Exam 2 Flashcards
(146 cards)
1
Q
Sulfonylureas MOA
A
stimulate insulin release by binding to pancreatic beta cell receptors, enhancing insulin exocytosis (requires functional beta cells)
2
Q
Sulfonylureas Adverse Effects
A
Hypoglycemia, sulfa allergy contradictions, alcohol use contradicted
3
Q
Sulfonylureas Efficacy
A
All agents lower glucose, have different half-life and side effects, and drug-to-drug interations
4
Q
Sulfonylureas First Generation
A
Chlorpropamide (Diabinese) only first generation still in use
5
Q
Sulfonylureas Second Generation
A
Glipizide, Glyburide, Glimepiride, Gliclazide
6
Q
Meglitinides Primary Agents
A
Repaglinide, Nateglinide
7
Q
Meglitinides MOA
A
Rapid acting insulin secretagogues stimulating pancreatic beta cells
8
Q
When should you take Meglitinides
A
Before meals to reduce postprandial hyperglycemia
9
Q
Meglitinides Adverse Effects
A
Hypoglycemia risk, especially if meals are skipped or delayed
10
Q
Biguanides Names
A
Metformin, Glucophage
11
Q
Biguanides MOA
A
Increase insulin sensitivity, inhibits hepatic gluconeogenesis/ liver production of glucose
12
Q
Biguanides Lipid Lab Changes
A
Lower triglycerides, LDL, total cholestrol, increase HDL, promotes weight loss
13
Q
Biguanides Dosing
A
once or twice daily, first line therapy (ADA, AACE)
14
Q
Biguanides Safety Profile
A
No hypoglycemia when used alone, GI upset, lactic acidosis but rare, may reduce vitamin B12
15
Q
Biguanides Contradictions
A
Hold for 48 hourse post contrast imaging until renal function is confirmed
16
Q
Thiazolidinediones Brand Name
A
Rosigliazone
17
Q
Thiazolidinediones MOA
A
Sensitize skeletal muscle/ adipose tissue to insulin, inhibit hepatic gluconeogenesis, weight gain
18
Q
Thiazolidinediones Glycemic Effect
A
low hypoglycemia risk when used as monotherapy
19
Q
Thiazolidinediones Considerations
A
Use caution in CHF, can reduce oral contraceptive efficacy
20
Q
Thiazolidinediones Monitoring
A
LFTs every 2 months in year 1, then periodically
21
Q
Alpha Glucosidase Inhibitor Name
A
Acarbose (precose)
22
Q
Alpha Glucosidase Inhibitor MOA
A
Inhibiting alpha glucosidase enzymes at the intestinal brush border, delaying carb digestion, lowering postprndial glucose
23
Q
Alpha Glucosidase Inhibitor Metabolic Effect
A
No effects on lipids or body weight, no hypoglycemia used alone
24
Q
Alpha Glucosidase Inhibitor Adverse Effects
A
GI: Bloating, flatulence, diarrhea
Monitor liver enzymes
25
Alpha Glucosidase Inhibitor Clinical Notes
Most effective for postprandial glucose
26
Incretin Mimetrics (GLP-1 and GIP Agonists) Incretins
GI hormones (GLP-1 and GIP), released after eating, stimulate glucose-dependent insulin secretion, preserve beta cell mast
27
Incretin Dystfunction in TD2M
Lowered GLP-1 in obesity and isulin resistance contributes to postprandial hyperglycemia
28
GLP-1 Agonist Medications
Semaglutide (Ozempic) also for weight loss
29
Incretin Mimetrics (GLP-1 and GIP Agonists) Prototype
Exenatide
30
Incretin Mimetrics (GLP-1 and GIP Agonists) MOA
enhance glucose depent insulin secretion, supresses postprandial glucagon, delays gastric emptying, promotes satiety and weight loss, improves beta cell mast
31
Incretin Mimetrics (GLP-1 and GIP Agonists) benefit
Low hypoglycemia risk unless used with sulfonylureas
32
Incretin Mimetrics (GLP-1 and GIP Agonists) Adverse Effects
mild to moderate GI and neurological symptoms, injection site reactions, hypoglycemia risk increases with sulfonylureas
33
Incretin Mimetrics (GLP-1 and GIP Agonists) Dosing
5mg subcutaneously twice daily
34
Incretin Mimetrics (GLP-1 and GIP Agonists) Contradictions
T1DM, DKA, severe GI disease
35
Amylinn Mimetics (Pramlintide - Symlin) MOA
