Final Flashcards
OXT
synthesized by magnocellular neurons, released through post. pituitary into general circulation
mech. stim (↑ pressure of cervix/myometrial contractions/suckling stim) triggers secretion from pituitary → stimulates OXT Rs in uterus/smooth m. of milk ducts in mammary glands = ↑ contraction
positive feedback: mechanoreceptors send impulses to hypot = ↑ OXT
also bonding effect
vasopressin
synthesized by magnocellular neurons, released through post. pituitary into general circulation
↑ blood osmolarity/↓bp/↓blood vol triggers secretion from pituitary
kidneys: insertion of aq-2 channels = ↑ water reabsorption
vasculature: vasoconstriction
anterior pituitary: ACTH release
inhibited by alcohol
GH
pulsatile release from somatotrophs in anterior pituitary
bone: induces growth (postnatal)
muscle: ↑ aa uptake
adipocytes: ↑ lipolysis + ↓ body fat
liver: secretion of IGF-1
therapeutic use: replacement therapy - inj
tx of pituitary dwarfism + adult GH deficiency, short stature of Turner’s syndrome
GH regulators
GHRH: positive central regulator = ↑ gene expr, ↑ GH release, induces somatotroph growth
STT: neg central regulator = ↓ GH release
ghrelin: pos peripheral reg = ↑ GH release from somatotrophs, ↑ GHRH + ↓ STT
IGF-1: neg peripheral reg = ↓ GHRH + ↑ STT, ↓ GH release
GH: autocrine factor - neg feedback
pegvisomant
recombinant GH antagonist
tx of acromegaly
octreotide
STT receptor agonist
tx of acromegaly + gigantism
cortisol
circadian rhythm/stress induce hypot. release of CRH → corticotrophs = release of ACTH → synthesis of cholesterol in adrenal cortex = ↑ cortisol
negative feedback = inhibit CRH + ACTH → terminate stress response
bound to CBG (+ albumin) = inactive
inactivated by 11βHSD2 in kidney to cortisone; reactivated by 11βHSD1 in liver
release from CBG - cross cell membrane - binds GR → translocation to nucleus → dimerizes = genomic effects (transactivation or transrepression)
17α hydroxylase
metabolism of pregnenolone in z. fasciculata + reticularis = involved in cortisol + androgen synthesis
inhibited by ketoconazole in tx of Cushings and prostate cancer
21β hydroxylase
metabolism of pregnenolone in z. fasciculata + glomerulus = involved in cortisol + aldosterone synthesis
genetic mutation or immune response = primary adrenal insufficiency
11β hydroxylase
metabolism of pregnenolone in z. fasciculata + glomerulus = involved in cortisol + aldosterone synthesis
inhibited by metyrapone = tx of cushings
hydrocortisone
glucocorticoid replacement therapy
fails to replicate circadian rhythym of cortisol secretion
Chronocort = better mimic → tx for congenital adrenal hyperplasia
prednisone
4x ↑ potency = greater affinity for GR receptor than cortisol
dexamethasone
30x ↑ potency = greater affinity for GR receptor (no MR interaction
vamolorone
selective glucocorticoid receptor modulator
favours transrepressing actions (anti-infl) of GR over transactivating (side effects)
ketoconazole
antifungal, inhibitor of 17α hydroxylase
tx of Cushing’s disease - ↓ synthesis of cortisol + androgens
side effects: ↑ P and aldosterone
metyrapone
inhibitor of 11β hydroxylase = ↓ cortisol + aldosterone
tx of Cushing’s disease
side effects: chronic use may cause hirsutism + hypertension
mifepristone
GC antagonist (high affinity for GR)
tx of inoperable patients with ectopic ACTH secretion or adrenal carcinoma
SPRM: selective P antagonist → ↓ embryo implantation
emergency contraception - single dose in late follicular phase inhibits LH surge = no ovulation
combined with misoprostol = medical 1st trimester abortion
estrogen
converted from androstenedione by aromatases
promote females sex development, growth, + endometrial proliferation
↑ binding proteins, ↑ HDL, ↓ LDL, kidney: salt + water retention
therapeutic uses: replacement therapy, contraception, menopause
adverse effects: ↑ cancer risk (breast, endometrial), thrombosis, edema
anastrozole
antiestrogen = inhibitor of aromatase → ↓ E synthesis
tx of early + advanced ER+ reast cancer in postmenopausal women
no ↑ risk for uterine cancer or thrombosis
clomiphene citrate
SERM → blocks ERs in hypot. + pit. - no negative feedback = ↑ gonadotropins
