D2. Drug delivery for contraception Flashcards
progestogens vs progestins?
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
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synthetic oestrogen and synthetic progesterone examples?
Synthetic oestrogens found in combined contraceptive methods include ethinylestradiol, and synthetic progestogens include gestodene, desogestrel, drospirenone, levonorgestrel, norethisterone.
what do synthetic progesterone and synthetic oestrogens do?
These substances prevent pregnancy by:
-Inhibiting ovulation
-Rendering the endometrium unfavourable for implantation
-Making the cervical mucus impenetrable for sperm
The Combined Contraceptive Pill Regimens?
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Advantages and disadvantages of the combined contraceptive pill?
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Describe the progesterone only pill
-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
Advantages and disadvantages of POP?
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Reasons for failure?
-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
Control of the plasma concentration of drug as demonstrated in the graph can lead to constant drug effect…
-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.
‘Monolithic’ or ‘matrix’ system?
‘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.
Describe polymers
-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
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Describe vaginal ring
-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
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How does the vaginal ring work?
-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
How should the vaginal ring be stored?
-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.
Describe Evra contraceptive patch
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.
How does the contraceptive patch work?
-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
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Patches can either be?
‘matrix’ or ‘reservoir’ type
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what kind of patch is Evra?
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.
Patches design considerations?
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Describe IUDs
-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.
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Describe the main mode of action of IUDs
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.
Advantages and disadvantages of IUDs
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What is the IUS- Intrauterine systems?
-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 %.
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PDMS in intrauterine systems?
PDMS in the core and the outer membrane controls the release of levonorgestrel. The extent of cross-linking effects release rate from the device.
the IUS and menstrual problems?
The IUS has relieved many women from menstrual problems, such as menorrhagia, which previously could only have been managed with hysterectomy.
How does IUS prevent pregnancy?
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.
advantages and disadvantages of intrauterine systems
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Describe the contraceptive implant- Nexplanon
-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)
How does the contraceptive implant- nexplanon work?
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.
Advantages and disadvantages of the contraceptive implant- Nexplanon?
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Drug release kinetics depends on what?
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.
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Describe matrix systems
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.
Describe reservoir devices
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.
Fick’s Law of Diffusion?
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.
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notable relationship in reservoir deices
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.
How to use Fick’s Law of Diffusion equation?
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