G is equal to _____. a. RT b. ΔG° + RT c. ΔG° d. ln [X]/[Y]

11. The ∆G° for the hydrolysis of ATP is -7.3 kcal/mol. What conditions in the cell would lead to a ∆G for ATP hydrolysis of -11 kcal/mol? a. An increase in the ATP/ADP ratio b. An increase in anabolic activity in the cell c. Transport of ATP out of the compartment where the reaction is occurring Incorrect d. A decrease in the ATP/ADP ratio

12. In the first reaction of glycolysis, a phosphate transferred from ATP to a glucose molecule to produce glucose-6-phosphate and ADP. Under conditions existing in the cell, the free energy change for this reaction is -8.0 kcal/mole. Which of the following statements is true? Recall that the ∆G° for the hydrolysis of ATP is -7.3 kcal/mol. a. Glucose concentrations in the cell are always low, making this reaction more favorable than would be expected. b. This reaction is less favorable than would be expected, given the ∆G° of ATP hydrolysis. c. Glucose-6-P concentrations in the cell are very low relative to glucose concentrations, making the reaction more favorable than would be expected. d. The ∆G° for the addition of a phosphate to glucose must be -0.7 kcal/mole.

13. Protein E can bind to two different proteins, S and I. The binding reactions are described by the following equations and values: E + S --> ES Keq for ES = 10 E + I> EI Keq for EI = 2 Given the equilibrium constant values, which one of the following statements is true? a. When S is present in excess, no I molecules will bind to E. b. E binds I more tightly than S. c. The binding energy of the ES interaction is greater than that of the EI interaction. d. Changing an amino acid on the binding surface of I from a basic amino acid to an acidic one will probably make the free energy of association with E more negative.

1. In addition to identifying the genetic material, the experiments of Avery, MacLeod, and McCarty with different strains of Streptococcus pneumoniae demonstrated that
DNA is a double helix.
DNA may be taken up by bacterial cells and be active.
DNA is present in bacteriophage T2.
eukaryotic cells may be genetically transformed.
DNA binds to the cell wall of the bacterium.
2. In order to show that DNA in cell extracts is responsible for genetic transformation in Streptococcus pneumoniae, important corroborating evidence should indicate that _______ also destroy transforming activity.
temperatures high enough to kill cells
enzymes that hydrolyze proteins
enzymes that hydrolyze DNA
enzymes that hydrolyze polysaccharides
enzymes that hydrolyze RNA
3. Based on what you have learned about the experiments conducted by Griffith and Avery and colleagues with bacteria, which of the following would result in transformation of living R cells?
Pure RNA from S cells
Cell-membrane extracts from S cells
A mixture of pure RNA and protein from S cells
Cell-free extracts from S cells
Pure protein from S cells
4. A-T base pairs in a DNA double helix
form three hydrogen bonds with each other.
are more heat-stable than G-C base pairs.
are of a substantially different length than G-C base pairs.
are not accessible to DNA binding proteins.
are chemically distinct from G-C base pairs.
5. If 23 percent of the bases in a sample of double-stranded DNA are adenine, what percentage of the bases are uracil?
27
50
0
73
23
6. The uniform diameter of the DNA structure provides evidence for
antiparallel DNA strands.
a right-handed helix.
a double-stranded helix.
3′ end phosphorylation.
purine–pyrimidine pairing.
7. If a sequence of one strand of DNA is 5′-TGACTATC-3′, what is the complementary strand?
5′-ACTGATAG-3′
3′-TGACTATC-5′
3′-ACTGATAG-5′
3′-ACTGATAG-3′
5′-TGACTATC-3′
8. What structural aspect of the DNA facilitates dissociation of the two DNA strands for replication?
3′ end phosphorylation
Purine–pyrimidine pairing
Antiparallel DNA strands
Covalent bonds between sugars and phosphate groups
Hydrogen bonding between paired bases
9. If the Meselson–Stahl density gradient experiment had resulted in two bands of DNA molecules after only one round of replication, one containing only 15N and the second only 14N, this result would have indicated that replication was
unidirectional.
dispersive.
conservative.
bidirectional.

