Endocrine Pharmacology

Question 1

Endocrine Pharmacology

Insulin

Answer 1

MOA: Binds insulin receptor (tyrosine kinase activity)
Liver: ↑ glucose stored as glycogen
Muscle: ↑ glycogen, prtoein synthesis, ↑ K+ uptake
Fat: ↑ TG storage

Use: Type I & II DM, GDM

Risks/Concerns: Hypoglycemia, lipodystrophy, rare hypersensitivity reactions

Question 2

Endocrine Pharmacology

Rapid-acting insulin examples

Answer 2

Lispro, Aspart, Glulisine

Question 3

Endocrine Pharmacology

Intermediate-acting insulin examples

Answer 3

NPH

Question 4

Endocrine Pharmacology

Long-acting insulin examples

Answer 4

Detemir, glargine

Question 5

Endocrine Pharmacology

Biguanides (metformin)

Answer 5

MOA: Exact mechanism unknown. ↓ gluconeogenesis, ↑ glycolysis, ↑ peripheral glucose uptake (↑ insulin sensitivity)

Use: Oral. 1st line therapy in type 2 DM, causes modest weight loss. Can be used in patients without islet function.

Risks/Concerns: Most serious adverse effect = lactic acidosis (contraindicated in renal insufficiency)

Question 6

Endocrine Pharmacology

Sulfonylureas (1st gen: chlorpropamide, tolbutamide; 2nd gen: glimepiride, glipizide, glyburide)

Answer 6

MOA: Closes K+ channel in β-cell membrane → cell depolarizes → insulin release via ↑ Ca2+ influx

Use: Stimulates release of endogenous insulin in DM 2, useless in DM 1.

Risks/Concerns: Risk of hypoglycemia ↑ in renal failure, weight gain.
1st gen: disulfiram effects
2nd gen: hypoglycemia

Question 7

Endocrine Pharmacology

Glitazones/thiazolidinediones (pioglitazone, rosiglitazone)

Answer 7

MOA: ↑ insulin sensitivity in peripheral tissue, binds to PPAR-γ nuclear transcription regulator.

Use: Used as monotherapy in type 2 DM or combined with above agents. Safe in renal impairment

Risks/Concerns: Weight gain, edema, hepatotoxicity, HF, ↑ risk of fractures, ↑ risk of urinary bladder cancer with long term use

Question 8

Endocrine Pharmacology

Meglitinides (nateglinide, repaglinide)

Answer 8

MOA: Stimulate postprandial insulin release by binding to K+ chanels on β-cell membranes

Clinical Use: Used as monotherapy in DM 2 or combined with metformin

Risks/Concerns: Hypoglycemia (↑ risk with renal failure), weight gain

Question 9

Endocrine Pharmacology

GLP-1 analogs (Exenatide, liraglutide)

Answer 9

MOA: ↑ glucose-dependent insulin release, ↓ glucagon release, ↓ gastric emptying, ↑ satiety

Use: Type 2 DM

Risks/Concerns: Nausea, vomiting, pancreatitis, modest weight loss

Question 10

Endocrine Pharmacology

DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin)

Answer 10

MOA: Inhibits DPP-4 enzyme that deactivates GLP-1, thereby ↑ glucose-dependent insulin release, ↓ glucagon release, ↓ gastric emptying, ↑ satiety.

Use: Type 2 DM

Risks/Concerns: Mild urinary or respiratory infections; weight neutral

Question 11

Endocrine Pharmacology

Amylin analogs (pramlintide)

Answer 11

MOA: ↓ glucagon, ↓ gastric emptying

Use: Type 1 and 2 DM

Risks/Concerns: Hypoglycemia (in setting of mistimed prandial insulin), nausea

Question 12

Endocrine Pharmacology

Sodium-glucose cotransporter 2 (SLGT-2) inhbitors (canaglifozin, dapaglifozin, empaglifozin)

Answer 12

MOA: Block reabsorption of glucose in PCT

Use: Type 2 DM

Risks/Concerns: Glucosuria, UTIs, vaginal yeast infections, hyperkalemia, dehydration (orthostatic hypotension)

Question 13

Endocrine Pharmacology

α-glucosidase inhibtors (acarbose, miglitol)

Answer 13

MOA: Inhibit intestinal brush-border α-glucosidases. Delayed carbohydrate hydrolysis and glucose absorption → ↓ postprandial hyperglycemia

Use: Type 2 DM

Risks/Concerns: GI disturbances

Question 14

Endocrine Pharmacology

Thionamides (PTU, methimazole)

Answer 14

MOA: Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) of iodine → inhibition of thyroid hormone synthesis. PTU also blocks 5’-deiodinase → ↓ peripheral conversion of T4 to T3

Use: Hyperthyroidism. PTU used in pregnancy

Adverse Effects: Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity. Methimazole is possible teratogen ( can cause aplasia cutis)

Question 15

Endocrine Pharmacology

Levothyroxine (T4), triiodothyronine (T3)

Answer 15

MOA: Thyroid hormone replacement

Use: Hypothyroidism, myxedema. Used off-label as weight loss supplements.

Adverse Effects: tachycardia, heat intolerance, tremors, arrhythmias

Question 16

Endocrine Pharmacology

ADH antagonists (conivaptan, tolvaptan)

Answer 16

Use: SIADH, block action of ADH at V2-receptors

Question 17

Endocrine Pharmacology

Desmopressin acetate

Answer 17

Use: Central (not nephrogenic) DI

Question 18

Endocrine Pharmacology

GH

Answer 18

Use: GH deficiency, Turner syndrome

Question 19

Endocrine Pharmacology

Oxytocin

Answer 19

Use: Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.

Question 20

Endocrine Pharmacology

Somatostatin (octreotide)

Answer 20

Use: Acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices

Question 21

Endocrine Pharmacology

Demeclocycline

Answer 21

MOA: ADH antagonist (tetracycline family)

Use: SIADH

Adverse effects: nephrogenic DI, photosensitivity, abnormalities of bone and teeth

Question 22

Endocrine Pharmacology

Glucocorticoids (beclomethasone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, triamcinolone)

Answer 22

MOA: Metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements, inhibition of phospholipase A2, and inhibition of transcription factors (NF-κB)

Use: Adrenal insufficiency, inflammation, immunosuppression, asthma.

Adverse Effects: Iatrogenic Cushing syndrome, adrenocortical atrophy, peptic ulcers, steroid diabetes, steroid psychosis, cataracts. Adrena insufficiency when stopped abruptly after chronic use

Question 23

Endocrine Pharmacology

Fludrocortisone

Answer 23

MOA: Synthetic analog of aldosterone with little glucocorticoid effects.

Use: Mineralocorticoid replacement in 1° adrenal insufficiency

Adverse Effects: Similar to glucocorticooids; also edema, exacerbation of heart failure, hyperpigmentation

Question 24

Endocrine Pharmacology

Cinacalcet

Answer 24

MOA: Sensitizes Ca2+-sensing receptor (CaSr) in parathyroid gland to circulating Ca2+ → ↓ PTH

Use: 1° or 2° hyperparathyroidism

Adverse Effects: Hypocalcemia