BCM6233 Drugs for Endocrine and Metabolic Diseases

pancreas

A retroperitoneal gland made up of islets of Langerhans which are scattered and distributed randomly among the acini throughout the glandular substance of the exocrine portion.

exocrine pancreas

This part of the pancreas is a digestive gland made up of acinar tissue.

endocrine pancreas

This part of the pancreas is a smaller portion which makes up 1-2% of the total mass; where the islets of Langerhans are located.

Islets of Langerhans

These are the functional units of the endocrine pancreas, made up of clusters of hormone-secreting endocrine cells.

B cells

Hormone-secreting endocrine cells of the Islets of Langerhans that secrete 60-75% of insulin, proinsulin, C-peptide, and amylin.

A cells

Hormone-secreting endocrine cells of the Islets of Langerhans that secrete 25% glucagon, proglucagon, GLP-1, and GLP-2.

D cells

Hormone-secreting endocrine cells of the Islets of Langerhans that secrete 10% somatostatin.

F cells

Hormone-secreting endocrine cells of the Islets of Langerhans that secrete 1% pancreatic polypeptide.

preproinsulin

A large peptide precursor first synthesized by ribosomes of the rough ER.

proinsulin

Preproinsulin is cleaved into _________; this peptide is composed of a B and A chain with a connecting peptide between them.

insulin

A protein hormone synthesized in the pancreas that regulates blood sugar levels by facilitating the uptake of glucose into tissues.

insulin and C-peptide

In the process of conversion of proinsulin to insulin, 2 pairs of basic amino acid residues are clipped out of the proinsulin molecule resulting in the formation of (2):

40-50 units/day in adults (pulsatile and rhythmic)

How much insulin is secreted in units/day in adults?

8-10 minuntes

Basal insulin levels increase in about how many minutes after a meal?

40-45 minutes

Insulin levels after a meal peak within how many minutes?

unbound form

Insulin circulates in (bound, unbound) form/

6 minutes

How long is the plasma half-life of insulin?

incretins (GLP-1, GIP)

*oral glucose → gut → incretins → bigger insulin spike

*IV glucose → no gut → smaller insulin spike

The presence of _______ is what allows insulin to spike higher when the individual is given glucose orally compared to intravenously.

GLUT1 and GLUT3

These glucose transporters are in charge of basal glucose uptake and is found in RBCs and the endothelial lining of the blood vessels in the brain.

GLUT2

This glucose transporter is a β-cell sensor; found in the β-cells of the pancreas.

GLUT4

This glucose transporter is in charge of insulin-stimulated glucose uptake and is found in striated muscles and adipose tissue.

GLUT5

This glucose transporter is in charge of fructose transport and is found in the small intestine and sperm.

GLUT7

This glucose transporter is in charge of G6P transport in the liver.

Type 1 Diabetes Mellitus

This type of DM is the result of interactions of genetic, environmental, and immunologic factors that ultimately lead to immune-mediated destruction of the pancreatic β-cells and insulin deficiency.

True.

Type 1 DM can develop at any age but most commonly develops before 20 years of age.

T or F?

Type 2 Diabetes Mellitus

This type of DM is where insulin resistance and abnormal insulin secretion are central to the disease's development.

hyperglycemia

Type 2 DM likely encompasses a range of disorders with the common phenotype of __________.

1. Lispro

2. Aspart

3. Glulisine

What are the 3 rapid-acting insulin drugs (inject at the first bite during a meal)?

CLUE: Limang Asong Gago

Humulin R (regular)

What is an example of a short-acting insulin drug?

1. Neutral Protamine Hagedorn (NPH)

2. Lente (Humulin N)

What are 2 intermediate-acting insulin drugs?

1. Ultralente

2. Glargine

3. Detemir

4. Insulin Degludec

What are 4 long-acting insulin drugs?

CLUE: Uy Gaga De Iyan

activation of insulin receptors reduce the circulating glucose by increasing glucose uptake; promoting glucose transport and oxidation, glycogen lipid and protein synthesis and regulates gene expression

What is the MoA of insulin?

1. Type 1 and 2 DM

2. diabetic emergencies (diabetic ketoacidosis, hyperosmolar hyperglycemic state: rapid-acting)

3. hyperkalemia

What are the 3 uses of insulin?

1. hypoglycemia

2. insulin allergy

3. immune insulin resistance

4. weight gain

5. increased cancer risk

What are the 5 adverse effects of insulin?

1. chlopropamide

2. tolbutamide

3. tolazamide

What are the 1st generation secretagogues/sulfonylureas (oral hypoglycemics)?

CLUE: Come To Tol

1. glipizide

2. glimepiride

3. glyburide/glibenclamide

4. gliclazide

What are the 2nd generation secretagogues/sulfonylureas (oral hypoglycemics)?

