Midterm #2 Flashcards
1
Q
What does PTH act on and on what tissue cells does it act on?
A
PTH acts by binding a transmembrane receptor and activating cells in bone, GI tract, and kidney.
2
Q
Levothyroxine
A
Simulates T4 and is used to treat hypothyroidism. The T4 products are prescribed more frequently and have fewer side effects because less potent.
3
Q
What is TSH?
A
TRH stimulates TSH release; T3 and T4 inhibit TSH release TSH regulates: Biosynthesis, storage, & release of thyroid hormones. Size & cellularity of thyroid.
4
Q
What are the clinical features of primary acute adrenal cortical insufficiency?
A
• Weakness • Nausea • Hyponatremia, hyperkalemia • Hypotension • Skin pigmentation (get increase of MSH with the ACTH) • May cause ‘adrenal crisis’- a sudden requirement for increased steroid, which is not available; e.g., ‘Waterhouse-Friderichson syndrome’ caused by hemorrhaging into the adrenal cortex caused by sepsis from meningococcal infection
5
Q
What are the physiologic functions of Insulin?
A
• Promote transport of glucose and amino acids through membranes of skeletal/smooth/cardiac muscle cells, fibroblasts, FAT cells (this is most important because can cause diabetes by selectively blocking insulin effects in fat cells ; it is an anabolic hormone • Does not affect glucose uptake in: neurons, kidney and red blood cells, retina, lens • Insulin and C-peptide (are linked in precursor peptide) are secreted from beta cells in islets of Langerhans (pancreas) in response to glucose
6
Q
What do patients on warfarin typically have for INR?
A
2.0-3.0
7
Q
Besides thioamides like Methimazole, what else can be used to treat Hyperthyroidism or Graves Disease?
A
Beta Blockers like Propranolol can inhibit T4 to T3 conversion, and help treat hyperthyroidism, and Radioactive iodine can destroy some of the gland to help out. A simple iodide can be given as well to inhibit organification and hormone release.
8
Q
What are the characteristics of type II diabetes?
A
It is non-insulin dependent diabetes, characterized by tissue resistance to the action of insulin combined with a relative deficiency in insulin secretion. Usually no ketoacidosis, except stressors (infections). May benefit from treatment with both insulin and other drugs.
9
Q
What percent of world population has Diabetes Mellitus? US? How many die annually in US because of it?
A
3%, 8-9%, 73,000
10
Q
Pioglitazone
A
Used to treat type II diabetes, is a Thiazolidinedione. reduces insulin resistance (especially muscle and fat cells) in type II DM by targeting PPAR-y receptor. Also increased GLUT-4 expression. Side effect: bone loss in women, weight gain.
11
Q
What does insulin help prevent with type I diabetes?
A
It prevents diabetic ketoacidosis (excess release of fatty acids leads to toxic levels of ketoacids).
12
Q
What are the main features of Paget Disease of Bone?
A
• Common (3-4% Caucasians)- second most frequent bone disease after osteoporosis; chronic • Usually >40 years of age; usually male • Often asymptomatic, can cause bone pain and fractures • Can cause arthritis if near joint • High serum alkaline phosphates • Vertebrae, skull and long bones common sites • Enhances osteoclastic activity—some rebound osteoblastic response; Described as a disorder of bone remodeling. • Often seen patches of radiolucency on radiographs
13
Q
What are the main oral problems associated with diabetes?
A
- Increased gingivitis and periodontitis and abscesses 2. Poor wound healing (issue with oral surgery or implants) 3. Abnormal infections such as thrush/candida 4. Xerostomia (increased caries) 5. Hypoglycemic event if patients don’t eat before experiencing the stress of a dental procedure
14
Q
Alendronate Sodium
A
Is a bisphosphonate taken daily that inhibits osteoclasts, thereby slowing bone loss. Used in the prevention and treatment of osteoporosis, Paget’s disease, bone metastasis (with or without hypercalcemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other conditions that feature bone fragility. Be careful of osteonecrosis of the jaw though after IV administration of bisphosphonates.
15
Q
Enoxaparin
A
Low molecular weight heparin. Improved morbidity and mortality for cancer patients for DVT as compared to warfarin.
16
Q
What are the lab findings of hyperparathyroidism?
A
Elevated ionized serum calcium • Elevated or high normal PTH – PTH and PTHrP can be distinguished – Differentiates primary hyperparathyroidism from paraneoplastic syndrome – Increased urinary Ca+ and phosphate • Hypophosphatemia
17
Q
Novolin (crystalline zinc)
A
Is a short-acting insulin, effects take 30 minutes, peaks at 2-3 hours, and persists 5-8 hours, helps to lengthen duration and delay onset
18
Q
What are the clinical findings of hyperthyroidism?
A
• Nervousness • Hot and sweating • Weight loss • Muscle weakness/tremor • Palpitations/tachycardia • “thyroid storm” (know symptoms)
19
Q
What are the main symptoms of posterior pituitary insufficiencies?
