Contraception and Safer Sex Contraception and Safer Sex Grade 10 PDCP.
Pharmacology of reproduction. ORAL CONTRACEPTION.
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Transcript of Pharmacology of reproduction. ORAL CONTRACEPTION.
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Pharmacology of reproduction
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ORAL CONTRACEPTION
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ORAL STEROID CONTRACEPTION
• COMBINED(COC) x only PROGESTIN (POP) x POSTCOITAL (PCC)
• efficacy- Pearl index 0,5 - 1 (COC), 0,5 - 4 (POP)
• ONE PHASE – stable estrogen (ethinylestradiol ) + stable progestin (derivát 19-
nortestosteronu )
• TWO PHASES – stable estrogen + 2 doses of progestin
• THREE PHASES - 2-3 doses of estrogen + 3 rising doses of progestin
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ORAL CONTRACEPTION - II
• ethinylestradiol - 20 - 50g (+progestin: levonorgestrel, norgestimat …)
• 1 tbl 21 days – 7-days break - pseudomenstruation bleeding• MECHANISM OF ACTION• inhibition of ovulation (progestin),
estrogen cycle frequency + cervical mucous changes (pentr. of spermia). + disturbed indometrial quality ( nidation) + motility of ovarian tubes
• OTHEr EFFECTS:• ovaria (function,), uterus (changes in cervical mucus, atrophy,
bleeding), breast (stimulation of proliferation, enlargment),CNS (excitability:E-,P-), endocrine fcion (GnRH, ACTH), hemocoagulation (f.VII, VIII, IX, X), liver (syntetic fction), lipid metabolism (LDL,HDL), glucose met. (insulin),
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ORAL CONTRACEPTION - III
• EFFECTS - BENEFITS• profylaxis of ectopic. gravidity, PID, anemia,
PMS, dysmenorhea, endometrial and ovarial ca, benign mastopathy, bone mass
• RISKS• KI: pregnancy, lactation, thromboembolic dis.,
liver dis, hypertension, smoking35 let,breast ca, gynekol. bleeding of unknown etiology, migrena
• AE: tension in breast, depresion, libido disorders, headache, TE events, GIT (nausea)
• DI: ! inductors of enzymes (carbamazepin, phenytoin, rifampicin)
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Emergency Contraception
Definition: emergency contraceptives are methods a woman can use after intercourse to prevent pregnancy
Methods: • Plan B − the only dedicated product marketed
specifically for emergency contraception• Off-label use of progestin-only contraceptive pills• Off-label use of combination estrogen-progestin pills• Insertion of a copper-releasing IUD
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Emergency ContraceptionIndications for use:
• contraceptive failure (condom broke, pills forgotten)• error in withdrawal or periodic abstinence• rape• any unintended “sperm exposure”
Contraindications:• pregnancyEC could prevent about ½ of unintended pregnancies −
1.5 million pregnancies in the U.S. every year.
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Emergency Contraception: Plan B
Contents: 750 µg levonorgestrel per pill
Directions:Take the first tablet as soon as
possible within 72 hours after unprotected intercourse.
Take the second tablet 12 hours later.
The sooner Plan B is taken, the better. It can be taken up to 120 hours after intercourse.
If taken within 72 hours as directed, Plan B reduces the risk of pregnancy from a single act of intercourse by 89%.
≈ $35.00 per pack
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Emergency Contraception: Plan B Mechanisms of Action
• Disruption of development and maturation of ovarian follicles
• Disruption of egg maturation and ovulation
• Interference with corpus luteum function
• Alteration of cervical mucus, blocking sperm transport
• Disruption of development of the zygote, morula, & blastocyst
• Impaired transport in the fallopian tube & uterine cavity
• Interference with development of the endometrium to impede implantation
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When does pregnancy start???The American College of Obstetricians and Gynecologists (ACOG), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH) have defined implantation as the beginning of pregnancy.
If fertilization has occurred, implantation starts about 7 days after ovulation.
Plan B disrupts the events leading up to implantation.
After implantation, it has no effect.
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Emergency Contraception: Plan B
Is Plan B an “abortion pill?”
No. The oral abortifacient is RU-486 (mifepristone, Mifeprex) which is an antiprogestin that blocks the effects of progesterone by binding to its receptors. It is usually given in combination with misoprostol (Cytotec) to medically induce abortion in gestational ages up to 49 days after LMP.
If implantation has occurred, Plan B will do nothing.
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Emergency Contraception
Alternatives to Plan B:20 tablets of a progestin-only pill (e.g., Micronor) x 2 doses, 12
hours apart
2 doses of a combined estrogen-progestin pill, 12 hours apartAlesse 5 pink pills (100 µg EE + 500 µg levonorgestrel)
Triphasil 4 yellow pills (120 µg EE + 500 µg levonorgestrel)
Ovral 2 white pills (100 µg EE + 500 µg levonorgestrel)
If you give estrogen, give an antiemetic also!
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Emergency Contraception
Standards of care:• providing information• providing post-coital
treatment• providing advance Rx
www.NOT-2-LATE.com
1-888-NOT-2-LATE
“Every woman, every visit.”
− ACOG
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Go get΄em!
