Case Study (Foye’s) “LM is an 80-year-old, black female resident in the Sweet Azalea's assisted-living facility where you are the consulting pharmacist. LM is a bright, intelligent widow, who visits with her children through cyberspace on her laptop. Her stage 1 (mild) hypertension is controlled with an angiotensin-converting enzyme (ACE) inhibitor, enalapril. However, LM has just been diagnosed with congestive heart failure (CHF), characterized by loss of appetite, constipation, ankle edema, and slight hepatomegaly, indicative of right ventricular dysfunction. Her physician wants to begin treatment with a cardiac glycoside or other positive inotropic agent and a diuretic, furosemide.” 1. Define the following terms
(a-b) LG-W21-Bello, Dowjat, Kaur, Obiakwata, Sallout, and Wilson
a. Positive inotropic agents and negative inotropic agents. Please give examples. Positive inotropic agents increase myocardial contractility, and are used to support cardiac function. Ex. Cardiac Glycosides- Digoxin and Catecholamines-Dobutamine. Negative inotropic agents decrease myocardial contractility, and are used to decrease cardiac workload. Ex-Beta Blocker, Calcium channel blockers (Verapamil and Diltiazem)
b. Glycone and aglycone Glycone-any compound containing a carbohydrate moiety (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into a sugar and a nonsugar component (aglycone), and named specifically after the sugar contained, as glucoside (glucose). Aglycone -the nonsugar component of a glycoside molecule that results from the hydrolysis of the molecule.
(c-e) LG-W22: Bhalodia, El-Zoghbi, Kazinich, Odumuko, Seth, and Wong
c. Glycoside and glycosidic bond Glycosides are molecules in which a sugar is bound to a non-carbohydrate moiety, like a small organic molecule. Glycosidic bond is a type of functional group that joins a sugar group to another group. This other group may or may not be a carbohydrate.
d. Anomer Anomer is a special type of epimer, that is a stereoisomer of a cyclic saccharide that differs only in its configuration at the hemiacetal or hemiketal carbon.
e. Mutarotation
Mutarotation refers to a change in specific rotation of a cyclic monosaccharide. This occurs as the molecule reaches an equilibrium between its alpha and beta form.
2. Please fill out the blank areas with appropriate key words (Please upload your files)
Work #1 by LG-W23-Blagg, Enwonwu, Kebulu, O'Halloran, Shah, Wood
MIlrenone - pDE3 inhibitor
Digitoxin
Digoxin - more water soluble
Work #2 by LG-W24-Blomgren, Erickson, Khodadadian, Opoku, Mensah, Sargent, Shateva, and Xhai
The first structure is milrinone, a phosphodiesterase III inhibitor. Milrinone is more potent compared to inamrinone, another PDE-III inhibitor. Milrinone is also better tolerated, having fewer side effects. It is excreted largely unchanged in the urine, therefore renal dysfunction should be considered when dosing.
The second structure is digitoxin, derrived from lanatoside A
The third structure is digoxin, derrived from lanatoside C-these both inhibit the Na/K/ATPase pump, as more OH groups are on the structure they are more water soluble.
3. Discuss additional drug therapies available for this patient in addition to ACE inhibitors, specifically the drugs listed in the above table. Based on your professional knowledge, provide your counseling tips to the patient.
this question has a lot more input required than the others...
Work #1 by LG-W25-Bourque, Fiore, Khorassani, Orock, Shim, and Youkhanna
Patient appears to be classified as stage 2, therefore the patient could use Digoxin, Inamrinone, or Milrinone from the above drugs (even though they are classified as CHF stage 4 drugs). This drugs are used for a patient that may have more severe symptoms and long term heart failure. The patient should be couseled on not combining Digoxin with Quinidine because of increased digoxin levels via P-GP efflux. Also, the patient should be told to avoid thiazide diuretics for added effects on electrolytes via NaK transport (hypokalemia).
Work #2 by LG-W26-Boyce, Fredette, Kum, Padron, Shindo, and Zbikowski
I don't have much personal experience with these drugs, but milrinone is used more for patients with stage 4 CHF. Classification into the correct category is difficult based on the information from the case, but it appears to be stage 2. I would just be using an IV loop such as furosemide, torsemide or bumetanide. If needed there are better alternatives to digoxin to lower heat rate like IV vasodilators. As an outpatient, options include ACE, ARB, diuretic, vasodilators, beta blockers. Purely in reference to the drugs listed above, digoxin coule be used to increase the contractility of the heart and improve its pumping. It is important for the patient to take the exact amount prescribed on a regular basis in order to maintain the plasma levels within the therapeutic range (~1). Milrinone has a similar effect, with fewer side effects, but is not frequently used in a clinical setting.
