Endocrine Drugs Flashcards
Treatment strategy for type 2 DM
Dietary modification and exercise for weight loss; oral hypoglycemics and insulin replacement
Treatment strategy for type 1 DM
Low sugar diet, insulin replacement
Rapid Acting Insulin
Lispro, Aspart, Glulisine
Short acting insulin
Regular insulin
Intermediate Insulin
NPH
Long acting insulin
Glargine, Detemir
Insulin: Action
Bind insulin receptor (tyrosine kinase activity)
Liver: increase glucose stored as glycogen
Muscle: increase glycogen and protein synthesis
Fat: aids TG storage
Insulin: Clinical Use
Type 1 DM, type 2 DM
Gestational Diabetes
Life-threatening hyperkalemia
Stress-induced hyperglycemia
Insulin : Toxicity
Hypoglycemia Hypersensitivity Reactions (very rarely)
Biguanides
Metformin
Metformin: Action
Exact mechanism is unknown
- decrease* gluconeogenesis
- increase* glycolysis, peripheral glucose uptake (insulin sensitivity)
Metformin: Clinical Use
Oral: 1st line therapy in type 2 DM
Can be used in patients without islet function
Metformin: Toxicity
GI upset; most serious adverse effect is lactic acidosis (thus contradicted in renal failure)
1st generation: Sulfonylureas
Tolbutamide
Chlorpropramide
2nd generation: Sulfonylureas
Glyburide
Glimepiride
Glipizide
Sulfonylureas
Close K+ channel in B-cell membrane, so cell depolarizes –> triggering of insulin release via increase of Ca+ influx
(JUST LIKE INSULIN)
Sulfonylureas: Clinical Use
Stimulate release of endogenous insulin in type 2 DM.
Require some islet function, so useless in type 1 DM
Sulfonylureas: Toxicity
1st generation: disulfiram-like effect.
2nd generation: hypoglycemia (avoid use with EtOH)
Glitazones/ thiazolidinediones
Pioglitazone
Rosiglitazone
Glitazones/thiazolidinediones (Pioglitazone, Riosiglitazone): Action
Increase insulin sensitivity in peripheral tissue. Binds to PPAR-gamma nuclear transcription regulator.
*PPAR-gamma regulate FA storage and glucose metabolism. Activation of PPAR-gamma increases insulin sensitivity and levels of adiponectin.
Glitazones/ Thiazolidinediones: Clinical Use
Used as monotherapy in type 2 DM or combined with above agents
Glitazones/ Thiazolidinediones: Toxicity
Weight gain, edema, hepatotoxicity, heart failure
Alpha Glucosidase inhibitors
Acarbose
Miglitol
Alpha-Glucosidase Inhibitors: Action
Inhibit intestional brush border alpha glucosidases
Delayed sugar hydrolysis and glucose absorption –> DECREASED postprandial hyperglycemia
Alpha-glucosidase inhibitors: Clinical Use
Used as monotherapy or in combination with other diabetic drugs
Alpha-glucosidase: Toxicity
GI disturbances
Amylin analogs
Pramlintide
Pramlintide: Action
Decrease glucagon
Pramlintide: Clinical Use
Type 1 and type 2 DM
Pramlintide: Toxicity
Hypoglycemia, Nausea, Diarrhea
GLP-1 analogs:
Exenatide
Liraglutide
GLP-1: Action:
Increase insulin
Decrease glucagon release
GLP-1 analog (Exenatide, Liraglutide): Clinical Use
Type 2 DM
GLP-1 analog (Exenatide, Liraglutide): Toxicity
Nausea, vomiting, pancreatitis
DPP-4 inhibitors:
Linagliptin, Saxagliptin, Sitagliptin
DPP-4 inhibitors: Linagliptin, Saxagliptin, Sitagliptin: Mechanism
Increase insulin, Decrease Glucagon release
DPP-4 inhibitors (Litaglipton, Saxagliptin, Sitagliptin): Clinical Use
Type 2 DM
DPP-4 inhibitors (Litagliptin, Saxagliptin, Sitagliptin): Toxicity
Mild urinary or respiratory infections
Thioamides
Propylthiouracil, Methimazole
Thioamides (Propylthiouracil, Methimazole): Mechanism
Block peroxidase, thereby inhibiting organification of iodine and coupling of thyroid hormone synthesis.
*Propylthiouracil also blocks 5’-deiodinase which decrease peripheral converseion of T4 to T3.
Thioamides (Propylthiouracil, Methimazole): Clinical Use
Hyperthyroidism
Thioamies (Propylthiouracil, Methimazole): Toxicity
Skin rash, agranulocytosis (rare), aplastic anemia
Propylthiouracil: hepatotoxicity, safer during pregnancy
Methimazole: possible teratogen
Levothyroxine, Triiodothyronine: Mechanism
Thyroxine replacement
Levothyrozine, Triiodothyronine: Clinical Use
Hypothyroidism, Myxedema
Levothyroxine, Triiodothyronine: Toxicity
Tachycardia, Heat intolerance, Tremors, Arrhythmias (signs of hyperthyroidism)
Growth Hormone: Clinical Use
GH deficiency, Turner Syndrome
Somatostatin (Octeotride): Clinical Use
Acromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices
Oxytocin: Clinical use
Stimulates labor, uterine contractions, milk-let down, controls uterine hemorrhage
ADH (desmopressin): Clinical Use
Pituitary (central NOT nephrogenic) DI
Demeclocycline: Mechanism
ADH antagonist (member of tetracycline family)
Demeclocycline: Clinical Use
SIADH
Demeclocycline: Toxicity
Nephrogenic DI, photosensitivity, abnormalities of bone and teeth
Glucocorticoids
Hydrocortisone, Prednisone, Triamcinolone, Dexamethasone, Beclamethasone
Glucocorticoids (-asone/ - isone): Mechanism
Decrease the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX2
Glucocorticoids: Clinical Use
Addison’s disease, inflammation, immune suppression, asthma
Glucocorticoids (-asone/-isone: Toxicity
Iatrogenic Cushing’s syndrome - buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic)
Risk of stopping glucocorticoids abruptly
Adrenal insufficiency – must taper the glucocorticoids to prevent this.
