Term
|
Definition
| portion of the renal juxtaglomerular apparatus that monitors BP in and out of the glomerulus |
|
|
Term
| adrenocortiocosteroid transport |
|
Definition
CBG binding ptn - blood
chaperone ptn - cytoplasm
Rc, cytoplasmic -> mucleus
Cortisol: 5% free, 75% transcortin (CBG), 20% albumin
Aldosterone: almost no binding |
|
|
Term
| effects of cortisol (hydrocortisone) |
|
Definition
numerous effects; direct and permissive
CHO, ptn, lipid met:
(liver: gluconeosis, glycogen storage)
(periphery: decrease glucose use, increase ptn, lipid breakdown)
anti-inflammatory and immunodulatory effects (inhibit pro'n of pro-in mediators)
stress coping
CNS: sense of well-being, mood, behaviour
CV integrity
fetal-lung surfactant |
|
|
Term
|
Definition
fluid and electrolyte balance: Na+ K+ homeostasis
(rapid activation of Na+ channels in the apical membrane of principal cells)
promotes Na+ reabsorption, H+/K+ excretion
CV support; BP |
|
|
Term
|
Definition
kidney, juxtaglomerular
reabsorption of 7% of Na+
impermeable to water -> further decrease in concentration to a value lower than plasma |
|
|
Term
|
Definition
reabsorption of 2-3% off Na+
permeability to water and of []d vs dilute urine dependent on presence of vasopressin (ADH) |
|
|
Term
| activity (potency) of short-medium acting (<24h) steroid H preparations |
|
Definition
cortisol:
anti-in 1
salt-retaining 1
prednisolone
anti-in 0.8
salt-retaining 0.8
methylprednisoline
anti-in 5
salt-retaining 0 |
|
|
Term
| activity (potency) of intermediate acting (24-48h) steroid H preparations |
|
Definition
triamcinolone
anti-in 5
salt-retaining 0 |
|
|
Term
| activity (potency) of long acting (>48h) steroid H preparations |
|
Definition
betamethasone :
anti-in 30
salt-retaining 0
dexamethasone:
anti-in 30
salt-retaining 0 |
|
|
Term
| activity (potency) of mdnderalocorticoids steroid H preparations |
|
Definition
fludricortisone:
topically active
anti-in 10
salt-retaining: 250
desoxycorticosterone acetate
anti-in 0
salt-retaining 20 |
|
|
Term
|
Definition
elevated cortisol
clinical signs: upper body obesity, thinning of skin, bruising, muscle wasting of arms and legs, weakinening of bones, osteopenia, elevated liver enzymes |
|
|
Term
|
Definition
hyperandrenocorticism
elevated cortisol |
|
|
Term
|
Definition
pituitary adenoma: women > men 5x
iatrogenic; l-t treatment for another problem
ectopic ACTH syndrome
adrenal gland tumours |
|
|
Term
|
Definition
surgery: resectable tumours: adrenal, pituitary, extopic
radiation: alone or follow-up to surgery
adrenocortiocosteroid inhibitors: mititane
H synth inhibitors: ketaconazole (most effective), aminoglutethimide, trilostane
glucocorticoid Rc antagonists: mifepristone |
|
|
Term
|
Definition
| adrenal insufficiency most commonly from autoimmune and adrenal destruction, could be abrupt steroid withdrawal possible following surgery for adrenal tumours or pituitary tumours |
|
|
Term
| acute vs chronic adrenal insufficiency |
|
Definition
acute often due to abrupt withdrawal of long-stanfing glucocorticoid therapy but can precipitate from exacerbation of chronic adrenal insufficiency; often an emergency: IV fluid supports and corticosteroids
chronic: less severe; glucocorticoid replacement therapy; fludricortisone if primary addison's disease |
|
|
Term
| non-endocrine use of glucocorticoids |
|
Definition
anti-inflammatory and anti-allergy therapy
intensive short-term or emergency therapy
immunosuppressive therapy
neoplasia |
|
|
Term
|
Definition
H-secreting cells is islets scattered through the pancreas
exocrine pancreas: digestive enzymes
alpha cells: glucagon
