Medicines in Reproductive Health Flashcards
(30 cards)
What are the drug targets of hormones?
GnRH- acts on GnRH receptors
- Progesterone = progesterone receptors - Oestriol, oestrone, oestradiol = act on oestrogen receptors
- Dihydrotestsosterone and testosterone - act on testosterone receptors
What are the classes of drugs in reproductive health?
-GnRH agonists and antagonists
- Oestrogens agonist, antagonists and modulators
- Progestogen agonists and antagonists
- Androgen agonists and antagonists
- 5-a reductase inhibitors
- Aromatase inhibitors
- Combinations
What are the receptors dor steroid hormones?
- Called cytoplasmic or nuclear receptors
- Steroids can pass through the cell membrane
- Acticvated receptors regulate gene transcription. Ligand - activated transcription factors
- ## May recruit co-activator molecules
What are the routes of administration for steroids?
- Steroids = quite lipophilic so they can reach their receptors )
- Can be applied topically, Nasal spray, patches
What are transdermal patches?
Advantages :
- Avoids first pass metabolism
- Better bioavailabilty
- Stable concentrations
- Better compliance
Disadvantages :
- Can get skin reactions/irritation
- Might fall off
Transdermal patch design - layers:
1.) Impermeable backing
2.) Reservoir for drug dissolved in liquid or gel or solid polymer matrix
3.) Semi-permeable membrane
4.) Adhesive layer
What is the intramuscular injection of esters?
- The hormone is esterified with, i.e., Valerate, cypionate - more lipophilic
- Prodrug - once absorbed the ester group is enzymatically removed
- CH - hyrdocarbons - oil/fats. Making it more lipophilic
What are the roles of oestrogen?
- Normal sexual maturation and growth of the female (uterine and breast growth)
- Endometrial hyperplasia
- Increased bone mass
- Increased triglycerides and HDL and decrease in total serum cholesterol, LDL
- Decrease in atherogenesis and increase in vasodilation
- Increase in clottting and increased risk of thromboembolism
- Increased water retention
What are the oestrogen receptors?
Two main types:
- ERa and ERB
- Form dimers, aa,ab and BB
- Signalling can be direct genomic or indirect genomic = complexity
- Present in many organs and tissues
- SOme modulators work in only breast/ bone tussue
What are oestrogen agonists (analogues) ?
- Oestrogens undergo enterohepatic cycling = the movement of bile acid from the liver to the small intestine and back to the liver
What is the significance of this for oral compared with transdermal administration?
- The inetraction of broad-spectrum antibiotics with oral contraceptives was previously thought to involve enterohepatic cycling but this is now somewhat controversial.
What are some clinical uses of oestrogen?
Replacement therapy:
* Primary hypogonadism — stimulate development of secondary sexual characteristics
- At or after menopause prevent menopausal symptoms (flushing, vaginal dryness, protect against osteoporosis)
- Contraception
What are some adverse effects of oestrogen agonists?
- tenderness in breasts
- endometrial hyperplasia
- risk of thromboembolism
- Retention of salt and water = oedema
- Migraines, hyperpigmentation, uterine bleeding (postmenopausal)
What is the link between oestrogen and breast cancer?
Many breast cancers are responsive to oestrogen — that is, there are oestrogen receptors on breast cancer cells and activation causes growth of the cancer cells.
Tamoxifen was originally developed as an antagonist at oestrogen receptors to treat breast cancer.
However, whilst tamoxifen can reduce growth of breast cancer cells, it does not appear to cause osteoporosis.
- “antagonist” raloxifene can be used to treat both breast cancer and prevent osteoporosis.
What are selective oestrogen receptor modulators (SERMs)?
- drugs that can be agonists in some tissues, partial agonists in others and antagonists in others
What is clomiphene?
- Oestrogen antagonists that induces ovultaion
- Antagonist in the hypothalamus and anterior pituitary gland, partial agonist in the ovaries
- Blocks oestrogen in pituitary - relief of negative feedback inhibition- increased release of GnRH and gonadotropins
- Increase in FSH - stimulate follicle growth- oestrogen trigger signal- LH surge - ovulation
What are progesterone receptors?
- PR-A and PR-B recpetors
- Inactive receptors is in nucleus
- Activation - PRE ( Progesterone Response Elements) - altered gene transcription
- Some effects are transcription independent
What are the roles of progesterone?
- GnRH suppression
- Decreases oestrogen stimulated endometrial proliferation
- Increased viscosity of cervical mucus
- Fat and carbohdyrate metabolism
- Decrease Na+ reabsorption
- Development of breast and endometrium
What are clinical uses of progesterone?
- Contraception
- With oestrogen in combined oral contraceptive pill
- Progesterone-only
- Injectable or implantable progesterone-only contraception
- Part of intrauterine contraceptive system
- HRT - combined with oestrogen
- Long-term ovarian supression (resulting in prolonged anovulation and amenorrhea
- Endometriosis
- Endometrial carcinoma
What are the adverse actions of progesterone agonists ?
Weak androgenic actions (see next section)
Acne
Fluid retention
Weight change
Depression
Change in libido
Breast discomfort
Irregular menstrual cycles and breakthrough bleeding
Increased risk of thromboembolism
What are progesterone antagonists?
- Mifepristone
- Competitive anatagonist but may have some partial agonist activity
- Used for medical termination of pregncnay (given with a prostaglandin (e.g. gemeprost)
- Caution : has anti-glucocortucoid activity so not to be used in women taking glucocorticoids
*
What are the androgen receptors?
- Testosterone - recpetor = AR
- Nuclear receptor
- Inactive receptor in cytoplasm, activated receptor translocates to nucleus - modifies gene transcription
- Testosterone is metabolised to oestrogen by aromatase and some effects result from action of oestrogen
What are the roles of testosterone?
Testosterone
Converted to dihydrotestosterone = active metabolite
Spermatogenesis in Sertoli cells.
Maturation of spermatozoa as they pass through the epididymis and vas deferens.
Feedback on the anterior pituitary, modulating its sensitivity to GnRH and thus influencing secretion of LH/ICSH.
Metabolic actions (anabolic agents — muscle, bone; sebum production)
Haematological actions ( Increases production of erythropoietin)
What are testosterone agonists?
- testosterone given via subcutaneous implant or transdermal patch since there is significant first pass metabolism
- Esters of testosterone ( testosterone proprionate) - intramuscular depot injections
What are some clinical uses of testosterone?
- Hormone replacement :
- Male hypogonadism (pituitary or testicular disease)
- Female hyposexuality following ovariectomy
- Illicit use of anabolic steroids (nandrolone, oxymetholone)
