Lipid lowering drugs, Drugs to treat Diabetes

Question 1

What are the steps in plaque formation and growth?

Answer 1

1) Cholesterol particles infiltrate the wall of the artery at the site of the damaged inner lining of the artery
2) Plaque develops in the artery
3) As more cholesterol and materials are incorporated into the plaque, the plaque grows
4) The plaque may continue to grow blocking blood flow through the artery or
5) The plaque may rupture and blood clots may form, completely blocking blood flow through the artery

Question 2

What are “bad cholesterols”?

Answer 2

LDL - stores cholesterol in the blood stream

Question 3

What are “good cholesterols”?

Answer 3

HDL - regulates LDL storage and promotes excretion

Question 4

What contributes to plaque buildup?

Answer 4

LDLs
Triglycerides
Inflammatory component

Question 5

What are some mechanical procedures to treat plaque buildup in the circulatory system?

Answer 5

Balloon angioplasty to treat blocked coronary artery
Stent placement in carotid artery
High pressure jetting

Question 6

Dyslipidemia

Answer 6

High cholesterol

An imbalance of lipids circulating in the blood stream

Question 7

What are drugs used to treat dyslipidemia?

Answer 7

Derivatives of fibric acid
Nicotinic acid
Bile Acid sequestrants
Inhibitors oh HMG CoA Reductase
Cholesterol absorption inhibitors

Question 8

What do fibric acids do?

Answer 8

Increase peripheral lipolysis

Decrease hepatic triglyceride production

Question 9

What are side effects of fibric acid derivatives?

Answer 9

Abdominal discomfort
Diarrhea
Nausea
Blurred vision
Increased risk of gallstones
Prolonged prothrombin time
Liver studies may show increased function

Question 10

What are the two mechanisms of action for Nicotinic acid?

Answer 10

1) Agonist for GPR 109A and 109B receptors

2) Inhibitor of diacylglycerol acyltransferase

Question 11

What is the result of using Nicotinic acid?

Answer 11

Increase HDL-particles

Decrease Triglyceride

Question 12

What are the side effects of nicotinic acid?

Answer 12

Flushing (due to histamine release)
Pruritis (itching)
GI distress

Question 13

What happens to cholesterol in the liver?

Answer 13

It is converted to bile acid, which is excreted to the intestine through the action of C7H
By preventing bile acid resorption, the sequestrants increase cholesterol metabolism to bile acid

Question 14

What are the major actions of bile acid sequestrants?

Answer 14

Reduce LDL-C 15-30%
Increase HDL-C 3-5%
May increase TG

Question 15

What are the major side effects of Bile acid sequestrants?

Answer 15

GI distress/constipation

Decreased absorption of other drugs

Question 16

Inhibitors of HMG CoA Reuctase

Answer 16

HMG-CoA reductase is an enzyme along the pathway of cholesterol synthesis
By inhibiting it, it prevents the synthesis of cholesterol

Question 17

Statins (HMG-CoA Reductase inhibitor) lowers cholesterol, but do they help people live longer?

Answer 17

The current prevailing opinion is that they are helpful for people at risk of having a heart attack

Question 18

NPC1L1

Answer 18

A transport protein moving cholesterol from the lumen into the enterocyte and ultimately back into the blood
Blocked by Ezetimbie (Cholesterol Absorption inhibitor)

Question 19

What do Cholesterol Absorption inhibitors do?

Answer 19

Inhibit absorption of both dietary and biliary cholesterol

Lower LDL formation - increases expression of hepatic LDL receptors

Question 20

What is the mechanism of Cholesterol Absorption inhibitors?

Answer 20

Inhibit LDL formation by increasing hepatic LDL receptors and taking it up to be secreted

Question 21

What are adverse effects of Cholesterol Absorption inhibitors?

Answer 21

Mild abdominal pain and diarrhea

Question 22

What is a major complication of diabetes that WE care about (hint, hint)

Answer 22

Dental disease

Question 23

Glycogenesis

Answer 23

Process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage
(glucose –> glycogen)

Question 24

Glycogenolysis

Answer 24

The reverse process to glycogenesis
The breakdown of glycogen to Glucose-6-Phosphate and glycogen
(glycogen –> glucose)

Question 25

Gluconeogenesis

Answer 25

Metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate One of the two main mechanisms used to maintain blood-glucose levels (Carbon substrates --> glucose)

Question 26

What are the principal hormones regulating blood sugar levels?