A
• Diabetes insipidus –no glucose or insulin involved • Polydipsia (thirst) • Inappropriate ADH secretion from pituitary • Consequences : alters kidney function-volume (water) expansion, hyponatremia (low blood sodium levels) and hemodilution • Causes: metastasized carcinoma, CNS infection But problems can correct with administration of ADH.
20
Q
Where is the thyroid gland derived from?
A
Endodermal thickening in floor of pharynx.
21
Q
What are the characteristics of secondary hyperparathyroidism?
A
• Intestinal malabsorption of vitamin D or calcium • Chronic reduction of serum of Ca++ usually a consequence of chronic renal failure Stimulates PTH secretion, causes hyperplasia
22
Q
What is the physiology of the thyroid gland, how is it regulated?
A
Pituitary secretion of TSH in response to low level of thyroid hormone with feedback inhibition. Hypothalamic TRH stimulates the release of TSH. Hypothalamic TRH stimulates release of TSH. Probably allows adaptation to starvation.
23
Q
What are the features of gestational diabetes?
A
• Gestational diabetes-due to stress of pregnancy (3-10% of pregnancies) • Usually goes away after pregnancy, although type II diabetes can develop later • Can have problems with placenta and babies are abnormally large with excessive insulin secretion and early hypoglycemia causing fetal malformations (e.g., cardiac, CNS, renal and limbs)
24
Q
What are the characteristics of a goiter?
A
• Most common lesion of the thyroid-usually a thyroid enlargement • Rarely associated with hypothyroidism • Not a cancer • Usually associate with deficiency of iodine • Diagnosed with fine needle aspiration (versus biopsy) to determine if have large follicles filled with colloid and relatively few cells • Can be confused with thyroid neoplasm—usually very cellular and little colloid
25
Orlistat
Is used for weight loss, is a lipase inhibitor. It diminishes fat absorption by the intestines.
26
Which cells is the pancreas made up of?
Alpha cells (20% of mass) - Secretes glucagon Beta cells (75% of mass) - Secretes insulin Delta cells G cells F cells
27
Teriparatide
An anabolic drug that increases the rate of bone formation, used for osteoporosis, is a synthetic form of parathyroid hormone. It activates osteoblasts.
28
What does 0.2% BAC mean?
Motor impairment and poor judgment
29
Glipizide
Is a 2nd generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain but a lot less likely to cause hypoglycemia than 1st generation sulfonylureas.
30
Why can't insulin be taken as a pill?
Metabolism
31
What does 0.05% BAC mean?
Relax, reduced reflexes
32
What is osteopetrosis?
Osteoclasts are defective and thus unable to resorb bone, bone density increases and growth becomes distorted.
33
Which coagulation factor does Heparin work on?
Xa, which converts Prothrombin to Thrombin (II to IIa)
34
What causes 90% of hyperthyroidism cases?
Graves Disease, found in 2% of adult females. The other cases are from toxic multinodular goiter (plummer's disease).
35
What is Cushing's syndrome?
Chronic high levels of the hormone cortisol, usually due to ACTH-secreting tumor. Symptoms include • Buffalo hump (fatty deposits on upper back between shoulders • Osteoporosis • Hypertension • Emotional
36
What is osteoporosis?
Excess osteoclast function results in loss of bone matrix and risk of fractures. Involutional osteoporosis is when you get older and your bone loss increases. Treatments include bisphosphonates which inhibit osteoclasts and increase mineral content of bone.
37
What are the features of Type I diabetes?
1. Type 1 (insulin-requiring) a. features: young (3-20 yrs old), loss of islet beta cells, 5% of cases, typically thin • no natural insulin • loss of beta cells an autoimmune process-probably triggered by environment such as a viral infection • ketoacidosis (Use of fatty acids in metabolism results in formation of ketone bodies (acetone)) (ketone bodies such as acetone)-dehydration; deep labored breathing (caused by acidosis); nausea, coma
38
What happens with proteins, normally, and with diabetes?
Usually insulin helps make proteins (anabolic effect), but with diabetes, protein catabolism of muscle happens.
39
What is the lab diagnosis of hyperthyroidism?
Elevated free T4 or T3. Low TSH. Presence of serum TSI (immunoglobulins) is diagnostic of Graves disease.
40
What is the most common thyroid neoplasm?
Follicular Adenoma
41
Ketoconazole
Used for Cushing's syndrome. Inhibits adrenal steroid synthesis.
42
What is coagulation factor I?
Fibrinogen
43
What is another name for Paget Disease of Bone?
Osteitis Deformans. It is the second most common bone disease after osteoporosis.
44
What is ADH and Oxytocin?
ADH is released due to: increased serum osmolality, decreased blood volume, decreased blood pressure. ADH causes renal water reabsorption. Oxytocin is released with suckling the breast by the infant and leads to uterine smooth muscle and breast myoepithelial cell contraction.
45
What is the mechanism of hydrocortisone?
It regulates transcription of target genes in nucleus to alter synthesis of inflammatory proteins. In plasma, In plasma, corticosteroid- binding globulin (CBG) binds 90% of the circulating hormone under normal circumstances. When plasma cortisol levels exceed 20–30 mcg/dL, CBG is saturated, and the concentration of free cortisol rise rapidly. Half-life is 60 minutes.
