D2. Drug delivery for contraception

Question 1

progestogens vs progestins?

Answer 1

Progestogens are natural or synthetic steroid hormones that bind to and activate the progesterone receptors. Progesterone is the main progestogenic hormone synthesised by the human body. Progestins are synthetic agents
ONE NOTE

Question 2

synthetic oestrogen and synthetic progesterone examples?

Answer 2

Synthetic oestrogens found in combined contraceptive methods include ethinylestradiol, and synthetic progestogens include gestodene, desogestrel, drospirenone, levonorgestrel, norethisterone.

Question 3

what do synthetic progesterone and synthetic oestrogens do? how do they prevent pregnancy?

Answer 3

These substances prevent pregnancy by:
-Inhibiting ovulation
-Rendering the endometrium unfavourable for implantation
-Making the cervical mucus impenetrable for sperm

Question 4

The Combined Contraceptive Pill Regimens?

Answer 4

ONE NOTE

Question 5

Advantages and disadvantages of the combined contraceptive pill?

Answer 5

ONE NOTE

Question 6

Describe the progesterone only pill

Answer 6

-Contain only a progestogen such as desogestrel, norethisterone, or levonorgestrel. Same quantity of progestogen throughout the packet and must be taken every day.
-Desogestrel progestogen pills (e.g. Cerazette, Cerelle) inhibit ovulation in 97 % of cycles and have a 12-hour window for missed pills.
-Norethisterone and levonorgestrel pills (e.g. Noriday, Norgeston) inhibit ovulation in some cycles, render the endometrium unfavourable for implantation, and make the cervical mucus impenetrable for sperm

Question 8

Advantages and disadvantages of POP?

Answer 8

ONE NOTE

Question 9

Reasons for failure?

Answer 9

-Compliance e.g. missing a pill
-Accessibility – can the patient get to the pharmacy to collect more?
-Efficacy and effectiveness, or ‘perfect use’ versus ‘typical use’. ‘Perfect use’ is a measure of maximum efficacy and describes use of the method as it is intended. ‘Typical use’ is a measure of effectiveness when a group of people use them. For methods which require user action, these values may differ1

Question 10

Control of the plasma concentration of drug as demonstrated in the graph can lead to constant drug effect… (reservoir system)

Answer 10

-In contraceptive terms, this means a reduced window for unplanned pregnancy to occur (especially if no user action is required).
-This can be achieved, for example, by surrounding a core which acts as a saturated reservoir of drug, by a membrane that is permeable to the drug. Drug can partition from the core, into the membrane, followed by diffusion across it into biological fluids. Whilst the core is saturated, the membrane mediates diffusion, and the rate of flux across the membrane is constant. This is known as a ‘reservoir’ system.

Question 11

‘Monolithic’ or ‘matrix’ system?

Answer 11

‘Monolithic’ or ‘matrix’ systems contain drug loaded uniformly into a matrix material, and release is controlled by diffusion through the matrix material or aqueous pores.

Question 12

Describe polymers

Answer 12

-Polymers are substances of a high molecular weight consisting of repeating monomer units.
-Huge variety of potential polymer structures
-Physicochemical properties of polymers vary considerably depending upon their makeup and structure
ONE NOTE

Question 13

Describe vaginal ring

Answer 13

-NuvaRing is a combined (progestogen and oestrogen) contraceptive ring, composed of ethylene-vinyl acetate (EVA) copolymers. In 24 hours, the ring releases:
120 micrograms etonogestrel (progestogen)
15 micrograms ethinylestradiol (oestrogen)
-It is a ‘reservoir’ type device thus drug release follows reservoir-type kinetics
ONE NOTE

Question 14

How does the vaginal ring work?

Answer 14

-Ovulation is inhibited, cervical mucus is altered so that it is impenetrable to sperm, and the endometrium is rendered unfavourable to implantation.
-The ring is inserted into the vagina on the first day of the period and remains in the vagina for three weeks, and then is removed for one week and the user experiences a withdrawal bleed. Following this, a new ring is inserted. Users should be shown how to remove and fit the ring. It does not need to be in a particular position but should be comfortable

Question 15

How should the vaginal ring be stored?

Answer 15

-NuvaRing should be kept in the pharmacy fridge (temperatures between 2 – 8 °C). It may be stored this way for 40 months. After dispensing, it can remain out of the fridge for no more that four months, therefore, only three months may be dispensed at one time.
-With careful use, the vaginal ring can be 99 % effective, and with less careful use, 91 % effective.

Question 16

Describe Evra contraceptive patch

Answer 16

Evra is a contraceptive patch available in the UK. Similar to NuvaRing, it is a combined method. Contraindications for Evra are the same as those for the combined pill. Effectiveness is also reduced by enzyme-inducing drugs (see ‘Note’ regarding combined oral contraceptive pill)1.

Question 17

How does the contraceptive patch work?

Answer 17

-The patch utilises the transdermal route of delivery and is changed every seven days. After three weeks of use, no patch is applied, and the user experiences a withdrawal bleed. Itmust be applied to clean, dry, hairless skin, and if the patch becomes partly detached or completely comes off, effectiveness is reduced.
-Ovulation is inhibited, cervical mucus is altered so that it is impenetrable to sperm, and the endometrium is rendered unfavourable to implantation. With careful use, Evra can be 99 % effective, and with less careful use, 91 % effective
ONE NOTE

Question 18

Patches can either be?

