Endo Flashcards
(217 cards)
1
Q
Describe amine hormone synthesis
A
Hormones get stored for release; cells typically contain many granules filled with stored hormone
2
Q
What are some amine hormones?
A
Catecholamines, thyroid hormone, releasing or stimulating hormones
3
Q
Describe peptide-protein hormone synthesis
A
Stored for release; cells typically contain granules filled with stored hormone
4
Q
Examples of peptide-protein hormones
A
Insulin, GH, gonadotropins, releasing or stimulating hormones
5
Q
Describe steroid hormone synthesis
A
Produced when needed and released immediately because they are lipophilic; have delayed biological effects
6
Q
Examples of steroid hormones
A
Sex steroids, corticosteroids, vitamin D, cholesterol precursor
7
Q
Release patterns of endocrine hormones
A
Constitutive, stimulated, pulsation, circadian rhythm
8
Q
Describe constitutive release pattern
A
Constant release of hormone
9
Q
Describe stimulated release pattern
A
Released when stimulated by environment or CNS activity
10
Q
Describe pulsatile release pattern
A
Released in pulses
11
Q
Hormones that follow constitutive pattern
A
Insulin, cortisol, thyroxine
12
Q
Hormones that are stimulated
A
Insulin, cortisol, thyroxine (?)
13
Q
Hormones that are released in pulses
A
Hypothalamic releasing hormones
14
Q
Hormones that follow circadian rhythms
A
Cortisol, thyroxine
15
Q
How are hormone receptors relevant to pharmacology?
A
Key points of intervention; agonists and antagonists
16
Q
Describe cell surface receptors
A
GPCRs; used by proteins, polypeptides, and amines because they are less lipophilic; cause intracellular signal transduction and rapid response
17
Q
Describe nuclear/cytosolic receptors
A
Used by steroids and vitamin D and retinoic acid because these ligands are lipophilic; ligand binding causes transcription; response is delayed (hours later)
18
Q
Traditional endocrine system
A
Hypothalamus-AP-target gland axes; gonads, thyroid, adrenal cortex; regulated by CBS feedback
19
Q
Name the independent endocrine glands
A
Pancreas, posterior pituitary, parathyroids
20
Q
Name the dispersed endo cells
A
IGFs from the liver, GI hormones, renin from kidney
21
Q
Etiologies of pathway dysfunction
A
Hypersecretion, hyposecretion, inappropriate target tissue response
22
Q
Hypersecretion etiology
A
Primary or secondary tutors
23
Q
Hyposecretion etiology
A
Autoimmune dysfunction, genetics, surgery, atrophy, toxicity
24
Q
Inappropriate response etiology
A
Abnormal receptor expression, mutated receptors, iatrogenic
25
Non-endo uses for glucocorticoids
Inflammation, allergy, septic shock, immunosuppression, hematologic malignancy
26
Alpha cells secrete ________, beta cells secrete ________
Glucagon; insulin
27
What controls insulin release?
increase: [Glucose], vagus, B2-adrenergic stimulation, leucine, arginine, gi hormones
Decrease: somatostatin, A-adrenergic stimulation
28
Process of insulin release
Glucose enters cell, ATP increases, ATP-K+ channel depolarizer cell, Ca2+ increases, insulin is released
29
Insulin receptor
Extracellular alpha and beta subunits with intracellular tyrosine kinase domain
30
Effects of insulin
*Anabolism
Increase glycogen storage in liver and muscle, increase fatty acid synthesis in liver, increase triglyceride synthesis in adipose, increase protein synthesis in muscle
31
Type 1 diabetes characteristics
Insulin deficiency, childhood or puberty onset, immune-mediated or idiopathic, coxsackievirus B1
32
Type 1 diabetes treatment
Insulin therapy
33
Type 2 diabetes characteristics
Insulin resistance and eventual insulin deficiency
34
Type 2 diabetes treatment
Lifestyle changes or oral hypoglycemic agents
35
What is lispro insulin?
Lysine and proline residues inverted so monomers are released quickly (fast acting)
36
What is aspart insulin?
One proline changed to aspartate so monomers are released quickly (fast acting)
37
What is NPH?
Protamine that modulates monomer release (intermediate acting)
38
What is Lente?