46
What are the characteristics of hypoparathyroidism?
Very uncommon. Most often accidental removal at thyroid surgery, congenital absence of all glands. Symptoms: hypocalcemia, anxiety, depression, decreases PTH, tetany, dental changes in children (poor enamel, brittle teeth, missing teeth).
47
What does the adrenal cortex make?
Mineralcorticoids, glucocorticoids and sex steroids
48
Vitamin D
Regulates gene transcription via the vitamin D receptor; Regulates intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption; decreases parathyroid hormone (PTH) production. Net effect is increased serum calcium and phosphate levels. It is used clinically for osteoporosis, osteomalacia, renal failure. Adverse effects include hypercalcemia, hypercalciuria.
49
Denosumab
Is a monoclonal anti-RANKL antibody treatment of excess bone resorption in osteoporosis and some cancers. it prevents RANKL from stimulating osteoclast differentiation and activity.
50
What are the three adrenocorticosteroids and what do they do?
1. Glucocorticoids - Regulate intermediary metabolism and immunity. Cortisol synthesized from cholesterol (hydrocortisone). 2. Mineralocorticoids - Aldosterone (Na retention/K+ loss). 3. Androgens - Dehydroepiandrosterone, DHEA, can be converted to estrogens.
51
Lorcaserin
Is used for weight loss, 5-HT2C agonist, suppresses appetite in hypothalamus.
52
Glyburide
Is a 2nd generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain but a lot less likely to cause hypoglycemia than 1st generation sulfonylureas.
53
What is the primary test for hypothyroidism?
TSH levels
54
What are some common uses of cortisol?
• Severe allergic reactions • Relieve inflammatory bowel disease • Relieve severe arthritis • Relieve bronchial asthma • Relieve severe dermatitis
55
Glimepiride
Is a 2nd generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain but a lot less likely to cause hypoglycemia than 1st generation sulfonylureas.
56
What are the four secondary hormonal regulators of bone mineral homeostasis?
1. Calcitonin - lowers serum calcium and phosphate 2. Glucocorticoids - Antagonizes Vitamin D stimulated intestinal Ca transport, net effect of lowering plasma calcium. Common cause of osteoporosis in adults when used too long. 3. Estrogens - Prevents bone loss in early postmenopausal period. 4. Selective Estrogen Receptor Modulators (SERMs) (e.g., Raloxifene) - Used for osteoporosis as well. -Fibroblast growth factor is also a regulator.
57
What does parathyroid hormone do?
Its main acLon is to mobilize calcium from bone to increase serum Ca2+ and and increase urinary phosphate excretion.
58
What are the features of Type II diabetes?
2. Type II DM, “adult onset”, Non-insulin dependent DM a. Features • 95% diabetics are type II • Insulin levels often normal, problem is resistance of insulin receptors to insulin stimulation • Correlates with excessive visceral fat (80-90% are obese): restricted diet controls ~20% of diabetic expression • Correlates with hypertension and risk for atherosclerosis • Metabolic syndrome (see below for details) • Some genetics-likely polygenic autosomal • Most over 30 yrs old, but increasing numbers of younger Type I DM patients due to obesity • Minimal ketones or acidosis, but very high glucose --Hyperosmolar coma—enough insulin to prevent lipolysis, but still have elevated glucose
59
What does 0.08% BAC mean?
Legally impaired to drive
60
Glucagon
Is produced in alpha cells of pancreas. It increases gluconeogenesis. Used to treat severe hypoglycemia, a side effect of diabetes drugs usually in an emergency setting.
61
What are the side effects of systemic glucocorticoids?
• Secondary infections • Mood and behavioral disruption • Osteoporosis • Cataracts • Hypertension • Moon face • Buffalo hump
62
Are thyroid diseases strongly female or male predominant?
Female
63
Asprin
Blocks thromboxane A2 = blocks degranulation of platelets. Irreversibly acetylates COX.
64
What percent of population is in the prediabetes state? And what are the cutoffs?
14%, 41 million in US. • 75 gm glucose tolerance test: glucose \>200 mg/dL after 2 hours • HbA1c\>6.5% (this determines the extent to which your hemoglobin is glucosylated-it provides a good estimate of the average level of glucose for the previous 3 months:
65
NPH (neutral protein hadedorn)
This is becoming less popular, but this helps more by trying to mimic the basal level o finsulin, it is considered intermediate-acting insulin. This is often combined with protamine to delay onset. Has onset of 2-5 hours and duration of 4-12 hours. Usually mixed with regular, lispro, aspart, or glulisine insulin and given two to four times daily.
66
What is coagulation factor Ia?
Fibrin
67
What is the definition of Diabetes Mellitus?
A relative or absolute deficiency of insulin, causing glucose intolerance.
68
What are the characteristics of primary hyperparathyroidism?
• A very common endocrine disorder; usually an adenoma (80% of time) • Symptoms: osteoporosis (fractures), constipation, nonspecific weakness, anorexia, stones, peptic ulcers, depression, or even coma. Bones, stones, groans, and moans. • Arrhythmias (1) Treatments usually surgical (2) Metastasis and carcinomas are rare
69
What secretes Parathyroid Hormone?
