Term
|
Definition
Released in response to hypocalcemia
Promotes release of Ca++ and phosphate into ECF
Stimulates bone remodeling and tubular reabsorption of calcium
Stimulates vitD3 activation in kidney |
|
|
Term
|
Definition
Increases GI absorption of Ca++ and phosphate
Augments bone mineral mobilization and renal Ca++ reabsorption
INsufficiency leads to reduced bone strength, fractures, decreased bone mass |
|
|
Term
|
Definition
Always released in response to hypercalcemia
Antagonizes effects of PTH
Inhibits osteoclast activity and osteolysis, decreases renal reabsorption of Ca++
Secretion stimulated by gastrin (normal 8.5-10.5) |
|
|
Term
|
Definition
Total serum calcium exceeding 10.5mg/dL
Presents with fatigue, confusion, nausea, polyuria, anorexia, and acute ventricular arrhythmias |
|
|
Term
| Treatment of hypercalcemia |
|
Definition
Normal saline for volume expansion, increased Ca++ excretion with Furosemide
Give calcitonin instead in cases of CHF and renal dysfunction, Bisphosphonates if chronic |
|
|
Term
|
Definition
Less than 8.5mg/dL serum Ca++
Primarily due to changes in PTH and VitD levels
Presents with muscle spasm, seizure, respiratory arrest |
|
|
Term
| Treatment of hypocalcemia |
|
Definition
| Give calcium through IV or oral calcitriol |
|
|
Term
| 60 yo man presents w/history of renal colic and high Ca++ renal stones. Which would be best in treating the recurrent calcium stones? |
|
Definition
| **Hydrochlorothiazde --> breaks down stones but retains Ca++ unlike furosemide |
|
|
Term
| Chronic glucocorticoid administration |
|
Definition
| Associated with osteoporosis due to upregulation of RANKL and down regulation of OBG and Ca++ binding protein, causes excessive osteoclast activity |
|
|
Term
|
Definition
| DEfined as a bone mineral density 2.5 stdev or more below that of normal young adults, confirmed via dexa-scan, secondary via calcitriol deficiency |
|
|
Term
|
Definition
| Disordered bone remodeling, increased bone resorption followed by erratic deposition of poor quality new bone, leads to bowing, fractures, arthritis |
|
|
Term
| What agents affect calcium homeostasis? |
|
Definition
Teriparatide [Forteo]
Calcitonin (Salmon) [Fortical, Miacalcin]
Ergocalciferol [Calciferol]
Doxercalciferol [Hecterol]
Calcitriol [Rocatrol] |
|
|
Term
| What do you give to patients with glucocorticoid induced osteoporosis? |
|
Definition
| Alendronate [Fosemax] which is a bisphosphonate |
|
|
Term
| The role of bisphosphonates in the treatment of osteoporosis |
|
Definition
| DOES NOT increase bone formation, reduces osteoclast activity and formation, increases osteoclastic apoptosis, inhibits osteoclast proton pumps, has VERY poor oral absorption |
|
|
Term
| Treatment of Paget's disease |
|
Definition
| Calcitonin is recommended |
|
|
Term
|
Definition
Only given in a hospital setting with a significant neoplasm that refuses to unlock calcium, acts inhibit paracalcemic action of VitD, inhibits PTH effects on osteoclasts
HIGH TOXICITY, LOW THERAPEUTIC INDEX
Contraindicated in pregnancy, electrolyte imbalance, myelosuppression, bleeding disorders, hepatic dysfunction |
|
|
Term
|
Definition
A VitD preparation, increases absorption of Ca++, elevates plasma calcium, reduces PTH levels
Indicated for hypocalcemic patients and patients with hypoparathyroidism
Well absorbed orally
Contraindicated alongside cardiac glycosides |
|
|
Term
|
Definition
VitD perparation
Elevates Ca++ levels and reabsorption, enhances calcium mobilization
Indicated for hypophophatemia, osteomalacia, osteoporosis, rickets |
|
|
Term
|
Definition
Vit D preparation, a VitD2 analog that is activated in the liver, increases absorption of Ca++ from GI
Indicated for hyperparathyroidism, reduction of PTH |
|
|
Term
|
Definition
| A calcimimetic, mimics effects of ionized Ca++ on Ca++ sensing receptors in parathyroid, increases sensitivity to Ca++ and reduces PTH secretion, indicated for hypercalcemia in parathyroid carcinoma, very long 1/2 life allows for single dose |
|
|
Term
| Post-menopausal female had a fracture a year ago, very low calcitriol levels, has hollow bone, given alendronate, 100mg Ca/day, and 800 units of VitD. Response was good, pain and kyphosis disappeared, presents 2yrs later with resurfacing bone pain, dexa-scan shows declining bone mass. Treatment? |
|
Definition
| Give recombinant form of PTH --> Teriparatide* |
|
|
Term
|
Definition
A recombinant form of PTH, stimulates osteoblastic activity and new bone formation to increase bone density
Administered paranterally, indicated in osteoporosis
Cannot be used beyond 21 months due to risk of osteosarcoma |
|
|
Term
| Chronic use of which of the following is likely to induce osteoporosis? |
|
Definition
| Prednisone (a glucocorticoid)* |
|
|
Term
|
Definition
An agonist in the bone and an antogonist in breast tissue that prevents osteoporosis and reduces the incidence of estrogen dependent breast cancer
Indicated in pts that fail bisphosphonate therapy |
|
|
Term
|
Definition
Released in pulsatile fashion, highest release at night
Stimulates the synthesis/release of IGNF-1 which serves to:
Stimulate osteoclast and osteoblast proliferation/activity
Increase myoblast differentiation
Increase muscle mass |
|
|
Term
|
Definition
A growth hormone mimetic
Recombinant GH, sequence is identical to GH
Rare SE includes idiopathic intracranial hypertension, possible risk of leukemia, and slipped disk in children. In adults, peripheral edema, carpal tunnel, arthralgia, myalgia |
|
|
Term
| Mecasermin (Recombinant IGF-1) |
|
Definition
Given to patients with mutations to GH receptor
Unfortunately causes hypoglycemia |
|
|
Term
|
Definition
Longer ½ life than somatostatin, given IV
Similar actions to somatostatin (inhibits the release of GH on the anterior pituitary) by binding to somatostatin receptors SSTR2 and SSTR5, inhibiting GH secretion
May cause gallstones, hypo/hyperglycemia |
|
|
Term
|
Definition
