Endocrine Flashcards
Insulin - Rapid acting
Insulin Rapid-Acting (45-75 mins)
Lispro, Aspart, Glulisine
ACTION: Bind insulin receptor (RTK activity)
Liver: Inc glucose stored as glycogen.
Muscle: Inc glycogen and protein synthesis, K+ uptake (insulin-induced translocation of Na+/K+ ATPase.
Fat: aids TG storage
CLNICAL USE: T1DM, T2DM, gestational diabetes, life-threatening hyperkalemia and stress-induced hyperglycemia.
TOXICITIES: Hypoglycemia (injection int a limb that is subsequently exercised increases subcutaneous insulin absorption and may precipitate hypoglycemia. Rescue by giving carbs (honey water). S/s of hypoglycemia include confusion, sweating, tremors and palpitations)
Hypersensitivity reactions
Intermediate-Acting Insulin
Insulin - Intermediate Acting (18h)
ACTION: Bind insulin receptor (RTK activity)
Liver: Inc glucose stored as glycogen.
Muscle: Inc glycogen and protein synthesis, K+ uptake (insulin-induced translocation of Na+/K+ ATPase.
Fat: aids TG storage
CLNICAL USE: T1DM, T2DM, gestational diabetes, life-threatening hyperkalemia and stress-induced hyperglycemia.
TOXICITIES: Hypoglycemia (injection int a limb that is subsequently exercised increases subcutaneous insulin absorption and may precipitate hypoglycemia. Rescue by giving carbs (honey water). S/s of hypoglycemia include confusion, sweating, tremors and palpitations)
Hypersensitivity reactions
Insulin - Long acting
Insulin - Long-acting (24h)
Glargine (ppt at injection site) , Detemir (attached FA binds albumin)
ACTION: Bind insulin receptor (RTK activity)
Liver: Inc glucose stored as glycogen.
Muscle: Inc glycogen and protein synthesis, K+ uptake (insulin-induced translocation of Na+/K+ ATPase.
Fat: aids TG storage
CLNICAL USE: T1DM, T2DM, gestational diabetes, life-threatening hyperkalemia and stress-induced hyperglycemia.
TOXICITIES: Hypoglycemia (injection int a limb that is subsequently exercised increases subcutaneous insulin absorption and may precipitate hypoglycemia. Rescue by giving carbs (honey water). S/s of hypoglycemia include confusion, sweating, tremors and palpitations)
Hypersensitivity reactions
Biguanides
Biguanides
Metformin
ACTION: Exact mech unknown; activates AMPK –> Dec PEPCK, Glc-6-phosphase; gluconeogen). Dec gluconeogenesis, dec glucose production in liver, inc glycolysis, inc peripheral glucose uptake, (inc insulin insensitivity)
CLINICAL USE: Oral. First line therapy in T2DM. Can be used in pts without islet function.
TOXICITIES: GI upset; most serious adverse effect is lactic acidosis (thus contraindicated in renal failure or hepatic dysfxn …. CHF, sepsis, alcoholism –> all predispose to inc lactate.)
Monitor creatinine.
Sulfonylureas - 1st Generation
First Gen Sulfonylureas:
Tolbutamide, Chlorpropamide
MECHANISM: Close K+ channel in B-cell membrane, so cell depolarizes –> triggering of insulin release via inc Ca2+ influx.
CLINICAL USE: Stimulate release of endogenous insulin in T2DM. Require some islet fxn, so useless in T2DM.
TOXICITIES: First gen - disulfiram-like effects,
SIADH (chlorpropamide)
Sulfonylureas - 2nd Generation
Sulfonylureas - 2nd Gen
Glyburide, Glimepiridine (long t1/2, qdaily), Glipizide (short t1/2, extended release often used)
MECHANISM: Close K+ channel in B-cell membrane, so cell depolarizes –> triggering of insulin release via inc Ca2+ influx.
CLINICAL USE: Stimulate release of endogenous insulin in T2DM. Require some islet fxn, so useless in T2DM.
TOXICITIES: 2nd gen - weight gain, hypoglycemia.
Repaglinide, nateglinide
Same action as sulfonylureas, short t1/2, use to decrease postprandial hyperglycemia.
MECHANISM: Close K+ channel in B-cell membrane, so cell depolarizes –> triggering of insulin release via inc Ca2+ influx.
Glitazones/thiazolidinediones
Glitazones/thiazolidinediones
Pioglitazone, Rosiglitazone
MECHANISM: Inc insulin sensitivity in peripheral tissue. Binds PPAR-gamma nuclear transcription regulator << (PPAR-gamma activates genes regulating fatty acid storage and glucose metabolism. Activation of PPAR-gamma increases insulin sensitivity and increases adiponectin. Inc GLUT4 transporter, inc FA transport protein into adipocytes) >>
CLINICAL USE: Used as monotherapy in T2DM or in combination with other agents.
TOXICITIES: Weight gain, edema, Hepatotoxicity (monitor LFT’s), HF (black box!)
Alpha-glucosidase inhibitors
Alpha-glucosidase inhibitors
Acarbose, Miglitol
MECHANISM: Inhibit intestinal brush-border alphaglucosidases. Delayed sugar hydrolysis and decreased glucose absorption –> post-prandial hyperglycemia.
CLINICAL USE: Used monotherapy in T2DM or in combination with above agents.
TOXICITIES: GI disturbances: gas due to CHO fermentation in colon
Amylin analogs
Pramlintide
Diabetes drug that decreases glucagon, slows gastric emptying.
CLINICAL USE: T1D and T2D
TOXICITIES: hypoglycemia, nause, diarrhea
GLP-1 analogs
Exenatide, Liraglutide
ACTION: Increased insulin, decreased glucagon release. Incretins (GLP1/GIP) normally secreted in gut during meal
CLINICAL USE: T2DM
TOXICITIES: Nausea, vomiting, pancreatitis
DPP-4 inhibitors
Linagliptin, Saxagliptin, Sitaglipton
ACTION: Increases insulin, decrease glucagon release. Prevents metabolism of incretins (GLP1/GIP)
CLINICAL USE: T2DM
TOXICITIES: Mild urinary or respiratory infections
Thionamides
Propylthiouracil, methimazole
MECHANISM: Blocks TPO Peroxidase, thereby inhibiting organification of iodide and coupling of thyroid hormone synthesis. Propylthiuracil also blocks 5’-diodinase, which decreases peripheral conversion of T4 to T3.
CLINICAL USE: Hyperthyroidism (for Thyroid storm - use beta-blockers!)
TOXICITY: Edema, skin rash, agranulocytosis (rare - check CBC’s immediately), aplastic anemia, hepatotoxicity (PTU).
Methmazole is a possible teratogen; give PTU for pregnant pts.
Levothyroxine, triiodothyronine
Levothyroxine (Synthetic T4), triiodothyronine (T3)
MECHANISM: Thyroxine replacement
CLINICAL USE: Hyperthyroidism, myxedema (facial/preorbital)
TOXICITY: Tachycardia, heat intolerance, tremors, arrhythmias (–> s/s of hyperthyroidism)
Democlocycline
Democlocycline
MECHANISM: ADH antagonist (member of the tetracycline family)
CLINICAL USE: SIADH
TOXICITY: Nephrogenic DI (kidney becomes unresponsive to inc inc ADH levels), photosensitivity (tetracyclines), abnormalities of bone and teeth