Chief cells of the parathyroid glands
70
What are the main effects of glucocorticoids (cortisol) on the body?
Stimulates gluconeogenesis and glycogen synthesis in the fasting state. Increases serum glucose levels and thus stimulates insulin release. Supraphysiologic amounts of glucocorticoids lead to decreased muscle mass and weakness and thinning of the skin. Increased insulin secretion stimulates lipogenesis and to a lesser degree, inhibits lipolysis, leading to a net increase in fat deposition. Suppresses synthesis of inflammatory cyotkines. Can cause osteoporosis in Cushing's syndrome.
71
What is normal PT time?
11-13.5 seconds
72
What is the reversal agent for the intrinsic pathway (PTT and Heparin)?
Protamine (+), which binds to (-) heparin and inactivates it.
73
Insulin Determir
Long-acting, good background insulin. Threonine has been dropped and myristic acid added to this to prolong the availability of insulin by increasing self-aggregation and altering albumin binding.
74
What is the infant of a diabetic (gestational) mother like?
Baby tends to be large (macrosomia) – Insulin is an anabolic hormone Baby develops hyperplasia of islets – Early hypoglycemia must be anticipated Increased risk for fetal malformation, mainly if the diabetes is poorly controlled – Cardiac, CNS, renal and limbs
75
Mifepristone
Used for Cushing's syndrome. Is an antagonist at steroid receptors.
76
What causes Graves disease?
Autoimmune-antibodies function as agonists to thyroid-related receptors-causing excessive thyroid receptor activation. T-cell related autoimmune reaction
77
Biguanide
Used to treat type II diabetes, also called Metformin. Mechanism not fully understood—decreases glucose production in the liver and likely increases efficiency of insulin binding • Advantage: insulin-sparing, does not provoke hypoglycemia when used alone • May prevent some of the CVS effects of type II DM • Side effect: GI irritation, B12 deficiency, not for use in alcoholics
78
Where does the posterior pituitary come from?
Neurohypophysis. Buds from the hypothalamus, with axons.
79
What is insulin's effect on adipose tissue?
1. Increased triglyceride storage
80
What is a pheochromocytoma?
• It is a tumor of adrenal medulla (usually benign) –increases secretion of catecholamines • Can be episodic or sustain secretion • Effects typically look like increased sympathetic nervous system function • Hypertension • Flushing • Increased urine catecholamines
81
What is the metabolic syndrome related to type II diabetes?
• Type II diabetes-insulin receptors refractory to insulin • Abnormal lipid metabolism-high triglycerides & LDL, low HDL • Hypertension • Increased risk for atherosclerosis • Prothrombic tendency (high fibrinogen) • Dyslipidemia (high triglycerides & LDL, low HDL) • Pro-inflammatory state
82
What is the cause of Paget Disease of Bone?
Cause not known, but may be triggered by viral infections
83
Ibandronate
Is a bisphosphonate taken monthly that inhibits osteoclasts, thereby slowing bone loss. Used in the prevention and treatment of osteoporosis, Paget's disease, bone metastasis (with or without hypercalcemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other conditions that feature bone fragility. Be careful of osteonecrosis of the jaw though after IV administration of bisphosphonates.
84
What is the reversal agent for the extrinsic pathway (PT and Warfarin)?
Vitamin K. And Coumadin/Warfarin are very inexpensive.
85
Chlorpropramide
Is a 1st generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain because they can bind to carrier proteins in the blood, be dislodged by other drugs, leading to rapid increase in their activity and hypoglycemia.
86
What does calcitonin do?
Inhibits bone resorption & stimulates renal secretion to reduce serum Ca2+ levels.
87
What is ACTH?
Controlled by hypothalamic CRH secretion. Controls the secretion of cortisol in adrenal cortex. Stress increases ACTH. Normal ACTH secretion has a diurnal variation; high in the early morning and low in late evening.
88
Methimazole
Is a thioamide that is used to treat hyperthyroidism. It inhibits thyroid peroxidase reactions, blocks iodine organification.
89
Where does Warfarin work?
Works everywhere you have vitamin K - 2, 7, 9, and 10
90
What does the HbA1c measure?
When the body processes sugar, glucose in the bloodstream naturally attaches to haemoglobin. The amount of glucose that combines with this protein is directly proportional to the total amount of sugar that is in your system at that time. Because red blood cells in the human body survive for 8-12 weeks before renewal, measuring glycated haemoglobin (or HbA1c) can be used to reflect average blood glucose levels over that duration, providing a useful longer-term gauge of blood glucose control. If your blood sugar levels have been high in recent weeks, your HbA1c will also be greater.
91
What is the half life of insulin?
3-5 minutes
92
Insulin lispro
Is a rapid-acting insulin, mimics after meal insulin, rapid onset, early peak action, can be taken right before a meal, duration is about 4 hours so it prevents post-meal hypoglycemia.
93
What are the three mechanisms of oral anti-diabetic agents?
