Endocrine Flashcards
1
Q
Clinical uses of endocrine drugs
A
- hormone replacement
- diagnosis of endocrine disorders
- treatment of excessive endocrine function
- exploitation of beneficial hormone effects
- uses of hormones to alter normal endocrine fx
- uses of hormones for non-endocrine disease
2
Q
hormone replacement Rx
A
- diabetes and hypothyroidism
3
Q
treatment of excessive endocrine function
A
use negative feedback to inhibit secretion/release
4
Q
exploitation of beneficial hormone effects:
A
prednisolone: 4x anti-inflammatory, < Na retention
Giving hormone to exploit beneficial effects
5
Q
Uses of hormones to alter normal endocrine fx
A
- contraceptives: progesterone inhibits LH and FSH
6
Q
Use of hormones for non-endocrine disease
A
Cancer treatment such as anti-estrogens (tamoxifen)
7
Q
Examples of Receptor Mechanisms
A
- Either work in the nucleus or work in the periphery
- Periphery are more superficial in their effect and faster acting
8
Q
Pituitary Hormones (anterior lobe)
A
- Growth Hormone: tissue growth and development
- Luteinizing hormone: Female ovulation, increase estrogen and progesterone; male increase spermatogenesis
- Follicle stimulating hormone: Female increase follicular development and estrogen; male increase spermatogenesis
- Thyroid stimulating hormone: synthesis of T3 and T4
- Adrenocorticotropic hormone: increase adrenal cortisol production
- Prolaction: lactation
9
Q
Andrenocorticosteroids
A
- produced in adrenal gland
- adrogens and testosterone (anabolic steroids)
- glucocorticosteroids
- mineralocorticosteroids
10
Q
Androgens and testosterone
A
- secondary sexual characteristics
- Androgen, androstenedione, nandrolone
11
Q
Glucocorticoids
A
- function is to regulate glucose metabolism and combat stress
- cortisol and corticosterone
12
Q
Mineralocorticosteroids
A
- Function: water and electrolyte balance
- Aldosterone
13
Q
Where is cortisol produced?
A
Fasiculata of the adrenal gland
14
Q
Physiologic dose
A
same concentration as hormone
is normally found in the body
15
Q
Pharmacological dose
A
- use higher dose to exploit effect
16
Q
See steroid synthesis on slide 8
A
17
Q
steroid synthesis facts
A
- there is a common pathway up to cholesterol
- 4 branching pathways lead to three classes of steroids
- many similarities in structure: cortisol differs from aldosterone by 1 OH and 1 COH group
18
Q
glucocorticoids in normal function
A
- primary glucocorticoid: cortisol
(hydrocortisone) - cortisol is under control of ACTH
- ACTH is under control of CRH
- hypothalamus controls release of CRH
- Circadian rhythm release
- peak around 8 am
- low point around 1 to 4 am
- need this to wake up
19
Q
Actions of glucocorticoids
A
- Released during stress: physical (ie. trauma) or
psychological stress (anxiety) - Alter cellular “protein expression” by altering
transcription of certain genes - Glucose, protein & lipid metabolism effects:
- Anti-inflammatory effect * Immunosupression
- Sodium and H2O reabsorption
- CNS changes (mood and behavior changes)
- Alter composition of blood & muscle
20
Q
Metabolic effects of cortisol
A
- Muscle: decrease glucose uptake, increase protein break down –> amino acids –> liver
- Fat Cells: decrease glucose uptake, increase fat breakdown –> free fatty acids –> liver
- once in the liver, there is gluconeogenesis —> glucose goes to blood and body
21
Q
Effects on Glucose, Protein & Lipid Metabolism
A
- Paradoxical Effect: increased blood glucose,
while at the same time increase glycogen
storage (in Liver) - Accomplishes by enhancing catabolism:
– Stored fat → free fatty acids
– Muscle protein→ free amino acids - Elevation in BG occurs at expense of muscle
– This accounts for one of the major side effects of
corticosteroids: muscle wasting
22
Q
Anti-inflammatory Effects of glucocorticoids
A
- Attenuate pain, erythema, swelling & tenderness by multiple cellular actions, But takes 3-5 days
23
Q
How do glucocorticoids decrease inflammation
A
1)-Inhibit eicosanoid synthesis (proinflamatory
substances like prostaglandins & leukotrienes) through lipocortins (inhibit eicosanoid synthesis by action on phospholipid substrates)
2) Inhibition of cellular inflammatory response:
-block chemotaxsis, -inhibit release of inflammatory mediators (interlukins, TNF, etc.)