Zinc aggregate in acetate buffer so monomer is slowly released (intermediate acting)
39
What is glargine?
Replacement with glycine in A chain and arginines in B chain, plus high zinc concentration, causing very slow release and metabolism (long acting)
40
What is ultralente?
Suspension of high concentration of zinc aggregate in acetate buffer (long acting)
41
Types of insulin therapy
Basal-bolus or split-mixed (NPH + lispro or aspart mixed)
42
Complications of insulin therapy
Hypoglycemia or immunopathology
43
Types of oral hypoglycemics
Insulin secretagogues, insulin sensitizers, alpha glucosidase inhibitors, and incretins
44
Insulin secretagogues mechanism
Bind and inhibit ATP-K+ channel, leading to cell depolarization and insulin release ; caution with hypoglycemia
45
Types of insulin secretagogues
Sulfonylureas- longer acting so can use once daily but has risk of hypo
Meglitinides- rapid action, can use in combo with long- acting agents, causes less hypo
46
Insulin sensitizer mechanism
Increase sensitivity of peripheral cells to insulin but do not promote its release
47
Thiazolidinediones
Type of insulin sensitizer; ligand at ppar-gamma; regulate genes for lipid and glucose metabolism (glucose transporters);work downstream of insulin
48
Alpha glucosidase inhibitors
Inhibit alpha-glucosidases so digestion and absorption of starches decreases; can cause abdominal pain, diarrhea, flatulence
49
Incretins
Stimulated by glucose in intestine; tell the pancreas to increase insulin release
50
Types of incretins
Gastric inhibitory peptide (GIP) and glucagon like peptide 1 (GLP-1); very similar in structure and both N terminals are severed by DPP-4; get recognized by the pancreas to increase sensitivity
51
DPP-4 inhibitors
Inhibit the enzyme that inactivates incretins; could be used as an oral hypoglycemic to treat type 2 diabetes; sitagliptin
52
Biguanides
Type of insulin sensitizer; reduce hepatic gluconeogenesis and increase insulin utilization by peripheral cells; can use with secretagogues or insulin
53
Synthetic GLP-1
Liraglutide and exenatide
54
Liraglutide
Long-acting synthetic GLP-1 with fatty acid residue so it is bound to albumin and slowly released; decreases appetite and serum triglycerides but must be injected because it's a peptide
55
Exenatide
GLP-1 agonist produced by gila monsters in saliva to rapidly activate beta cells and release insulin; may cause nausea, diarrhea, etc.
56
Glucagon
Hormone produced by alpha cells that opposes insulin; used in hypoglycemic emergency
57
Cortisol regulation
Hypothalamus is stimulated by stress, cold, etc. To release CRH, which causes ACTH release from the AP and results in cortisol synthesis from the adrenal cortex; negatively feeds back
58
Aldosterone regulation
Adrenal cortex is stimulated by ATII, potassium, and somewhat by ACTH
59
The zona glomerulosa releases
Aldosterone
60
The zona fasciculata releases
Primarily cortisol
61
The zona reticularis releases
Androgens and estrogen
62
Function of the renal juxtaglomerular apparatus
Monitors osmolarity and BP using macula densa and renin-secreting cells; when BP drops, renin increases
63
Action of renin
Produces angiotensin I
64
Effects of angiotensin II
Vasoconstriction and increased aldosterone secretion from adrenals
65
Rate limiting step of steroidogenesis
Conversion of cholesterol to pregnenolone by p450scc by knocking off the side chain
66
Key enzyme for glucocorticoid synthesis
P450c11, which hydroxylates carbon 11 so it can now bind the glucocorticoid receptor
67
Production of androgens
Pregnenolone follows a different conversion pathway to produce androstenedione
68
Production of aldosterone from pregnenolone
P450aldo adds additional groups to the molecule so it can now bind the mineralocorticoid receptor
69
Function of transcortin (CBG)
Carries cortisol in the blood stream and protects it from degradation until it reaches the target cell
70
How is aldosterone unique among the steroids?
