4.1 Sex Hormone Drugs Flashcards
How do Sex Steroids Travel in the blood?
The travel bound to Albumin and Sex Hormone Binding Globulin (oestrogen increases this production)
Therefore have a long half life
Except progesterone which travels as a free drug (1st pass effect!)
What is the structure of SHs?
They all have a common ring structure
Derived from Cholesterol
2 Pathways to produce (one gives testosterone, the other O and P)
They are lipophilic and get stored in tissues
How does oestrogen get metabolised?
It is absorbed in the gut
Travels to the liver
Gets conjugated with glucoronide
Then in bile into the small intestine where it isn’t reabsorbed
It is then unconjugated by gut bacteria and reabsorbed in the blood
It can then affect peripheral tissues
Requires CYP450 enzymes
Pathway of Action for Oestrodiol
Lipophilic so passes through the cell membrane to intracellular receptors Goes to the nucleus with receptor 2 Receptors (alpha and beta forms) with similiar structures
What factors change the actions of SHs?
The tissue
The receptors present (number and type)
Co-activators/repressers present
The gene targets
How does receptor density change throughout the menstrual cycle?
P receptors are high until the mid secretory stage of the cycle
O receptor beta is high at the start of the mid secretory stage and alpha is high after the early secretory stage
Density is high in the female repro tract
What does Oestrogen do?
Proliferation of Endometrium and Breast Tissue (tenderness!)
Retain Na/H20
Increases HDLs, Lowers LDLs
Anabolic (increases weight gain, glucose insensitivity)
Increases coagulation
Decreases bone resorption
Increases number of PRs
What does progesterone do?
Create secretory endometrium ready for implantation Maintains pregnancy Decreases number of ERs Mood Changes Acne Anabolic, Fluid Retention, Bone Density
What does testosterone do?
Male Characteristics Aggression Acne Voice Changes Increases the LDL/HDL ratio (more risk of atherosclerosis)
How do we utilise sex hormones?
Contraceptive Use (pill, implant) HRT Androgen Replacement - BPH, Hair Loss Oestrogen Receptor Blockers (using mild oestrogens) - cancer Anti-progestins
How does the COCP work?
Oestrogen and Progesterone together prevent ovulation (no O only rise -> LH surge)
Oestrogen - non-secretory endothelium
Progesterone - thicker cervical mucus, decreases motility
Types of COCP?
Oral, Nasal, Vaginal
Implant,Transdermal
Monophasic, Biphasic, Triphasic
(If levels of P change)
What are the adverse effects of the COCP?
Increase risk of DVT - PE - Stroke (Thrombus) Headaches Weight Gain Acne Increase risk of gallstones Mood Changes Decreases glucose tolerance
What are the DDIs with the COCP?
CYP inducers/inhibitors
Soy (increases absorption)
Broad spectrum antibiotics (affects one oestrogen more than others)
How does the Progesterone Only Pill work?
Types
It prevents implantation, ovulation, and thickens the mucus
Use when cannot use COCP
IUCD
Implant
Oral - emergency contraception