beta cells: insulin |
|
|
Term
| control of insulin release |
|
Definition
produced by beta cells of islets of langerhans
released primarily in response to glucose
inhibited by somatomstatin and a-adrenergic stim |
|
|
Term
insulin actions/effects
(liver, skeletal muscle, adipose) |
|
Definition
liver:
promotes glucose uptake; storage as glycogen
increase FA synth; storage
skeletal muscle:
ptn synth from AA intake
increase glucose uptake; storage as glycogen
adipose tissue:
increases TAG synth; storage |
|
|
Term
|
Definition
insulin preparation, penultimate lysin and proline residues order inverted
no effects on Rc binding but release into blood as monomer increased -> faster acting |
|
|
Term
|
Definition
insulin preparation; one proline changed to aspartate
no effects on Rc binding but release into blood as monomer increased -> faster acting |
|
|
Term
| short-acting insulin preparations |
|
Definition
regular insulin, lispro, aspart
sol'n, zinx, no added ptn, buffer
used to cover prandial hyperglycemia and emergencies |
|
|
Term
| intermediate-acting insulin preparations |
|
Definition
NPH (neutral protamine hagedorn) and lente
cloudy suspensions with buffers and zinc
basal and prandial hyperglycemia |
|
|
Term
| long-acting insulin preparations |
|
Definition
ultrelente insulin and insuline glargine
coverage for 24h
ultralente: cloudy and buffered
glargine: clear, no buffer; peakless
higher [Zn], aggregates
basal insulin coverage |
|
|
Term
| intermediate-acting insulin preparations |
|
Definition
NPH (neutral protamine hagedorn) and lente
cloudy suspensions with buffers and zinc
lente: suspension of zinc aggregates in acetate buffer
NPH: complexed with basic ptn (protamine) which modulates its release
basal and prandial hyperglycemia |
|
|
Term
| long-acting insulin preparations |
|
Definition
ultrelente insulin and insuline glargine
coverage for 24h
ultralente: cloudy and buffered
glargine: clear, no buffer; peakless
higher [Zn], aggregates
basal insulin coverage |
|
|
Term
|
Definition
1. near-normalize bl. glucose and metabolism
- fasting bl. glocse 90-129 mg/dL
- post--prandial bl. glucose <150 mg/dL
2. maintain diet, exercise, insulin therapy and monitoring
3. Prevent long-term problems (blindness, kidney disease, peripheral nerve damage, CVD |
|
|
Term
| Regimens of insulin therapy |
|
Definition
1. Basal-bolus
(basal admin of intermediate or long acting; prandial injections of short-acting: lispro, aspart)
2. split-mixed regimens
(pre-breakfast and pre-supper mix of short-acting and intermediate acting insulins) |
|
|
Term
|
Definition
1. Insulin secretagogues (sulfonylureas, meglitinides)
2. insulin sensitizers (metformin, thiazolidinediones)
3. alpha glucose inhibitors (acarbose)
4. incretins |
|
|
Term
|
Definition
bind and inhibit B-cell ATP-sensitive-K+ chnnels -> cell depolarization -> insulin release
sulfonylureas (glyburide, glipizide)
- 2nd gen; lonfer acting, once daily dose, less adverse effects
meglitinides (repaglinide)
- rapidly absorbed; short T1/2, multiple pre-prandial use; combo w. longer acting; less hypoglycemia seen than with sulfonylureas |
|
|
Term
|
Definition
| natural H that enhance the insulin response to rising plasma glucose |
|
|
Term
|
Definition
glucagon-like peptide 1
long-acting agonist, analogue; inhibits Dpp-4 |
|
|
Term
|
Definition
Liraglutide
-modified so it is carried bound to albumin and slowly released into tissues
-decreases apetite
-lowers serum TAG
-must be injected
Exenatide
-use in Type II with other hypoglycemic agents
-augments glucose-dep. insulin secretion
-SQ injection