3) stabilize WBC lysosomal membranes
4) decrease vascular permeability & inhibit histamin
24
Q
Glucocorticoid Effects on other systems
A
- Inhibit “hypersensitivity” reactions
- Increases kidney reabsorption of Na+ & H2O
– impaired ability to excrete water load - “Personality” or mood changes
- impaired skeletal & cardiac muscle function (too little or too much harmful
25
How do glucocorticoids inhibit hypersensitivity reactions
decrease in chemotaxis, decrease “killing ability” of T and B cells, and decrease activation of T & B cells secondary to decrease in mediators (interlukins and TNF)
26
Therapeutic uses of glucocorticoids for anti-inflammatory effects:
Injection (into joints, tendons, bursa, etc...)
Topical & transdermal: Phonophoresis (US) and Iontophoresis (E-stim)
Systemic (SLE, MS, RA, scleroderma, etc...)
27
in terms of hormone replacement therapy, cortisol is given for:
- Addisons disease (primary adrenal insufficiency)
- secondary adrenal insufficiency (decrease ACTH or CRF)
28
Indications for glucocorticoids
- allergic reactions
- collagen disorders
- dermatological disorders
- hematological and GI disorders
- non-rheumatic inflammation
- neoplastic disease
- respiratory disorders
-rheumatic disorders
- neurological conditions
- ophthalmic disorders
29
most common drugs for iontophoresis
dexamethasone and lidocaine
30
What is Cushing's syndrome?
chronic over-production of glucocorticoids
31
what are the symptoms of Cushing's syndrome
– “moon face”
– centripetal obesity
– bone and connective tissue damage
– muscle wasting especially of limbs
– behavioral changes (mood swings)
– Hyperglycemia and type II DM
- Buffalo Hump
32
Side Effects of Glucocorticoids
* Adrenocortical Suppression: negative feedback on the hypothalamic/pituitary axis suppresses CRH production
– even after a single systemic dose, or after topical administration if given over large area (in child)
* Drug-induced Cushings Syndrome:
* Round face, fat deposition on trunk, muscle wasting, hypertension, osteoporosis, hyperglycemia
* Connective Tissue destruction
* Peptic ulcer, growth retardation in children, immunosupression, glaucoma, mood changes & psychosis, Na and water reabsorption
33
Why is the pancreas unique?
It is both an endocrine and exocrine gland.
34
What do acinar cells make?
powerful digestive enzymes
35
What does Islet of Langerhans contain?
alpha cells: make glucagon
beta cells: make insulin
36
What are the 3 peptide hormones
- insulin
- glucagon
- glucagon like peptide (GLP)
37
What does insulin do?
decreases BG, facilitates glycogen synthesis
and anabolism and acts as trophic hormone on muscle & other tissues
38
What does glucagon do?
increases blood glucose (antagonizes insulin)
39
What does glucagon like peptide do
- causes production of glucagon and insulin
- also called incretin
40
what is glucagon-like peptide secreted in response to?
feeding
41
characteristics of GLP
– Very short half-life (<2 min) secondary to degraded by dipeptidyl peptidase-4 (DP-4)
– GLP-1 promotes glucose-dependent insulin
secretion by increasing insulin-sensitivity in beta-cells
– Decreases glucagon secretion
– Inhibits gastric emptying in the stomach.
– Promotes satiety in brain to decrease hunger
– Promotes insulin sensitivity in peripheral tissue
42
Why is GLP good?
- insulin tends to make you hungry
- GLP can break that cycle of hungriness to help you lose weight
43
Insulin action on skeletal muscles
* Insulin causes GLUT proteins to function
* These GLUT proteins are responsible for transporting glucose out of the blood
* Located on skeletal & cardiac muscle, adipose GLUTs tissue and live
44
What is normal blood glucose?
80-90 mg/ml of blood
45
what happens with a severe drop in blood glucose?
- hypoglycemia
- can cause death/coma
46
what happens with chronically elevated blood glucose
- hyperglycemia
- causes pathologic neural, immune, and cardiovascular changes
47
How does insulin work?
- negative feedback
- increase in BG stimulates insulin release from beta-cells via glucose receptors
– decrease in BG inhibits insulin release
– Insulin is high after a meal and gradually decrease
48
how does glucagon work?
- negative feedback
- decrease in BG stimulates release, increase in BG inhibits release
– glucagon is highest in PREparandial state (before a meal)
49
How does GLP-1 work?
with insulin and glucagon to regulate blood glucose, satiety, and insulin action
50
What is type 1 diabetes caused by?
- insulin deficiency: usually due to auto-immune mechanism (10%)
- beta cells are destroyed and there is little or no insulin
- blood insulin is markedly reduced
51
What is type II diabetes cause by?