tx: induce ovulation, infertility, amenorrhea, PCOS
adverse effects: ovarian cysts, hot flashes, multiple births
tamoxifen
SERM, prodrug (CYP2D6 → endoxifen)
combined with SSRIs (↓ CYP2D6) to ↓ hot flashes
tx of breast cancer; osteoporotic
adverse effects: ↑ risk of uterine cancer, blood clots
raloxifen
SERM = neutral in uterine tissue = no ↑ risk of cancer
still risk of blood clots
fulvestrant
SERD → binds ER monomer + prevents dimerization = degradation through ubiquitin pathway
tx of metastatic ER+ breast cancer
inhibits growth of tamoxifen-resistant tumors
PROTACs
proteolysis targeting chimeras = bind ER + E3 ligase = induce ubiquitination → degradation of ER
tx of ER+ breast cancer
progesterone
bound to albumin
facilitates implantation + pregnancy maintenance; development of mammary gland; immune role; neuroprotective
abnormal P responses: endometrial cancer, endometriosis, breast cancer, uterine fibroids, PMS/PMDD, lactation
therapeutic uses: hormonal contraception, menopause, dysmenorrhea, endometriosis
ulipristal acetate
SPRM
tx of uterine fibroids; emergency contraceptive - prevent/delay ovulation)
caused liver damage
levonorgestrel
Plan B - progestin = emergency contraceptive
prevents/delays ovulation + impairs luteal function
testosterone
secreted by Leydig cells when stimulated by LH
bound to SHBG
therapeutic uses: replacement therapy (hypogonadism: 1 = ↓T, ↑FSH/LH; 2 = ↓FSH/LH → ↓ T; pituitary deficiency, aging); protein anabolic agents; osteoporosis
antiandrogens: tx of benign prostatic hyperplasia, prostate cancer
abiraterone acetate
2nd gen antiandrogen → inhibits 17α hydroxylase and 17, 20 lyase
tx of androgen dependent prostate cancer
adverse effects: cortisol deficiency
finasteride
5α reductase inhibitor = prevents T conversion to DHT
tx of BPH; ↓ risk of impotence, infertility, ↓ libido
flutamide
competitive antagonist of AR
tx of prostate cancer → mutation of AR can cause resistance
darolutamide
2nd gen AR blocker
inhibits both WT and mut AR; more potent
SARMs
tx for osteoporosis (selective for bone) → attracted sports doping
risks: ↑ heart attack/stroke, hallucinations, infertility
AAS
mimic T
↑ muscle mass + strength
many adverse effects
cocaine
ester local anesthetic
metabolism by plasma cholinesterase to PABA
short half life
lidocaine
amide local anesthetic
high protein binding
metabolized in liver, slower = can accumulate
max safe dose = 5mg/kg
bupivocaine
cardiotoxic → R(+) binds cardiac Na+ channels
max safe dose = 2mg/kg
sevoflurane
inhalational anesthetic
propofol
IV anesthetic
rapid onset (lipid soluble) + emergence (rapid clearance)
anti emetic + anticonvulsant
positive allosteric modulator of GABA A receptor → ↑ Cl- mvt = inhibition
ketamine
IV anesthetic
NMDA R antagonist
analgesia + (dissociative) anesthetic
CV stability: ↑ hr + bp
montelukast
LTB4 antagonist
misoprostol
synthetic PGE1
uses: labor induction, tx of gastric ulcers
glucocorticoids
induce lipocortin = inhibit PLA2 (indirect inhibition of COX)
NSAIDs
analgesic, anti pyretic, anti inflammatory
inhibit COX = ↓ PG synthesis
inhibit PGE2 in hypothalamus = antipyretic action
adverse effects: gastric ulcers
ASA
anti infl: ↓ adhesion + migration of immune cells; prevent infl cascade
anti pyretic: ↓ PGE2 in hypot
antiplatelet: irreversible antagonist of TXA2 in platelets (low dose = ↓ CV risk)
risks: gastric irritation, Reye’s Syndrome, renal effects
ibuprofen
more potent than ASA = analgesia at lower dose (↓ risk of gastric ulcers)
↑ risk of hypertension
indomethacin
inhibits both COX + PLA2
tx of gout
celecoxib
selective COX2 inhibitor
no antiplatelet action, ↓ gastric irritation
tx of arthritis
risk: ↑ MI/stroke
acetaminophen
analgesic + anti pyretic (less effect on COX)
tx of mild pain, fever in children (↓ risk of Reye’s)
liver toxicity → buildup of toxic metabolite
N-acetylcysteine
tx of acetaminophen-induced liver toxicity
hormonal contraceptives
progestin: ↓GnRH = ↓LH = no ovulation; ↓ sperm survival
estrogen: ↓ GnRH = ↓ LH = no ovulation; prevent development of dominant follicle
prostate cancer
preventative/early stage → tx = HRT (↑T)
advanced → tx = antiandrogens