Synthetic amylin analogue slows gastric emptying, suppreses glucagon, promotes satiety leading to weight loss
36
Amylin Mimetics (Pramlintide- Symlin) Use
T1DM or T2DM or insulin with poor postprandial control
37
Amylin Mimetics (Pramlintide- Symlin) Administration
SC injections at meals, never mix with insulin
38
Amylin Mimetics (Pramlintide- Symlin) Adverse Effects
GI Upset, risk of severe hypoglycemia with insulin
39
DPP-4 Inhibitors (Gliptins) Example
Sitagliptin
40
Amylin Mimetics (Pramlintide- Symlin) MOA
Inhibit DPP- 4 (enzyme that degrades GLP-1 and GIP), prolongs incretin activity, enhance glucose dependent insulin release, suppresses postprandial glucagon
41
Amylin Mimetics (Pramlintide- Symlin) Adverse Effects
GI upset
42
SGLT-2 Inhibitors (Glucoretics) Example
Canagliflozin (Invokana)
43
Amylin Mimetics (Pramlintide- Symlin) Therapeutic Effect
lower fasting and postprandial glucose, modest weight loss, potential CV and renal benefit
44
Amylin Mimetics (Pramlintide- Symlin) MOA
Inhibit renal SGLT-2 protein, block glucose reabsorption in the proximal tubule, promote glucose excretion in urine
45
Combination Therapies
DPP-4 Inhibitor + Metformin= EX: Janumet
SGLT-2 Inhibitor + Metformin= EX: Xigudo
46
What is DM?
chronic metabolic disorder with persistent hyperglycemia due to insufficient insulin production or impaired insulin action
47
Different types of DM?
T1DM: autoimmune destruction of beta cells
T2DM: insulin resistance and decreased beta cell function
GDM: during pregnancy with insulin resistance related to hormonal changes
48
DM epidemiology
11.3% population, T2DM 90%, T1DM 5%, Hispanics 22%, blacks 20%, asians 19%, whites 12%, prevelance expected to rise to 165%
49
What is Glycogenolysis?
liver breaks down stored glycogen into glucose, facilitated by glucagon and epinephrine
50
What is Gluconeogenesis?
when glycogen is depleted the liver creates glucose from main acids, glycerol and lactate
51
What is Ketogenesis?
fatty acid oxidation produce ketones, leads to ketosis causing metabolic acidosis, fruity breath, fruity urine
52
What is DKA?
Occurs without any insulin, lipolysis is unchecked, ketogenesis is excessive, and acidosis develops,
53
Range for hypoglycemia
Glucose at 70mg/dl or less, the brain cannot then metabolize fats or proteins, very dependent on glucose
54
Range for hyperglycemia
glucose at 200 mg/dl or above, fasting is 100-125
55
What is the role of insulin?
binds insulin receptors, triggering intracellular signaling cascade, causing GLUT4 translocatio,n causing cellular glucose uptake (Key to the cell)
Promotes anabolism: glycogenesis, lipogenesis, protein synthesis and inhibits catabolic processes
initial rapid release, but then slows
56
What are Glucagon Alpha Cells?
antagonist to insulin: increase blood glucose, stimulate glycogenolysis and glucogenesis, inhibit glycogen storage and fat deposition, sectreion is inhibited by hyperglycemia and stimulated by hypoglycemia
57
What are Incretins (GLP-1, GIP)?
Secreted from the GI tract post-meal, enhances insulin secretion and suppresses glucagon during hyperglycemia
GLP-1 delays gastric emptying and promotes satiety
58
What other hormones impact glucose metabolism
Cortisol, epinephrine, GH, estrogen, progestrone
59
s/s of T1DM
polydipsia, polyuria, polyphagi, weight loss, fatigue, poor vision, possible initial presentation of DKA, gential candida can be early indicator
60
s/s of T2DM
gradual onset, poluria, polydipsia, polyphagia, poor wound healing, visual changes, rarely has DKA, more commonly has hypersomolar hyperglycemic syndrome (HHS)
61
What is Hyperosmolar hyperglycemic syndrome (HHS)?
