D3. Drug delivery to the vagina Flashcards
(52 cards)
structure of the vagina?
-S-shaped fibromuscular tube 6-10cm in length.
-Connects the uterus (starting at the cervix) to the external environment
ONE NOTE
the vaginal wall consists of what four layers?
the epithelial layer, lamina propria, the muscular layer and the tunica adventitia
ONE NOTE
How does the thickness of the vaginal epithelial cell layer change during the menstrual cycle?
During the menstrual cycle, the thickness of the vaginal epithelial cell layer changes by approximately 200–300 μm.
vagina surface?
Surface is covered in rugae which provide distensibility, support, and an increased surface area.
where does fluid arise in vagina?
The vagina does not possess a gland; fluid arises from cervical secretion, transudation from the blood vessels, and secretion from the endometrium and fallopian tubes
how does the vaginal fluid change?
-Women of reproductive age produce fluid at a rate of 3–4 g/ h, while the discharge produced by postmenopausal women is reduced by 50 %.
-the quantity and composition of the vaginal fluid also changes throughout the menstrual cycle
what can the vaginal fluid contain?
The human vaginal fluid may contain enzymes, enzyme inhibitors, proteins, carbohydrates, amino acids, alcohols, and aromatic compounds.
how can sexual activity affect vaginal drug delivery?
Sexual activity can alter drug release patterns from a vaginal drug delivery system since this will affect the volume and composition of fluid.
Lactobacillus acidophilus is present in the vagina…
Lactic acid is produced from glycogen from the epithelial cells, maintaining the pH between 3.8 and 4.2.
when can pH of vaginal fluid change?
-During menstruation, the pH of vaginal fluid increases.
-Frequent acts of coitus may also cause an increase in the vaginal pH.
-pH tends to rise in presence of local infection and in the post-menopausal stage.
vaginal drug delivery can be used for?
both local and systemic effects but the use of this route for local effects is much more common
Describe drug delivery used for local action
-Treatments for infections, dryness and irritation, for contraception and induction of labour and abortion.
-Vaginal administration allows the use of smaller doses with reduced systemic delivery and toxicity, for example, in the case of miconazole for the treatment of vaginal infections.
Describe vaginal drug delivery in systemic action
-Dense network of blood vessels. Vaginal vein form venous plexuses along the side of the vagina, and blood from the vaginal vein moves into the inferior vena cava, avoiding the hepatic portal system…
-Drugs delivered via the intravaginal route may exhibit higher bioavailability compared with the oral route since first-pass metabolism is avoided.
-Suitable for patients where oral administration is restricted e.g. in the case of severe vomiting.
-The vaginal route has the potential for preferential delivery to the uterus, known as the ‘first uterine pass effect’
-It is possible to self-administer and remove the dosage form.
challenges of vaginal drug delivery?
-Gender specificity
-Local irritation
-Cultural sensitivity
-Influence of sexual intercourse (and many other factors)
-Variability in epithelium thickness, fluid volume, and pH
-Leakage of the dosage form is inherent
Describe vaginal systemic delivery
-Similar to other mucosal routes of delivery, drugs may be absorbed transcellularly, paracellularly, or via receptor mediated routes. Good vascularisation provides the potential for maintaining a concentration gradient for passive diffusion.
-Avoids first pass metabolism
-Higher molecular weight drugs absorbed well compared to other mucosae
cons of vaginal systemic delivery?
can only be used by 50% of population therefore development is for female related conditions only
Absorption in vaginal systemic delivery?
Hormones, prostaglandins given vaginally have demonstrated absorption. Greater plasma concentration achieved with oestrogen by vaginal than oral delivery
Cyclic changes in fluid volume may have either a negative or positive effect on drug absorption…
-For drugs that display poor water solubility, increases in fluid volume may result in greater absorption.
-On the other hand, increase fluid may remove the drug from the vaginal cavity and limit absorption.
-Overly viscous cervical mucus may present an extra barrier.
how can changes in pH affect drug absorption?
Cyclic changes in pH and changes in pH due to disease state or menopausal status may change the degree of ionisation and alter absorption characteristics of weak electrolyte drugs.
how do changes in vaginal epithelium thickness impact drug absorption?
Changes in the vaginal epithelium thickness impact absorption. For example, the vaginal absorption of steroids is decreased by increase thickness
how does the menstrual cycle pose challenges to drug absorption?
-Mucus secretion varies throughout the menstrual cycle.
-In the cervix, secretion is considerably increased by oestrogen (to produce a favourable medium for spermatozoa).
-Oestrogen causes cornification of cells and enlargement of nuclei, with increased deposits of glycogen.
-Luteal phase: fluid thin and less acidic. Ovulation: Jelly-like (resembling egg-whites)
-At ovulation pH is lowest and epithelium thickest
-Vaginal pH increases during menstruation.
-Use of oral contraceptives eliminates cyclic variations
how does pregnancy pose a challenge for drug absorption?
-The vaginal mucosa becomes thicker.
-Increased desquamation of the superficial vaginal mucosal cells with increased vaginal discharge
how does age pose a challenge for drug absorption?
Pre-puberty:
Mucosal epithelium thin.
Vaginal pH ~ 5.
Post- menopause & after hysterectomy:Oestrogen deficiency means…
Epidermis much thinner ( 4 cell layers).
Reduced elasticity and vascularisation.
Reduced secretions.
Reduced glycogen – pH can return to pH 7.
Consequences are: patients are more prone to dryness, irritation, infection (Menopausal Atrophic Vaginitis). Even if not sexually active, patients may need lubrication.
vaginal therapy for infections and STDs?
Antibacterials, antifungals, antiseptics, acidifying agents