-nausea, vomiting, diarrhea |
|
|
Term
|
Definition
| GLP-1 analog found in gila monster saliva |
|
|
Term
|
Definition
produced by alpha cells of pancreas
used in ER treatment of hypoglycemia in type I |
|
|
Term
|
Definition
iodinated forms of the AA, thyronine
tetraiofothyronin [thyroxine] (T4)
triiodothyronine (T3)
(higher activity)
reverse T2 (rT3)
(inactive) |
|
|
Term
action of deiodinases
D1, D2, D3 |
|
Definition
D1 - inner and outer ring (T3 pro'n; T4, T3, rT3 inactivation/degradation)
D2 - outer ring (intracellular T2 pro'n)
D3 - inner ring (T2 & T3 inactivation) |
|
|
Term
| serum T3 and T4 pharmacokinetics |
|
Definition
T4:T3 is released 4:1 by thyroid
circulate bound to thyroid binsing globulin ~99%
T1/2:
T4 = 7 days
T3 = 1 day
T3 has 4x biological potency as T4 |
|
|
Term
|
Definition
peripheral conversion T4->T3
Type I: liver, kidney, skeletal/cardiac muscle
Type II: brain, pituitary gland |
|
|
Term
| physiological actions of TH |
|
Definition
reg. of met. - maintains E set-pt
(CHO, lipids, ptns - calorigenesis)
cellular O2 consumption by affects of Na+K+ATPases
growth & development
myocardial contractile ptns |
|
|
Term
|
Definition
most common thyroid disorder
primary most common (TSH insufficiency much less common)
iodine deficiency-child(cretinism)/adult = most common cause of hypothyroid world-wide
congenital absence of gland/development
autoimmune thyroiditis (Hashimoto's)
(Ab agaisnt thyroid peroxidases, etc)
iatrogenic |
|
|
Term
|
Definition
severe, end-stage hypothyrodism, emergency
water intoxication, hypothermia, hypoglycemis, hypoventilation, hyponatremia, shock, coma |
|
|
Term
|
Definition
enlargement of the thyroid gland
goitroud hypothyroidism
causes:
I- def (easy to fix)
neoplasms
autoimmune destruction |
|
|
Term
| Therapy for hypothyroidism |
|
Definition
LEVOTHYROXINE (T4)
6-8w for steady state
Liothyronine available
Loitrix (T4:T3 4:1)
remove cause* |
|
|
Term
Hyperthyrodism
(thyrotoxicosis)
causes |
|
Definition
Grave's disease "diffuse toxic goiter"
(most common cause, autoimmune IgG Abs bind/activate TSH Rc)
Iatrogenic
neoplasms (benign adenomas)
infection/inflammation of the thyroid |
|
|
Term
|
Definition
ANTITHYROID DRUGS
Thioamines
(methomazole, propylthiouracil, block H synth only)
iodinated contrast media
(inhibit T4 -> T3)
Adjunct drugs
(beta blockers eg propanolol; Ca channel blockers eg diltiazem)
RADIOIODINE THERAPY
(I131, 80% of Pt become hypothyroid)
SURGERY |
|
|
Term
|
Definition
decapeptide produced by hypothalamic neurofibers
release influenced by cortisol, IGF-1, prolactin, gonadal steroids
released in pulsatile manner to bind Rc on ant. pituitary-responsible for release of LH/FSH
drug: Gonadorelin stims |
|
|
Term
|
Definition
| produced by Sertoli cells (testes) and granulosa cells (developing follicles) inhibits further FSH release |
|
|
Term
FSH
follicle-stimulating H |
|
Definition
glycoptn
bind to surface Rc on cells of ovaries/testes
ovary:
stim follicular development
needed for steroiddogenesis
testes:
acts of Sertoli cells -> spermatogenesis
*inhibin suppress pituitary FSH |
|
|
Term
|
Definition
glycoptn
bind surface Rc on cells of ovaries/testes
ovaries:
stim ovulation
needed for steroidogenesis
testes:
major regulator of testosterone pro'n via activation of Leydig cells
*testosterone |
|
|
Term
|
Definition
stimulation: Gonadorelin (both sexes for infertility)
suppression: Leuprolide (more common)
uses: prostatic cancer, benign hyperplasia, uterine fibroids, endometriosis, central precocious puberty, assisted productive tech procedures. |
|
|
Term
|
Definition
hMG: human menopausal gonadotropins