It is almost completely unbound in the bloodstream
71
Actions of cortisol
Increase carb, lipid, and protein metabolism, as well as gluconeogenesis and glycogen synthesis in liver; inhibits production of proinflammatory mediators; short-term mood enhancement; vasoconstriction and CV support; stimulates fetal lung surfactant
72
Aldosterone actions
Fluid and electrolyte balance; promotes sodium reabsorption and proton/potassium excretion; maintains BP
73
Where aldosterone exerts effects
Distal tubule and collecting duct
74
3 categories of steroid preparations
Short-medium acting, intermediate acting, long-acting
75
Short-medium acting steroids
Cortisone, prednisolone, methylprednisolone
76
Intermediate-acting steroids
Triamcinolone
77
Long-acting steroids
Betamethasone, dexamethasone
78
Mineralocorticoid preparations
Fludricortisone, desoxycorticosterone; strong salt-retaining ability
79
What is fluticasone propionate (Flonase)
Topically active glucocorticoid that binds the corticosteroid receptor, but is hydrolyzed as soon as it hits the bloodstream and is inactivated; useful for asthma inhalers
80
What is mifepristone
Glucocorticoid and progesterone antagonist; binds receptor but prevents receptor folding
81
Cushing's syndrome
Hyperadrenocorticism; buffalo hump, thin skin, muscle wasting at periphery, osteopenia, prone to infection, high BP
82
Causes of cushing's syndrome
Pituitary adenoma (cushing's disease), iatrogenic, ectopic ACTH syndrome, adrenal gland tumors
83
Diagnosis of cushing's syndrome
Adrenal: elevated cortisol, low ACTH, glucocorticoid injection will do nothing
Pituitary: elevated ACTH, glucocorticoid injection will suppress ACTH
84
Adrenocorticosteroid inhibitors
Mitotane; inhibits production of cortisol
85
Corticosteroid synthesis inhibitors
Ketoconazole, aminoglutethimide, trilostane
86
Addison's disease
Adrenal insufficiency; usually from autoimmune destruction of adrenals, can also be from abrupt steroid withdrawal or removal of adrenal or pituitary tumors
87
Acute adrenal insufficiency
Emergency; need IV fluid and corticosteroids
88
Chronic adrenal insufficiency
Less severe; can use long-term glucocorticoid and mineralocorticoid replacement therapy
89
Minimizing adverse effects of steroids
Use low dose and low potency steroids (prednisone), use alternate day therapy, taper reduction
90
Mineralocorticoid antagonists
For primary aldosteronism (see hypertension and hypokalemia); spironolactone, eplerenone block the mineralocorticoid receptor
91
3 forms of thyroid hormones
T4, T3, rT3
92
3 deiodinases
D1, D2, D3
93
D1 deiodinase action
Deiodinates both the inner and outer ring (produce T3, inactivate everything)
94
D2 iodinase action
Deiodinates the outer ring (T4 —> T3 intracellularly)
95
D3 iodinase action
Deiodinates the inner ring (inactivates T4 and T3)
96
T4 production in thyroid
Tyrosine is iodinated by TPO and then these are combined to form T4. Thyroglobulin is then proteolyzed and release into the blood as either T4 or T3
97
Ratio of t4 to t3
4:1
98
Action of TBG
Bind thyroid hormone and greatly increase their half-life
99
T3 is __________ as potent as T4
4 times
100
Actions of thyroid hormones
Control transcription and translation of genes for metabolism; increase cellular oxygen use; allow for growth and development of tissues; increase myocardial contractile proteins
101
Hypothyroidism etiology
Most commonly primary; can also be TSH insufficiency or iodine deficiency; gland absence; autoimmune thyroiditis (Hashimoto’s; AB’s against TPO); surgery, radioactive iodine; thioamides; chemo
102
Hypothyroidism clinical signs
Lethargy, weakness, fatigue, cold intolerance, weightgain, Bradycardia, myxedema
103
Goitrous hypothyroidism
From iodine deficiency, neoplasms, autoimmune destruction; causes gland growth
104
Hypothyroidism diagnosis
Low T4, elevated TSH
105
Levothyroxine
Synthetic T4; long half-life so you can take once daily, easily monitored, reaches steady-state in 6-8 weeks
106
Liothyronine
T3; has shorter half-life so it is used much less
107
Liotrix
Mixture of T4/T3 in 4:1 ratio; used for long-standing disease, in elderly, for CV disease, given in myxedema medical emergency
108
Other treatments for hypothyroidism
Removal of drugs, iodine supplementation
109
Hyperthyroidism ethology
Graves' disease (antibodies activate TSH receptor), too much t4 supplementation, neoplasms, infection o inflammation of thyroid (transient)
110
Clinical signs of hyperthyroidism
Hyperactive, nervous, insomnia, heat intolerance, tachycardia, weight loss, muscle wasting, exophthalmos
111
Hyperthyroidism diagnosis
High T3/T4, low TSH, can use radioiodine uptake scan, MRI, or ultrasound
112
Thioamides
Inhibit TPO so hormone synthesis is blocked; given orally
113
Iodinated contrast medic
Inhibit conversion of t4 to t3 so there is less biological effect, but have short-term effects
114
Adjunct drugs for hyperthyroidism
Beta blockers or calcium channel blockers
115
Radioiodine therapy
Use i131- give orally and gets taken up by thyroid to destroy cells; some need second treatment, but most become hypo
116
Thyroidectomy
Used for large glands or multinodular goiters;use antithyroid drugs pre-surgery; will need replacement t4 therapy after surgery
117
Type of release of GNRH
Pulsatile (same with FSH and LH but less so)
118
What is GNRH?