Stimulated release via thyrotropin releasing hormone and dopamine
Activates JAK-STAT pathway leading to gene expression associated with lactation and mammary development |
|
|
Term
|
Definition
| Excessive secretion by adenomas, decreased dopamine release, renal failure, or dopamine receptor antagonists, is treated with dopamine D2-receptor agonists |
|
|
Term
| Bromocriptine and Pergolide side effects |
|
Definition
| Nausea, vomiting, headache, postural hypotension, nasal congestion, CNS effects |
|
|
Term
Gonadorelin, Goserelin, Nafarelin
Gonadotropin-releasing hormones) Indications |
|
Definition
| Female and male infertility, decreasing endometriosis pain, prostate cancer, precocious puberty |
|
|
Term
Gonadorelin, Goserelin, Nafarelin
MoA |
|
Definition
Pulsatile administration causes steady release of FSH and LH from anterior pituitary
Non-pulsatile administration causes FSH/LH “flare” and subsequent inhibition of release |
|
|
Term
Gonadorelin, Goserelin, Nafarelin
Contraindications |
|
Definition
In women: headache, menopause symptoms, hot flashes, reduced bone density, avoid in pregnancy or breast feeding
In men: Hot flashes, edema, gynecomastia, decreased libido, decreased bone density |
|
|
Term
|
Definition
Competitive GnRH receptor antagonist, acts to prevent LH surge during ovarian hyperstimulation
Ovarian hyperstimulation syndrome is main side effect |
|
|
Term
Urofollitropin
(FSH preparation) |
|
Definition
| Directs ovarian follicle development, primary regulator of spermatogenesis |
|
|
Term
|
Definition
Only used with follitropin-alpha in infertile women w/LH deficiency
Increases androgen production, controls luteal phase
Only given for profound LH deficiency |
|
|
Term
Propasi, Pregnyl
(hCG preparation) |
|
Definition
Ovulation induction reserve for those failing other tx to treat ovarian hyperstimulation or male infertility hypogonadism
May cause ovarian hyperstimulation syndrome, multiple pregnancies |
|
|
Term
|
Definition
Used to induce labor
Acts on Gq-coupled GPCR
Increases intracellular Ca++ to contract myometrium smooth muscle
Initiates prostaglandin production to increase contraction
Stimulates alveoli myoepithelial contraction for milk ejection
High concentration may have vasopressor/antidiuretic effect |
|
|
Term
|
Definition
Regulates the release of coagulation factor VIII and von Willebrand factor
Activates both Gq-coupled V1 receptors in the vasculature as well as V2 receptors in the collecting tubules that lead to increased water resorption |
|
|
Term
|
Definition
synthetic vasopressin analog
Administered orally, longer acting than vasopressin |
|
|
Term
|
Definition
vasopressin antagonist
Nonpeptide antagonist at V1 and V2 receptors
Can be used to treat hyponatremia which may be associated with elevated circulating levels of vasopressin |
|
|
Term
|
Definition
Blockade of dopamine receptors, moderate action against chemotherapeutic agents
Used in treatment of vomiting, uniquely also causes sedation |
|
|
Term
|
Definition
Is the most effecatious class of antiemetic
Used for chemo, pos-surgery nausea, pregnancy |
|
|
Term
| 5HT3 inhibitor formations |
|
Definition
Ondansetron (Zofran)
Granisetron (Kytril)
Dolasetron (Anzemet) |
|
|
Term
|
Definition
Is a central dopamine antagonist, elevates CTZ threshold
Used for gastroperesis and prevention of chemo induced emesis |
|
|
Term
| Metoclopramide side effects |
|
Definition
High dose may cause extrapyramidal side effects
induces parkinsons-like symptoms |
|
|
Term
|
Definition
Usually combined with other antiemetics to prevent motion sickness
Limited by sedation, dizziness, confusion, dry mouth, and urinary retention |
|
|
Term
| H1 Antihistamine formulations |
|
Definition
Diphenhydramine (Benadryl)
Meclizine (Atarax)
Hyoscine (Scopolamine) |
|
|
Term
|
Definition
Used to prevent straining during defecation
Acts on small and large intestine to increase bulk and moisture content in stool, stimulate peristalsis
Can cause obstruction if taken w/o enough fluids |
|
|
Term
|
Definition
Used in prevention and treatment of portal systemic encephalopathy
Also treats constipation
Acts on colon to retain ammonia, producing osmotic effects that stimulate bowel evacuation |
|
|
Term
|
Definition
Facilitates defecation in diminished colonic motor response
Used to evacuate colon prior to surgery
SE: Urine discoloration, abd cramping, fluid and electrolyte depletion |
|
|
Term
|
Definition
Used in short term treatment of constipation, evacuation of colon prior to surgery
Acts on intestines to lower surface tension, facilitate penetration of fat and water into stool |
|
|
Term
|
Definition
Recommended for “traveler’s diarrhea”
Inhibits mucosal peristaltic reflex to reduce GI motility, metabolized to active metabolite Difenoxin |
|
|
Term
| Diphenoxlate is given with what? |
|
Definition
| atropine in order to reduce abuse |
|
|
Term
|
Definition
Indicated for non-specific diarrhea and increases in stool frequency in IBD or IBS
Unique in that there are no CNS effects or sedation |
|
|
Term
|
Definition
Used to reduce hypermotility and inflammation
Also used for peptic ulcers, is bactericidal against H. pylori |
|
|
Term
|
Definition
Used to treat Crohn’s disease to suppress inflammation and alleviate symptoms
Inhibits synthesis of prostaglandins and inflammatory leukotriens |
|
|
Term
| Aminosalicylate formulations |
|
Definition
*Sulfasalazine (Azulfidine®)
Olsalazine (Dipentum®)
Balsalzide (Colazal®) |
|
|
Term
|
Definition
Used to treat Crohn’s disease
Modulates local chemical mediators of inflammatory response, especially leukotrienes
Free radical scavenger and inhibitor of TNF |
|
|
Term
|
Definition
Pentasa® (time release)
Asacol ®
Rowasa®
Canasa® |
|
|
Term
| Used to treat Crohn’s via potent anti-inflammatory effect. Used for short term management |
|
Definition
|
|
Term
| Immunosuppressants used to treat Crohn’s |
|
Definition
Azathioprine (Imuran)
6-Mercaptopurine (Purinethol))
