Test 1 (Week 2&3) Flashcards
What are some potential manifestations of a decrease in extracellular free calcium levels?
–Paresthesias (numbness with “pins” and needles” sensations) –Tetanic contractions of skeletal muscle (often in hands, feet, or larynx)
How does 21-hydroxylase deficiency present ?
presents in infancy as salt wasting or childhood as precocious puberty; girls can present with virilization
The primary stimulus for insulin release is ____.
glucose
What is Cinacalcet and what do you use it for?
it’s a calcium mimetic used to decrease PTH secretion in secondary hyperparathyroidism (the result of chronic renal failure)
defined as adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection: Typically the pathogen is the meningococcus Neisseria meningitides. Hypotension, then shock, then DIC
Waterhouse-Friderichsen syndrome
How does diazoxide, an antihypertensive, inhibit insulin secretion?
it increases the activity of the ATP sensitive K+ channel on the Beta cell
What are the 3 things to remember about MEN type 1?
-Parathyroid (Hyperplasia and adenomas) -Pancreas( Gastronoma or Insulinoma) -Pituitary (Prolactinoma)
In Pseudohypoparathyroidism, Serum Ca2+ is low, but the PTH concentration is normal or elevated. How is this happening?
In most patients with pseudohypoparathyroidism, there is a congenital reduction in the activity of Gs, and PTH fails to produce a normal increase in cyclic AMP.
What’s the criteria for the diagnosis of diabetes mellitus based on hemoglobin A1C?
>6.5%
Whats the rate limiting step in adrenal steroidal biosynthesis?
transport of cholesterol to mitochondria by StAR
What’s the mechanism of action of Spironolactone ?
–Competes with aldosterone for receptors —-Prevents action of aldosterone —-K sparing diuretic
What’s the name of the synthetic aldosterone?
Fludrocortisone
What’s the diagnostic test for adrenal insufficiency?
inject Cosyntropin (first 24 Amino acids of ACTH) and measure plasma cortisol response
How does Calcitonin decrease serum calcium?
1) inhibits mobilization of calcium from bone 2) increases renal excretion of calcium
Cortisol can bind to the same mineralocorticoid receptor as aldosterone. How do cells with these receptors ensure that only aldosterone binds?
these cells have 11 beta-hydroxysteroid dehydrogenase, type 2, which converts cortisol to the inactive derivative, cortisone
What’s the rate limiting step in catecholamine biosynthesis?
conversion of tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase
What do you give to treat Addison’s? What if this fails to correct fluid and electrolyte imbalances?
hydrocortisone b/c it has both glucocorticoid and mineralocorticoid activity; if this fails to correct fluid and electrolyte disturbances, use fludrocortisone (primarily mineralcorticoid activity)
What are some risk factors of Type 1 diabetes mellitus ?
family history (genetics), geography, viral exposure (particularly coxsackievirus)
What causes hypercalcemia associated with malignancy?
tumors that hyper secrete parathyroid hormone related protein (PTHrP)
What’s the mechanism of action of sulfonylureas?
close potassium channel in beta cell membrane –> cell depolarizes–> insulin released via increased Ca++ influx
How do sulfonylureas work?
directly inhibit the ATP sensitive K+ channels which depolarizes the membrane and activates voltage sensitive Ca++ channels which will trigger the release of insulin from the Beta cells (simply put, they lower blood glucose by stimulating insulin secretion)
What is the major metabolic effect of glucocorticoids (cortisol)?
stimulation of liver gluconeogenesis
What are the only two adrenal hormones essential for human life?
cortisol and aldosterone
List the second generation sulfonylureas
glimepiride, glipizide, and glyburide
What will you find in MEN-2B?
-thyroid medullary carcinoma -adrenal pheochromocytoma + neuromas and marfanoid body habitus
What are the 3 polys of diabetes?
polyuria, polydipsia, and polyphagia
List the Glitazones/thiazolidinediones.
pioglitazone and rosiglitazone
At what time of day is it best to give glucocorticoids systemically?
in the morning, when endogenous production is highest
What’s the mechanism of action of ketoconazole?
blocks 11 beta hydroxyls and 17,20 lyase;
primary use is anti fungal agent
Glucose inters Beta cells of the pancreas via what transporters?
GLUT 2
What’s the name of the amylin analog?
Pramlintide
What will you find in MEN-2A?
-parathyroid hyperplasia -thyroid medullary carcinoma -adrenal pheochromocytoma
What does aldosterone cause to be excreted?
potassium and hydrogen
What is the name of the SGLT-2 inhibitor and what is its action?
Canagliflozin; blocks reabsorption of glucose in proximal convoluted tubule
What’s the name of the syndrome where you have a solitary aldosterone secreting adenoma?
Conn syndrome
List the long acting insulin preparations.
Detemir and Glargine
What are the potential toxicities of alpha-glucosidase inhibitors?
