Endocrine and Metabolic Agents

Question 1

__amide, Gly__, Gli__

Answer 1

Sulfonylureas. Anti-Diabetic Agents.

Stimulate insulin release by inhibiting K+ channels on beta cells, increase insulin action by prolonging binding to target tissues, and reduce serum glucagon by directly inhibiting secretion.

Tx: non-insulin-dependent T2 diabetes. SE: hypoglycemia, skin rash, allergic rxn, disulfiram reaction with EtOH (C). Contraindicated in pregnancy (cross placenta, insulin depletion). Caution in renal/hepatic insufficiency.

Ex: 1st - Chlorpropamide, Tolbutamide, Tolazamide. 2nd - Glyburide, Glipizide. 3rd - Glimepiride.

Question 2

Metformin

Answer 2

Anti-Diabetic Agent. Biguanide.

Reduces serum glucose by: inhibiting hepatic gluconeogenesis, decreasing glucose absorption in GI, increasing peripheral use of glucose in fat/muscle.

Rx: non-insulin-dependent T2 diabetes, polycystic ovarian syndrome. SE: GI upset, lactic acidosis, impaired vitamin B12 absorption. Contraindicated in renal insufficiency, stop when undergoing radiology studies with contrast (cause renal insuf.). Does NOT cause hypoglycemia.

Question 3

__litazone

Answer 3

Anti-Diabetic Agents. Thiazolidinediones.

Binds PPAR-gamma, which upregulates genes, result is decreased insulin resistance.

Rx: non-insulin-dependent T2 diabetes. SE: hypoglycemia, edema, liver damage (T - removed from market). Contraindicated in hepatic insufficiency, watch LFTs b/c hepatotoxic.

Ex: Rosiglitazone, Pioglitazone, Troglitazone.

Question 4

Acarbose, Miglitol

Answer 4

Anti-Diabetic Agents. Alpha-Glucosidase Inhibitors

Inhibit alpha-glucosidase (breaks down sugars at small intestine brush border), which decreases absorption of postprandial carbs, resulting in lower blood glucose after meals.

Rx: non-insulin-dependent T2 diabetes, used with insulin in insulin-dependent. SE: GI upset (flatulence, diarrhea).

Question 5

__glinide

Answer 5

Anti-Diabetic Agents. Meglitinides.

Binds K+ channel on beta-cell, stimulating insulin release. Different channel than sulfonylureas). SE: weight gain, hypoglycemia.

Rx: non-insulin-dependent T2 diabetes

Ex: Repaglinide, Nateglinide.

Question 6

__agliptin

Answer 6

Anti-Diabetic Agents. Dipeptidyl Peptidase-4 inhibitors.

Inhibiting DPP-4 increases GLP-1 levels (normally degrades it), leading to increased insulin secretion.

Rx: non-insulin-dependent T2 diabetes. SE: nausea.

Ex: Sitagliptin, Vildagliptin.

Question 7

Exanatide

Answer 7

Anti-Diabetic Agents. Glucagon-Like Peptide-1 analog.

Mimics GLP-1, increasing insulin and decreasing glucagon secretions.

Rx: non-insulin-dependent T2 diabetes. SE: pancreatitis, hypoglycemia.

Question 8

__vastatin

Answer 8

Lipid Lowering Agents. HMG-CoA Reductase Inhibitors.

Inhibits HMG-CoA reductase, interrupting the first step of cholesterol synthesis in liver. Also increases number of LDL receptors on hepatocytes to extract more LDL and VLDL from serum - does NOT work in pts that lack LDL receptors (Familial Hypercholesteolemia) so drug overall less effective (use Ezetimibe instead). Results in decreased total cholesterol, LDL, and triglycerides with mild increase of HDL.

Rx: elevated cholesterol levels. SE: myopathy, abnormal LFTs, teratogen.

Ex: Atorvastatin, Pravastatin, Lovastatin, Rosuvastatin, Simvastatin, Fluvastatin.

Question 9

Choles__, Coles__

Answer 9

Lipid Lowering Agents. Bile Acid Resins.

Inhibit the reabsorption of bile acids in jejunum and ileum leading to bile wasting, resulting in increased conversion of cholesterol to bile acids. Cell responds to lower intracellular cholesterol by increasing number of LDL receptors on surface, uptaking more LDL from serum - does NOT work in pts that lack LDL receptors (Familial Hypercholesteolemia) so drug overall less effective (use Ezetimibe instead). Results in decreased LDL.