*Methotrexate (Rheumatrex))
Cyclosporine (Sandimmune)
Infliximab (Remicade |
|
|
Term
|
Definition
Symptomatic treatment of severe Crohn’s
TNF-alpha antagonist
Inhibits induction of pro-inflammatory cytokines |
|
|
Term
|
Definition
Modulates pain via effects on neurotransmitter reuptake
Reduces visceral hypersensitivity
Formulations:
Amitriptyline
Doxepin |
|
|
Term
|
Definition
Modulates pain via effects on neurotransmitter reuptake
Reduces visceral hypersensitivity
Formulations:
Paroxetine
Fluoxetine
Sertraline |
|
|
Term
| Cimetidine (H2 Antagonists) |
|
Definition
| Suppresses all phases of daytime and nocturnal basal gastric secretion for the treatment of peptic ulcers |
|
|
Term
| Cimetidine (H2 Antagonists) MoA |
|
Definition
Decreases hepatic metabolism of warfarin, phenobarbital, phenytoin, diazepam, and propranolol. Has anti-androgen effects and inhibits CP450
Least effective in treatment of peptic ulcers
Requires frequent dosage |
|
|
Term
Ranitidine
(H2 Antagonists) |
|
Definition
Anti-ulcer agent that blocks daytime and nocturnal basal gastric acid secretion stimulated by histamine
No CP450 inhibition |
|
|
Term
|
Definition
| The most effective treatment for peptic ulcers |
|
|
Term
Omeprazole
(proton pump inhibitor) |
|
Definition
Onset within 1hr, lasts 24hrs
*1st line alongside 2 antimicrobials for peptic ulcers, irreversible inhibits H+/K+ATPase
Inhibits CYP450-2C19, decreases elimination of phenytoin, diazepam, and warfarin |
|
|
Term
Esomeprazole
(proton pump inhibitor) |
|
Definition
Onset within 1hr, lasts 24hrs
*1st line alongside 2 antimicrobials for peptic ulcers, irreversible inhibits H+/K+ATPase
Inhibits CYP450-2C19, decreases elimination of phenytoin, diazepam, and warfarin |
|
|
Term
| Other Proton Pump Inhibitors |
|
Definition
Lansoprazole
Pantoprazole
Rabeprazole |
|
|
Term
| Rabeprazole and pantoprazole uniquely DO NOT interact with CYPO450* |
|
Definition
| Rabeprazole and pantoprazole uniquely DO NOT interact with CYPO450* |
|
|
Term
| Bismuth Subsalicylate (Pepto-Bismol) |
|
Definition
| A cytoprotective agent, selectively coats for base of peptic ulcer, may provide passive protection against acids and pepsin, bactericidal against H. pylori |
|
|
Term
| H. pylori first line therapy |
|
Definition
| Omeprazole + Clarithromycin + Amoxicillin |
|
|
Term
| Which of the following antimicrobials would not be appropriate to treat recurrent peptic ulcers due to H. pylori? |
|
Definition
|
|
Term
| What is the Bismuth-based-4-drug regimen for the treatment of peptic ulcers? |
|
Definition
| Omeprazole + Bismuth subsalicylate + Metronidazole + Tetracycline |
|
|
Term
| What is always contraindicated in the treatment of peptic ulcers if cardiac problems are also present? |
|
Definition
|
|
Term
| What is Zollinger-Ellison (ZE) Syndrome? |
|
Definition
| Gastric acid hypersecretion and concurrent peptic ulceration |
|
|
Term
| How is Zollinger-Ellison syndrome treated? |
|
Definition
| Proton pump inhibitors are first line, Omeprazole can effectively control acid output and relieve symptoms |
|
|
Term
| What stimulates Pituitary to secrete LH and FSH? |
|
Definition
| GnRH released by the hypothalamus |
|
|
Term
| What transports testosterone locally? |
|
Definition
| Significant amounts diffuse into seminiferous tubules and become concetrnated by binding to androgen binding protein (ABP) |
|
|
Term
| What transports testosterone systemically? |
|
Definition
| Systemic movement in circulation, bound to sex hormone binding globulin (SHBG) and albumin |
|
|
Term
| What's the difference between type I and type II Dihydrotestosterone? |
|
Definition
Type I: Predominantly in non-genital skin, liver and bone
Type II: Found in male urogenital tissue and genital skin in both sexes |
|
|
Term
| Where do androgen receptors reside? |
|
Definition
| In the cytoplasm bound to chaperone proteins when not bound to their ligands |
|
|
Term
| Which formulations of androgen drugs can uniquely be taken orally? |
|
Definition
| 17alpha-alkylated androgens, can be hepatotoxic |
|
|
Term
| What are the testosterone esters? |
|
Definition
Testosterone enanthate (Delatestryl)
Testosterone cypionate (Depo-testosterone) |
|
|
Term
| What are the 17alpha-alkylated androgens? |
|
Definition
Methyltestosterone (Oretin methyl)
Oxandrolone (Oxandrin)
Stanozolol (Winstrol)
Danazol (Danocrin |
|
|
Term
| What are the potential side effects of androgen drugs/anabolic steroids? |
|
Definition
| Decreased testicle size with long term use, increased RBC production, gynecomastia, hepatotoxicity in 17alpha-alkylated androgens, decreased HDL, increased LDL, advancement of benign prostatic hypertrophy or prostate cancer |
|
|
Term
| What potential side effects do androgen drugs have on prepubescent youths? |
|
Definition
| Premature closure of epiphyses and stunted growth |
|
|
Term
| What are some other potential side effects associated with androgen drugs? |
|
Definition
Cardiovascular: Increased cardiac risk factors, Hypertension, Increased LDL/HDL ration, Reported strokes/ myocardial infarctions
Elevated liver enzymes, tumors
Steroid receptors are expressed in the brain: Affect aggression, sexuality, cognition, emotion, and personality “roid rage” |
|
|
Term
| What are the effects of GnRH analogs? |
|
Definition
| Desensitizes GnRH in a non-pulsatile fashion to decrease production of testosterone |
|
|
Term
| What are the GnRH analogs? |
|
Definition
|
|
Term
| What are the effects of GnRH antagonists? |
|
Definition
| Competitive antagonists of GnRH receptors in the ant pituitary, decreases testosterone secretion |
|
|
Term
| What are the GnRH antagonists? |
|
Definition
|
|
Term
| What are the androgen receptor antagonists? |
|
Definition
Flutamide, Bicalutamide, Nilutamide
Spirinolactone** |
|
|
Term
| Which androgen receptor antagonist is used to treat hirsutism in women? |
|
Definition
|
|
Term
| Which androgen receptor antagonists are used to treat prostate cancer? |