1. Bind to sulfonylurea receptors and stimulate insulin secretion (sulfonylureas) 2. Lower glucose levels by action on liver, muscles, and adipose tissue (biguanides, thiazolidinediones) 3. Other mechanisms: e.g., slow intestinal absorption of glucose (alpha-glucosidase inhibitors)
94
What is the leading cause of hypercortisolism?
Cushing Disease.
95
Clopidogrel
Is an anti-platelet aggregation agent, inhibits ADP pathway irreversibly.
96
What is Paget Disease of the Bone (Osteitis Deformans)?
• Osteoclast are more active than osteoblasts leading to malformed bones-large, dense and brittle. Osteoblasts become overreactive and make excess bone that is very chaotic, weak, brittle, and deformed. Treatment is Alendronate Sodium.
97
What is the most common strength that insulin is available in?
U-100
98
Propylthiouracil
Is a thioamide that is used to treat hyperthyroidism and Graves Disease. It inhibits thyroid peroxidase reactions, blocks iodine organification.
99
What are the main two mineral components of bone and two most important minerals for cellular function?
Calcium and Phosphate
100
What causes type III diabetes?
Pancreatitis
101
What secretes Calcitonin?
Parafollicular cells of the thyroid gland.
102
What is DIC?
Disseminated Intravascular Coagulation: if coagulation and fibrinolytic systems become dually activated. More common in instances of major tissue damage, cancer, OBGYN emergencies.
103
What are the four common kinds of pituitary adenoma?
1. Prolactinoma (32%, galactorrhea, mass effects) 2. Growth Hormone (20%, acromegaly, gigantism) 3. Null cell / unclassified (30%, mass effects, can make clinically trivial amounts of FSH/LH) 4. Corticotroph (14%, Cushing disease)
104
What is more common, an adrenocortical carcinoma or adrenal adenoma?
Adrenal adenoma, the other ones are very uncommon.
105
At what age are pituitary adenomas most common? And what can they do to eyesight?
• Most common in 40-70 year olds • Can damage optic nerve and sight
106
Where are two main abnormal sites of ectopic thyroid?
Intralingual thyroid and lingual thyroid tissue.
107
What are the typical symptoms of type I diabetes?
• Polydipsia & polyphagia (hunger and thirst) • Polyuria (lots of diluted urine) • Unexplained weight loss
108
What is the most common cause of hypopituitarism?
• Most common cause are nonsecretory pituitary adenomas
109
What is 1,25-Dihydroxycholecalciferol?
It is a steroid hormone formed from vitamin D which undergoes hydroxylations in the skin catalyzed by then sun followed by successive hydroxylations in the liver and kidneys. Its primary acLon is to increase calcium absorption from the intestine to increase Ca2+ in serum and bone.
110
Insulin Glargine
Long-acting "peakless" insulin, good background insulin, the attach arginine and glycine to make a complex that is soluble in acid.
111
What are the two hormones secreted from the posterior pituitary?
The posterior pituitary receives axons of nerves from hypothalamus, where ADH and oxytocin are produced. ADH (for water retention) & oxytocin (for nursing) are stored and released from neurohypophysis into systemic circulation, avoiding blood-brain barrier.
112
What is a normal INR?
0.8-1.1
113
What are FSH and LH?
FSH stimulates ovarian follicle growth, estrogen production. FSH plus testosterone promotes spermatogenesis. LH surge or “spike” induces ovulation. LH stimulates testosterone production in testicular Leydig cells; testosterone inhibits LH secretion.
114
What happens with glycogen, normally, and with diabetes?
Glucose is usually converted to glycogen, but with diabetes, glycogenolysis and gluconeogenesis take place instead.
115
What is Growth Hormone?
GHRH sUmulates GH release GIH (somatostaUn) inhibits GH release GH has anabolic effect - promotes collagen & protein synthesis Growth effects of GH are mostly due to sUmulaUng somatomedins (esp. IGF-1) GH is insulin antagonist; GH secreUon is sUmulated by hypoglycemia and blocked by hyperglycemia
116
What are the short-to-medium acting glucocorticoids?
Hydrocortisone, cortisone, prednisone
117
What is Subacute Granulomatous Thyroiditis?
• Viral cause (e.g., flu virus) • Painful • Usually self-limited and surgery not advised
118
Does PTH and 1, 25-(OH)2D act on osteoblasts or osteoclasts?
Has direct effects on osteoblasts (rapid); also stimulates expression of the protein RANK ligand receptor (RANKL), which then activates the osteoclasts. Thus indirect effect on osteoclasts is slower.
119
What are the clinical features of secondary adrenocortical insufficiency?
Due to hypothalamic or pituitary problem Features; • No hyperpigmentation • Aldosterone usually normal • usually due to exogenous treatment with steroids and their abrupt discontinuation An ACTH challenge test will result in increased cortisol levels
120
What is coagulation factor IIa?
Thrombin
121
What is Hashimoto's Thyroiditis?
