“TLH is a 35-year-old, full-blooded, female member of the Navajo tribe. An artisan, she lives and works outside of Taos, New Mexico, and spends her days making and selling jewelry in a silver and turquoise shop. Like many women of Native American heritage, TLH has cholelithiasis (gallstones). Fortunately, her condition has been, for the most part, asymptomatic; and she has declined to have her gallbladder surgically removed. Her medical history also includes adult-onset diabetes mellitus, for which she is taking the sulfonylurea hypoglycemic agent chlorpropamide (250 mg daily). She has a family history of cardiovascular disease, and her father died after suffering a severe myocardial infarction (MI) secondary to atherosclerosis at the age of 63. Her liver and kidney function is normal.
TLH tries to keep her blood sugar and the symptoms of her cholelithiasis under control by monitoring her diet but finds it difficult to exercise regularly. In fact, she is getting no exercise at all these days, as she has been recuperating from surgery to repair a torn ligament in her left knee. Oral warfarin therapy has also been started to treat deep-vein thrombosis that commonly occurs after mobility-limiting surgery of this type. Her physician is recommending a longer course of therapy than usual (i.e., 4–6 months) owing to her sedentary lifestyle.
TLH's presurgery blood workup showed normal triglyceride levels, but a significant elevation of her total serum cholesterol (280 mg/dL) and low-density lipoproteins (LDL; 190 mg/dL). Her high-density lipoprotein (HDL) level is borderline-low (52 mg/dL).”
1. Please fill out the blank areas with appropriate key words
Work #1 by LG-M5: Alqahtani, Chaudhari, Foreman, Lauze, Poku, and Varieur structure 1: nicotinic acid
MOA: convert fats and proteins to glucose and assist in the oxidation of glucose.
SAR: water-soluble solid is a derivative of pyridine with a carboxyl group (COOH) at the 3-position. structure 2: fenofibrate
MOA: induces lipoprotein lipase and decreases hepatic production of apolipoprotein CIII via PPAR activity, which enhances plasma catabolism and clearance of triglyceride-rich particles.
SAR: isobutyric acid group is essential for activity. if contain an ester, is a pro-drug and requires in vivo hydrolysis. substitution at the para position of the aromatic ring with a chloro group or a chlorine containing isopropyl ring produces compounds with longer half-life. structure 3: fluvastatin
MOA: interferes with the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a hepatic enzyme. Inhibition of HMG-CoA reductase interrupts the pathway within the body responsible for the majority of human cholesterol biosynthesis.
SAR: replacement of various substituted aromatic rings. mimic the intermediate HMG CoA. structure 4: atorvastatin
MOA: interferes with the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a hepatic enzyme. Inhibition of HMG-CoA reductase interrupts the pathway within the body responsible for the majority of human cholesterol biosynthesis.
SAR: substitued pyrrole retains 30% of activity. bicyclic ring can be replaced with other lipophilic rings and size and shape of these rings were important to the overall activity of the compounds. mimic the intermediate HMG CoA. structure 5: cholestyramine
MOA: resin releases chloride and combines with bile acids in the intestine to form insoluble, nonabsorbable complexes that are excreted in the feces along with unchanged resin.
SAR: copolymer consisting primarily of polystyrene, with a small amount of divinylbenzene as the cross-linking agent. positively charged groups function as binding sites for anion.
Work #2 by LG-W5: Alberding, Carr, Guillemette, Loring, Patel, and Stover
2. Define and compare the following terms:
a. Triglyceride and triglycerol Triglyceride: glyceride in which the glycerol is esterified with three fatty acids. Triglycerides are a major component of vegetable oil and animal fat. Triglycerol: organic compound that has three hydrophilic hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. It forms the base upon which triglycerides are formed as it becomes esterified with three fatty acids.
b. Bile acid and bile salt Bile acid: steroid acids found predominately in the bile of mammals. They are made in the liver via the oxidation of cholesterol and conjugated with taurine, glycine, sulfate, or with a glucuronide to form a bile salt. Bile salt: is a bile acid conjugated to glycine or taurine.
LG-W15-Aubin, Dauphinais, Jashari, Nayar, Potvin, and Tran
a. Triglyceride: a naturally occurring ester of three fatty acids and glycerol which is the major constituent of fats and oils.
triglycerol: also know as triacylglyceride, is a glyceride in which the glycerol is esterified with 3 fatty acids.
LG-W16-Badavas, Davis, Jorgensen, Nelson, Pratt, and Vakil
b. Bile acid and bile salt
Bile salts are surface-active agents that act as anionic detergents. Cholesterol can be converted to bile acids and bile salts in the liver. Bile acids/salts can then be stored in the gallbladder and later released into the intestine. The terms bile acid and bile salt refer to the unionized and ionized forms, respectively, of these compounds. Bile salts are bile acids conjugated to an amino acid, usually glycine or taurine. Bile acids and salts help emulsify dietary lipids and fat soluble vitamins.
3. What are the diagnoses for this patient? Your clinic has the above drugs. Discuss the possible therapeutic uses of these compounds in this case.