GI disturbances
beta2-adrenergic stimulation ____ insulin secretion.
stimulates (increases cAMP)
How does 17alpha-hydroxylase deficiency present ?
in males: pseudohermaphroditism (ambiguous genitalia, undescended testes) in females: lack of secondary sexual development you lack production of androgens
Which corticosteroid is used specifically for seasonal allergies and asthma via nasal spray and inhalers?
beclomethasone
Does exercise increase or decrease glucagon secretion?
increases; all the glucose present gets sucked up into the muscles
What is Paget’s disease characterized by?
excessive resorption and abnormal remodeling of bone
What are the potential toxicities of the amylin analogs?
hypoglycemia, nausea, diarrhea
What is multiple endocrine neoplasia 2B comprised of?
medullary thyroid cancer, pheochromocytomas, and multiple mucosal neuromatas
What effect does aldosterone play on K+ and H+?
aldosterone increases the secretion of these ions
Many of the metabolic effects of insulin, particularly those that occur rapidly, are mediated by ______ and _____ reactions.
protein phosphorylation and dephosphorylation reactions
The adrenal medulla is innervated by _____.
cholinergic preganglionic fibers.
What causes secondary hyperaldosteronism?
activation of renin-angiotensin system; this can be caused by decreased renal perfusion, CHF, pregnancy
List the DPP-4 inhibitors
linagliptin, saxagliptin, sitagliptin
What are the adverse effects of Cinacalcet?
hypocalcemia, adynamic bone, use with caution with CYP3A4
In skin and connective tissue, high levels of glucocorticoids will promote tissue breakdown and inhibit ______
collagen synthesis= thinning of skin, thinning of capillaries (easy bruising), purple striae on stomach
List the first generation sulfonylureas.
chlorpropamide and tolbutamide
What’s the most serious adverse effect of metformin?
lactic acidosis (thus contraindicated in renal insufficiency)
What’s the mechanism of action of Raloxifine?
a selective estrogen receptor modulator; enhances calcium retention and retards bone loss; It is the only SERM approved to prevent or delay bone loss in post menopaulsal women.
List the bisphosphonates we are supposed to know.
alendronate, risedronate, ibandronate, zolendronate
What’s the most frequent oral calcium supplement given for hypocalcemia?
calcium carbonate
What plasma calcium levels would qualify as severe hypercalcemia?
>14mg/dL
List the rapid acting insulin preparations
- aspart
- glulisine
- lispro
What are the target tissues of glucagon?
liver and adipose tissue
How do you make an early (and potentially life saving) diagnosis of 21-hydroxylase deficiency?
neonatal dried blood spot test will show increased 17alpha hydroxyprogesterone
Amino acids stimulate insulin secretion, but they also stimulate _____ release.
glucagon
beta cells of the pancreas secrete what?
insulin
What are the GLP-1 analogs?
Exenatide and Liraglutide
What’s the primary toxicity for bisphosphonates taken orally?
gastric and esophageal irritation, esophagitis
How does 11beta hydroxyls deficiency present?
girls can present with virilization
What’s the mechanism of action of alpha-glucosidase inhibitors?
inhibit intestinal brush border alpha glucosidases; this delays carb hyrdolysis and glucose abosorption which will decrease postprandial hyperglycemia
What causes primary hyperaldosteronism?
aldosterone producing adrenal adenomas
What is Teriparatide and how does it work?
It’s a PTH analog that, like PTH, when administered at low doses intermittently will produce a net increase in bone formation
What are the potential toxicities of DPP-4 inhibitors?
mild urinary or respiratory infections
Glucocorticoids decrease the number of thymus derived lymphocytes, their transport to the site of antigenic stimulation, and their function. How?
glucocorticoids block the release of interleukin-1 from macrophages and interleukin-2 from helper T-cells
Does the amount of protein bound calcium increase or decrease in acidosis?
Acidosis decreases binding and increases ionized calcium
How do bisphosphonates work?
Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss.
What are we going to be looking for in the labs of someone we suspect of having a pheochromocytoma?
urinary excretion of free catecholamines and metabolites (VMA or metanephrine) as well as free plasma metanephrines
What connects the A and B chains of insulin?
disulfide bridges
The A chain of insulin contains ____ amino acids. The B chain of insulin contains ___ amino acids.
A=21 B=30
How do salicylates increase insulin secretion?
they inhibit cyclooxygenase which is necessary for the production of prostaglandins (prostaglandins inhibit insulin release)
What’s a side effect of Teriparatide?
may increase risk of osteosarcoma and bone tumors
What are the side effects of Glitazones/thiazolidinediones?
weight gain, edema, hepatotoxicity, HF, increased risk of fractures
What’s the suffix for all bisphosphonate drugs?
