Endocrine drugs Flashcards
Treatment strategy for Type 1 DM
low-carb diet, insulin replacement
Treatment strategy for Type 2 DM
diet and exercise; oral agents, non-insulin injectables, insulin replacement
Treatment strategy for gestational DM
dietary and exercise modifications, insulin replacement if that fails
Insulin, rapid acting
Aspart, Glulisine, Lispro
Mechanism: Binds insulin receptor
- liver: increased glucose stored as glycogen
- muscle: increased glycogen, protein synthesis; increased K+ uptake
- fat: increased TG storage
Use: Type 1 and 2 DM, Gestational DM (postprandial glucose control)
Toxicity: Hypoglycemia, rare hypersensitivity rxn
Insulin, short acting
insulin
Uses: Type 1 and 2 DM, Gestational DM, *DKA (IV), hyperkalemia (+glucose), stress hyperglycemia
Insulin, intermediate acting
NPH
Use: Type 1 and 2 DM, GDM
Insulin, long acting
Detemir, Glargine
Use: Type 1 and 2 DM, GDM (basal glucose control)
Metformin
Drug class: Biguanides
Action: exact mech unknown, decreases gluconeogenesis, increases glycolysis, increases peripheral glucose uptake (increased insulin sensitivity)
Use: Oral. 1st line in T2DM, causes modest weight loss. Can be used in patients w/out islet fxn
Toxicity: GI upset (can cause decreased B12 and folate absorption) Lactic acidosis (most serious side effect) -> contraindicated in: renal insufficiency, CHF, liver dysfunction, sepsis, EtOH abuse
Sulfonylureas
1st gen: Chlorpropamide, Tolbutamide
2nd gen: Glimepiride, Glipizide, Glyburide
Mechanism: Closes K+ channel in beta-cell membrane -> cell depolarizes -> increases insulin release via increased calcium influx
Use: T2DM; requires some islet fxn so useless in T1DM
Toxicity:
Weight gain
Cardiac effects (sulfonylurea channels in heart too)
Hypoglycemia risk increase in renal failure
1st gen: disulfiram-effects
2nd gen: hypoglycemia
Glitazones/ Thiazolidinediones
Pioglitazone, Rosiglitazone
Mechanism: Binds to PPAR-gamma nuclear transcription regulator -> increases insulin sensitivity in peripheral tissue; PPAR-gamma regulates fatty acid storage and glucose metabolism –> activation will increase insulin sensitivity and adiponectin levels
Clinical use: Used as monotherapy in T2DM or combined with other oral hypoglycemic drugs
Toxicity: Weight gain, edema
Hepatotoxicity, HF, increased risk of fractures
Increased LDL, HDL
Meglitinides (repaglinide)
Mechanism: Similar to sulfonylureas without sulfa; Close ATP dependent K+ channels -> increase insulin release. Short half life, metabolized by CYPs to glucuronic acid
Clinical use: T2DM with sulfa allergy
Toxicity:
GLP-1 analogs
Exenatide, Liraglutide
Mechanism: GLP-1= glucagon like peptide, incretin released by stomach when food is present. Increase insulin, decrease glucagon release.
Clinical use: Type 2 DM
Toxicity: Nausea, vomiting, pancreatitis
DDP-4 Inhibitors
Linagliptin, Saxagliptin, Sitagliptin
Mechanism: Increases insulin, decreases glucagon
Clinical use: T2DM
Toxicity: Mild urinary or respiratory infections
Amylin analogs
Pramlintide
Mechanism: Decreases gastric emptying, decreases glucagon
Clinical use: T1DM and T2DM
Toxicity: Hypoglycemia, nausea, diarrhea
SGLT-2 inhibitors
Canagliflozin
Mechanism: Block reabsorption of glucose in PCT
Clinical use: T2DM
Toxicity: Glucosuria, UTIs, vaginal yeast infections
alpha-glucosidase inhibitors
Acarbose, Miglitol
Mechanism: Inhibit brush-border alpha-glucosidases. Delayed carbo hydrolysis and glucose absorption -> decreases postprandial hyperglycemia (given w/ meals)
Clinical use: Can be monotherapy in T2DM or combo
Toxicity: GI disturbances- malabsorption diarrhea, can lower absorption of other drugs
Propylthiouracil (PTU), methimazole
Mechanism: Block thyroid peroxidase, inhibiting the oxidation of iodide, and organification of iodine -> inhibits thyroid hormone synthesis
PTU also inhibits 5’-deiodinase which decreases peripheral conversion of T4->T3
Clinical use: Hyperthyroidism; PTU blocks peripheral conversion, used in pregnancy
Toxicity: Skin rash, agranulocytosis (rare), aplastic anemia,
hepatotoxicity (PTU)
Methimazole is possible teratogen (aplasia cutis)
Levothyroxine (T4), Triiodothyronine (T3)
Mechanism: Thyroid hormone replacement
Clinical use: Hypothyroidism, myxedema; used off-label as weight loss supplements
Toxicity: Tachycardia, heat intolerance, tremors, arrhythmias
Demeclocycline
Mechanism: ADH antagonist (tetracycline family)
Clinical use: SIADH
Toxicity: nephrogenic DI, photosensitivity, abnormalities of bone and teeth
Glucocorticoids
Beclomethazone, dexamethasone, fludrocortisone (mineralo- and glucocorticoid activity), hydrocortisone, methylprednisolone, prednisone, triamcinolone
Mechanism: Interacts with glucocorticoid response elements, inhibits phospholipase A2 and inhibits TFs like NF-kB. Metabolic, catabolic, anti-inflammatory and immunosuppressive effects
Clinical use: Adison disease, inflammation, immunosuppression, asthma
Toxicity:
- Cushing syndrome (HTN, weight gain, moon facies, truncal obesity, buffalo hump, thinning skin, striae, osteoporosis, hyperglycemia, amenorrhea, immunosuppression)
- Adrenocortical atrophy
- Peptic ulcers
- Steroid diabetes
- Steroid psychosis
- Adrenal insufficiency when stopped abruptly
Cinacalcet
Mechanism: Sensitizes calcium sensing receptor (CaSR) in parathyroid gland to circulating calcium -> decreases PTH
Clinical use: hypercalcemia due to primary or secondary hyperparathyroidism
Toxicity: hypocalcemia
ADH antagonists
conivaptan, tolvaptan
Mech: Block action of ADH at V2 receptor
Clinical use: SIADH
Desmopressin acetate
Use: central (NOT nephrogenic) DI
Also used in von Willlebrand disease -> induces procoagulation factors including vWF
GH
GH deficiency, Turner Syndrome