4. Name the structures below and discuss their stereochemical features (Plerase upload your files)
Work #1 by LG-W27-Boyd, Gandhi, Lally, Paige, and Shoemaker
The aglycone portion of these chemical structures (cardiac glycosides) is the steroid nucleus of the drug. This nucleus consists of Rings A-B and C-D which are cis fused compared to the B-C rings that have a trans configuration. This fusion gives the cardiac glycosides a “U-shape.” Carbon 10 and 13 usually has two angular methyl groups and hydroxyl groups are located at the C-3 (the site of sugar attachment) and at C-14, which is usually unsubstituted. C-12 and C-16 may also have hydroxyl groups, which distinguishes one genin from another (e.g. digitoxigenin, digoxigenin, and gitoxigenin). These hydroxyls have a large impact on the partitioning and pharmacokinetics for each gylcoside. The lactone ring at the C-17 is another important structural feature of cardiac aglycones. (Foyes, pg 699)
Work #2 by LG-W28: Broek, Gemma, Le, Park, and Simonds Problem sets (MS Word; PDF)
Please go to the following link to view the strutues. The answer for all the structures is the same and is as follows: These are all cardiac glycosides. The aglycone portion has the steroid nucleus. Rings A-B and C-D are cis fused and rings B-C have a trans configuration. The steroid nucleus has methyl groups at C-10 and C-13 and hydroxyl groups at C-3. The site of sugar attachment is C-14 (normally unsubstitued) however additional hydroxyl groups may be found at C-12 and C-16 (and have significant impact on the pharmacokinetics for each). Lactone ring at C-17 is a major structure. The size and degree of unstaturation varies with the glycoside. Hydroxyl at C-3 is usually conjugated to a mono or polysacchariede with B-1-4 glucosidic linkages. The number and identity of the sugars vary from one glycoside to another.
Who answered these? The structures are a aglycone, cholic acid, cholesterol and pregnelone.
Case Study (Foye’s) “LM is an 80-year-old, black female resident in the Sweet Azalea's assisted-living facility where you are the consulting pharmacist. LM is a bright, intelligent widow, who visits with her children through cyberspace on her laptop. Her stage 1 (mild) hypertension is controlled with an angiotensin-converting enzyme (ACE) inhibitor, enalapril. However, LM has just been diagnosed with congestive heart failure (CHF), characterized by loss of appetite, constipation, ankle edema, and slight hepatomegaly, indicative of right ventricular dysfunction. Her physician wants to begin treatment with a cardiac glycoside or other positive inotropic agent and a diuretic, furosemide.”
1. Define the following terms
(a-b) LG-W21-Bello, Dowjat, Kaur, Obiakwata, Sallout, and Wilson
a. Positive inotropic agents and negative inotropic agents. Please give examples.
Positive inotropic agents increase myocardial contractility, and are used to support cardiac function. Ex. Cardiac Glycosides- Digoxin and Catecholamines-Dobutamine. Negative inotropic agents decrease myocardial contractility, and are used to decrease cardiac workload. Ex-Beta Blocker, Calcium channel blockers (Verapamil and Diltiazem)
b. Glycone and aglycone
Glycone-any compound containing a carbohydrate moiety (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into a sugar and a nonsugar component (aglycone), and named specifically after the sugar contained, as glucoside (glucose).
Aglycone -the nonsugar component of a glycoside molecule that results from the hydrolysis of the molecule.
(c-e) LG-W22: Bhalodia, El-Zoghbi, Kazinich, Odumuko, Seth, and Wong
c. Glycoside and glycosidic bond
Glycosides are molecules in which a sugar is bound to a non-carbohydrate moiety, like a small organic molecule.
Glycosidic bond is a type of functional group that joins a sugar group to another group. This other group may or may not be a carbohydrate.
d. Anomer
Anomer is a special type of epimer, that is a stereoisomer of a cyclic saccharide that differs only in its configuration at the hemiacetal or hemiketal carbon.
e. Mutarotation
Mutarotation refers to a change in specific rotation of a cyclic monosaccharide. This occurs as the molecule reaches an equilibrium between its alpha and beta form.