Decapeptide from hypothalamic neurofibers
119
What releases FSH and LH
Anterior pituitary
120
Effect of continuous release of GnRH
Down-regulation of the receptor
121
What is inhibin?
Protein produced by sertoli cells and granulosa cells; inhibits FSH release selectively
122
Action of FSH
Stimulates follicular development; converts androgen to estrogen j acts on sertoli cells to increase spermatogenesis
123
Action of LH
Stimulates ovulation; produces androgens; regulates testosterone production
124
Gonadorelin
Synthetic GnRH used in both sexes for hypogonadotrophic hypogonadism
125
Leuprolide
Long-acting GnRH agonist used to induce hypogonadism; used for prostate cancer and hyperplasia, uterine fibroids, early puberty, assisted reproduction
126
FSH analogues
human menopausal gonadotropins extracted from urine of postmenopausal women (have to use in conjunction with LH) ; recombinant FSH
127
LH analogues
Human chorionic gonadotropins produced by placenta and excreted in urine; recombinant LH and hCG
128
Where testosterone is produced
Leydig cells
129
Testosterone synthesis
Comes from cholesterol and pregnenelone; converted to estradiol by aromatase and DHT by 5alpha-reductase in peripheral tissues
130
What is TeBG
Testosterone binding globulin; carries 98% of testosterone in the blood
131
DHT versus testosterone
DHT has higher affinity for the receptor
132
Effects of androgens
Secondary sex characteristics; spermatogenesis, deepening of voice, facial hair, libido, behaviorer, body mass, erythropoiesis, decreased HDL, growth plate closure
133
Testosterone preparations
1:1 androgen: anabolic effect
134
Long-acting testosterone analogues
Have a longer half-life due to ester addition
135
Side effects of androgen preparations
Prostate enlargement, aggression, hepatic dysfunction, sterility, heart disease, masculinization of women
136
Androgen replacement therapy
Replaces or augments androgens in hypogonadal men; use testosterone
137
Uses for androgens and anabolic steroids
1. Androgen replacement therapy
2.Gynecologic disorders
3. Use as protein anabolic agent
4. Growth stimulators and aging
5. Steroid abuse
138
Danazol
Weak synthetic androgen used in endometriosis that inhibits estrogen-induced growth of endometrial tissue
139
Uses for Anti androgens
For prostatic cancer, benign prostatic hyperplasia, endometriosis, male pattern baldness, excessive sex drive, early puberty in men
140
Ways to suppress androgen action
1. GnRH agonists (leuoprolide)
2. Testosterone synthesis inhibitors (ketoconazole, spironolactone)
3. Inhibition of 5alpha-reductase (finasteride)
4. Androgen receptor antagonists (flutamide, cyproterone)
141
Estrogen synthesis in premenopausal women
Estradiol mostly, produced by ovary
142
Steroidal estrogens
From testosterone or androstenedione in ovaries, converted to estrogen via aromatase
143
Estriol
Synthesized from estradiol in liver, as well as in placenta during pregnancy
144
Estrogen synthesis in post menopausal women
From adipose tissue, adrenals also produce estrone
145
Estrogen synthesis in men
Extra-gonadal conversion of testosterone, DHEA, and androstenedione
146
Synthetic estrogens
Ethinyl estradiol, diethylstilbesterol
147
Progestin meaning
Any steroid with progesterone activity
148
Progesterone
Most important natural progestin in women,produced in ovaries, adrenals, and placenta; can be precursor for estrogens, androgens, and adrenocorticoids
149
Synthetic progestins
L-norgestrel, norethidrone, medroxyprogesterone
150
Progestins in men are produced where?
