Endocrine Pharmacology Flashcards
Endocrine Pharmacology
Insulin
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
Endocrine Pharmacology
Rapid-acting insulin examples
Lispro, Aspart, Glulisine
Endocrine Pharmacology
Intermediate-acting insulin examples
NPH
Endocrine Pharmacology
Long-acting insulin examples
Detemir, glargine
Endocrine Pharmacology
Biguanides (metformin)
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)
Endocrine Pharmacology
Sulfonylureas (1st gen: chlorpropamide, tolbutamide; 2nd gen: glimepiride, glipizide, glyburide)
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
Endocrine Pharmacology
Glitazones/thiazolidinediones (pioglitazone, rosiglitazone)
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
Endocrine Pharmacology
Meglitinides (nateglinide, repaglinide)
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
Endocrine Pharmacology
GLP-1 analogs (Exenatide, liraglutide)
MOA: ↑ glucose-dependent insulin release, ↓ glucagon release, ↓ gastric emptying, ↑ satiety
Use: Type 2 DM
Risks/Concerns: Nausea, vomiting, pancreatitis, modest weight loss
Endocrine Pharmacology
DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin)
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
Endocrine Pharmacology
Amylin analogs (pramlintide)
MOA: ↓ glucagon, ↓ gastric emptying
Use: Type 1 and 2 DM
Risks/Concerns: Hypoglycemia (in setting of mistimed prandial insulin), nausea
Endocrine Pharmacology
Sodium-glucose cotransporter 2 (SLGT-2) inhbitors (canaglifozin, dapaglifozin, empaglifozin)
MOA: Block reabsorption of glucose in PCT
Use: Type 2 DM
Risks/Concerns: Glucosuria, UTIs, vaginal yeast infections, hyperkalemia, dehydration (orthostatic hypotension)
Endocrine Pharmacology
α-glucosidase inhibtors (acarbose, miglitol)
MOA: Inhibit intestinal brush-border α-glucosidases. Delayed carbohydrate hydrolysis and glucose absorption → ↓ postprandial hyperglycemia
Use: Type 2 DM
Risks/Concerns: GI disturbances
Endocrine Pharmacology
Thionamides (PTU, methimazole)
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)
Endocrine Pharmacology
Levothyroxine (T4), triiodothyronine (T3)
MOA: Thyroid hormone replacement
Use: Hypothyroidism, myxedema. Used off-label as weight loss supplements.
Adverse Effects: tachycardia, heat intolerance, tremors, arrhythmias
Endocrine Pharmacology
ADH antagonists (conivaptan, tolvaptan)
Use: SIADH, block action of ADH at V2-receptors
Endocrine Pharmacology
Desmopressin acetate
Use: Central (not nephrogenic) DI
Endocrine Pharmacology
GH
Use: GH deficiency, Turner syndrome
Endocrine Pharmacology
Oxytocin
Use: Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.
Endocrine Pharmacology
Somatostatin (octreotide)
Use: Acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices
Endocrine Pharmacology
Demeclocycline
MOA: ADH antagonist (tetracycline family)
Use: SIADH
Adverse effects: nephrogenic DI, photosensitivity, abnormalities of bone and teeth
Endocrine Pharmacology
Glucocorticoids (beclomethasone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, triamcinolone)
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
Endocrine Pharmacology
Fludrocortisone
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
Endocrine Pharmacology
Cinacalcet
MOA: Sensitizes Ca2+-sensing receptor (CaSr) in parathyroid gland to circulating Ca2+ → ↓ PTH
Use: 1° or 2° hyperparathyroidism
Adverse Effects: Hypocalcemia