• Autoimmune; usually females --antithyroid peroxidase Ab present • May start as hyperthyroidism followed by permanent hypothyroidism • Thyroid enlarges- then atrophies over years • Most often in females • Radiation may cause • Most common cause of thyroid deficiency • High TSH, low free T3 and T4.
122
What are the three characteristics of insulin?
1. Onset - the length of time before insulin reaches the bloodstream and begins lowering blood glucose 2. Peaktime - the time during which insulin is at maximum strength in terms of lowering blood glucose 3. Duration - how long insulin continues to lower blood glucose
123
What are the three medications used for anti-resorptive medications for osteoporosis?
1. Bisphosphonates 2. Calcitonin 3. Denosumab
124
What is insulin's effect on the liver?
1. Inhibits glycogenolysis 2. Inhibits conversion of fatty and amino acids to keto acids 3. Inhibits conversion of amino acids to glucose 4. Anabolic action (promotes glucose storage as glycogen)
125
How does the pituitary gland secrete?
1. Brain’s endocrine gland, secretes through blood-brain barrier either: • Anterior-portal circulation from hypothalamus (sends “releasing” factors) • Posterior-axons go into systemic circulation
126
Thyroid carcinomas are typically high risk, and have high metastatic rates. True or False?
False. Low risk, and low metatastasis. All papillary thyroid neoplasms are called malignant, but most are low risk. 10-year survival \>95%.
127
What is the percentage prevalence of adrenal cortical tumors?
They are very common, 1% of population has them. Most are nonfunctional.
128
Cinacalcet
Activates the calcium sensing receptor in the parathyroid gland to inhibit more PTH secretion to decrease serum Calcium.
129
What causes type IV diabetes?
Gestational
130
Teriparatide
Treats osteoporosis by selectively activating osteoblasts. It is the first and only drug that stimulates new bone formation. Contraindicated in individuals at risk for osteosarcoma, Paget's disease, because it is associated with risk of osteosarcoma.
131
What are some of the negative consequences that diabetes does to the body?
• Causes abnormal glucose management and metabolism • Protein catabolism • Abnormal adipocytes • Triglycerides in muscle and hepatic tissue • Increased inflammatory cytokines • Increased thrombosis and arthritis
132
What are the six main hormones released from the hypothalamus to the anterior pituitary?
1. TRH 2. CRH 3. GNRH 4. GHRH 5. GIH 6. Dopamine
133
Metyrapone
Used for Cushing's syndrome. Reduces cortisol synthesis by inhibiting steroid 11-hydroxylation.
134
What is the function of the parathyroid gland?
• Secrete parathyroid hormone (PTH) regulated by free calcium in blood-reverse relationship (low calcium increases PTH) • PTH activates osteoclasts and bone resorption and increases serum calcium; also increases tubular reabsorption of calcium, activates vitamin D and increases GI absorption • Usually 4 glands close to thyroid poles
135
What is the most common problem of the pituitary?
Pituitary adenomas
136
Thrombolytics
• Dissolve clot • Drugs include: streptokinase and urokinase • Are potentially very dangerous and can cause hemorrhagic strokes • Don’t use unless formed clot is in a very dangerous place
137
For which types of diabetes is insulin replacement required?
For all type I, and for severe cases of type II.
138
What are the main features and symptoms of Cushing Disease?
• Leading cause of hypercortisolism: women 5X more likely • Adrenal hyperplasia • ACTH low, cortisol high • Adrenals act autonomously • Symptoms: moon face, osteoporosis, hypertension, buffalo hump, obesity, thin skin, amenorrhea, muscle weakness, mood changes, poor wound healing (remember: this looks like someone on chronic corticosteroid treatment-e.g., for chronic major arthritis or other inflammatory diseases)
139
What is Prolactin?
Prolactin secretion is normally inhibited by dopamine from the hypothalamus. Prolactin increases during pregnancy, and stimulates milk production. Blocking dopamine signalling (tumor, portal vascular problem) increases PRL secretion.
140
What does the adrenal medulla make?
Makes and releases catecholamines (epinephrine and norepinephrine)
141
What is the physiology of alcohol in the body?
• Affects GABA A receptors (although not an agonist)—ethanol interacts with other sedative/hypnotic drugs in a synergistic manner and can lead to OD deaths due to respiratory depression. • Increases release of dopamine and endorphin • Affects almost all organs: e.g., • Liver toxin-increases fat deposits and can cause fatty livers in the extreme -causes cirrhosis in ~5-10% alcoholics -bad combination with acetaminophen • Kidneys- it is a diuretic • G.I.- irritating to mouth through the intestines—causes inflammation and enhances chances of cancer -stimulates gastric secretions -food slows its absorption • Suppresses immune system/perhaps partially due to malnutrition • CVS- low doses increase HDL—high doses increase hypertension, coronary artery disease, and arrhythmias • Brain: order of effects--- cortex (cognition)-limbic (emotions and reward)-cerebellum (motor and balance)-hypothalamus (endocrine)-medulla (respiration and CV regulation) • Disrupts lipid membranes
142
Where does the anterior pituitary arise from?
Adenohypophysis. Arises from evagination of roof of mouth (Rathke's Pouch).
143
What does excessive activation of the thyroid cause?
