Endocrine Pharm from FA Flashcards
General strategies for treatment of T1DM?
T2DM?
Gestational DM?
T1DM: low-sugar diet, insulin replacement
T2DM: dietary modification and exercise for wt loss, oral agents, non-insulin injectables, insulin replacement
GDM: dietary change, exercise, insulin replacement if diet/exercise fail
Lispro, Aspart, Glulisine
Class? Action? Clinical use? Tox?
Rapid acting Insulin
Action: bind insulin receptor (tyrosine kinase activity). In Liver, incr glucose stored as glycogen. In Muscle, increase glycogen and protein synth, incr K+ uptake. Fat: Incr TG storage.
Use: T1DM, T2DM, GDM (postprandial glucose control)
Tox: hypoglycemia, rare hypersens reactions
Regular insulin, short-acting: Clinical use?
T1DM, T2DM, GDM, DKA (IV), hyperkalemia (+ glucose), stress hyperglycemia
NPH
Class? Use?
Intermediate-acting insulin
(NPH = neutral protamine Hagedorn, something about how it is chemically packaged to be medium-acting)
Use: T1DM, T2DM, GDM
Glargine, Detemir
Class? Use?
Long-acting insulin
Use: T1DM, T2DM, GDM (basal glucose control)
Metformin
Class? Action? Use? Tox?
Class: Diabetes/Biguanide
Action: exact mech unknown. decr gluconeogenesis, incr glycolysis, incr peripheral glucose uptake (insulin sensitivity)
Use: oral. First line therapy in T2DM. Can be used in patietns without islet cell function
Tox: GI upset, lactic acidosis (CI in renal failure)
Tolbutamide, Chlorpropamide
Class? Action? Use? Tox?
First generation sulfonylureas (diabetes)
Action: close K+channel in Beta cell membrane -> cell depolarizes -> triggers insulin release via C2+ influx
Use: Stimulates release of endogenous insulin in T2DM. requires some islet function (useless with T1DM)
Tox: risk of hypoglycemia increased in renal failure, Disulfiram-like effects.
Glyburide, Glimepiride, Glipizide
Class? Mech? Use? Tox?
Second generation sulfonylureas (diabetes)
Action: close K+channel in Beta cell membrane -> cell depolarizes -> triggers insulin release via C2+ influx
Use: Stimulates release of endogenous insulin in T2DM. requires some islet function (useless with T1DM)
Tox: risk of hypoglycemia increased in renal failure, Hypoglycemia
Pioglitazone, Rosiglitazone
Class? Mech? Use? Tox?
Glitazones/Thiazolidinediones (diabetes)
Mech: increased insulin sensitivity in peripheral tissue. Binds to PPAR-gamma nuclear transcription regulator
Use: monotherapy in T2DM or in combination with insulins, metformin, sulfonylureas
Tox: weight gain, edema, hepatoxicity, heart failure
Acarbose, Miglitol
Class? Mech? Use? Tox?
Diabetes/alpha-glucosidase inhibitors
Action: inhibits intestinal brush-border alpha-glucosidases; delayed sugar hydrolysis and glucose absorption decreases postprandial hyperglycemia
Use: Monotherapy for T2DM or im combination with other agents
Tox: GI disturbances
Pramlintide
Class? Action? Use? Tox?
Diabetes/Amylin analog
action: decreases gastric emptying, decreases glucagon
Use: T1DM, T2DM
Tox: hypoglycemia, nausea, diarrhea
Exenatide, Liraglutide
Class? Mech? Use? Tox?
Diabetes/GLP-1 analogs
Action: increases glucose, decreases glucagon release
Use: T2DM
Tox: N/V, pancreatitis
Linagliptin, Saxagliptin, Sitagliptin
Class? Mech? Use? Tox?
Diabetes/DPP-4 inhibitors
Action: increase insulin, decr glucagon release
Use: T2DM
Tox: mild urinary or resp infections
What do genes activated by PPAR-gamma do?
regulate fatty acid storage and glucose metabolism.
Activation of PPAR-gamma increases insulin sensitivity and levels of adiponectin
What drug is first-line therapy in T2DM? when is it contraindicated?
Metformin
(biguanide class)
CI with renal failure because it can cause lactic acidosis. can also cause GI upset.
Which diabetes drugs require some islet cell function and are therefore not useful with T1DM? (3 classes)
Sulfonylureas (Tolbutamide, Chlorpropramide, Glyburide, Glimepiride, Glipizide)
GLP-1 analogs (Exenatide, Liraglutide)
DPP-4 inhibitors (Linagliptin, Saxagliptin, Sitagliptin)
Propylthiouracil, Methimazole
Mech? Use? Tox?
Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) of iodine, leading to inhibition of thyroid hormone synthesis. Propylthiouracil also blocks 5’deiodinase, which decreases peripheral conversion of T4 to T3.
Use: Hyperthyroidism. “PTU blocks Peripheral conversion, used in Pregnancy”
Tox: Skin rash, agranulogytosis (rare), aplastic anemia, hepatotoxicity (PTU). Methimazole is a possible teratogen (can cause aplasia cutis)
Of the two drugs that are used for hyperthroidism, which one is possibly teratogenic?
Which drug do we use for preg women? tox of that drug?
Methimazole is a possible teratogen (can cause aplasia cutis - derm condition, absence of a patch of skin/hair)
For preg women, use Propylthiouracil (PTU) instead
“PTU blocks Peripheral conversion, used in Pregnancy”
PTU may cause hepatotoxicity.
Levothyroxine, Triiodothyronine
Mech? Use? Tox?
Mech: Thyroxine replacement
Use: hypothyroidism, myxedema (mucopolysaccharide deposition in the dermis –> results in swelling. ie pretibial myxedema in Graves’ Disease)
Tox: Tachycardia, heat intolerance, tremors, arrythmias
Growth Hormone
Use?
Hypothalamic/pituitary drug
Use: GH deficiency, Turner syndrome
Somatostatin/Octreotide
Use?
Hypothalamic/pituitary drug
Acromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices
Oxytocin
Use?
Hypothalamic/pituitary drug
Stimulates labor, uterina contractions, milk let-down; controls uterine hemorrhage
ADH (DDAVP)
Use?
Hypothalamic/pituitary drug
Pituitary (central, not nephrogenic) DI
vWF d/o - stimulates vWF release from endothelial cells
Demeclocycline
Mech? Use? Tox?
ADH Antagonist (member of the tetracycline family)
Use: SIADH
Tox: nephrogenic DI, photosensitivity, bone/teeth abnormalities
Glucocorticoids
Mech?
Use?
Tox?
Mech: metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements and inhibition of transcription factors such as NF-KB
Use: Addison’s disease, inflammation, immune suppression, asthma
Tox: Iatrogenic Cushing syndrome (buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic). Adrenal insufficiency when drug stopped abruptly after chronic use.
Osteoporosis due to glucocorticoid use: what is treatment?
bisphosphonates
List the glucocorticoids (6)
Hydrocortisone
Prednisone
Triamcinolone
Dexamethasone
Beclomethasone
Fludrocortisone (mineralocorticoid and glucocorticoid activity)
(From UWorld)
Pheochromocytoma: treatment?
-Irreversible alpha-blockers (ex: phenoxybenzamine) and beta-blockers followed by tumor resection.
Alpha blockade must be achieved before giving beta-blockers to avoid a hypertensive crisis.