|
Definition
| Flutamide, Bicalutamide, Nilutamide |
|
|
Term
| Which 5alpha-reductase inhibitors are used to treat BPH? |
|
Definition
Finasteride: type I
Dutasteride (Avodart): type I & II
Takes roughly 6-9mo to take effect |
|
|
Term
| What are the side effects of 5alpha-reductase Inhibitors |
|
Definition
| impotence, decreased libido, gynecomastia, contraindicated in pregnancy, should not donate blood |
|
|
Term
| What Alpha-1 Blockers are used to treat BPH? |
|
Definition
| Terazosin, doxazosin, tamsulosin, alfuzosin |
|
|
Term
| What is first line in the treatment of BPH? |
|
Definition
| Alpha-1 Blockers: Terazosin, doxazosin, tamsulosin, alfuzosin |
|
|
Term
| What are the side effects of alpha-1 blockers? |
|
Definition
| Decreased ejaculation, alfuzosin prolongs cardiac QT interval |
|
|
Term
| What is postprandial plasma glucose (PPG)? |
|
Definition
| Glucose reading 1-2 hours after eating, reflects glucose uptake after a meal |
|
|
Term
| What is hemoglobin A1c (HbA1c or A1C)? |
|
Definition
| Glycosylated hemoglobin that indirectly measures glucose level over preceding 2-3 months, used with PPH to gauge effectiveness of anti-diabetic agents |
|
|
Term
| What are the rapid acting insulin formulations? |
|
Definition
| Insulin-Lispro, Insulin Aspart, Insulin Glulisine |
|
|
Term
| How long does it take for rapid-acting insulin to take effect? |
|
Definition
| Onset of action in 10-15 minutes, duration is 3-5 hours |
|
|
Term
| What are the short acting insulin formulations? |
|
Definition
| Regular human insulin, effect peaks in 2-3 hours and lasts 5-8 hours, should be taken 30-45min before meals |
|
|
Term
| What are the intermediate-acting insulin formulations |
|
Definition
| NPH (neutral protamine Hagedorn) insulin: Humulin and Novolin |
|
|
Term
| How do intermediate-acting insulin formulations work? |
|
Definition
Insulin is mixed with protamine so that neither protein is present in an uncomplexed form
After injection subcutaneous proteases degrade the protamine, releasing the insulin |
|
|
Term
| What are the long acting insulin formulations? |
|
Definition
| Glargine (Lantus) and Detemir (Levemir) |
|
|
Term
| What are the characteristics of Glargine? |
|
Definition
| “Peakless” insulin designed to provide reproducible, convenient, background insulin replacement. Maximum activity in 4-6 hours, maintained for 11-24 hours, must be kept acidic |
|
|
Term
| What are the characteristics of Detemir? |
|
Definition
Modifications prolong availability by increasing self-aggregation and tissue albumin binding
Most reproducible effects of intermediate- and long-acting
Maximum activity in 1-2 hours, maintained for 24 or more hours |
|
|
Term
| What are the classes of insulin secretagogues? |
|
Definition
Sulfonylureas
Meglitanides
D-phenylalanine derivatives |
|
|
Term
| What are the classes of insulin sensitizers? |
|
Definition
Biguanides
Thiazolidinediones |
|
|
Term
| What is the mechanism of action of sulfonylureas? |
|
Definition
Cause hypoglycemic effect by stimulating the release of insulin from pancreatic b cells
They bind to the SUR1 subunit of the K+ channel causing depolarization, influx of Ca2+ and insulin release
Increase peripheral insulin sensitivity |
|
|
Term
| What are sulfonylureas used for? |
|
Definition
| Control of hyperglycemia in type 2DM patients |
|
|
Term
| What are the sulfonylureas (insulin secreatagogue)? |
|
Definition
|
|
Term
| What is the mechanism of action of Sulfonylureas? |
|
Definition
Cause hypoglycemic effect by stimulating the release of insulin from pancreatic b cells
They bind to the SUR1 subunit of the K+ channel causing depolarization, influx of Ca2+ and insulin release
Increase peripheral insulin sensitivity |
|
|
Term
| What are sulfonylureas used for? |
|
Definition
Control of hyperglycemia in type 2DM patients
Requires dietary restrictions |
|
|
Term
| When are sulfonylureas contraindicated? |
|
Definition
All preparations - Type 1 DM
Older preparations – hepatic/renal insufficiency
Pregnacy |
|
|
Term
| What are the adverse effects of sulfonylureas? |
|
Definition
Hypoglycemic reactions, including coma, elderly, compromised hepatic/renal function
N/V, agranulocytosis, dermatological reactions, aplastic and hemolytic anemia
Secondary failure – “beta-cell burnout” ↓insulin release, 34% fail in 5 years
Weight gain, up to 4 kg
Possible sulfa allergy |
|
|
Term
| What is the best replacement for basal insulin levels? |
|
Definition
|
|
Term
| What is the mechanism of action of Repaglinide and Nateglinide? |
|
Definition
Like sulfanylureas, cause hypoglycemia by stimulating the release of insulin from pancreatic b cells
They close the ATP-dependent K+ channel causing depolarization, influx of Ca2+ and insulin release
Less effective at reducing HbA1c- .6-1% |
|
|
Term
| What are Repaglinide and Nateglinide used for? |
|
Definition
Absorbed rapidly, peak level in 1 hour, allows preprandial use
Use in combo with insulin sensitizers, not with Sus |
|
|
Term
| What kind of drug is Metformin? |
|
Definition
|
|
Term
| What is the mechanism of action for Metformin? |
|
Definition
First-line drug reduce A1C by 1-2%
Actions are antihyperglycemic – no hypoglycemica
Does not stimulate insulin secretion, but insulin must be present
Leads to AMP-dependent protein kinase (AMPK) activation |
|
|
Term
| What are the adverse effects and contraindications of Metformin? |
|
Definition
CI in renal or hepatic dysfunction and in those treated for heart failure such as conditions that predispose to lactic acidosis
Anemia – vitamin B12 absorption
N/V abdominal pain, flatulence in up to 50% - should be titrated
Vitamin B12 deficiency may develop with long-term use
Lactic acidosis is rare, but should be monitored
Discontinue if undergoing radiographic imaging requiring contrast reagent |
|
|
Term
| What is the mechanism of action of Pioglitazone and Rosiglitazone |
|
Definition