-dronates
What are some of the more important risk factors for Type II diabetes?
sedentary lifestyle, obesity, family history, age
What screening test is used to check patients for diabetic nephropathy?
urine microalbumin levels
What are the bisphosphonates used specifically for Paget’s disease?
etidronate, pamidronate, zolandronate
What’s the mechanism of action of metyrapone?
blocks 11 beta hydroxylase to prevent synthesis of cortisol
alpha cells of the pancreas secrete what?
glucagon
Glucagon increases/decreases fructose 2,6-bisphosphate concentration. What’s the consequence?
decreases; stimulates gluconeogenesis
What is Virilization?
the development of male physical characteristics (such as muscle bulk, body hair, and deep voice) in a female or precociously in a boy, typically as a result of excess androgen production.
What’s the emergency treatment for hypercalcemia?
3 pronged approach: –Volume expansion (saline infusion) –Salmon Calcitonin (inc. renal excretion) –Bisphosphonates—zolendronic acid or palmidronate
What’s the rate limiting step for making all of the endogenous steroids?
the conversion of cholesterol to pregnenolone
Which corticosteroid has the longest half life?
dexamethasone (36-54)
What’s the most potent glucocorticoid?
Dexamethasone (9-fluoro-16-methylprednisolone)
what’s the first line blood pressure drug for diabetics?
ACE inhibitors (prils)
What are the toxicities of the GLP-1 analogs?
nausea, vomiting, pancreatitis
What’s the name of the enzyme that catalyzes the conversion of NE to Epi? What induces its production?
phenylethanolamine N- methyl transferase; it’s production is induced by cortisol from fasciculata layer
List the alpha-glucosidase inhibitors
acarbose and miglitol
What causes Addison’s disease?
Addison’s Disease occurs when the adrenal glands do not produce enough adrenocorticosteroid hormones —AKA “chronic adrenal insufficiency”
In those cells in which insulin increases facilitated diffusion of glucose, this is due to increased recruitment of _____ transporter units.
GLUT 4
What’s the IV drug of choice for a hypocalcemia patient?
Calcium gluconate
delta cells of the pancreas secrete what?
somatostatin
What are the three mechanism by which Cushing syndrome occurs endogenously?
- Hypothalamic-pituitary disease with hypersecretion of ACTH
- Hypersecretion of cortisol by adrenal adenoma, carcinoma or nodular hyperplasia
- Secretion of ectopic ACTH by non-endocrine neoplasms
rare autoimmune mediated destruction of the adrenal cortex
Addison’s disease
What are the 3 release stimulators of aldosterone?
1.Renin-angiotensin system 2.Extracellular potassium and sodium 3.ACTH
When removing a pheochromocytoma, what must be given perioperatively to prevent a hypertensive crisis?
phenoxybenzamine (irreversible alpha blocker)
What is the cause of most cases of Cushing syndrome?
administration of exogenous glucocorticoids
Infants born to diabetic mothers often have what?
high birth weights and large organs (macrosomia)
How do you treat moderate to severe Paget’s disease?
salmon calcitonin, human calcitonin, bisphosphonates
What are the potential toxicities of SGLT-2 inhibitors?
glucosuria, UTIs, vaginal yeast infections
How does theophylline, a phosphodiesterase inhibitor, stimulate the release of insulin?
inhibition of phosphodiesterase in beta cells increases cAMP (thereby reading intracellular Ca++)
How do you test for Cushings?
24 hour urinary free cortisol; >250micrograms/d = cushings
What’s normal plasma glucose levels?
90 mg/dl
What are the primary target tissues of insulin ?
muscle, liver, and adipose tissue
What’s the mechanism of action of Glitazones/thiazolidinediones?
increase insulin sensitivity in peripheral tissue by binding to and activating PPAR-gamma nuclear transcription factor
What is 90% of cortisol bound to?
corticosteroid binding globulin (CBG)
Which cells secrete renin?
juxtaglomerular cells
How are patients with pheochromocytoma typically going to present?
Classic presentation–abrupt onset of BP elevation with tachycardia, palpitations, headache, sweating, tremor and apprehension
What drug class is Metformin in?
biguanides
What’s an intermediate acting insulin preparation?
NPH
A number of congenital enzyme deficiencies in the pathways of adrenocortical hormone synthesis occur. Which is by far the most prevalent?
21-hydroxylase deficiency
alpha2- adrenergic stimulation ____ insulin secretion.
inhibits (decreases cAMP)
What blood glucose level is considered diabetic?
fasting: 126 mg/dl and above
Glucocorticoids (like cortisol) inhibit the synthesis of prostaglandins, thromboxanes, and leukotrienes, substances thought to play important roles in inflammation. What do they block specifically to accomplish this?
block phospholipase A2 (Which was making arachidonic acid from phophatidyl choline)
What does renin do?
converts angiotensinogen to angiotensin 1
How do you treat mild cases of Paget’s disease?
analgesics and anti-inflammatory drugs
Does the amount of protein bound calcium increase or decrease in alkalosis?
Alkalosis increases binding and decreases ionized calcium.