- alterations in insulin receptors (90%)
- receptors are down regulated in response to increased blood glucose
- blood insulin is typically normal or increased
52
Signs, symptoms, and effects of DM - Hyperglycemia
– Glucosurea (spilling of glucose into urine)
– Dehydration: glucose takes H2O w/ it in urine
– Electrolyte imbalance
– Metabolic shift: decreased intracellular glucose causes fat and protein catabolism
– Ketoacidosis: decrease pH secondary to ketone bodies and free fatty acids in blood
– Glycosolation of vascular & neural structures
– Atherosclerosis and ischemic heart disease
53
T2DM Management
- Lifestyle!
- Self-monitoring
- Weight management
- Activity
- Nutrition
- Education
54
2 Types of insulin:
- Insulin Preps: basic differences in length of action
* rapid acting (short half life): given when BG is hard to control (such as in “brittle diabetic”)
– check BG and give insulin often
* long acting (long half life) given when BG is stable
55
How are insulin preps given?
injected secondary to insulin broken down in the GI tract
56
What is the best type of insulin? Producing fewest side effects?
Human (recombinant)
57
Insulin Administration
* Given “subcutaneously” secondary to must be
absorbed slowly
* In emergency (diabetic coma) given IV, but unless BG is extremely high, if given IV hypoglycemia and death may result
58
Considerations for self administration:
– adequate refrigeration and storage
– sterility of the needle and injection site
– accurate measurement of the dose (insulin needle)
– rotation of the site (thigh, abdomen, arm etc)
59
Dietary considerations in insulin dosing
- need to monitor BG to accurately determine when dose is given
– increase dose if given before a meal
– decrease if no meal planned for a while
60
Exercise considerations in insulin dosing
- dramatically affects BG: so plan for exercise
or PT by adjusting dose down
– pts often need something to boost BG during exercise or PT if insulin dose not adjusted
61
Is implantable-insulin delivery better than self injection?
- no
- there is still a continued need for hour-hour or day-day adjustments
62
Goal of insulin:
maintain BG as close to normal as possible, with minimal fluctuation
63
Intensive Insulin treatment
- pt carefully monitors BG (4 or more x/day and gives frequent (3-4x/day) small doses)
* Requires more cooperation, compliance and
motivation by patient
* Long term studies show this strategy has the
best outcome (decreased complications)
64
Side Effects of Insulin: Hypoglycemia
decrease in BG below 80 mg/ ml
– HA, tachycardia, fatigue, anxiety or nervousness, hunger, diaphoresis, confusion
– symptoms become progressively worse w/ decreasing BG
– severe hypoglycemia: LOC, coma, death
65
How does insulin act with exercise
- synergistically to decrease BG
- a 30-35% or > decrease in insulin dose required if exercise is intense
66
How can you recover from hypoglycemia
20 g of D-glucose IV or comparable amount orally
will temporally restore BG
– orange juice or some other beverage w/ fructose
67
Side Effects of Insulin: Allergic Reaction
to non-recomninant human insulin:
– rash, anaphylactic reaction, etc
68
Smoggy Effect or "rebound"
An increase in BG due to antibodies to insulin
- Causes a decrease in the effectiveness and “insulin resistance” to that particular type.
– Most often due to non-human insulin
– Need to switch brand or go to Humalin (recombinant)
69
What patients are oral hypoglycemics used for?
Pts with T2DM
70
How do oral hypoglycemics work?
* These drugs can both increase insulin release from the pancreas and increase sensitivity of peripheral tissues to insulin
* Effective in about 1/2 of patients w/ INDDM
– can sometimes eliminate need for insulin
- Especially useful when combined with dieting
71
Most oral hypoglycemics are ....
Sulfonylureas
72
What is Glucovance?
a new combo drug that mixes Glyburide and
Metformin together:
– Have complementary mechanisms of action to improve glycemic control in patients with T2DM
73
How does Glucovance work?