Agonist for nuclear peroxisome proliferator-actived receptor-g (PPARg)
Activates insulin-responsive genes that regulate lipid and carbohydrate metabolism
Requires insulin to be present for action
Principle effect by increasing insulin sensitivity in peripheral tissue for Type 2 diabetes |
|
|
Term
| What are the adverse effects of Pioglitazone and Rosiglitazone |
|
Definition
Liver function should be monitored – problems rare
Anemia, weight gain, edema, plasma volume expansion possibly leading to heart failure
Increased fracture risk in women after 3-4 years of therapy
Should not be used in nursing mothers
Rosiglitazone – available through restricted-use program due to high incidence of CV problems, including heart attack and stroke. Restricted to patients unable to control T2DM in other way |
|
|
Term
| What are the alpha-glucosidase inhibitors? |
|
Definition
|
|
Term
| What is the mechanism of action of alpha-glucosidase inhibitors? |
|
Definition
Competitively inhibit enzymes involved in glucose metabolism, primarily a-glucosidase in the intestine
This slows the absorption of carbohydrates, must be administered prior to meals
No direct effect on insulin release (don’t cause hypoglycemia) |
|
|
Term
| What are the adverse effects of alpha-glucosidase inhibitors? |
|
Definition
Dose-related malabsorption of carbohydrates
Miglitol- dose reduction with creatinine clearance < 30mL/min
Flatulence, diarrhea and abdominal bloating
Slowly increasing dose over several weeks can decrease GI-related adverse effects |
|
|
Term
| What types of diabetic drug combinations are not recommended? |
|
Definition
2 types of insulin secretagogue
SUs in Type 1 DM
SU with insulin |
|
|
Term
| As a class, the insulin secretagogues have the following effects except...? |
|
Definition
| All have hypoglycemia, weight gain, and block ATP sensitive L+ channels. Do NOT decrease insulin resistance in peripheral tissues |
|
|
Term
| What is the function of Amylin? |
|
Definition
Protein co-secreted in granules containing insulin
Delays gastric emptying
Inhibits glucagon secretion
Actions are synergistic with those of insulin |
|
|
Term
| What is the amylin analog? |
|
Definition
|
|
Term
| What are the GLP-1 analogs? |
|
Definition
Exenatide and Liraglutide
Exendin-4 was isolated from the salivary gland of the gila monster. |
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Term
| What is the mechanism of action of GLP-1 analogs? |
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Definition
Stimulates the GLP-1 receptor (a GPCR)
Gs-coupled, causes increase insulin gene expression and increased b-cell mass
Actions are glucose dependent, thus it does not cause hypoglycemia when used alone
An incretin mimetic because it acts through the same pathway as endogenous incretins
Administered twice daily before a meal |
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Term
| What is the benefit of GLP-1 analogs that is rarely seen in insulin analogs? |
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Definition
| Weight loss, no beta-cell burnout |
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Term
| What are the DPP-IV Inhibitors? |
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Definition
| Sitagliptin and saxagliptin |
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Term
| What is the mechanism of action of DPP-IV Inhibitors? |
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Definition
Inhibits DPP-IV, preventing the degradation of GLP-1 and other GLP-1-like molecules
Therapeutic effects are a result of GLP-1 activity
Sitagliptin is a competitive inhibitor, axagliptin is a non-competitive inhibitor
Stimulate glucose-dependent insulin secretion
Taken orally
A combination (Janumet) is available |
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Term
| What are the adverse effects of DPP-IV Inhibitors? |
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Definition
Sitagliptin is excreted unchanged in the urine
Reduce dose in renally compromised |
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Term
| What releases corticotropin-releasing hormone (CRH)? |
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Definition
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Term
| What are the effects of CRH? |
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Definition
| Causes the anterior pituitary to synthesize and release ACTH, which in turn causes the adrenal gland to synthesize and release cortisol. |
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Term
| What hormone causes negative feedback on the hypothalamus/anterior pituitary system? |
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Definition
| Cortisol decreases the release of both CRH and ACTH |
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Term
| GFR --> Sweet, Salty, Sex |
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Definition
Glomerulusa, Fasciculata, Reticulosum
Cortisol (anti-insulin), Aldosteorne (Na+ preservation), Androgens (sex hormones) |
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Term
| Rate of circadian rhythm is governed by what? |
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Definition
| ACTH pulses (peaks in the morning and after meals) |
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Term
| What are the effects of cortisol? |
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Definition
| Increased metabolism, Na+ and water retention, helps mediate hypertension and hypotension, modulates CNS mood, promotes osteoporosis, blocks vit D |
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Term
| What are the effects of cortisol on a developing fetus? |
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Definition
| Normal stimulation of lung maturation in the fetus |
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Term
| Administration of what drugs to the mother when delivery is expected prematurely (before 34 weeks) decreases the incidence of respiratory distress syndrome? |