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MEN HORMONAL CONRACEPTION
• low doses of testosterone
• GnRH antagonists
• 17-methyl-19-nortestosteron (MENT)
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TERATOGENITY of DRUGS
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THALIDOMIDE
• Thalidomide (Contergan) - 1956 –morning nausea of pregnant women– in 28 countries 100 000 kg of thalidomide,
– malformed more than 10.000 children - phocomelie
– teratogenic dose in men very low ! (0,1 mg/kg)
– tested several animal species (instead of rabbitt) - 20-300 mg/kg
– only one dose is sufficient 50-100 mg in critical period (21.-36. after
conception)
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7 wks pc
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A teratogen is an agent that can produce a
permanent alteration of structure or function in an organism exposed
during embyronic or fetal life.
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Many agents can produce a teratogenic
effect under some circumstances.
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Nature of the agent
Factors That Influence Teratogenicity
Dose Route Frequency of exposure Duration of exposure
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Gestational timing
Factors That Influence Teratogenicity
Concurrent exposures Concurrent illness Genetic susceptibility
– Mother– Fetus
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Principal Mechanisms of Teratogenesis
Cell growth or proliferation Cell death Cell migration Cell and tissue interactions Disruptions
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Mutagenesis
Principal mechanisms– Gene mutation– Chromosomal abnormalies
Before or after conception Males and females both
affected
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Multifactorial42%
Unknown37% Chromosomal
3%
Monogenic8%
Teratogens10%
Baird et al. AJHG 42:677, 1988
Birth Defects in Childhood
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Teratogens
Birth Defects in Childhood
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Birth Defects Caused By Teratogenic Exposures Are
Preventable.
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Prevention of Birth Defects Caused by
Teratogenic Exposures is an Important Public
Health Problem.
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Prevention of known teratogenic exposures
Public Health Concerns
– Alcohol – Infectious diseases– Isotretinoin, thalidomide
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Occupational exposures
Public Health Concerns
Environmental exposures Drugs of abuse Medications
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Over-the-counter medicines
Medications
Herbals and dietary supplements
Prescription drugs
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Frequently used by pregnant women
Medications
Biologically active Taken systemically Taken in high doses Information about
teratogenicity very limited
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Teratogenic Risk of 468 Drugs Approved 1980-2000
0%
20%
40%
60%
80%
100%
0-4 5-9 10-14 15-20
Years Since FDA Approval
Undetermined None, Minimal or Unlikely Small, Moderate or High
Lo & Friedman, 2002
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Teratogenic Risk of 468 Drugs Approved 1980-2000
Lo & Friedman, 2002
11 (2.4%) of treatments pose a “small”, “moderate” or “high” teratogenic risk
On average, 6.0 ± 4.1 years after FDA approval required to recognize risk in humans
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Teratogenic Risk of 468 Drugs Approved 1980-2000
Lo & Friedman, 2002
30 (6.4%) of treatments unlikely to pose a risk in human pregnancy
On average, 9.1 ± 4.5 years after FDA approval required to show safety in humans
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Animal teratology studies are valuable
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Animal teratology studies are valuable
but false positives and false
negatives do occur.
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Chlorpheniramine
Animal Teratology Studies: False Positives
Hydroxyzine Propoxyphene
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Captopril, enalapril
Animal Teratology Studies: False Negatives
Carbimazole, methimazole Misoprostol
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Pregnant women may not receive treatments that benefit their own health or that of the fetus
Lack of Knowledge Is a Problem
Exposures that really do pose a risk remain unrecognized
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Women may be advised or choose to terminate pregnancy to avoid risk
Lack of Knowledge Is a Problem
Labeling tends to provoke anxiety, often unnecessarily
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Characterizing teratogenic risks of important exposures
Public Health Priorities
Prevention of exposures that are known to be teratogenic
Recognition of pregnancies at high risk
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categories of risk - FDA• A – controlled trials in pregnant women -
levothyroxin, liothironin, folic acid• B – animal studie negative and controlled clinical
trials not available - paracetamol• C - teratogenic in animals, no clinical trials or not
available in animals in women - teofylin, amlodipin• D – there are known risks, but you can not
substituten - beta-blockers, ACEi (III. trimestr)• X – risks overweights the benefits oral
contracetives, statins, finasterid, isotretinoin, warfarin, misoprostol, androgens
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Teratogens in first trimester
• phenytoin, carbamazepine, valproate - neura tube defects (spina bifida)
• lithium – cardiac malformations• warfarin - bone deformation, chondrodysplasy, CNS
defects heparin (demineralization of bone in mother –
switch to LMW)• retinoids-def. CNS, heart, limbs, liver• danazol• oncologic drugs (fluorouracil, metotrexat,
cyclofosfamid, busulfan,…)
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Teratogens in fetal period• ACEI –renal failure, oligohydramnion• tyreostatics (carbimazol, thiamazol, propylthiouracil)• benzodiazepins - dependency• barbiturátes - dependency• beta-blockers (atenolol)• NSA – constriction of ductus • tetracyklins – disturbances of bone mass, teeth • warfarin – intracranial hemorhagies• aspirin - bleeding• cytostatika
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