semiconservative.
10. The nucleoside analogue acyclovir, which is used to treat herpes simplex virus (HSV) infections, lacks a 3′ hydroxyl group (–OH). Predict what will happen if the host cell DNA polymerase incorporates a molecule of acyclovir into an elongating strand of HSV DNA.
The replication complex will no longer bind to origins of replication.
The DNA polymerase will only incorporate acyclovir molecules.
Acyclovir will bind single-strand binding proteins.
DNA polymerase will not be able to link a successive nucleotide.
Acyclovir will block the activity of the DNA helicase.
11. Which of the following does not demonstrate the stability of the DNA double helix?
Single-strand binding proteins are required to keep the strands apart.
Paired bases form hydrogen bonds.
High temperatures are required to denature it.
DNA synthesis requires energy.
DNA helicases require ATP.
12. What effect would a primase inhibitor have on DNA replication?
DNA polymerase would not be able to add bases to the DNA.
Primase would be blocked from joining the DNA replication complex.
Primase would not be able to provide primers for DNA polymerases.
DNA polymerase would not be able to use DNA as a template.
There would be no effect on DNA replication.
13. To replicate their DNA in a timely manner, most eukaryotic chromosomes
normally have uncoiled DNA.
have multiple origins of replication.
contain linear molecules of single-stranded DNA.
have two replication forks that move in the same direction.
are composed entirely of DNA.
14. Which statement about DNA replication is false?
Okazaki fragments are synthesized as parts of the leading strand.
Error rates for DNA replication are reduced by proofreading of the DNA polymerase.
The sliding clamp increases the rate of DNA synthesis.
Replication forks represent areas of active DNA synthesis on the chromosomes.
Ligases and polymerases function in the vicinity of replication forks.
15. In many eukaryotes, there are repetitive sequences called telomeres at the ends of chromosomes. After successive rounds of DNA replication, the _______ strand becomes shorter. In some cells, an enzyme called _______ repairs the shortened strand.
leading; telomerase
lagging; telomerase
lagging; DNA polymerase I
leading; DNA polymerase I
leading; replicase
16. A researcher studies normal human fibroblast cells. They can be maintained in culture but die off after about 30 cell generations. Unexpectedly, a colony of cells continues to survive and divide past 30 generations. Which scenario is most likely true for these cells?
DNA polymerase is constantly active.
Primase is able to extend the telomeres.
The mismatch repair system is extra efficient.
The telomerase gene is being expressed.
The cells do not need the ends of their chromosomes.
17. If DNA polymerase III introduces an incorrect nucleotide, what is the first corrective action made by the DNA repair system?
The replication complex excises the incorrect nucleotide.
The excision repair proteins remove the incorrect nucleotide.
The mismatch repair system scans for base-pairing mismatches.
There is no correction, because nucleotide errors by DNA polymerases are not repaired.
DNA ligase connects the correct nucleotide.
18. Choose the correct order of the following four events in the excision repair of DNA:
(1) Base-paired DNA is made complementary to the template.
(2) Damaged bases are recognized.
(3) DNA ligase seals the new strand to existing DNA.
(4) Part of a single strand is excised.
1, 2, 3, 4
2, 1, 3, 4
3, 4, 2, 1
2, 4, 1, 3
4, 2, 3, 1
19. Six complete cycles of PCR should result in a _______-fold increase in the amount of DNA.
64
32
12
128
6
20. When double-stranded DNA is heated to temperatures above 90°C, it denatures. Denaturation is a process that
breaks covalent bonds.
hydrolyzes DNA.
separates double-stranded DNA into two single strands.
causes new hydrogen bonds to form.
irreversibly destroys the double helical structure.