Causes hypermetabolic state causing protein catabolism and enhanced sympathetic nervous system activity.
144
Which hormones from the hypothalamus act on which hormones from the anterior pituitary?
1. TRH - TSH 2. CRH - ACTH 3. GNRH - FSH, LH 4. GHRH - GH 5. GIH 6. Dopamine And Prolactin by itself.
145
What is pro-insulin?
It is a small peptide that when hydrolyzed, released C-peptide and insulin. That is where it comes from.
146
Rosiglitaone
Used to treat type II diabetes, is a Thiazolidinedione. reduces insulin resistance (especially muscle and fat cells) in type II DM by targeting PPAR-y receptor. Also increased GLUT-4 expression. Side effect: bone loss in women, weight gain.
147
What are the seven main long-term complications of Diabetes Mellitus?
1. Ketoacidosis/hyperosmolar coma/urinary tract infections 2. Ophthalmic-swelling, cataracts, retinopathy, neuropathy, glaucoma and blindness 3. Accelerated atherosclerosis, unhealthy cholesterols and negative consequences on heart (e.g., MI), kidneys (e.g., glomerulosclerosis, pyelonephritis, etc.), brain (stokes) 4. Peripheral neuropathies –loss of touch and pain in extremities; gangrene and amputations of feet 5. Autonomic nerve dysfunction: abnormal GI motility; hypotonic bladder, increased UTI 6. More prone to infections, slow healing 7. Elevated HbA1c (reflects average blood glucose over prior 1-3 months
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What is a normal PTT time?
25-35 seconds, patients on heparin may have PTT time 2-3 times higher than normal.
149
Most thyroid neoplasms are cancerous. True or False?
False, they are usually benign, nodular goiters.
150
What are the differences between Primary and Secondary Hyperaldosteronism?
Primary is called Conn syndrome, and has to do with an adenoma. You get Na+ retention and K+ excretion, Suppression of renin-angiotensin system, Women most often. Secondary typically results from renal disease, or cirrhosis. Increased renin stimulates aldosterone.
151
How is most insulin prepared for use?
Most formulations prepared in laboratory (i.e. genetics; from genetically modified benign e. coli-e.g., Humulin), but can still obtain animal insulin (e.g, bovine, porcine) for special cases
152
Tolbutamide
Is a 1st generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain because they can bind to carrier proteins in the blood, be dislodged by other drugs, leading to rapid increase in their activity and hypoglycemia.
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Repaglinide
Is a glitinide, that acts in a very similar manner to sulonylureas, but doesn't bind as strong. So it is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain.
154
What does 0.4% BAC mean?
Coma
155
What are the five steps getting to insulin secretion?
1. Increased glucose binds to GLUT2 receptor on beta cell in pancreas 2. This leads to metabolism of glucose and increased ATP 3. This ends up closing the potassium channel by depolarizing the cell 4. Which then allows increase in Ca to the cell 5. Which allows insulin stored in vesicles to be released and leave the beta cells
156
What is Rickets (children) and Osteomalacia (adults)?
Defective bone matrix calcification due to Vitamin D and or Calcium deficiency. Treatment involves replenishing vitamin D and calcium.
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What happens when you take too much insulin?
You can get hypoglycemic, which involves tachycardia, bizarre behavior, seizures, convulsions, and coma. You can also get local irritation and subdermal atrophy.
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What are the five main types of Insulin used for diabetes?
(1) Rapid-acting (e.g., Insulin lispro): • Rapid onset, early peak action, duration ~4 hours • Taken immediately before meal (2) Short-acting (crystalline zinc- helps to delay onset and lengthen duration) (Novolin): • 30 min. onset, peaks 2-3 hours, persists 5-8 hours • Often combined with NPH (3) NPH (neutral protein hagedorn) • Immediate-acting • Absorption and onset delayed because insulin linked to peptide called protamine for delayed release after injection • Pharmacokinetic features: onset=2-15 hrs; duration=4-12 hours • Often mixed with other shorter acting insulins for both immediate insulin and sustained insulin needs. • Becoming less popular (4) Insulin glargine • Long-acting sustained insulin: no peaks and valleys • Good as a background insulin (5) Insulin determir • Long-acting • Background insulin
159
What is coagulation factor II?
Prothrombin
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What are the four main organ complications of diabetes mellitus?
1. Heart-coronary artherosclerosis and myocardial infarctions (most common cause of death in diabetics) 2. Kidney failure—renal nephropathy 3. Brain- stroke 4. Eye-retinopathy, cataracts, glaucoma
161
What is Qysmia?
It is a drug used for weight loss and it is a combination of Phentermine and Topiramate (anti-convulsant). Qysmia is contraindicated during pregnancy. Topiramate can give feeling of "fullness" through decreased GI motility, increased taste aversion, increased energy expenditure.
162
Tolazamide
Is a 1st generation sulfonylurea that is used to treat type II diabetes by increasing insulin release from beta cells by blocking potassium channels on their membranes. Side effects include hypoglycemia and weight gain because they can bind to carrier proteins in the blood, be dislodged by other drugs, leading to rapid increase in their activity and hypoglycemia.