Rx for elevated cholesterol levels, pruritis associated with liver failure, diarrhea after gallbladder removal. SE: GI upset, bad taste, decreased absorption of fat-soluble vitamins (A, D, E, K) and folic acid, poor absorption of other drugs.

Ex: Cholestyramine, Colestipol, Colesevelam.

Question 10

__fibrate, __fibrozil

Answer 10

Lipid Lowering Agents. Fibrates.

Stimulate lipoprotein lipase, which catalyzes the breakdown of triglycerides into VLDL and chylomicrons, then removed from circulation. May decrease hepatic cholesterol biosynthesis. Results in decreased triglycerides, mild LDL decrease, and mild HDL increase.

Rx for elevated cholesterol levels. SE: GI upset, increased gallstone incidence, myositis, abnormal LFTs. Compete for plasma protein binding, increasing other drug effects (Warfarin).

Ex: Gemfibrozil, Ciprofibrate, Bezafibrate, Fenofibrate.

Question 11

Niacin

Answer 11

Lipid Lowering Agent.

Decreases lipolysis in adipose tissue, decreasing VLDL and LDL precursors. Results in increased HDL and decreased LDL.

Rx for elevated cholesterol levels. SE: flushing.

Question 12

__dronate

Answer 12

Endocrine and Metabolic Agents. Bisphosphonates.

Decrease osteoclastic bone reabsorption by decreasing activity and increasing cellular death of osteoclasts.

Prevention and Rx of osteoporosis, Paget disease, bone metastasis with hypercalcemia, multiple myeloma. SE: GI upset, esophageal erosions, osteonecrosis of jaw, A-fib.

Ex: Alendronate, Etidronate, Ibrandronate, Zoledronate, Pamidronate, Risedronate.

Question 13

Propylthiouracil, Methimazole

Answer 13

Thyroid Agents.

Inhibits thyroid peroxidase (iodine organification) by inhibiting the coupling of iodotyrosines. Results in inhibited TH synthesis and peripheral conversion of T4 to T3.

Rx of hyperthyroidism. SE: maculopapular skin rash, agranulocytosis, arthralgias.

Question 14

Levothyroxine

Answer 14

Thyroid Agent.

Synthetic form of T4, increasing active TH levels (T3). Treats hypothyroidism.

Question 15

Colchicine

Answer 15

Gout Agent.

Induces microtubular depolymerization by binding tubulin, results in decreased leukocyte migration to affected site. Also blocks formation of Leukotriene B4.

Rx of acute gouty attack, Behcet disease, scleroderma. SE: diarrhea, bone marrow suppression.

Give when beginning Allopurinol therapy to prevent attack.

Question 16

Probenacid

Answer 16

Gout Agent.

Blocks active transport of uric acid proximal tubule, reducing reabsorption.

Prevention of future gouty attacks. Prevention and Rx of hyperuricemia (tumor lysis syndrome). SE: GI upset, inhibition of renal excretion of penicillin and NSAIDs.

Question 17

Allopurinol

Answer 17

Gout Agent.

Inhibits xanthine oxidase in the purine degradation pathway (converts xanthine to uric acid).

Prevention of future gouty attacks. Prevention and Rx of hyperuricemia (tumor lysis syndrome). SE: GI upset, hypersensitivity rxn, decreased metabolism of 6-mercaptopurine and Azathioprine.

Give with Colchicine or NSAID when beginning therapy for a few weeks to prevent acute gouty attack.

Question 18

__sone

Answer 18

Synthetic Corticosteroids.

Mimics actions of endogenous glucocorticoids: vasoconstriction, stimulate hepatic gluconeogenesis and protein catabolism, decreased leukocytes, inhibits prostaglandin and leukotriene formation (inhibits phospholipase A2), stimulates gastric acid and pepsin production.

Rx for adrenocortical insufficiency, collagen-vascular disorders (SLE, RA, polymyositis), IBD, asthma, spinal cord compression, ITP, allergic reactions, arthritis, MS, nephrotic syndrome, leukemia and lymphoma (with chemo). Diagnose Cushings, stimulate fetal lung maturity, immunosuppression in organ transplant.

SE: Cushing syndrome, osteoperosis, irritability, hyperglycemia, fat redistribution (buffalo hump, central obesity, moon facies), impaired wound healing HTN, psychosis, susceptible to infection, thin skin with triae, peptic ulcer disease, peripheral muscle wasting, edema.

Ex: Prednisone, Hydrocortisone, Cortisone, Prednisolone, Methylprednisolone, Betamethasone, Dexamethasone.