Answer 18

‘matrix’ or ‘reservoir’ type
ONE NOTE

Question 19

what kind of patch is Evra?

Answer 19

Evra is a matrix-type system which consists of three layers: A polyethylene and polyester backing layer, a middle layer of polyisobutylene/polybutene adhesive, polyester, crospovidone, lauryl lactate, 0.75 mg ethinylestradiol and 6mg norelgestromin, and a release liner that is removed before application1,2.

Question 20

Patches design considerations?

Answer 20

ONE NOTE

Question 21

Describe IUDs

Answer 21

-IUD’s are inserted through the cervical canal, sit within the uterus, and have threads which sit in the vagina. The threads allow a woman to check that the device is correctly in place. You may hear IUD’s referred to as the coil. IUD’s do not contain hormones.
-Multiple IUD’s available in the UK, examples including Nova T 380, Multiload Cu375, and MiniTT 380. Many have a lifespan of 5 years, and a small selection have a lifespan of 10 years.
ONE NOTE

Question 22

Describe the main mode of action of IUDs

Answer 22

The main mode of action of IUD’s is the impairment of sperm viability. The IUD initiates a ‘foreign body reaction’ involving the release of endometrial prostaglandins and leukocytes, enzymes, and copper ions. A secondary effect is that the endometrium is left inhospitable to implantation of an embryo.

Question 23

Advantages and disadvantages of IUDs

Answer 23

ONE NOTE

Question 24

What is the IUS- Intrauterine systems?

Answer 24

-The IUS is a progestogen-secreting device that contains the hormone levonorgestrel. It consists of a polymer T-shaped frame with a hormone reservoir around the stem. Examples include Mirena, Levosert, Kyleena, and Jaydess. The reservoir consists of levonorgestrel in poly(dimethysiloxane) PDMS. The release of levonorgestrel suppresses the endometrium (lining of the uterus), preventing implantation. Cervical mucus is also thickened, rendering it impenetrable to sperm.
-The frame of Mirena also contains barium sulphate, rendering it radio-opaque. Mirena has a failure rate of less than 0.2 %.
ONE NOTE

Question 25

PDMS in intrauterine systems?

Answer 25

PDMS in the core and the outer membrane controls the release of levonorgestrel. The extent of cross-linking effects release rate from the device. It acts as a rate controlling membrane.

Question 26

the IUS and menstrual problems?

Answer 26

The IUS has relieved many women from menstrual problems, such as menorrhagia, which previously could only have been managed with hysterectomy.

Question 27

How does IUS prevent pregnancy?

Answer 27

It prevents pregnancy by suppression of the endometrium, and in some women, reduces ovarian function. The cervical mucus is thickened rendering it impenetrable to sperm, and there is a foreign body reaction to the presence of the IUS.

Question 28

advantages and disadvantages of intrauterine systems

Answer 28

ONE NOTE

Question 29

Describe the contraceptive implant- Nexplanon

Answer 29

-Nexplanon is currently the only licensed implant in the UK. Jadelle is available outside of the UK. It is a single radio-opaque rod containing 68 mg etonorgestrel. It is (4 cm in length and has a diameter of 2 mm). It is inserted with a sterile applicator. -Nexplanon uses an ethylene vinyl acetate membrane reservoir system3. Release rates change over a three-year period and the implant must be removed after year three (Year 1 = 40 µg/day, Year 2 = 34 µg/day, Year 3 = 25 - 30 µg/day)

Question 30

How does the contraceptive implant- nexplanon work?

Answer 30

Ovulation is inhibited, cervical mucus is altered so that it is impenetrable to sperm, and the endometrium is rendered unfavourable to implantation, all preventing pregnancy. Nexplanon is over 99 % effective1.

Question 31

Advantages and disadvantages of the contraceptive implant- Nexplanon?

Answer 31

ONE NOTE

Question 32

Drug release kinetics depends on what?

Answer 32

Release kinetics depends on the design of the system. Devices can either be ‘matrix’ or ‘reservoir’ based, although more complicated devices may involve both systems. ONE NOTE

Question 33

Describe matrix systems

Answer 33

In the case of matrix systems, drug is uniformly distributed throughout the polymer matrix, and in general, release follows the Higuchi equation. Rate of release is more rapid initially and slows as the concentration of drug near the polymer surface decreases.

Question 34

Describe reservoir devices

Answer 34

In the case of reservoir devices, a rate-limiting membrane controls release of drug from a core. Reservoir devices typically display more constant release rates. Release from a reservoir device follows Fick’s Law of Diffusion.

Question 35

Fick’s Law of Diffusion?

Answer 35

This equation tells us that the rate of change in concentration of dissolved drug is proportional to the concentration difference between two sides of a membrane. ONE NOTE

Question 36

notable relationship in reservoir deices

Answer 36

the release rate from the device is inversely proportion to membrane thickness. The thicker the membrane, the slower the release. The greater the area available for molecular diffusion, the greater the release rate.

Question 37

How to use Fick’s Law of Diffusion equation?

Answer 37

ONE NOTE