Drugs Used as Contraceptives Flashcards
What is a hormone
A biochemical modulator of cell function
What do hormones regulate
Homeostatic functions
What is a paracrine effect
A short range effect (small blast radius)
What is an autocrine effect
Acts on itself (feedsback on itself)
What is an endocrine effect
Transport in the blood stream to a distant organ (distally acting)
What do hypothalamic paracrine hormones influence secretion on
Endocrine hormones from the anterior pituitary gland
What do endocrine anterior pituitary gland influence hormone secretion on
Hormone secretion in the ovaries
Describe the classic homeostatic negative feedback
Hypothalamus stimulates anterior pituitary gland which stimulates the ovaries which inhibits hypothalamus and anterior pituitary gland
What do sex hormones all start with
Cholesterol
Describe production of progesterones and oestrogens
A cascade of enzyme activity from pre-cursor cholesterol in the ovaries and placenta: cholesterol -> pregnenolone -> progesterone -> androstenedione -> oestrogens
What converts cholesterol to pregnenolone
Mitochondrial CYP450scc
What converts pregnenolone to progesterone
Dehydrogenase
What converts progesterone to androstenedione
Hydrolyase and lyase
What converts androstenedione to oestrogen
Aromatase
What are the different types of oestrogen
Oestradiol, oestriol, oestrone
Where does the generation of cholestrol and oestrogen occur
In the ovaries and the placenta
When do steroids only have an effect
When they bind to receptors
What are steroids agonists for
Mobile nuclear receptors
What does the steroid receptor complex often require
A chaperone protein to mediate association
What does the steroid-receptor complex act as
A transcriptional regulator of nuclear DNA
What are steroid receptors
Mobile cytoplasmic receptors that eitehr up or down regulate a gene which means that steroids have diverse and potent effects
How long is the menstrual cycle
28 days
What is the menstrual cycle controlled by
GnRH, FSH, LH, oestrogen and progesterone
Where is FSH secreted from
Anterior pituitary
What does FSH cause
A Graafian follicle to develop and be viable
When do FHH levels peak
Around the point of follicle rupture (ovulation)
Where is oestrogen secreted from
As the follicle develops it secreted oestrogen in increasing amounts
What does oestrogen cause
Thickening of the endometrium
Describe the feedback mechanisms of oestrogen
Negatively feeds back on the pituitary during follicular phase. The peak of oestrogen transiently sensitises LH-secreting cells to effects of GnRH causing a mid-cycle surge of LH
What elicits follicle rupture
The surge of LH causes by oestrogen
Where is LH secreted from
Anterior pituitary
What does LH cause
A Graafian follicle to develop and mature
When does ovulation occur
At day 14- LH surge causes the follicle to rupture resulting in ovulation
What does the ruptured follicle turn into
Corpus luteum
Where is progesterone secreted from
The corpus luteum
Describe the feedback activity of progesterone
Progesterone negatively feeds back on the pituitary decreasing LH
What effect does progesterone have on the endometriumin regard to implantation
Makes it viable for fertilised egg implantation
What effect does progesterone have on endometriumin regard to sperm
Makes endometrium inhospitable to sperm
What causes the development of one Graafian follicle
FSH and LH
What happens to the egg after ovulation
If fertilised it implants into the endometrium. If not fertilised menstruation occurs
What happens to the endometrium in anticipation of implantation
It thickens and becomes more vascularised by oestrogen
How is the normal menstrual cycle suppressed
By giving regular synthetic or structural analogues of oestrogen and progesterone the normal menstrual cycle is suppressed because of the effects on reproductive tissue and the negative feedback on the hypothalamus and the pituitary
What does of drug suppresses the normal menstrual cycle
A chronic dose
What are the routes of administering contraception
Oral, implant, coil
Describe oestrogen mechanisms and effects
Oestrogen and receptor complexes -> transcriptional regulation of genes causing: seconday sexual characteristics, endometrial & uterine growth, vaginal lubrication, ovulation, up-regulation of progesterone receptors, reduces bone loss, increases bone density, increases clotting factors & platelet adhesivity, suppression of gonadotroph cell secretions in the pituitary