CLUE: lahat Gli- ung una so: Please Meet Ben, Class

1. meglitinide

2. repaglinide

3. nateglinide

4. mitiglinide

What are the 3rd generation secretagogues (oral hypoglycemics/non-sulfonylureas)?

CLUE: Meg Reproduced Nat's Milk

increases insulin secretion from pancreatic β-cells by closing ATP-sensitive K+ channels

Type 2 DM

What is the use of 1st generation secretagogues/sulfonylureas?

Type 2 DM with functioning β-cells

What is the use of 2nd generation secretagogues/sulfonylureas?

Type 2 DM (postprandial hyperglycemia)

What is the use of 3rd generation secretagogues/non-sulfonylureas?

1. hypoglycemia

2. weight gain

3. hyperemic flush

4. dilutional hyponatremia

5. rash

6. hypersensitivity

What are the 6 adverse effects of 1st generation secretagogues/sulfonylureas?

1. hypoglycemia (less)

2. weight gain

3. photosensitivity

4. cholestatic jaundice (glibenclamide)

What are the 4 adverse effects of 2nd generation secretagogues/sulfonylureas?

1. hypoglycemia (least)

2. headache

3. upper respiratory tract infections

What are the 3 adverse effects of 3rd generation secretagogues/non-sulfonylureas?

metformin

What is an example of a sensitizer under biguanides?

1. pioglitazone

2. rosiglitazone

3. troglitazone

What are the 3 thiazolidinedione (sensitizers)?

CLUE: Pretty Rose Teehee

activates AMP-stimulated protein kinase leading to inhibition of hepatic and renal gluconeogenesis; increases peripheral glucose uptake.

What is the MoA of metformin (biguanide)?

regulates gene expression by binding to PPAR-γ and PPAR-α

What is the MoA of thiazolidinediones (sensitizers)?

type 2 DM (DoC for obese diabetics)

What is the use of metformin (biguanide)?

1. Type 2 DM

2. diabetes prevention

What are the 2 uses of thiazolidinedione (sensitizers)?

1. GI disturbance

2. weight loss

3. lactic acidosis*

4. Vit. B12 malabsorption

What are the 4 adverse effects of metformin (biguanide)?

1. fluid retention

2. anemia

3. weight gain

4. congestive heart failure

5. bone fractures especially in women

6. cardiovascular events (rosiglitazone)

7. hepatotoxicity (troglitazone0

8. macular edema

9. dyslipidemia (high HDL and LDL; low TG)

10. increased risk of myocardial infarction (rosiglitazone)

What are the 10 adverse effects of thiazolidinediones?

1. acarbose

2. miglitol

3. voglibose

What are the 3 α-glucosidase inhibitors?

CLUE: Ackkkk Mhie Vongga

pramlintide

What is an example of an amylin analog?

1. dapagliflozin

2. empagliflozin

3. canagliflozin

What are the 3 SGLT-2 inhibitors?

inhibits intestinal α-glucosidases

What is the MoA of α-glucosidase inhibitors?

activates amylin receptors

What is the MoA of pramlintide (amylin analog)?

inhibits Na+-Glc co-transporter 2 (SGLT-2)

What is the MoA of SGLT-2 inhibitors?

1. Type 2 DM

2. Diabetes prevention

What are the 2 uses of α-glucosidase inhibitors?

Type 1 and 2 DM

What is the use of pramlintide (amylin analog)?

Type 2 DM

What is the use of SGLT-2 inhibitors?

1. GI disturbance (flatulence, diarrhea, abdominal pain)

2. hypoglycemia

3. increased liver enzymes

What are the 3 adverse effects of α-glucosidase inhibitors?

1. hypoglycemia

2 GI disturbances

3. nausea

4. anorexia

5. headache

What are the 5 adverse effects of pramlintide (amylin analog)?

1. dizziness

2. strong smell of urine

3. edema

4. weakness

5. nausea

6. vomiting

7. decreased urine output

What are the 7 adverse effects of SGLT-2 inhibitors?

1. exenatide

2. liraglutide

3. lixisenatide

4. semaglutide

5. dulaglutide

What are the 5 GLP-1 agonists?

CLUE: Eating Liver Lovers Seem Disgusting

1. sitagliptin

2. saxagliptin

3. linagliptin

4. vildagliptin

5. teneligliptin

What are the 5 DPP-4 inhibitors?

CLUE: So Sassy Like Vongga Talaga

activates GLP-1 receptors; reduction of post-meal glucose excursions

What is the MoA of GLP-1 agonists?

inhibits dipeptidyl peptidase-4 that degrades GLP-1 and other incretins; reduces post-meal excursions

What is the MoA of DPP-4 inhibitors?

Type 2 DM

What is the use of GLP-1 agonists and DPP-4 inhibitors?

1. hypoglycemia

2. acute pancreatitis

3. nausea

4. vomiting

5. anorexia

6. mild weight loss

What are the 6 adverse effects of GLP-1 inhibitors?

