Pharmacology + Puberty Flashcards
Tacrolimus side effects
Calcineurin inhibitor
HTN
T2DM
Hypomagnesemia
Nephrotoxicity
Tremor
Alopecia
Hyperlipidemia less common than cyslosporin
Seizures
Cyclosporine side effects
Calcineurin inhibitor
Hirsutism
Gingival hyperplasia
Nephrotoxicity
HTN
Parasthesia
Hyperlipidemia
Hypomagnesemia
Mycophenolate side effects
gastrointestinal ( nausea, diarrhoea) and haematological side effects
a. Most can be treated with dose reduction and/or brief discontinuation
Enteric-coated mycophenolic acid reduces upper GI side effects
carbimazole side effects
agranulocytosis
neutropenia
liver failure
myalgia/arthralgia
Carbimazole MOA
inhibits of iodination of tyrosine
may have some action on peroxidase
doesnt affect the uptake of iodine by thyroid gland
thyroid storm
life threatening
precipitated by surgery, trauma, infection
severe thyrotoxicosis
tachycardia, CCF arrythmia
fever
trumor agitation
delerium
psychosis
neonatal graves
1-5% of neonates born to mums with graves disease
develop hyperthyroidism (transient) due to TRAB antibodies crossing placenta
—> tachycardia, goitre, advanced bona age, poor growth, craniosynestosis
sick euthyroid
normal- ish TSH with low T3 (ESPECIALLY) and T4, but elevated rT3
T4 can sometimes be high, but T3 always low in sick euthyroid
TSH has a short half life, T4 has a a long half life, so TSH recovers first, and T4/T3 recover later
is radioiodine useful for eye disease in graves?
no, contraindicated in eye disease
treatment thyroid eye disease
doesnt respond to normal graves treatment and may get worse with carbimazole
treat mild disease with eye drops, mod disease with steroids, radiation and surgery
monoclonal antibody- teprotumumab
and stop smoking!
Gonadarche
pulsatile release of GnRH from the hypothalamus–> activation of the gonads by secretion of pituitary hormones (LH/ FSH)
Girls: breast develomment (first sign puberty), menarche
Boys: increased testicular volume >4ml , muscularity, deepening voice, body hair
Adrenarche
Release of adrenocortical androgens (DHEA/ DHEAS) due to maturation of zona reticularis
1. Results in development of pubic/axillary hair, oiliness of hair/skin, acne, body odour
2. Can occur BEFORE OR AFTER gonadarche (but gonadarche starts first in 70%)
iii. Though temporally correlated, gonadarche and adrenarche are physiologically distinct events. Individuals with defects in the hypothalamic-pituitary-gonadal axis can still undergo adrenarche. Individuals with no adrenal function can achieve gonadarche
Thelarche
breast development, primarily due to the action of estradiol from the ovarie
Pubarche
Specifically refers to the appearance of pubic hair due to adrenal androgens
ie the phenotypic result of adrenarche
Normal progress through puberty
Age:
Girls: average age 11, range 8-13 yo
Boys: average age 12, range 9-14 yo
Girls = Gonadarche (thelarche) –> adrenarche/pubarche –> growth peak –> menarche
Boys = Gonadarche (increased testicular volume) –> adrenarche/ pubarche –> growth speak –> sperm in urine
Girls Pubarche onset 2-6 months after breast development Menarche 2 years post thelarche Peak height velocity occurs 0.5 years before menarche - Peak rate = 8.5 cm/year However growth spurt starts at the onset of puberty ie at same time or soon after beginning breast development
Boys
Pubarche occurs ~6 months after testicular enlargement
Spermarche 2 years post pubarche
Facial hair 3 years post pubarche
Pubertal growth spurt starts 2 years later – additional two years of pre-pubertal growth (rate of 3-8cm per year) Usually age 13-14 years
-Peak rate = 9.5-10cm/year
Actions of oestrogen
B-estradiol most potent
ii. Functions
1. Stimulates development of genitalia, breast, female fat distribution
2. Stimulates epiphyseal closure
3. Stimulates GH growth spurt
Growth of follicle, endometrial proliferation
iii. Role in menstrual cycle:
1. Stimulates upregulation of oestrogen, LH, progesterone receptors
2. Initially provides negative inhibition of FSH/ LH
At set point, feedback changes to +ve LH feedback = LH surge stimulating ovulation
Testosterone
i. Made by Leydig cells
ii. Synthesized via 5-alpha reductase into dihydrotestosterone in target tissues
iii. Functions
1. Descent of testes (in utero)
2. Differentiation of epididymis, vas, seminal vesicles
3. Deepening of voice
4. Closure of epiphyseal plates (less action than estrogen )
5. Libido
6. ↑ basal metabolic rate
iv. Regulation
1. High in fetus due to placental hCG + fetal pituitary stimulation
2. Persists until 10 weeks of life, then decreases
3. Increases again in puberty
DHT
DHT is essential for the development of the male sex characteristics before birth, particularly the formation of the external genitalia. In the adult, DHT is needed to develop and maintain male gender characteristics, such as facial hair, deep voice, and muscle growth.
In males, about 70% of DHT is derived from the conversion of testosterone by 5α–Reductase in the prostate, testes, hair follicles, and adrenal glands.
DHT has approximately 3 times greater affinity for androgen receptors than testosterone and has 15-30 times greater affinity than adrenal androgens.
Action gonadotropins
n males
1. FSH Sertoli cells spermatogenesis
2. LH Leydig cells testosterone
iii. In females
1. 1. FSH follicular stimulation and growth. Stimulates granulosa cells to synthesize aromatase, which converts androgen produced by thecal cells to estradiol
LH Surge causes release of oocyte from follicle + stimulates the formation of corpus luteum which produces progesterone
Theca cells of ovary
Site of production of progesterone –> 17 a OH progesterne –> androstenedione and testosterone (which are metabolised by aromatase to produce estradiol)
Stimulated by LH
Granulosa cells
Stimulated by FSH
Produce aromatase which converts androgens produced by theca cells into estradiol
Produce progesterone from cholesterol
Also secrete inhibins which act on the anterior pituitary and reduce FSH secretion
Estrogen feedback to brain
normally exhibit negative feedback
shifts to positive feedback mid cycle—> LH surge and FSH –> ovulation
Why is 17 a hydroxyprogesterone measured instead of progesterone
progesterone binds to albumin with low affinity so has a very short half life ~5 min so unable to measure
Role of progesterone
breast development
suppresses milk production
reduced endometrial growth
increased secretions and increased thicness of mucosal secretions
Ovarian cycle
Follicular + luteal phases
Follicular: development of mature graafian follicle and secondary oocyte
estrogen gradually increases, causing + feedback and LH/FSH peak, while progesterone remains low throughout
–> ovulation, formation of corpus luteum (CL)
Luteal: CL = residucal theca and granulosa cells of follicle; synthesise and secrete estrogen and progesterone t maintain the feralised oocyte
If fertalisation doesnt occur (ie no HCG produced), the CL regresses and forms corpus albicans (non functional scar like structure)–> occurs 10-12 days after ovulation in absence of HCG
Endometrial cycle