USMLE (Fach) / Pharmacology - Endocrine (Lektion)
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- Metformin Biguanide. Oral drug. Inhibit hepatic gluconeogenesis and the action of glucagon, by inhibiting mGPD. ↓ gluconeogenesis, ↑ glycolysis, ↑ peripheral glucose uptake (↑ insulin sensitivity) Clinical ...
- Sulfonylureas 1st generation: Chlorpropamide, tolbutamide2nd generation: Glipizide (short-acting), glyburide, glimeperide (long-acting) Close K+ channel in β-cell membrane → cell depolarizes → insulin release ...
- Glitazones/thiazolidinediones Pioglitazone, rosiglitazone Binds to PPAR-γ nuclear transcription regulator → ↑ insulin sensitivity and levels of adiponectin → regulation of glucose metabolism and fatty acid storage. Used ...
- Thioamides Propylthiouracil (PTU), methimazole Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis. Propylthiouracil ...
- Cinacalcet Sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ → ↓ PTH Clinical use: Refractory hypercalcemia in 1° or 2° hyperparathyroidism, or parathyroid carcinoma Adverse ...
- Fludrocortisone Synthetic analog of aldosterone with little glucocorticoid effects. Clinical use: Mineralocorticoid replacement in 1° adrenal insufficiency. Adverse effects: Similar to glucocorticoids; also edema, exacerbation ...
- ADH antagonists Conivaptan, tolvaptan Clinical use: SIADH, block action of ADH at V2-receptor
- Desmopressin Clinical use: - Central (not nephrogenic) diabetes insipidus- von Willebrand disease- Sleep enuresis- Hemophilia A
- GH Clinical use: GH deficiency, Turner syndrome
- Oxytocin Clinical use: - Labor induction (stimulates uterine contractions)- Milk let-down- Controls uterine hemorrhage
- Somatostatin Ocreotide Clinical use: - Acromegaly- Carcinoid syndrome- Gastrinoma- Glucagonoma- Esophageal varices
- Demeclocycline ADH antagonist (member of tetracycline family) Clinical use: SIADH Adverse effects: Nephrogenic DI, photosensitivity, abnormalities of bone and teeth
- Glucocorticoids Beclomethasone, dexamethasone, hydrocortisone, methylprednisolone, prenisone, triamcinolone Inhibition of phospholipase A2 and inhibition of transcription factors such as NF-κB. Clinical use: Adrenal ...
- Meglitinides Nateglinide, repaglinide Close K+ channel in β-cell membrane → cell depolarizes → insulin release via ↑ Ca2+ influx (binding site differs from sulfonylureas). Clinical use: Used as monotherapy ...
- GLP-1 analogs Exenatide, liraglutide (sc injection) ↑ glucose-dependent insulin release, ↓ glucagon release, ↓ gastric emptying, ↑ satiety Clinical use: Type 2 DM Risks/concerns: Nausea, vomiting, pancreatitis. ...
- DPP-4 inhibitors Linagliptin, saxagliptin, sitagliptin Inhibits DPP-4 enzyme that deactivates GLP-1. ↑ glucose-dependent insulin release, ↓ glucagon release, ↓ gastric emptying, ↑ satiety. Use: Type 2 DM Risks/concern: ...
- Amylin analogs Pramlintide (sc injection) ↓ gastric emptying, ↓ glucagon release, ↑ satiety Use: Type 1 DM, type 2 DM Risks/concerns: Hypoglycemia (in setting of mistimed prandial insulin), nausea
- Sodium-glucose co-transporter 2 (SGLT-2) inhibitors ... Canagliflozin, dapagliflozin, empagliflozin Block reabsorption of glucose in proximal convoluted tubule. Risks/concerns: Glucosuria, UTIs, vaginal yeast infections, hyperkalemia, dehydration (orthostatic ...
- α-glucosidase inhibitors Acarbose, miglitol Inhibit intestinal brush-border α-glucosidases → delayed carbohydrate hydrolysis and glucose absorption → ↓ postprandial hyperglycemia. Risks/concerns: GI disturbances- Not ...
- Insulin - rapid acting Lispro, aspart, glulisine Alteration of the amino acid structure at the C terminal of the insulin B chain prevents polymerization and allows rapid absorption from the injection site.Binds insulin receptor ...
- Insulin - short acting 2-3 hour peak Regular Use: Type 1 DM, type 2 DM, DKA (IV), hyperkalemia (+ glucose), stress hyperglycemia
- Insulin - intermediate acting 4-10 hour peak NPH Composed of a crystalline suspension of insulin with protamine and zinc. This delays absorption of insulin from the subcutaneous injection site.
- Insulin - long acting Detemir, glargine No real peak Detemir – Has a fatty acid bound to one of the lysine amino acids on the insulin molecule. This fatty acid side chain allows detemir to bind to albumin and slowly dissociate, ...
- Glipizide 2nd generation sulfonylurea - Short-acting
- Glyburide 2nd generation sulfonylurea - Long-acting
- Glimepiride 2nd generation sulfonylurea - Long-acting
- Nateglinide Meglitinide (sulfonylurea analog)
- Repaglinide Meglitinide (sulfonylurea analog)
- Injectible antidiabetic drugs - Insulin preparations - Amylin analogs - GLP-1 analogs
- -glitazone Glitazone/thiazolidinedione
- -gliptin DPP-4 inhibitors
- -gliflozin SGLT2 inhibitors
- Miglitol α-glucosidase inhibitor
- Levothyroxine (T4), Iiothyronine (T3) Thyroid hormone replacement Use: Hypothyroidism, myxedema.- May be abused for weight loss Adverse effects: Tachycardia, heat intolerance, tremors, arrhythmias
- Sevelamer Nonabsorbable phosphate binder that prevents phosphate absorption from the GI tract. Use: Hyperphosphatemia in CKD. Adverse effects: Hypophosphatemia, GI upset.
- Tesamorelin Growth-hormon-releasing-hormone analog Use: HIV-associated lipodystrophy
- Diabetes mellitus management All patients with diabetes mellitus should receive education on diet, exerise, blood glucose monitoring, and complication management. Treatment differs based on the type of diabetes:- Type 1 DM – insulin ...
- Pramlintide Amylin analog
- Chlorpropamide 1st generation sulfonylurea
- Tolbutamide 1st generation sulfonylurea
- Linagliptin DPP-4 inhibitor
- Saxagliptin DPP-4 inhibitor
- Sitagliptin DPP-4 inhibitor
- Hyperthyroidism treatment Beta blockers (eg, propanolol): Blunt the adrenergic manifestations while awaiting definitve management (eg, surgery, radioiodine). Reduce conversion of T4 to T3, by inhibiting 5'-monodeiodinase in peripheral ...
- Major drug interactions of levothyroxine ↓ Levothyroxine absorption:- Iron, calcium, aluminum hydroxide- Bile acid binding agents (eg, cholestyramine)- Proton pump inhibitors, sucralfate ↑ TBG concentration:- Estrogen (oral), tamoxifen, ...