Produced in testes
151
Estrogen binds to ______ in the blood stream, while progesterone binds to ______
TeBG; CBG
152
Estrogen receptor types
Alpha and beta
153
Effects of estrogens
Sexual maturation, sense of well-being, ovulation, parturition, endometrial growth, reduced resorption of sone, increased clotting factors, growth, epiphysis closure
154
Effects of progesterone
Modulates carb metabolism, suppresses ovulation, deposits adipocytes, sexual maturation, behaviour, mood
155
Uses for estrogens, progestins, and gonadal inhibitors
1. Fertility control (Post-coital contraception, Contragestation)
2. Hormone replacement therapy
3. Ovulation induction
4. Cancer chemo
156
Post-coital contraception
Large dose of estrogen alone or with progestin; prevents implantation; must be taken within 72 hours
157
Contragestation
Mifepristone; antiprogestin that blocks progesterone receptor so implantation cannot occur and endometrium is shed; usually given with prostaglandin for contraction
158
Two types of oral contraceptives
Combination of Estrogen and progestins or continuous therapy of only progestins
159
Combined oral contraceptives
Ethinylestradiol plus l-norgestrel or norethindrone; can vary levels of progestin throughout 28 day cycle; inhibits ovulation because estrogen and progestin inhibit gonadotropin release; thickens cervical mucus; progestins protect endometrium
160
Progestin-only mini pill
Slightly higher failure, higher incidence of menstrual irregularity; contains either norgestrel or norethindrone; still inhibits cycle and thickens mucus
161
Alternative contraceptives
Norplant-2 placed subcutaneously in arm, medroxyprogesterone intramuscular injections, progesterone IUDs
162
2 uses for estrogen or progesterone replacement therapy
Congenital primary hypogonadism, menopause/surgical removal of ovaries
163
Treatment for congenital primary hypogonadism
Low dose estrogen for most of month and then progestin to initiate uterine bleeding
164
Treatment for menopause/surgical removal of ovaries
Estrogens and progestins to antagonize estrogen effects on endometrium
165
Symptoms of menopause or ovarectomy
Atrophy of genitalia, depression, loss of libido, lack o energy, hot flashes (vasomotor spasm), osteoporosis, cardiovascular disease
166
Drugs for ovulation induction
GnRH analogues it pituitary is functioning, gonadotropins if ovary is functioning; clomiphene citrate
167
Clomiphene citrate
Partial agonist/antagonist at estrogen receptor that decreases estrogen to stop negative feedback on hypothalamus/pituitary → increases FSH → increased follicles; repeat every cycle (SERM)
168
Drugs for cancer chemo
Diethylstilbesterol for prostate cancer, selective estrogen receptor modulators, estrogen synthesis inhibitors
169
Selective estrogen receptor modulators
Selectively antagonize certain estrogen receptors; used for treatment of breast cancer but have low risk of osteoporosis
170
Estrogen synthesis inhibitors
Aromatase inhibitors that function everywhere in the body so they're more effective for breast cancer but have higher risk of osteoporosis; can use with tamoxifen
171
Mild effects of estrogens and progestins
Nausea, headaches, endocrine changes
172
Moderate effects of estrogens and progestins
Weight gain, vaginal and uterine tract infections, bleeding, depression
173
Severe effects of estrogens and progestins
Hepatic dysfunction, cancers (breast, endometrial) thromboembolic disease, MI, hypertension, stroke, concern with other risk factors
174
Oxytocin structure
Nonapeptide
175
Oxytocin synthesis
In paraventricular nuclei and supraoptic nuclei, secreted from nerve endings, also synthesized in luteal cells of ovary, uterus, and fetus
176
Oxytocin stimulation
Sensation from cervix and vagina, suckling
177
Effects of oxytocin
Increases frequency and force of uterine contractions, stimulates milk ejection
178