* Glyburide lowers BG by stimulating the release of insulin from the pancreas
* Metformin improves glucose tolerance in T2DM by decreasing hepatic glucose production, decreasing intestinal absorption of glucose and increasing insulin sensitivity of peripheral tissues
74
Concerns with Rosiglitazone (Avandia):
* 50% more weight gain than similar medications
* 2 X risk of fluid retention
* Elevate the risk of bone fractures
* Heart problems (46% increase risk of MI)
* GlaxoSmithKline, the maker of Avandia, says the
analysis included too few long-term studies to
produce reliable results
** has black box warning
75
Other Agents used to treat hypo and hyperglycemia
Cyclosporin: used in the early treatment of pts w/
type 1: inhibits autoimmune reaction against the beta- cells of the pancreas (blocks production of anti-bodies)
* Glucagon: used to Rx hypoglycemia-induced coma
76
New Agents for Treating Diabetic Complications: Microangiopathy, neuropathy, nephropathy, retinopathy
- Aldose Reductase Inhibitors
- Anti-advanced glycation end-product drugs
- Free-Radical scavengers
- Visoactive Agents
- Growth Factor Inhibitors
- Growth Factors themselves
77
Aldose Reductase Inhibitors (ARI’s):
- inhibit an enzyme in the microvasculature and in neurons that is responsible for converting glucose to sorbitol
78
Anti-advanced glycation end-product drugs:
– AGE’s on long lived proteins (like Hb) inhibit protein function
79
Free Radical Scavengers
combat the oxidative stress generated by reaction of sugars with proteins in DM
– Probocol, Vit E, glutathione, butylated hydroxytoluene and other
80
Vasoactive Agents
these are designed to prevent the peripheral nerve ischemia in DM: potent locally
acting vasodilators
- Anyone with T1 OR T2 should be on one of these
81
What is paramount for patients with both T1 and T2DM
Nutrition
82
Nutrition: Type 1
watching carbohydrate and saturated fat
is important in minimizing complications
- minimize simple sugars; fiber is good to prolong breakdown of food
83
Nutrition: Type 2
total caloric intake as well as carbohydrate and saturated fat are important
84
Exercise for T2DM
- especially critical
– facilitates wt loss (decrease amount of tissue requiring insulin), increased glucose uptake (independent of insulin), decreased CV and neurologic complication
85
PT and Pharmacological management
- Treat the underlying problem through non-pharmacological menas
- Awareness of metabolic derangement (ketoacidosis and hypoglycemia.. keep D-glucose tablets, OJ, or snack handy)
- reinforce compliance
86
Thyroid hormone:
regulates metabolism and works synergistically with other hormones to promote growth and development
87
What works together to regulate blood calcium and bone mineralization
parathyroid hormone, calcitonin, and vitamin D
88
2 Hormone from the Thyroid Gland:
1. Thyroxin - T4 (back up)
2. Triiodothyronine (T3)
** most physiological effects are due to T3
89
See regulation slide 50
90
Production of T3 and T4
-Thyroid gland takes up Iodine from the blood
- Iodine is combined with Thyroglobin in the thyroid follicle producing Iodothyroglobin
- Iodothyroglobin then is broken down into T3 and T4 and released into blood stream
91
Goiter
a build up of thyroglobin in the follicles secondary to lack of Iodine (enlarged thyroid gland)
92
How a goiter forms:
* If Iodine is not present in the diet, then thyroglobin cannot be converted to iodothyroglobin and T3 & T4.
* Thyroglobin builds up and causes swelling of thyroid
93
Effects of Thyroid hormone
- Plays direct role (stimulating metabolism) but also plays a “permissive” role, allowing other hormones such as androgen and growth hormone to work
- Thermogenesis
- Growth and Development
- CV effect
- Metabolic effect
94
Thermogenesis effect of thyroid hormone
T3 and T4 increase metabolic rate to increase heat production
95
Growth and development effect of Thyroid hormone
T3 stimulated the release and facilitates the effects of growth hormone on skeletal and cardiac muscle, nervous, and skeletal systems
96
CV effects of thyroid hormone
increases HR and contractility causing greater CO
- also sensitizes heart to NE and epi
97
Metabolic effect of thyroid hormone
increased cellular metabolism
98
Hyperthyroidism
- Graves disease
- sweating, hot all the time, tachycardia, body temp increased, nervous, shaky, increased CO
99
Hypothyroidism
- primary or secondary
- mental slowing, cold all the time, body temp drops, wound healing, metabolism slowed, myxedema, bradycardia
100
Treatment of hyperthyroidism consists of either
1) surgical removal of the thyroid gland if surgery is performed secondary to thyroid tumor, them often RT or radioactive I is given for follow up.
2) radioactive Iodine, which destroys the gland
101
See parathyroid hormone regulation slide 56
102
Metabolic Bone diseases
- Hypoparathyroidism: impaired bone resorption and hyocalcemia
- Hyperparathyroidism: excessive resorption and hypercalcemia
- Osteoporosis
- Rickets: Vitamin D deficiency
- Osteomalacia: adult Rickets
- Paget Disease: excessive bone formation, ineffective remodeling, abnormalities
- Renal Osteodystrophy: chronic renal failure, excessive bone resorption
103
Concerns for Rehab Patients
* Be alert for over-medication with thyroid drugs:
– generally, symptoms of over-medication with thyroid supplementation are similar to hyperthyroidism
– generally, symptoms of under-medication with thyroid supplementation are similar to hypothyroidism
* Don’t over tax CV system in patients w/ either
hypo or hyperthyroidism
104
What can drugs to treat osteoporosis have?
serious, life threatening toxic effects so be alert for the early side effects