FSH- and LH-like activity
stim ovarian follicular development in women and spermatogenesis in men
used w. LH
*recombinant FSH also available |
|
|
Term
|
Definition
hCG: human chorionic gonadotropins
produced by human placenta and excreted in the urine of pregnant women
used in conjecture with hMG for infertility
recombinant LH and hCG is also available |
|
|
Term
|
Definition
testosterone:
~95% Leydig cells, 5% adrenals in men
small amts og dihydrotestosterine, DHEA and androstenedione
in women small amts of testosterone are derived from ovaries and adrenals -> some coverted to estrogen in body fat and bone
little to no storage of androgens |
|
|
Term
Androgens
actions & effects |
|
Definition
secondary sex characteristics
spermatogenesis
genitalia, secondary sex glands
deepening of voice
facial hair
libido and behaviour
lean body mass
erythropoiesis, decrease HDL
estradiol - closure of growth plates in long bones |
|
|
Term
|
Definition
testosterone
1:1 androgen:anabolic
more anabolic: Stanazolol, Nandrolone decanoate, Oxandrolone
added esters to change T1/2: enanthate cyprionate, undecanoate |
|
|
Term
| Androgens and anabolic steroids |
|
Definition
1. Androgen replacement therapy
2. gynecologic disorders
(decrease breast enlargement post-partym, chemo unoperable breast cancer, endometriosis (danazol), combo with estrogens post-menopause)
3. ptn anabolic agent
4. growth stimulators and aging
5. anabolic steroid abuse in sports |
|
|
Term
androgen suppression
antiandrogens |
|
Definition
GnRH antagonists
(continual delivery; leuprolide)
Testosterone synth inhibition
(ketoconazole, spironolactone)
inhibition of 5a-reductase
(finasteride)
androgen Rc antagonists
(flutamide, cyproterone) |
|
|
Term
|
Definition
dihydrotestosterone by 5alpha-reductase
(many sites)
estradiol by aromatase
(liver, adipose, bone, brain) |
|
|
Term
|
Definition
estradiol produced by ovaries
steroidal estrogen formed from testosterone or androstenedione precursors in the ovaries by aromatase
estrone and estriol are synth'd from estradiol largely by the liver + some peripheral conversion |
|
|
Term
synth of estrogens
postmenopausal women |
|
Definition
adipose produces estrogen
adrenals produce estrone from DHEA
synthetic estrogens: commonly ethinyl estradiol, diethylstilbersterol |
|
|
Term
|
Definition
progesterone (most important) produced in ovaries and adrenals, as well as placenta during pregnacy
precursor for estrogens, androgens, and adrenocorticoids
common synthetics: L-norgestrel, norethidrone, medoxyprogesterone
produced by testes in men |
|
|
Term
actions of effects of
estrogens and progestins |
|
Definition
normal sexual maturation
ovulatory and parturition (birth)
form'n endometrial lining
bone turnover and density (less reabsorption)
adipocyte deposition
blood cagulation
growth - puberty spurt, growth plate closure |
|
|
Term
| actions and effects of progesterone |
|
Definition
modulation of CHO met
control of pregnancy, suppress ovulation
adipocyte deposition
sexual maturation: breasts, reproductive tract
behaviour, mood |
|
|
Term
actions of effects of
estrogens and progestins |
|
Definition
normal sexual maturation
ovulatory and parturition (birth)
form'n endometrial lining
bone turnover and density (less reabsorption)
adipocyte deposition
blood cagulation
growth - puberty spurt, growth plate closure |
|
|
Term
| actions and effects of progesterone |
|
Definition
modulation of CHO met
control of pregnancy, suppress ovulation
adipocyte deposition
sexual maturation: breasts, reproductive tract
behaviour, mood |
|
|
Term