2. Please fill out the blank areas with appropriate key words (Please upload your files)
Work #1 by LG-W23-Blagg, Enwonwu, Kebulu, O'Halloran, Shah, Wood
MIlrenone - pDE3 inhibitorDigitoxin
Digoxin - more water soluble
Work #2 by LG-W24-Blomgren, Erickson, Khodadadian, Opoku, Mensah, Sargent, Shateva, and Xhai
The first structure is milrinone, a phosphodiesterase III inhibitor. Milrinone is more potent compared to inamrinone, another PDE-III inhibitor. Milrinone is also better tolerated, having fewer side effects. It is excreted largely unchanged in the urine, therefore renal dysfunction should be considered when dosing.
The second structure is digitoxin, derrived from lanatoside A
The third structure is digoxin, derrived from lanatoside C-these both inhibit the Na/K/ATPase pump, as more OH groups are on the structure they are more water soluble.
3. Discuss additional drug therapies available for this patient in addition to ACE inhibitors, specifically the drugs listed in the above table. Based on your professional knowledge, provide your counseling tips to the patient.
this question has a lot more input required than the others...
Work #1 by LG-W25-Bourque, Fiore, Khorassani, Orock, Shim, and Youkhanna
Patient appears to be classified as stage 2, therefore the patient could use Digoxin, Inamrinone, or Milrinone from the above drugs (even though they are classified as CHF stage 4 drugs). This drugs are used for a patient that may have more severe symptoms and long term heart failure. The patient should be couseled on not combining Digoxin with Quinidine because of increased digoxin levels via P-GP efflux. Also, the patient should be told to avoid thiazide diuretics for added effects on electrolytes via NaK transport (hypokalemia).
Work #2 by LG-W26-Boyce, Fredette, Kum, Padron, Shindo, and Zbikowski
I don't have much personal experience with these drugs, but milrinone is used more for patients with stage 4 CHF. Classification into the correct category is difficult based on the information from the case, but it appears to be stage 2. I would just be using an IV loop such as furosemide, torsemide or bumetanide. If needed there are better alternatives to digoxin to lower heat rate like IV vasodilators. As an outpatient, options include ACE, ARB, diuretic, vasodilators, beta blockers. Purely in reference to the drugs listed above, digoxin coule be used to increase the contractility of the heart and improve its pumping. It is important for the patient to take the exact amount prescribed on a regular basis in order to maintain the plasma levels within the therapeutic range (~1). Milrinone has a similar effect, with fewer side effects, but is not frequently used in a clinical setting.
4. Name the structures below and discuss their stereochemical features (Plerase upload your files)
Work #1 by LG-W27-Boyd, Gandhi, Lally, Paige, and Shoemaker
The aglycone portion of these chemical structures (cardiac glycosides) is the steroid nucleus of the drug. This nucleus consists of Rings A-B and C-D which are cis fused compared to the B-C rings that have a trans configuration. This fusion gives the cardiac glycosides a “U-shape.” Carbon 10 and 13 usually has two angular methyl groups and hydroxyl groups are located at the C-3 (the site of sugar attachment) and at C-14, which is usually unsubstituted. C-12 and C-16 may also have hydroxyl groups, which distinguishes one genin from another (e.g. digitoxigenin, digoxigenin, and gitoxigenin). These hydroxyls have a large impact on the partitioning and pharmacokinetics for each gylcoside. The lactone ring at the C-17 is another important structural feature of cardiac aglycones.
(Foyes, pg 699)
Work #2 by LG-W28: Broek, Gemma, Le, Park, and Simonds
Problem sets (MS Word; PDF)
Please go to the following link to view the strutues. The answer for all the structures is the same and is as follows:
These are all cardiac glycosides. The aglycone portion has the steroid nucleus. Rings A-B and C-D are cis fused and rings B-C have a trans configuration. The steroid nucleus has methyl groups at C-10 and C-13 and hydroxyl groups at C-3. The site of sugar attachment is C-14 (normally unsubstitued) however additional hydroxyl groups may be found at C-12 and C-16 (and have significant impact on the pharmacokinetics for each). Lactone ring at C-17 is a major structure. The size and degree of unstaturation varies with the glycoside. Hydroxyl at C-3 is usually conjugated to a mono or polysacchariede with B-1-4 glucosidic linkages. The number and identity of the sugars vary from one glycoside to another.
Who answered these? The structures are a aglycone, cholic acid, cholesterol and pregnelone.