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Definition
Glucocorticoids: betamethasone and dexamethasone
Similar to cortisol |
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Term
| Actions of cortisol at mineralcorticoid receptors is blocked by what? |
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Definition
11b-hydroxysteroid dehydrogenase
Converts cortisol to cortisone (no effects) |
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Term
| Where are glucocorticoid receptors located? |
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Definition
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Term
| Where are mineralglucocorticoid receptors located? |
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Definition
| kidney (distal tubule, collecting ducts), colon, sweat glands |
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Term
| Describe the cortisol signalling pathway |
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Definition
Crosses membrane, binds to glucocorticoid receptor which dissociates from heat shock proteins to which it's normally bound
GR/cortisol complex crosses the nuclear membrane and enters the nucleus to bind directly to DNA and alter transcription of DNA to mRNA |
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Term
| What are the symptoms of Cushing's syndrome? |
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Definition
| Weight gain, muscle weakness, excess hair growth, hair loss, fat redistribution, HTN, osteoporosis, gonadal dysfunction |
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Term
| How is cushing's syndrome diagnosed? |
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Definition
| Dexamethasone stress test |
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Term
| What drugs are used to inhibit ACTH release for the treatment of Cushing's syndrome? |
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Definition
| Ketoconazole, Metyrapone, AMinoglutethimide, Spironolactone, Mifepristone, and Pasireotide |
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Term
| What are the effects of Ketoconazole? |
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Definition
Inhibits all gonadal and adrenal steroid hormone synthesis
SE: Hypersensitivity, GI disturbance |
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Term
| What are the effects of Metyrapone |
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Definition
Inhibits 11-betahydroxylase, increases 11-deoxycorticosteroids, leads to an increase of adrenal androgens and suppression of cortisol
SE: Salt and water retention, hirsutism, transient dizziness |
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Term
| What is the drug of choice for the treatment of actopic ACTH syndrome? |
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Definition
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Term
| What is the drug of choice for the treatment of pregnant women with Cushing's syndrome? |
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Definition
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Term
| What is the mechanism of action of Aminoglutethimide? |
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Definition
| Inhibits the conversion of cholesterol to pregnenolone which is the initial step in production of all steroids in the adrenals |
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Term
| What are the uses of Aminoglutethimide |
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Definition
| Treatment of Cushings syndrome associated with adrenal carcinoma, ectopic ACTH producing tumors (not 1st line), adrenal hyperplasia |
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Term
| What are the side effects of Aminoglutethimide? |
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Definition
| Lethargy, drowsiness, headache, nausea/vomitting |
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Term
| What is the mechanism of action of spironolactone? |
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Definition
| Antagonist at the mineralcorticoid receptor used to decrease the resorption of Na+ and secretion of K+ |
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Term
| What are the uses of spironolactone |
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Definition
Used to treat cushings but efficancy is directly related to the amount of aldosterone present
May also be used for hyperaldosteronism |
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Term
| What is the function of Mifepristone? |
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Definition
| Antagonist at the glucocorticoid receptor |
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Term
| What are the uses of Mifepristone? |
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Definition
| Hyperglycemia secondary to hypercortisolism, used specifically in Type II diabetes |
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Term
| What are the side effects of Mifepristone? |
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Definition
Nausea, fatigue, headache, vaginal bleeding and endometrial changes
Is a progesterone receptor antagonist, causes endometrial proliferation |
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Term
| What are the containdications for Mifepristone? |
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Definition
Pregnancy, drugs metabolized by CYP3A, simvastatin, lovastatin, or other drugs with narrow therapeutic index, women with risk of vaginal bleed, corticosteroid therapy
Not recommended with long QT, hypokalemia, hypocortisolism |
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Term
| What are the uses of Pasireotide? |
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Definition
Inhibits the release of ACTH by acting as an agonist at somatin receptors.