Describe progesterone mechanisms and effects
Progesterone + receptor complexes -> transcriptional regulation of genes causing: promotion of hospitable endometrial domain for implantation, alters viscosity & pH of cervical mucus to make inhospitable to sperm, suppresses maternal immune system during pregnancy, decreases uterine contractility, inhibits lactation, suppression of gonadotroph cell secretions in the pituitary and GnRH from hypothalamus
Describe how the combined oral contraceptive pill works
The combination of oestrogen (e.g. ethinylestradiol) and progesterone (e.g. levonorgestrel) is a highly effective contraception. Oestrogen suppresses FSH secretion stopping follicle development. Progesterone inhibits LH secretion stopping ovulation and preventing sperm traffic. Both hormones chronically make the endometrium inhospitable to implantation
Describe how progesterone-only preparations (POP) work
Typically contains noresthisterone or levonorgestrel. progesterones prevent sperm traffic by increasing cervical mucus viscosity and altering pH (more acidic). Chronic use of progesterone inhibits egg implantation in the endometrium. Trick the body into thinking its pregnant
Where may progesterone-only preparations be used
Where oestrogen is contraindicated
When should emergency contraception be used
As soon as possible post-coitally if not already taking contraception
Describe how emergency contraception works
A large dose of progesterone (ulipristal or levonorgestrel) is effective in causing contraception in about 60%-99% of cases
What are such large doses as in emergency contraception likely to cause
Nausea, vomitting, heachaches and irregular bleeding
Describe the adverse side effects of drugs used to prevent pregnancy
Combined pill contains lots of oestrogen therefore there is an increased risk of thrombo-embolism. ADRs from serious to inconvenient: thrombo-embolism, stroke, myocardial infarction, increased risk of breast cancer, exposure to STId (if unprotected intercourse), hypertension, skin pigmentation changes, weight gain, nausea, irregular bleeding, mood changes
What are contraindications for the pill
Pregnant, pre-existing cardiovascular disease, obese, hypercholestererolaemic, smoker over 40, ‘oestrogen sensitive’ breat/ bowel cancer, liver cirrhosis. If patienst is morbidly obese must ensure they are not pregnant, if they are obese= excessive cholsterol
Describe labour induction using prostaglandins
Uterine muscle contractile sensitivity to prostaglandins increases through pregnancy. PGE-analogues (dinoprost and misoprostol) may be used to induce the coordinated uterine muscle contractions.
How can PGE-analogues be given
PGE-analogues are prostaglandin-analogues that are given as gels or intravaginally
How can unprotected sex trigger labour
When couples have unprotected sex the ejaculate from the male contains lots of prostaglandins which can trigger labour
Describe labour induction using oxytocin
Oxytocin is usually secreted by theh posterior pituitary in response to cervical dilation and suckling. It causes uterine contractions (to expel the placenta). A slow IV infusion of oxytocin induces regular waves of myometrial contraction
What happens if the baby suckles straight away after birth
Oxytocin is releases which causes waves of myometrial contraction which helps expel the afterbirth
Why is oxytocin given as a slow IV infusion
A big dose would result in uterine spasm
Name an abortifactant used
Mifepristone
What is mifepristone
A progesterone receptor antagonist (means progesterone can’t bind to the receptor) that causes endometrial degeneration and sensitises uterine contraction to prostaglandins
What is gemeprost
A methyl ester analogue of a PGE1 and is used with mifepristone. It also helps reduce obstetric bleeding causing vasoconstriction
What do the social and ethical issues associated with the use of these types of drugs mean
You need to think carefully about how you educate your patient about their use in an unbiassed way and whether your own views may interfere with the best management of your patient (this can’t happen)
What best describes the composition of the combined oral contraceptive pill
It typically contains ethinylestradiol and levonorgestrel
Why is there a (small) increased risk of thrombo-embolic events if using contraceptives containing oestrogens
Oestrogens increase the levels of some blood-clotting factors and increase the aggregatory potential of platelets