Hormones needed for oxytocin to work
Estrogen for contractions, prolactin for milk formation
179
Hormone that antagonizes oxytocin
Progesterone; necessary to prevent premature labour
180
Pitocin
Synthetic oxytocin given intravenously to induce labour or by nasal spray for postpartum lactation
181
Contraindications for oxytocin administration
Fetal distress, premature labor, abnormal fetal positioning, cephalopelvic disproportion
182
Atosiban
Oxytocin antagonist used for premature labour (not used in NA)
183
What is vasopressin
Nonapeptide from posterior pituitary that acts as ADH
184
Stimuli for vasopressin
Increasing toxicity by osmoreceptors, BP drop by baroreceptors
185
Actions of vasopressin
Promotes water retention via v2 receptors, constricts vessels via v1 receptors
186
Synthetic vasopressin types
Vasopressin, desmopressin (long-acting, no vasoconstriction)
187
Uses for synthetic vasopressin's
Pituitary diabetes insipidus, nocturnal enuresis
188
What electrolytes regulate bone homeostasis
Calcium and phosphate
189
Effects of bone abnormalities
Neuromuscular excitability, weakness, tetany, joint malfunction, decreased hematopoiesis
190
Effects of PTH
Increases serum calcium, decreases serum phosphate
191
Effects of vitamin D
Increases both serum calcium and phosphate; directly suppresses PTH production
192
Effects of calcitonin
Lowers serum calcium and phosphate; inhibits osteoclasts
193
Effect of estrogen on bones
Inhibit osteoclasts; slow bone turnover; increases vitamin D
194
What is osteoporosis
Low bone mass in long bones
195
Primary osteoporosis
Loss of estrogen production in postmenopausal women (and older men)
196
Osteoporosis risk factors
Female, Caucasian, smoking, fracture, age, low weight, family history
197
Secondary osteoporosis
From diet, gi disease, hyperparathyroidism, liver disease, alcoholism, vitamin D deficiency, corticosteroid use
198
Primary regulators of bone mass
Physical activity, calcium intake, reproductive statues
199
Therapies for osteoporosis
SERMs, bisphosphonates, PTH analogues, calcitonin, vitamin D
200
SERMs for osteoporosis
Raloxifene; Estrogen agonist in bone, antagonist in breast and uterus, doesn’t prevent hot flashes
201
Bisphosphonates
Most successful therapy; inhibit osteoclast function
202
PTH analogues
Recombinant PTH, stimulates bone formation at low doses
203
Calcitonin therapy
Inhibits osteoclasts
204
Vitamin D therapy
Improves intestinal calcium absorption to improve mineral density
205
Negative and positive stimuli for gh
Negative: somatostatin, positive: growth hormone releasing hormone
206
Effects of GH
Stimulates synthesis and release of IGF-1 from liver and growth plate; promotes lipolysis, gluconeogenesis, and protein synthesis, as well as skeletal and soft tissue growth
207
Causes of GH deficiency
Genetics, hypothalamus problem or pituitary problem
208
Signs of GH deficiency
Cardio problems, psychosocial problems, decreased muscle and bone mass, increased fat, less energy, poor libido
209
Diagnosis of gh deficiency
Measurement of serum gh levels
210
Gh deficiency treatments
Recombinant GH, rhIGF1/rhIGFBP3 for receptor defects of GH antibodies, synthetic GHRH (not if issue is at pituitary)
211
Effect of excess gh
Gigantism when young, acromegaly in adulthood
212
Signs of acromegaly
Soft tissue overgrowth, elevated serum IGF1 or GH
213
Therapies for gh excess
Ocreotide (somatostatin analogue) , pegvisomant (GH antagonist)
214
What is prolactin
Peptide hormone from ap that causes breast development and milk production
215
Effects of excess prolactin
Inappropriate breast development and lactation, reproductive difficulties
216
Effect of dopamine on prolactin
Decreases prolactin secretion from pituitary
217
Bromocriptine and cabergolide
Stimulates d2 receptors in ap to decrease prolactin; used for prolactinomas, acromegaly; can give orally or intravaginally