Question 19

Orlistat, Sibutramine

Answer 19

Anti-Obesity Agents

Orlistat: inhibits pancreatic lipase, reducing fat absorption. Rx of obesity. SE: steatorrhea, fecal incontinence, decreased absorption of fat-soluble vitamins (A, D, E, K).

Sibutramine: neurotransmitter reuptake inhibitor. Rx of obesity. SE: nausea, sexual dysfunction, HTN, arrhythmias.

Question 20

Flutamide

Answer 20

Endocrine Agent.

Competitive antagonist at the androgen receptor, decreasing testosterones growth effects on prostate and releasing inhibition of gonadotropin secretion. Lower testosterone detection increases serum LH release - must be counteracted with a Leuprolide.

Treatment of prostate cancer. SE: GI upset, gynecomastia, abnormal LFTs.

Question 21

Finasteride

Answer 21

Endocrine Agent.

5-alpha-reductase converts testosterone to dihydrotestosterone, which acts to stimulate growth of prostate gland. Drug inhibits 5-alpha-reductase, so prostate growth is decreased.

Rx for BPH, prostate cancer, early male-pattern baldness. SE: decreased libido, ED.

Question 22

Danazol

Answer 22

Endocrine Agent.

Mild agonist at androgen and progesterone receptors, resulting in decreased LH and FSH secretion.

Rx of endometriosis and fibrocystic disease of breast.

Question 23

Anastrozole

Answer 23

Endocrine Agent.

Inhibits aromatase to decrease conversion of androgens into estrogens.

Rx of estrogen-receptor positive breast cancer.

Question 24

Leuprolide, Nafarelin, Goserelin

Answer 24

Endocrine Agents. GnRH Agonists.

Binds GnRH receptors in pituitary, initially releasing LH and FSH. Continuous administration leads to desensitization and downregulation of GnRH receptors and results in decreased LH and FSH release. Ultimately results in decreased estrogens and testosterone.

Rx of metastatic prostate cancer, leiomyomas, endometriosis. SE: impotence, hot flashes, GI upset.

Question 25

Clomiphene

Answer 25

Endocrine Agent.

Partial agonist at estrogen receptors in pituitary, increasing gonadotropin release (LH, FSH)

Rx of infertility by inducing ovulation. SE: hot flushes and multiple pregnancies.

Question 26

Oral Contraceptive Pills

Answer 26

Endocrine Agents. Combined Oral Contraceptives.

Estrogens: at low levels decrease FSH release and don’t feedback enough to release LH.
Progestin: decrease GnRH release, decreasing FSH and LH.

Decrease in FSH results in inhibited follicular development and decreased LH results in absence of ovulation. Used to prevent pregnancy, Rx for dysfunctional uterine bleeding, PCOS, endometriosis, and dysmenorrhea. SE: breast fullness, n/v, HA, increased clot risk (especially >35 years and smokers). Decreases risk of ovarian and endometrial cancer.

Progestin-only: no risk of clot.
Emergency pill: high dose progestin, take up to 72 hours after.

Question 27

Mifepristone

Answer 27

Endocrine Agent. Steroid. Chemical Abortion.

Competitive antagonist at progesterone receptor. High doses acts as an abortifacient by causing breakdown of endometrial lining and cervical dilation.

Question 28

Octerotide, Somatostatin

Answer 28

Endocrine Agents.

Octreotide: synthetic analog of somatostatin (hormone).
Somatostatin: pancreatic hormone that inhibits release of others (secretin, gastrin, TSH, VIP, GH), reduce GI motility, and vasoconstrict.

Rx of many endocrine disorders: diarrhea associated with VIP-producing tumors, acromegaly, Zollinger-Ellison syndrome, esophageal varices associated with cirrhosis-induced portal hypertension. SE: GI upset, arrhythmias.

Question 29

__opressin

Answer 29

Endocrine Agents.

Vasopressin is a posterior pituitary hormone that interacts with receptors:
V1: vascular smooth muscle, vasoconstrict.
V2: renal tubule cells in collecting ducts, increases permeability to H2O and reabsorption.
V2-like: increase factor VIII activity.

Rx of central diabetes insipidus, septic shock and cardiac arrest. SE: hyponatremia, hypersensitivity rxn, vasoconstriction (Vaso only), HA. Desmopressin acetate given before surgery for Hemophilia A or von Willdebrand disease.

Ex: Vasopressin, Desmopressin

Question 30

Somatotropin (GH)

Answer 30

Endocrine Agent. Pituitary Hormone Replacement.

Treats pituitary hormone deficiency leading to short stature, such as Turners, Prader-Willi, intrauterine growth retardation, chronic renal failure, idiopathic.