Work #1 by LG-M6-Al-Ruthia, Cormier, Friesen, Lee, Potak, and Zamoiski
-This patient is diagnosed with 1. cholelithiasis (gallstones), 2. Diabetes Mellitus type 2, 3. post-op torn left knee ligament, 4. DVT, 5. dylipidemia (inc. TC and LDL, slight dec. HDL)
-Atorvastatin would be the best option to choose to help this patient decrease the LDL, and in turn, lower the TC. Statins also can increase HDL as well. However, there would need to be some monitoring because of the warfarin the patient also takes.
Work #2 by LG-W6-Aleksiewicz, Casavant, Haibi, Manouchehrian, Patel, and Sultan
Diagnoses
- cholelithiasis (gallstones) - DM 2
- torn ligament in her left knee
- dyslipidemia
Drugs
The bile acid will be good to help this patient decrease her LDL and slightly increase her HDL which will lead to an overall decrease in cholesterol.
4. If you notice some drug could interact with the drugs that the patient has already taken, please discuss it.
Work #1 by LG-M7-Anderson, DaCosta, Hannemann, McCarthy, and Raphael
atorvastatin will increase warfarin levels; may increase bleeding risk.
fibrates are contraindicated in cholelthiasis.
Work #2 by LG-W7: Aletti, Charron, Hamidi, Marcus, Patel, and Sureja Atorvastatin can interact with patient's warfarin. Atorvastatin increases the levels of Warfarin in body and this can lead to incresed risk of bleeding.
Also, patient has cholelthiasis, so fibrates are contraindicated as they may worsen the condition.
5. With your professional knowledge, please provide your counseling tips.
Work #1 by LG-M8-Ball, Decelle, Harkins, McMahon, and Sanford Atorvastatin:
- Do not take if pregnant or breast feeding
- Contraindicated in rhabdomyolysis, hepatitis, liver failure, and pregnancy.
- Avoid grapefruit juice
- If you notice muscle pain or weakness, contact your doctor.
- Monitor liver enzymes while on this medication
- Monitor INR and PT when taking with warfarin.
- Take this medication at the same time everyday to maximize effects.
Work #2 by LG-W8-Ali, Chau, Heinzelmann, Mathew, Patel, and Sylvestre
For Atorvastatin:
Avoid drinking grapefruit juice while taking this medication.
Let your doctor know if you start taking any new medications, as they may interact with this drug.
Do not use this medication if you become pregnant
You can take atorvastatin with or without food
Should be on a low-cholesterol diet to help manage your high cholesterol
Let your Dr know if you have any unexplained muscle pain or weakness
“TLH is a 35-year-old, full-blooded, female member of the Navajo tribe. An artisan, she lives and works outside of Taos, New Mexico, and spends her days making and selling jewelry in a silver and turquoise shop. Like many women of Native American heritage, TLH has cholelithiasis (gallstones). Fortunately, her condition has been, for the most part, asymptomatic; and she has declined to have her gallbladder surgically removed. Her medical history also includes adult-onset diabetes mellitus, for which she is taking the sulfonylurea hypoglycemic agent chlorpropamide (250 mg daily). She has a family history of cardiovascular disease, and her father died after suffering a severe myocardial infarction (MI) secondary to atherosclerosis at the age of 63. Her liver and kidney function is normal.
TLH tries to keep her blood sugar and the symptoms of her cholelithiasis under control by monitoring her diet but finds it difficult to exercise regularly. In fact, she is getting no exercise at all these days, as she has been recuperating from surgery to repair a torn ligament in her left knee. Oral warfarin therapy has also been started to treat deep-vein thrombosis that commonly occurs after mobility-limiting surgery of this type. Her physician is recommending a longer course of therapy than usual (i.e., 4–6 months) owing to her sedentary lifestyle.
TLH's presurgery blood workup showed normal triglyceride levels, but a significant elevation of her total serum cholesterol (280 mg/dL) and low-density lipoproteins (LDL; 190 mg/dL). Her high-density lipoprotein (HDL) level is borderline-low (52 mg/dL).”
1. Please fill out the blank areas with appropriate key words
Work #1 by LG-M5: Alqahtani, Chaudhari, Foreman, Lauze, Poku, and Varieur
structure 1: nicotinic acid
MOA: convert fats and proteins to glucose and assist in the oxidation of glucose.
SAR: water-soluble solid is a derivative of pyridine with a carboxyl group (COOH) at the 3-position.
structure 2: fenofibrate
MOA: induces lipoprotein lipase and decreases hepatic production of apolipoprotein CIII via PPAR activity, which enhances plasma catabolism and clearance of triglyceride-rich particles.
SAR: isobutyric acid group is essential for activity. if contain an ester, is a pro-drug and requires in vivo hydrolysis. substitution at the para position of the aromatic ring with a chloro group or a chlorine containing isopropyl ring produces compounds with longer half-life.
structure 3: fluvastatin
MOA: interferes with the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a hepatic enzyme. Inhibition of HMG-CoA reductase interrupts the pathway within the body responsible for the majority of human cholesterol biosynthesis.
