🔴ADRS OF PDE5 INHIBITORS 🔴
✔️Headache
✔️Nasal congestion
✔️Dizziness
✔️Facial flushing
✔️Fall bp
✔️Impairment of colour vision specially blue n green discrimination
✔️Gastric reflux and dyspepsia
✔️

🔴 Mechanism of Action 🔴

🔺Estrogen (female sex hormone) :-

Estrogen acts on nuclear receptors lacated within target cells ( details in general pharmacology).

Estrogen receptors (ERs) designated ER alpha & ER beta.

🔸ER apla :- Dominates in uterus, vagina, breast, bone, hypothalamus and blood vessels.

🔸ER beta :- Predominates prostate gland of Males and ovaries of Females.

Estradiol binds to both the receptors with equal affinity but certain ligands have different affinities.

🔺 Actions :-

🔸1. Sex organs :- Estrogen bring about pubertal changes in female including growth of uterus, fallopian tubes and vagina etc.

🔸2. Secondary sex characters.

🔸3.Metabolic effect :- estrogens are weaker anabolic than testosterone.

🔺 Classification of Estrogens.

🔸A. Natural estrogens:-
Estradiol
Estrone
Estriol

🔸B. Synthetic estrogens
I. Steroidal e.g. Ethinylestradiol
Mestranol
Tibolone.
II. Nonsteroidal
e.g. Diethylstilbestrol
Dienestrol
Hexestrol.

🔴ADRS OF ESTROGEN🔴
✔️Gynacosmastia and feminization in males
✔️Fusion of epiphyseal and reduction of adult stature when given to children
✔️Risk of irregular bleeding
✔️Endometral carcinoma
✔️Breast cancer
✔️Gallstones
✔️Benign hepatomas
✔️Migraine
✔️Endometriosis

🔴 Mechanism of Action 🔴

🔺1. Antiestrogen :- e.g.Clomiphene citrate :-
It binds with both ER alpha and ER beta receptor.
Trans isomer i.e. enclomiphene acts as a pure ANTAGONIST in all human tissues.
Cis isomer i.e. zuclomiphene and racemate display weak antagonistic action in rats.

🔺2.Selective estrogen receptor down-regulator :- e.g.Fulvestrant :- It inhibits ER Dimerization so that ER interaction with DNA is prevented and receptor degradation is enhanced.

🔺3. Selective Estrogen receptor modulator (SERMs) :-
These are drugs which exert estrogenic as well as sntiestrogenic action in a tissue selective manner.
That ligand binding could change the configuration of ER in multiple ways allowing interaction with different coactivators and corepressors in a tissue specific manner has paved the way for development of compounds with unique profile if agonistic and antagonistic actions in different tissues.
e.g. Tamoxifen citrate,
Toremifene, Ralixifene.

🔺4. Aromatase Inhibitors :-

Aromatization of 'A' ring of Testosterone and Androstenedione is the final and key step in the production of estrogens ( estradiol and /or estrone) in the body. In addition to circulating hormone, locally produced estrogens appear to play an important role in the development of breast cancer. So, Aromatse inhibitors are widely used now in the treatment of Breast cancer (Exemestane) .
e.g. Letrozole, Anastrozole, Exemestane.