Answer 26

Glucagon | Insulin

Question 27

What cells secrete glucagon?

Answer 27

alpha cells

Question 28

What cells secrete insulin?

Answer 28

beta cells

Question 29

A1C test

Answer 29

Measures glycation of hemoglobin | It provides a window into the average blood sugar of an individual over a period of months

Question 30

What are the ranges of A1c test scores

Answer 30

Excellent = 4-6 Good = 7-8 Action suggested = 9-14

Question 31

What are the actions of insulin?

Answer 31

``` Glucose uptake Glycolysis Glycogen syntesis Protein synthesis Uptake of Ions Stop gluconeogenesis Stop glucogenolysis Stop liposysis Stop ketogenesis Stop proteolysis ```

Question 32

Type 1 diabetes

Answer 32

Not enough insulin, so cells can't absorb glucose

Question 33

Type 2 diabetes

Answer 33

Cells do not respond to insulin, so cells can't absorb glucose

Question 34

What drugs can be used to treat diabetes?

Answer 34

``` Insulin Sulfonylureas Meglitinides Drugs working on GLP-1 receptors Biguanides Thiazolidinediones a-glucosidase inhibitors ```

Question 35

Secretagogues

Answer 35

A K+ channel that regulates insulin release from pancreatic B cells by sensing ATP/ADP

Question 36

What happens to secretagogues when ATP/ADP is low (fasting)

Answer 36

The channel opens, the cell hyperpolarizes, L-type Ca channels close, and insulin is not secreted

Question 37

What happens to secretagogues when ATP/ADP is high (after a meal)

Answer 37

Channel is closed, cell depolarizes, L-type Ca channels open, and insulin is secreted

Question 38

What drugs affect the secretagogues process?

Answer 38

Sulfonylureas Meglitinides Drugs working on GLP-1 receptors

Question 39

Sulfonylureas

Answer 39

Have a duration of 12-24 hours | Used to generally beat down glucose levels

Question 40

Sulfonylureas mechanism

Answer 40

Sulfonylureas binds to an ATP/ADP regulated K channel complex, reducing the efflux of K ions, leading to the channel to close, depolarizing the membrane, leading to an influx of Ca and secretion of insulin

Question 41

Meglitinides

Answer 41

More rapid onset of action and shorter duration than sulfonylureas Used before meals Hypoglycemia is a concern if drug is taken and person doesn't eat

Question 42

Meglitinides mechanism

Answer 42

Very similar to Sulfonylureas Binds to a ATP/ADP regulated K channel complex, reducing the efflux of K ions, leading to the channel to close, depolarizing the membrane, leading to an influx of Ca and secretion of insulin

Question 43

GLP-1 receptor

Answer 43

Glucagon-like peptide 1 (GLP-1) and Glucose dependent insulinotropic polypeptide (GIP) act at the GLP-1 receptor on B cells and stimulate insulin release

Question 44

Metformin (Biguinide)

Answer 44

A first-line medication used for treatment of type 2 diabetes in conjunction with diet, exercise, and weight loss Does no stimulate insulin secretion, but is insulin 'sparing' Usually not accompanied by hypoglycemia

Question 45

What is the mechanism of action of metformin?

Answer 45

Decrease hepatic glucose produciton through a mild inhibition of the mitochondrial respiratory-chain complex Decreases intestinal absorption of glucose

Question 46

Thiazolidinediones

Answer 46

Decrease insulin resistance | Agonists of the peroxisome proliferator-activated receptor y (PPAR-y)

Question 47

Insulin resistance

Answer 47

Pathological condition in which cells fail to respond to the normal actions of insulin

Question 48

What happens when the body produces insulin under the condition insulin resistance?

Answer 48

The cells in the body are unable to use it efficiently, leading to high blood sugar

Question 49

PPAR-y

Answer 49

Regulates fatty acid storage and glucose metabolism | The genes activated by PPAR-y stimulate lipid uptake and adipogenesis by fat cells

Question 50

What do PPAR-y agonist do?

Answer 50

Diminish insulin resistance

Question 51

a-glucosidase inhibitors

Answer 51

Act by inhibiting the digestion of glucose | Delay digestion and absorption of carbs in the GI tract

Question 52

a-glucosidase

Answer 52

Breaks down starch and disaccharides to glucose