1. headache

2. nasopharyngitis

3. upper respiratory tract infection

4. hypersensitivity reactions

5. pancreatitis

What are the 5 adverse effects of DPP-4 inhibitors?

1. proliferative (preparation for fertilization)

2. secretory (secretes lining (mens) if no fertilization)

What are the 2 phases of the endometrial cycle?

1. follicular phase

2. ovulation

3. luteal phase

What are the 3 phases of the ovarian cycle?

follicular phase

This first phase in the ovarian cycle occurs before ovulation; the primordial follicle develops into a mature follicle as the primary oocyte within undergoes the first meiotic division.

Day 1 - 14

How long is the follicular phase?

ovulation

The second phase in the ovarian cycle when the mature ovum is released into the fallopian tube each month.

luteal phase

The third phase in the ovarian cycle that occurs after ovulation; secretes progesterone and a small amount of estrogen if the fertilization of the secondary oocyte occurs.

The egg is prepped for fertilization at the ampulla, moves to the uterus if fertilization is successful; if not, follows with menstruation.

follicular-stimulating hormone (FSH)

The secretion of this hormone increases before ovulation which in turn stimulates follicles to develop and secrete estrogen.

estrogen

This hormone causes the endometrium to proliferate and the hypothalamus to increase luteinizing hormone (LH).

ovulation

The increase in luteinizing hormone (LH) secretion result in the LH and FSH surge prior to __________.

corpus luteum

The luteinizing hormone (LH) surge causes a follicle to mature and ovulate. The ____________ develops and secretes progesterone and some estrogen.

progesterone

This hormone causes hypertrophy of the endometrium and has a negative-feedback effect on LH and FSH secretion.

12 days

The corpus luteum continues to secrete progesterone for approximately how many days after ovulation?

menses

This refers to the period of a mild hemorrhage that occurs approximately once each month, during which the functional layer of the endometrium is sloughed and expelled from the uterus.

Occurs during the uterine cycle.

proliferative phase

This 1st phase in the uterine cycle occurs between the ending of menses and ovulation; the endometrium begins to regenerate and forms spiral glands.

secretory phase

This 2nd phase in the uterine cycle occurs after ovulation and before the next menses; the endometrium thickens and spiral glans further develop and began secreting fluid-rich glycogen.

1. ethinyl estradiol

2. mestranol

3. estradiol cypionate

4. estriol

What are 4 examples of estrogen drugs?

CLUE: Eto May Early Exit

diethylstilbestrol

What is an example of synthetic estrogen?

activates estrogen receptors; leads to changes in rates of transcription of estrogen-regulated genes

What is the MoA of estrogen/synthetic estrogen?

1. primary hypogonadism

2. postmenopausal hormonal replacement therapy

3. osteoporosis

4. contraception

5. intractable dysmenorrhea

What are the 5 uses of estrogen?

1. atrophic vaginitis

2. hormone replacement therapy

3. prevention of adverse pregnancy outcomes

4. metastic prostate cancer

What are the 4 uses of diethylstilbestrol (synthetic estrogen)?

1. breakthrough bleeding

2. nausea

3. breast tenderness

4. migraine

5. thromboembolism (DVTs)

6. gallbladder disease

7. hypertriglyceridemia

8. hypertension

9. premature closure of the epiphys in young females

10. increased risk of breast and endometrial cancer (remedy: add progesterone to the preparation)

What are the 10 adverse effects of estrogen/synthetic estrogen?

1. norgstrel

2. norethindrone

3. ethynodiol

4. megastrol

5. degogestrel

6. norelgestromin

7. norgestimate

8. etonogestrel

9. progesterone

10. levonorgestrel

11. dydrogesterone

What are the 11 progestins?

CLUE: God bless nalang

activates progesterone receptors; changes rates of transcription of progesterone-regulated genes

What is the MoA of progestins?

1. hormone replacement therapy (given together with estrogen to prevent estrogen-induced endometrial cancer)

2. contraception

3. assisted reproduction (for maintenance of pregnancy)

4. anovulation induction (given in high doses to suppress FSH and LH)

What are the 4 uses of progestins?

1. hypertension

2. decreased HDL

3. weight gain

4. reversible decrease in bone mineral density

5. delayed resumption of ovulation after use

What are the 5 adverse effects of progestins?

monophasic

This type of oral contraceptive is a combination of estrogen and progestin tablets that are taken in constant dosage throughout the menstrual cycle.

biphasic or triphasic

This type of oral contraceptive is a combination preparation in which progestin or estrogen dosage or both changes during the month.

progestin-only preparations

This type of oral contraceptive is recommended for breastfeeding moms since they do not affect lactation.

postcoital contraceptives/emergency contraception

This type of oral contraceptive is used to prevent pregnancy if administered within 72 hours after unprotected sex.

Can be progestin (L-norgestrel) alone, estrogen alone, or a combination of both.