Used in adults with Cushing's that are not candidates for surgery or when surgery was not curative |
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Term
| Waht are the adverse effects of Pasireotide? |
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Definition
| Hypocortisolism, hyperglycemia, diabetes, QT prolongation, liver test elevations, cholithiasis, decreased pituitary function, GI dysterbance |
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Term
| Primary adrenal insufficiency is also known as what? |
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Definition
| Addison's disease, caused by defective adrenal function |
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Term
| How do you distinguish between primary and secondary adrenal insufficiency? |
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Definition
ACTH suppression test
Synthetic ACTH is administered and cortisol levels are drawn in the morning |
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Term
| What labs do you see with Addison's disease? |
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Definition
Low cortisol, low aldosterone
High ACTH |
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Term
| How is Addison's disease treated? |
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Definition
Hydrocortisone for glucocorticoid replacement
Fludrocortisone for mineralcorticoid replacement |
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Term
| What causes secondary adrenal insufficiency? |
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Definition
| Defective anterior pituitary or hypothalamic function causing decreased ACTH |
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Term
| What is distinguishes hormone levels in secondary adrenal insufficiency from what is seen in Addison's disease? |
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Definition
| Aldosterone levels are classically normal, zona glomerulosa is intact |
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Term
| What is the most common cause of Addison's disease? |
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Definition
Exogenous corticosteroid administration causing atrophy of the anterior pituitary and hypothalamus
Sudden withdrawal of steroids after prolonged therapy may cause acute adrenal insufficiency |
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Term
| What is acute adrenal insufficiency? |
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Definition
| Abrupt withdrawal of glucocorticoids with stress in adrenally compromised patients, can be life threatening |
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Term
| How is acute adrenal insufficiency treated? |
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Definition
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Term
| What causes congenital adrenal hyperplasia? |
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Definition
A defect in the enzymes of cortisol synthesis causing hyperplasia and overexcretion of the other adrenal hormones. Caused by deficiency in:
11-hydroxylase
17-hydroxylase
21-hydroxylase |
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Term
| What are the effects of a 21-hydroxylase deficiency? |
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Definition
Most common cause of congenital adrenal hyperplasia
Causes increased androgen secretion, decreased mineralcorticoid secretion
Cortisol synthesis is defective |
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Term
| What are the effects of a 11-hydroxylase deficiency? |
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Definition
Causes increased androgens and mineralcorticoids
Cortisol synthesis is defective
A cause of congenital adrenal hyperplasia |
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Term
| What are the effects of a 17-hydroxylase deficiency? |
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Definition
Causes increased mineralcorticoids, decreased androgens
Cortisol synthesis is defective
A cause of congenital adrenal hyperplasia |
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Term
| How is congenital adrenal hyperplasia treated? |
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Definition
Suppress the release of CRH and ACTH to decrease the production of androgens using Dexamethasone or Hydrocortisone
Replace appropriate deficient hormone based on the deficient enzyme
Anastrazole or Letrazole to inhibit aromatization of androgens to estrogens
Flutamide (anti-androgen) |
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Term
| Hydrocortisone is given for replacement of what? |
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Definition
| Glucocorticoid (cortisol) replacement |
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Term
| Fludrocortisone is given for replacement of what? |
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Definition
| Mineralcorticoid (aldosterone) repleacement |
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Term
| Dexamethasone is given for the replacement of what? |
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Definition
| Glucocorticoids (cortisol), particularly in the fetus due not being bound by CBG |
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Term
| During the basal growth phase, follicles are dependent on what hormone? |
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Definition
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Term
| During the rapid growth phase, follicles are extremely sensitive to what? |
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Definition
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Term
| What hormone predominates the mid-late follicular phase? |
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Definition
Estrogen from ovaries
Induces proliferative phase of endometrium |
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Term
| What hormone predominates during the secretory phase? |
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Definition
Progesterone
Inhibits further endometrial growtha nd induces differentiation of epithelial and stroma |
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Term
| What enzyme converts androgens to estrogen compounds? |
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Definition
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Term
| What are the different estrogen formulations? |
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Definition
Estradiol: principal estrogen in circulation
Estrone: liver converts circulating estradiol to estrone. Can also be synthesized in adipose tissue
Estriol" both estradiol and estrone are converted to estriol |
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Term
| What are the biological actions of estrogen? |
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Definition
Promotes bone strength
Improves lipid profile
Lowers risk of cardiovascular disease
Decreases adipose tissue
Is neuroprotective
Promotes healthy skin |
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Term
| What is the principle mechanism of action of estrogen in contraceptives? |
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Definition
| Constant non-physiological levels of estrogen suppress FSH secretion, dominant follicle fails to mature |
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Term
| What is the principle mechanism of action of progestins in contraceptives? |
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Definition
Suppresses LH secretion to prevent ovulation
Thickens cervical mucus to prevent proliferative effects of estrogen and to reduce likelihood of implantation |