Severe complications where blood sugar is too high for too long, causing dehydration and confusion, seizures
62
Pathological Mechanisms of T2DM
Oxidative stress, proinflammatory cytokines, insulin receptor and post-receptor defects, mitochondrial dysfunction,
insulin resistance and impaired glucose uptake
63
Metabolic Syndrome and association with T2DM
Central obesity, hypertriglyceridemia, Low HDL cholesterol, hypertension, fasting glucose of 100 or more
64
Blood Glucose Diagnosis of DM
Fasting plasma glucose of 126 or more, random plasma glucose of 200 or more, HbA1c: 5.7-6.4 pre, 6.5+ DM
65
Urine testing for DM
Glucosuria, Ketonuria
66
Hypoglycemia symptoms
sweating, hunger, tremors, dizziness, seizures
67
Somogyi Effect vs Dawn phenomenon
Somogyi Effect: Nocturnal hypoglycemia stimulates hepatic glucose production, resulting in rebound morning hyperglycemia
Dawn Phenomenon: elevated growth hormone levels overnight reduce glucose utilization, causing morning hyperglycemia
68
Short-term problems with Hyperglycemia
Polydipsia, polyuria, polyphagia, weight loss, blurred vision, electrolyte imbalance
69
What is DKA?
absolute insulin deficiency, lipolysis causes ketone production leading to metabolic acidosis, symptoms of Hyperglycemia plus fruity breath and urine
Treat with IV fluids/ insulin and electrolyte monitoring
70
Long Term Vascular Damage Via DM
can be microvascular like retinopathy, neuropathy
macrovascular: CAD, stroke, PAD
71
What is Neuropathy?
peripheral neuropathy: begins in the feet burning numbness and gait instability
autonomic neuropathy: bladder problems, HTN, hypoglycemia unawareness
72
What is Retinopathy?
Pathogenesis: retinal ischemia from microvascular injurt can cause retinal detachment
73
What is Nephropathy?
glomerular hyperfiltration causing microalbuminuria, causing glomerulosclerosis (thickening of GBM and atherosclerosis
causes renal insufficiency, end-stage renal disease, typically found with retinopathy
74
Why is there a Risk of foot injury
Due to peripheral neuropathy can't always feel toes, slow wound healing and dry skin so skin breakdown is easy
75
Infection problems associated with DM
Impaired WBC, phagocytosis and chemotaxis
Common Infections: UTI, pneumonia, candida
76
What range should blood sugar remain at for diabetics?
70-140 mg/dl to prevent hyper or hypoglycemia
77
Blood glucose level that shows hyperglycemia
above 140
78
Blood glucose level that shows hypoglycemia
Below 70
79
When is insulin therapy initiated
at blood glucose of 180 or more
80
what is target glucose range for most patients
140-180 mg/dl
81
Lifestyle management of DM
new diet to address insulin reistance based on BMI, sex, activity level, healthier diet, regular exercise
82
Surgical intervention for T1DM
Pancreatic or islet cell transplantation can be considered, with lifelong immunosuppression is needed
83
Self-Monitoring for DM
Use of glucometers, ADA targets: A1c at most 7%, preprandial 80-130 mg/dl, postprandial at most 180 mg/dl
84
Health Maintenance for DM
Cardiovascular management: BP less than 140/90, LDL less than 100, HDL more than 60, triglycerides at 150 or less
Immunizations, foot care, ophthalmic screening, renal monitoring
85
What is downregulation?
occurs with prolonged exposure to high hormone levels, reducing receptor sensitivity and density
86
What is upregulation?
occurs in resposne to hormone deficency, increasing receptor number and response
87
Classification of Endocrine Dysfunction (3 classes)
Hormone deficency (T1DM)
Hormone excess (Graves Disease)
Hormone resistance (T2DM)
88
Endocrine Dysfunction: Primary vs Secondary
Primary: dysfunction originates in the target endocrine gland
Secondary: arises from pituitary tropic hormone secretion
89
What is neoplasia, and what does it cause?