clinical app for estrogens, progestins, and gonadal inhibitors
fertility control |
|
Definition
oral contraceptives (convey health benefits unrelated to contraception; combo or mini-pill)
post-coital contraception (large doses of estrogens alone or with progestins; must be taken w/in 72h; makes endometrium unreceptive to blastocyst)
contragestation (Mifepristone RU486 = potent antiprogestin; blocks progesterone's actions, usually given w/ PGE analogue; used to terminate a pregnancy very early)
Norplant-2: SQ, L-norgestrol silastic capsules, last up to 5 years)
Medroxtprogesterone [Depo-provera] (IM depot injection of crystals every 3 months)
IUD |
|
|
Term
clinical app for estrogens, progestins, and gonadal inhibitors
hormone replacement therapy |
|
Definition
congenital primary hypogonadism (treatment begin around puberty to mimic physiology of puberty, low does of estrogen, add progestin at menarche; adult maintenance dose of both)
menopause[&surgical removal of ovaries] (estrogen + progestins are used based on symptoms and Pt. needs) |
|
|
Term
clinical app for estrogens, progestins, and gonadal inhibitors
ovulation induction
(infertile women) |
|
Definition
20-39% infertility due to anovuatory conditions
GnRH analogues; if fxnal pit/ovary
FSH/LH if fxnal ovary
Clomiphene citrate (partial estrogen Rc antagonist, if fxnal hypo/pit/ovary; inhibit (-) feedback inhibition by estrogen of hypo-pit-gonad axid); FSH lvls increase, single ovulation with a single course of therapy) |
|
|
Term
clinical app for estrogens, progestins, and gonadal inhibitors
cancer chemo and other uses |
|
Definition
advanced prostate cancer (diethylstilbesterol)
selective estrogen Rc modulators [SERMs] (tamoxifen, estrogen Rc antagonist, early breast cancer)
estrogen synth inhibitors [anastrozole, exemestane, letrozole] (aromatase enzyme inhibitors, alone or with tamoxifen for breast cancer) |
|
|
Term
adverse effects of
progestins and estrogens |
|
Definition
mild effects: nausea, headache, endocrine changes
moderate effects: weight gain, vaginal/UT infection (reduce mucus), breakthrough bleeding, depression
severe effects: hepatic dysfxn, dyslipidemias, cancer (breast, endometrium), circulatory (thromboembolic, MI, atherosclerosis, hypertension, cerebrovascular disease; less so now)
**concern when other risk factors |
|
|
Term
|
Definition
synth in paraventricular nuclei (+ lesser extent the supra optic nuclei + luteal sites of the ovary, uterus, fetal membranes)
release occurs following: sensory stimuli from the cervix and vagina at birth; suckling by newborn |
|
|
Term
|
Definition
enhances frequency and force of uterine contractions (w/ permissive effects of estrogen priming)
stims milk ejection
drug of choice for labour induction |
|
|
Term
| oxytocin contraindicators |
|
Definition
fetal distress
prematurity
abnormal fetal positing
cephalopelvic disproportion |
|
|
Term
|
Definition
oxytocin antagonist currently used outside of N. Am
analogue that block Rc
safety concerns? |
|
|
Term
|
Definition
| Oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3), the thyroid hormones. |
|
|
Term
|
Definition
nonapeptide, primary antidiuretic H
Actions:
1) kidney -> promotes water retention via V2 Rc
2) vasopressor responses in blood vessel via V1 Rc |
|
|
Term
|
Definition
increasing tonicity; osmoRc (hypothalamus)
BP drop; baroRc |
|
|
Term
|
Definition
vasopressin
desmopressin; longer acting vasopressin analogues; no vasoC
treatment for pituitart diabetes insipidus
nocturnal enuresis
admin IV IM intranasal (desmopressin) |
|
|
Term
| what problems can bone mineral abnormalities lead to? |
|
Definition