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Term
| What is the treatment regimen when using the combined oral contraceptive pill? |
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Definition
| 21 days of active pills, 7 days of placebo, 28 pills total |
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Term
| What are the differences in the generations of the combined oral contraceptive pills? |
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Definition
1st gen: higher concentrations of estrogen and progestins
2nd gen: Less side effects (clot formation) of 1st gen, this one has less estrogen and progestins, more modern
3rd gen: Similar to 2nd gen except type of progestin has fewer androgenic side effects |
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Term
| What are the common side effects of oral contraceptives? |
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Definition
Weight gain, nausea, flushing, dizziness, depression, irritability, acne, increased pigmentation, amenorrhea
Estrogen may cause HTN, migraines, breast tenderness, edema
Progestin may increase appetite, cause acne, oily scalp, hairloss/hirsutism, breast regression, depression, vaginal yeast infection |
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Term
| What are the potentially serious side effects of oral contraceptives? |
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Definition
ACHES: Abdominal pain, Chest pain, headaches, Eye problems, Severe leg pain
Risk of MI, stroke, venous thromboembolism |
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Term
| What increases the risk of cardiovascular disease when taking oral contraceptives? |
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Definition
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Term
| What is the main risk of transdermal contraceptives? |
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Definition
| Deep vein thrombosis due to significantly higher estrogen levels |
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Term
| What are the dangers of drosperinone, an oral contraceptive? |
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Definition
| Increases serum K+ levels when used with certain anti-hypertensives (ACE-I, K+ sparing, etc) |
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Term
| What metabolic disturbances can oral contraceptives cause? |
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Definition
Impaired glucose intolerance, increases LDL and reduces HDL due to progestins
Use pills with more estrogen than progesterone if a concern |
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Term
| What are the effects of oral contraceptives on cancer development? |
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Definition
Slight increase of breast cancer risk (but treatable)
Decreases endometrial and ovarian cancers |
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Term
| What are the advantages of the mini-pill? |
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Definition
Avoids estrogen side effects
Useful in smokers with a history of cardiovascular disease
Decreases dysmenorrhea, bleeding, PID, endometrial cancer
Used in women who are breast feeding |
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Term
| What are the disadvantages of the mini-pill? |
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Definition
Less effective, strict compliance is necessary, back-up contraception may be necessary
Breakthrough bleeding is more frequent
Contraindicated in women with history of breast cancer, vaginal bleed, or hepatic diseases |
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Term
| What is considered a long acting progestin-only contraceptive? |
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Definition
Depot Medroxyprogesterone Acetate
and Progestin implants |
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Term
| How does depot medroxyprogesterone acetate (DMPA) work? |
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Definition
Given every 3 months, close to 100% effective, menstrual irregularities and weight gain are common
Infertility can persist for months after stopping the drug, new mothers not breastfeeding can resume almost immediately |
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Term
| How do progestin implants work? |
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Definition
Sub-dermal capsules containing etonorgestrel or levenogestrol
Cheaper than oral and lasts for over 3 years without patient compliance
Fertility rapidly returns upon removal |
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Term
| What metabolizes contraceptive drugs? |
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Definition
CYP450
Increased levels increases clearance |
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Term
| What antibiotics can cause contraceptive drugs fail? |
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Definition
| Rifampin and Tetracycline |
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Term
| What anti-epileptic drugs can cause contraceptive drugs to fail? |
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Definition
| Carbamazepine and Phenytoin |
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Term
| What are the postcoital contraceptive drugs and how do they work? |
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Definition
Ovral, Plan B, and Previn
High doses of progesterone |
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Term
| What hormone replacement formulations are used in the treatment of menopause? |
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Definition
Conjugated equine estrogens
Short-acting estrogen mixtures
Esterified estrogens |
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Term
| What are the uses of hormone replacement therapy in menopausal patients? |
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Definition
| Ovarian failure and menopause symptoms such as hot flashes, vaginal dryness, and osteoporosis |
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Term
| Menopausal women on hormone replacement therapy with an intact uterus should also take what? |
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Definition
| Progestin to decrease the risk of endometrial cancer |
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Term
| What are the risks of menopausal hormone replacement therapy? |
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Definition
Increased risk of breast cancer (disappears 5yrs after cessation)
Increased risk of venous thromboembolism and stroke |
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Term
| What alternatives to HRT can reduce hot flashes? |
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Definition
Clinidine, Desvenlaflaxine, other SSRIs
Exercise |
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Term
| What is the goal of hormonal therapy when treating endometriosis? |
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Definition
| Interrupt cycles of stimulation and bleeding of endometriotic tissues |
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Term
| What hormonal treatments exist for endometriosis? |
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Definition
| Contraceptives, progestins, danazol, GnRH analogs, Aromatase inhibitors |
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Term
| How does Danazol help treat endometriosis? |
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Definition
Inhibits GnRH release and LH/FSH surge
Inhibits estrogen production |
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