tumor growht and can cause hyper or hypo function
90
What are autoimmune endocrinopathies?
result from the immune response against endocrine tissues, which causes glandular destruction (hypo) or stimulation (hyper)
91
Hypopituitarism symptoms
Infants: dwarfism, seizures, congenital anomalies
Adults: weakness, HTN, weight gain or loss, infertility, polyuria/ dehydration
92
What do pituitary glands secrete?
pituitary gland secretes tropic hormones (TSH, ACTH, LH, FSH, GH, PRL), posterior stores ADH and oxytocin
93
How to diagnose Hypopituitarism?
decreased tropic hormones TSH, ACTH, FSH, LH. GH, PRL, ADH
decreased targe gland hormones T4, cortisol, testosterone, estrogen
94
Hyperpituitarism prolactinomas in women
Woman: amenorrhea, galactorrhea, infertility, osteopenia
Men: gynecomastia, erectile dysfunction, infertility
95
Hyperpituitaryism GH- GH-secreting tumors
Children: gigantism
Adults: acromegaly (jaw/hands/feet enlargement, insulin resistance)
96
ACTH vs TSH-secreting tumors
ACTH: cushingoid features, moon face, buffalo humop, purple striae, hair thinning
TSH: hyperthyroidism symptoms, palpitations, tremors, heat intolerance
97
What is a goiter, and what does it cause?
enlarged thyroid gland, causes iodine deficiency which impairs T3/T4 synthesis causing increased TSH and thyroid enlargement
98
What is Hashimoto's hypothyroidism
autoimmune thyroiditis, immune system attacks thyroid decreasing thyroid secretion of hormones
99
Clinical Presentation of Hypothyroidism
cold intolerance, weight gain, puffy face, hyperlipidemia, renal dysfunction, cretinism, myxedema
100
Diagnosis of Hypothyroidism
Primary Hypothyroidism: high TSH, low t3/t4
Secondary: low TSH and low t4
101
Hypothyroidism treatment
Levthyroxine replacement and monitor TSH every 6-8 weeks
102
What is Graves disease?
TSH stimulates excess t3 and t4
Graves' disease is the most common cause of hyperthyroidism
103
Primary vs Secondary hyperthyroidism
Primary: excess thyroid hormone from the thyroid gland
Secondary: elevated TSH from the pituitary
104
Clinical Presentation of Hyperthyroidism
systemic effects: weight loss, heat intolerance, nervousness
Graves ophthalmopathy: periorbital edema, exophthalmos
Pertibial myxedema: skin thickening over the lower legs
105
Diagnosis for Hyperthyroidism
TSH suppression with elevated T3/T4
106
Hyperthyroidism Treatment
antithyroid drugs like methimazole, radioactive iodine (contradicted in pregnancy), and surgical removal if needed, lifelong levothyroxine as post-treatment
107
What is a Thyroid storm?
life-threatening surge in thyroid hormones
triggered by surgery, trauma, or infection
108
Thyroid storm symptoms
Symptoms include high fever, tachycardia, delirium, and coma
109
Thyroid storm treatment
triggered by surgery, trauma, or infection
110
What is hypoparathyroidism
Low PTH causing low calcium and high phosphate
111
Symptoms of hypoparathyroidism
tetany, cramps, seizures, chovestks and trousseau's signs
112
Treatment for hypoparathyroidism
calcium and vitamin D supplementation
113
What does the adrenal medulla produce?
Glucocorticoids (cortisol)
Mineralocorticoids (aldosterone)
Androgens
114
What does the adrenal cortex produce?
catecholamines (epinephrine and norepinephrine)
115
Pathophysiology of Addison's Disease (hypoadrenalism)
Autoimmune destruction leads to decreased cortisol and aldosterone
Exogenous corticosteroids suppress CRF/ACTH, causing adrenal atrophy
Adrenal crisis may occur during stress if not enough cortisol
116
What can long-term corticosteroids cause?
decreased secretion to no secretion of cortisol, making the body dependent on exogenous use
leading to adrenal atrophy
117
What do the hypothalamus and pituitary gland do due to excessive corticosteroids in the blood?
