Endocrine Drugs Flashcards
Name the rapid acting insulins
aspart, glulisine, lispro
Mechanism of rapid acting insulins
binds insulin receptor (tyrosine kinase activity)
liver: increases glucose stored as glycogen
mucles: increases glycogen, protein synthesis; increases K+ uptake into cells
fat: increases TG storage
Use of rapid acting insulins
type 1 and 2 DM gestational diabetes (postprandial glucose control)
Toxicity of rapid acting insulins
hypoglycemia
rare hypersensitivity reactions
Treatment strategy for type 1 DM
low-carbohydrate diet
insulin replacement
Treatment strategy for type 2 DM
dietary modification and exercise for weight loss
oral agents
non-insulin injectables
insulin replacement
Treatment strategy for gestational diabetes
dietary modifications
exercise
insulin replacement if lifestyle modification fails
Name the insulin short acting agent
INSULIN
Use of short acting insulin
type 1 DM type 2 DM GDM DKA (IV) hyperkalemia (+ glucose) stress hyperglycemia
Name the intermediate acting insulin
NPH
Use of intermediate acting insulin
type 1 DM
type 2 DM
GDM
Name the long acting insulins
detemir
glargine
Use of long acting insulins
type 1 DM
type 2 DM
GDM (basal glucose control)
Action of detemir vs. glargine
detemir binds albumin tightly and is slowly offloaded throughout the day
glargine stays at constant level throughout the day, resembles basal insulin secretion
Name the biguanides
metformin
Mechanism of metformin
exact mechanism unknown
- decrease gluconeogenesis, increase glycolysis, inrease peripheral glucose uptake (increase insulin sensitivity)
Use of metformin
ORAL
first line therapy in type 2 DM - causes modest weight loss
can be used in pts without islet function
Toxicity of metformin
GI upset
MOST SERIOUS IS LACTIC ACIDOSIS
Contraindication of metformin
pts with renal insufficiency due to risk for lactic acidosis
Name the sulfonylureas
first generation:
- chlorpropamide
- tolbutamide
second generation:
- glimepridie
- glipizide
- glyburide
Mechanism of the sulfonylureas
close K+ channels in the beta-cells –> depolarization –> insulin release via increased Ca2+ influx
Use of sulfonylureas
stimulate release of endogenous insulin in type 2 DM
requires some islet function so useless in type 1 DM
UNLESS HAVE CHILDHOOD MUTATION in ATP-K+ channel
Toxicity of sulfonylureas general
risk of hypoglycemia is increased in renal failure
Toxicity of 1st generation sulfonylureas
disulfiram-like effects
Toxicity of 2nd generation sulfonylureas
hypoglycemia
What is disulfiram-like effects?
immediate hangover effect caused by a build up of acetylaldehyde due to inhibition of aldehyde dehydrogenase
ethanol –> acetaldehyde via alcohol dehydrogenase
acetaldeyhyde –> acetic acid via acetaldehyde dehydrogenase
Other drugs causing a disulfiram like toxicity?
metronidazole (some abx)
1st generation sulfonylureas
some cephalosporins
griseofulvin
Name the glitazones/thiazolidinediones
“-glitazones”
pioglitazone and rosiglitazone
Mechanism of glitazones/thiazolidinediones
increase insulin sensitivity in peripheral tissue
binds PPAR-gamma nuclear transcription regulator
Use of glitazones/thiazolidinediones
used as monotherapy in type 2 DM or combined with above agents
Toxicity of glitazones/thiazolidinediones
weight gain, edema
hepatotoxicity, HF, increased risk of fractures
Name the GLP-1 analogs
Exenatide, liraglutide
Mechanism of GLP-1 analogs
increase insulin, decrease glucagon release
Use of GLP-1 analogs
Type 2 DM
Toxicity of GLP-1 analogs
nausea, vomiting, pancreatitis
Name the DPP-4 Inhiubitors
linagliptin, saxagliptin, sitagliptin
Mechanism of DPP-4 inhibitors
increase insulin and decrease glucagon release
prevents GLP-1 breakdown
Use of DPP-4 inhibitors
type 2 DM
Toxicity of DPP-4 inhibitors
mild urinary or respiratory infections
Name the amylin analog
pramlintide
Mechanism of pramlintide
decrease gastric emptying and decrease glucagon
Use of pramlintide
type 1 or 2 DM
Toxicity of pramlintide
hypoglycemia, nausea, diarrhea
Name the SGLT-2 inhibitors
canagliflozin
Mechanism of the SGLT-2 inhibitor
block reabsorption of glucose in PCT
Use of SGLT-2 inhibitor
type 2 DM
Toxicity of SGLT-2 inhibitor
glucosuria, UTIs, vaginal yeast infections
Name the alpha-glucosidase inhibitors
acarbose, miglitol
Mechanism of alpha-glucosidase inhibitors
inhibit intestinal brush-border alpha-glucosidases
delayed carbohydrate hydrolysis and glucose absorption –> decreased post-prandial hyperglycemia
Use of alpha-glucosidase inhibitors
monotherapy in type 2 DM or in combination with above agents
Toxicity of alpha-glucosidase inhibitors
GI disturbances
Mechanism of propylthiouracil and methimazole
block thyroid peroxidase (propyl- also blocks 5’-deiodinase) –> inhibition of oxidation of iodide and organification (coupling) of iodine –> inhibited thyroid hormone synthesis
Effects of 5’-deiodinase block
via propylthiouracil
prevents peripheral conversion from T4 to T3
Use of propylthiouracil and methimazole
hyperthyroidism
Special use of propylthiouracil
used in pregnancy because blockers peripheral conversion
Toxicity of propylthiouracil and methimazole
skin rash
agranulocytosis (rare)
aplastic anemia
hepatotoxicity (propylthiouracil)
Toxicity of methimazole
possible teratogen that can cause aplasia cutis
Levothyroxine (T4) and Triiodothyronine (T3) Use
thyroid hormone replacement
- hypothyroidism
- myxedema
- off label weight loss supplements
Toxicity of T4 and T3 as replacement
tachycardia, heat intolerance, tremors, arrhythmias
Use and names of ADH antagonists
conivaptan, tolvaptan
SIADH, block action of ADH at V2 receptor
Use of desmopressin acetate
central (not nephrogenic) DI
ADH analog
Use of GH supplements
GH deficiency, Turner syndrome
Use of oxytocin
stimulates labor, uterine contractions and milk let-down
controls uterine hemorrhage
Use of somatostatin
GH excess (acromegaly), carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices
Mechanism of demeclocycline
ADH antagonist (tetracycline family member)
Use of demeclocycline
SIADH
Toxicity of demeclocycline
nephrogenic DI
photosensitivity
abnormalities of bone and teeth
Name some glucocorticoids
beclomethasone, dexamethasone, fludrocortisone, hydrocortisone, methylprednisone, prednisone, triamcinolone
Special attribute of fludrocortisone
mineralocorticoid and glucocorticoid activity
Use of glucocorticoids
Addison disease, inflammation, immunosuppression, asthma
Toxicity of glucocorticoids
Iatrogenic Cushing Syndrome: HTN, immune suppression, central/truncal obesity, buffalo hump, osteoporosis, moon facies, insulin resistance, striae
Adrenocortical atrophy
peptic ulcers
steroid diabetes
steroid psychosis
Complication of quick discontinuation of glucocorticoids
adrenal insufficiency when stopped after chronic use
Mechanism of cinacalcet
sensitizies Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ –> decreased PTH
Use of cinacalcet
hypercalcemia due to primary or secondary hyperparathyroidism
Toxicity of cinacalcet
hypocalcemia