163
What are the findings and symptoms of Graves Disease?
Find elevated Ab to TSH receptor. Thyroid gland has a diffuse enlargement (2-3 times normal size). Symptoms: • Hyperthyroidism • Exophthalmos (protrusion of eyeballs), 1/3 of the cases
164
What is the long-acting glucocorticoid?
Dexamethasone
165
What is insulin's effect on muscle?
1. Increased protein synthesis 2. Increased glycogen synthesis 3. Increased glucose transport
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Phentermine
Is used for weight loss, is an amphetamine. Phentermine inhibits norepinephrine and dopamine uptake • Side effect: weight loss, dry mouth, hypertension, palpitation • Interactions with sympathomimetics like MAOIs and SSRIs (including vasoconstrictors in local anesthetics)
167
What are the clinical findings of hypothyroidism?
• Hypometabolic state (result of reduced thyroid activity) • In children, cretinism with reduced mental and physical development • Wide set eyes • Thick, dry and cool skin (cold intolerant) • Sluggish • Enlarged thyroid • Low temperature • Dry coarse skin and hair • Sluggish • Cold intolerance • Modest weight gain
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What is the main cause of hypercalcemia?
Hyperparathyroidism
169
What is commonly used to help suppress appetite for weight loss?
Amphetamines
170
What are the two categories of Osteoporosis Medications?
1. Anti-resorptive medications (slow bone loss) 2. Anabolic drugs (increase rate of bone formation)
171
How are fat cells normally formed and what happens in diabetes?
Glucose is converted to triglycerides in fat cells normally, but in diabetes lipolysis results in ketosis and triglycerides in blood.
172
While insulin receptors are found on most tissues, what are its three primary targets?
1. Liver 2. Muscle 3. Adipose tissues
173
What is and what are the symptoms of Addison's Disease?
Addison’s—adrenal glands produce too little cortisol (chronic)—often insufficient aldosterone as well • Symptoms • Weakness • Fatigue • Weight loss • Hyperpigmentation • Treatment—corticol supplements: cortisones (hydro-) or prednisone
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What are the symptoms of a "thyroid storm?"
Fever, congestive heart failure, coma.
175
What is the physiology of hypothyroidism?
Decreased free T4. • Increased TSH if cause is “primary” hypothyroidism. [Most cases] • TSH is normal or low with “secondary” hypothyroidism due to lack of pituitary function detected by decrease in other pituitary hormones or a TRH stimulation test. [Rare] • Since nearly all cases are primary, high TSH is a good screening test for hypothyroidism.
176
What are the three main delivery systems of insulin?
1. S.C. (subcutaneous) Injection 2. Portable pen injectors 3. Continuous S.C. insulin infusion (needs constant monitoring)
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Heparin
Administered via continuous drip.
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Warfarin
Oral Vitamin K antagonist, requires bridging when initiated, monitoring with INR, very cheap.
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What is the end target for the hormones from the anterior pituitary?
1. TRH - TSH - Thyroid, T4 2. CRH - ACTH - Adrenal Cortex, Cortisol 3. GNRH - FSH, LH - Reproductive tissues 4. GHRH - GH - Liver, IGF-1 5. GIH 6. Dopamine And Prolactin is released from the anterior pituitary and is for lactation.
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Liothyronine
Simulates T3 and is used to treat hypothyroidism.
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What is another name for primary chronic adrenocortical insufficiency? What is the cause and symptoms?
Addison's Disease. • Cause: autoimmune • More common in white women • 65% of adrenal insufficiency cases • Adrenals reduced • Increased infection ACTH is increased Caused by infections such as TB
182
What does \>0.4% BAC mean?
Death
183
What is an adrenal neuroblastoma?
• Usually children Metastatic Can secrete catecholamines
184
Hydrochlorothiazide
Is a thiazide diuretic that reduces renal excretion by increasing calcium reabsorption at the distal tubule.
185
Acarbose
Used to treat type II diabetes, is an alpha-glucosidase inhibitor. Slows the digestion and absorption of starch, disaccharides, etc. by inhibiting alpha-glucosidase in the brush border of the small intestines and pancreatic alpha-amylase. Side effects are bloating and flatulence.
186
What are the main symptoms of anterior pituitary insufficiencies?
• Loss of sex characteristics-sterility • Retard growth in children • Hypothyroidism
187
Difference between primary and secondary adrenocortical insufficiency?
Primary - weakness, nausea, hyperpigmentation of skin, hyponatremia, hyperkalemia, adrenal crisis is when steroids are needed right away, waterson-friederichson syndrome is a hemorrhage into cortex from menigococcal infection. Addison's disease.
Secondary - no hyperpigmentation, aldosterone is normal, due to steroid treatment.
188
Difference between primary and secondary hyperaldosteronemia?
Primary - adenoma caused, sodium retention and potassium excretion. Secondary - results form renal disease or cirrhosis.
189
What is high serum alkaline phosphates associated with?
Paget's disease
190
Glucocorticoids antagonize the effects of Vitamin D. True or False?
True