neuromuscular abnormalities, weakness and tetany
skeletal structural support disturbances
lose of hematopoietic capacity |
|
|
Term
|
Definition
increases serum Ca and decrease PO4
- promotes bone remodelling
- excess PTH -> net bone reabsorbtiom
- promote renal Ca absorp. PO4 excret. |
|
|
Term
Vit D
1,25-dihydroxyvitamin D |
|
Definition
increases serum Ca2 and PO4
promotes Ca, PO4 absorption by intestinal tract and kidney; promotes bone resorption
directly suppresses PTH pro'n |
|
|
Term
|
Definition
parafollicular C cells
lowers serum Ca2 and PO4
inhibits osteoclast activity
reduces Ca2, PO4 reabsorp. by kidney |
|
|
Term
| estrogens and bone mineral homeonstasis |
|
Definition
oppose PTH actions by slowing bone turnover
produce increase lvl of Vit D |
|
|
Term
Bone Mineral Homeostasis
Key H |
|
Definition
PTH (up Ca, down PO4)
Vit D (up Ca down PO4, suppress PTH)
Calcitonin (down Ca down PO4; inhibit osteoclast)
Estrogens (oppose PTH, slow bone turnover, increase Vit D) |
|
|
Term
|
Definition
low bone mass
primary: most commonly seen in post-menopausal women, low estrogen
secondary: post- or peri- menopausal, males |
|
|
Term
| Prevention/Therapy of Osteoporosis |
|
Definition
1. Raloxifene (SERM, Selective Estrogen Rc Modulator) bone/liver estrogen Rc
2. Bisphosphonates (risendronate) - most successful - inhibit osteoclast fxn, bone reabsorption
3. PTH analogues (teriparatide)
-recombinant PTH
- daily SQ injections
- stim born formation
-TREATMENT
4. Calcitonin
- inhibits bone reabsorption by osteoclasts
5. Vit D (calcitriol)
- improve intestinal Ca absorption |
|
|
Term
GH and IGF-1
Rcs and actions |
|
Definition
GH stim synth/release of IGF-1 from liver/growth plate
anabolic effects
GH directly promotes lipolysis, gluconeogenesis, and pth synth
both promote skeletal and soft tissue growth
Rc are similar in str and action |
|
|
Term
|
Definition
retarded growth, possibly dwarfism
clinical manifestation: CV, psychosocial, decreased muscle/bone mass, increase body fat, low nrg reduced strength, poor libido, sleep patterns
diagnosis: measure basal and stim GH lvls |
|
|
Term
| therapy for GH deficiency |
|
Definition
1. recombinant human H (rhGH)
-somatropin, given SQ
-kids: GH def. CRD, Turner's
adults: GH def., AIDS, short boewl syndrome, anti-aging?, abused in athletes
2. Mecasermin (rhIGF-1/rhIGFBP-3) children w/ GH Rc defecs or Ab to Gh
3. Sermorelin (synth GHRH) not useful if problem is at level of pituitary, diagnostic R/O hypo vs pit |
|
|
Term
|
Definition
gigantism: excessive linear growth when epiphyses of growth plates still unfused in young
acremegaly:
GH excess in adulthood; uncommon
-arthropathy, visceromegaly, resp & CV problems, GI tumours
-cause usually tumour of ant. pituitary |
|
|
Term
|
Definition
Octreotide: inhibit GH release
Pegvisomant: GH antagonist, decrease IGF-1, dopamine agonist |
|
|
Term
|
Definition
peptide H, produced in ant. pit.
breast development and milk pro'n following birth
too much prolactin may cause innapropriate breast development and lactation; reproductive difficulties
no treatment for prolactin deficiencies |
|
|
Term
|
Definition
| normally released by hypothalamus to decrease prolactin secretion from the pit, dopamine-like drugs can be used to decrease prolactin |
|
|
Term
|
Definition
Bromocriptine, cabergolide
stim D2 dopamine Rc in the ant. pit. to decrease prolactin secretion
prolactin secreting tumours: hyperprolactinemia, galactorrhea, mastodynia, hypogonadism in women and men
acromegaly: pituitary tumour may secert GH, prolactin
admin'd orally or intravaginally; long acting SQ depots |
|
|