The hypothalamus will stop releasing corticotropin-releasing hormone
118
What is an adrenal crisis?
A lack of cortisol in the body can be a life is a life-threatening condition with hypotension, electrolyte imbalances (hyponatremia, hypokalemia), hypoglycemia, and fever and hyperpigmentation
119
Labs for Adrenal Crisis
high ACTH, and low cortisol = primary
120
Treatment for Adrenal Crisis
daily glucocorticoids and mineralocorticoids
IV hydrocortisone (glucocorticoid) during surgery, infection, or trauma
121
What is Cushing syndrome (Hyperadrenalism)
excess cortisol from adrenal gland, ectopic ACTH, or exogenous steroids
122
What is Cushing's disease
pituitary adenoma (tumor) secreting ACTH
123
Pathophysiology of Cushing's syndrome
Excess ACTH causes adrenal hyperplasia, causing cortisol overproduction
124
Clinical Features of Cushing's
fat distribution: moon face, buffalo hump, truncal obesity
Skin: striae, bruising, poor wound healing
Metabolic: hyperglycemia, osteoporosis, HTN
Immune suppression so increases infection risk
and hirsutism in women
125
Cushing's Diagnosis Labs and Tests
leukocytosis, hyperglycemia, hyperkalemia
24 hour urinary cortisol and dexamethasone suppresion test
126
Treatment for Cushing's
Surgery: transsphenoidal resection (pituitary adenoma)
Adrenalectomy (adrenal tumors)
127
What is Pheochromocytoma
A rare tumor that secretes catecholamines (epinephrine and norepinephrine) and comes from tissue in the adrenal medulla
128
Pathophysiology of Pheochromocytoma
Excess catecholamines overstimulate alpha and beta adrenergic receptors, causing HTN, arrhythmias, tachycardia, cardiac hypercontractility
129
Classic symptom triad of Pheochromocytoma
palpitations, headache, profuse sweating
130
Treatment of Pheochromocytoma
Surgical resection of the tumor is definitive, alpha adrenergic blockade followed by beta blockade
131
What is diabetes insipidus
disorder of ADH dysregulation, typically involving insufficient action or production
132
Two forms of DI
Central DI (CDI): lack of ADH secretion by the posterior pituitary
Nephrogenic DI (NDI): renal resistance to ADH
133
Etiology of DI
CDI: tumors
NDI: nephrotoxic drugs, renal disease, electrolyte disturbances, obstructive uropathy
134
Pathophysiology of DI
Impaired ADH action results in failure of antidiuresis
nephrons do not reabsorb water, causing polyuria. Dilute urine dehydration and hypernatremia
135
Symptoms of DI
polyuria, polydipsia, polyphagia, confusion, seizures, coma
136
Labs to diagnose DI
serum osmality, urine osmality, hypernatremia
137
Test to diagnose DI
Fluid restriction test distingusihes DI from psychogenic polydipsia
138
Treatment for CDI
desmopressin (DDAVP) orally or intranasally
139
What is Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Excessive ADH leads to water retention, dilutional hyponatremia, and concentrated urine
140
What patients typically get SIADH
Patients with brain injuries, neurosurgery, or stroke
141
What causes SIADH
neurological problems: stroke, meningitis, TBI, neurosurgery, small cell lung cancer
142
Pathophysiology of SIADH
ADH overproduction causes water reabsorption at collecting ducts, leading to hypervolemia, dilutional hypernatremia, and low serum osmolarity
cerebral edema can occur in rare cases
143
Symptoms of SIADH
mild: nausea, dizziness
Severe: seizures, slow reflexes, balance issues, coma
general signs: confusion, weakness
144
Lab findings of SIADH
hyponatremia, serum osmolality, urine osmolality, urine sodium elevated
145
Treatment of SIADH
fluid restriction, remove underlying causes (like tumor), hypertonic saline (3%), ADH receptor antagonist, loop diuretics
146
Urine volume in DI vs SIADH
DI: polyuria
SIADH: oliguria