SAR: replacement of various substituted aromatic rings. mimic the intermediate HMG CoA.
structure 4: atorvastatin
MOA: interferes with the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a hepatic enzyme. Inhibition of HMG-CoA reductase interrupts the pathway within the body responsible for the majority of human cholesterol biosynthesis.
SAR: substitued pyrrole retains 30% of activity. bicyclic ring can be replaced with other lipophilic rings and size and shape of these rings were important to the overall activity of the compounds. mimic the intermediate HMG CoA.
structure 5: cholestyramine
MOA: resin releases chloride and combines with bile acids in the intestine to form insoluble, nonabsorbable complexes that are excreted in the feces along with unchanged resin.
SAR: copolymer consisting primarily of polystyrene, with a small amount of divinylbenzene as the cross-linking agent. positively charged groups function as binding sites for anion.
Work #2 by LG-W5: Alberding, Carr, Guillemette, Loring, Patel, and Stover
2. Define and compare the following terms:
a. Triglyceride and triglycerol
Triglyceride: glyceride in which the glycerol is esterified with three fatty acids. Triglycerides are a major component of vegetable oil and animal fat.
Triglycerol: organic compound that has three hydrophilic hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. It forms the base upon which triglycerides are formed as it becomes esterified with three fatty acids.
b. Bile acid and bile salt
Bile acid: steroid acids found predominately in the bile of mammals. They are made in the liver via the oxidation of cholesterol and conjugated with taurine, glycine, sulfate, or with a glucuronide to form a bile salt.
Bile salt: is a bile acid conjugated to glycine or taurine.
LG-W15-Aubin, Dauphinais, Jashari, Nayar, Potvin, and Tran
a. Triglyceride: a naturally occurring ester of three fatty acids and glycerol which is the major constituent of fats and oils.
triglycerol: also know as triacylglyceride, is a glyceride in which the glycerol is esterified with 3 fatty acids.
LG-W16-Badavas, Davis, Jorgensen, Nelson, Pratt, and Vakil
b. Bile acid and bile salt
Bile salts are surface-active agents that act as anionic detergents. Cholesterol can be converted to bile acids and bile salts in the liver. Bile acids/salts can then be stored in the gallbladder and later released into the intestine. The terms bile acid and bile salt refer to the unionized and ionized forms, respectively, of these compounds. Bile salts are bile acids conjugated to an amino acid, usually glycine or taurine. Bile acids and salts help emulsify dietary lipids and fat soluble vitamins.
3. What are the diagnoses for this patient? Your clinic has the above drugs. Discuss the possible therapeutic uses of these compounds in this case.
Work #1 by LG-M6-Al-Ruthia, Cormier, Friesen, Lee, Potak, and Zamoiski
-This patient is diagnosed with 1. cholelithiasis (gallstones), 2. Diabetes Mellitus type 2, 3. post-op torn left knee ligament, 4. DVT, 5. dylipidemia (inc. TC and LDL, slight dec. HDL)
-Atorvastatin would be the best option to choose to help this patient decrease the LDL, and in turn, lower the TC. Statins also can increase HDL as well. However, there would need to be some monitoring because of the warfarin the patient also takes.
Work #2 by LG-W6-Aleksiewicz, Casavant, Haibi, Manouchehrian, Patel, and Sultan
Diagnoses
- cholelithiasis (gallstones)
- DM 2
- torn ligament in her left knee
- dyslipidemia
Drugs
The bile acid will be good to help this patient decrease her LDL and slightly increase her HDL which will lead to an overall decrease in cholesterol.
4. If you notice some drug could interact with the drugs that the patient has already taken, please discuss it.
Work #1 by LG-M7-Anderson, DaCosta, Hannemann, McCarthy, and Raphael
atorvastatin will increase warfarin levels; may increase bleeding risk.
fibrates are contraindicated in cholelthiasis.
Work #2 by LG-W7: Aletti, Charron, Hamidi, Marcus, Patel, and Sureja
Atorvastatin can interact with patient's warfarin. Atorvastatin increases the levels of Warfarin in body and this can lead to incresed risk of bleeding.
Also, patient has cholelthiasis, so fibrates are contraindicated as they may worsen the condition.
5. With your professional knowledge, please provide your counseling tips.
Work #1 by LG-M8-Ball, Decelle, Harkins, McMahon, and Sanford
Atorvastatin:
- Do not take if pregnant or breast feeding
- Contraindicated in rhabdomyolysis, hepatitis, liver failure, and pregnancy.
- Avoid grapefruit juice
- If you notice muscle pain or weakness, contact your doctor.
- Monitor liver enzymes while on this medication
- Monitor INR and PT when taking with warfarin.
- Take this medication at the same time everyday to maximize effects.
Work #2 by LG-W8-Ali, Chau, Heinzelmann, Mathew, Patel, and Sylvestre
For Atorvastatin: