Pharmacotherapy in obstetrics. Medical ethics and deontology Pharmacotherapy in obstetrics. Medical ethics and deontology. Pharmacokinetics and pharmacodinamics of drugs. By Korda I.

TREATMENT OF THE PREGNANT WOMAN MEANS THAT ONE IS CARING FOR TWO PATIENTS, NOT ONE

The use of drugs during pregnancy graviora quadem sunt remedia persculis (some drugs worse than the disease - Lat.)

Drugs may be divided into three groups: Do not cross the placenta, and therefore does not cause direct harm to the fetus; cross the placenta, but no adverse effects on the fetus; cross the placenta and accumulate in fetal tissues, also has a damaging effect.

Categories of Risk for Drugs During Pregnancy CATEGORY DESCRIPTION These drugs are the safest. Well-designed studies in people show no risks to the fetus. ------------------------------------- Studies in animals show no risk to the fetus, and no well-designed studies in people have been done. Or Studies in animals show a risk to the fetus, but well-designed studies in people do not. A------------------------------- B------------------------------

Categories of Risk for Drugs During Pregnancy CATEGORY DESCRIPTION C D X No adequate studies in animals or people have been done. Or In animal studies, use of the drug resulted in harm to the fetus, but no information about how the drug affects the human fetus is available. ------------------------------------------------------------------------- Evidence shows a risk to the human fetus, but benefits of the drug may outweigh risks in certain situations. For example, the mother may have a life-threatening disorder or a serious disorder that cannot be treated with safer drugs. ------------------------------------------------------------------------ Risk to the fetus has been proved to outweigh any possible benefit.

Oxytocin (Syntocinon) Octapeptide Strong rhythmical contraction of myometrium Large doses- sustained contraction(↓ placental blood flow & fetal hypoxia/death) Clinical use: - IOL (IVI 3U syntocinon+50 ml of saline) - Augment slow labour (IVI same as above) -3rd stage of labour- 5 U IM for HTN ,cardiac disease - IVI 40 U in 500ml saline ( PPH) -Surgical termination of preg./ERPC- 5U slow IV

Ergometrine Sustained myometrial contraction & vasoconstriction Syntometrine IM: 5U syntocinon(rhythmic contraction in 2min) + 500µg ergometrine(sustained contraction in 7 min) Side effects – Nausea, vomiting, abdominal pain, chest pain, palpitation, severe HTN , Stroke & MI Contraindication- HTN, Cardiac disease Clinical use: - Management of 3rd stage - Management of PPH - 2nd dose give. Alternatively IV ergometrine can be given (works with in 40 sec)

Dinoprostone ( prostin E2) Vaginal pessary/gel Clinical use: IOL – 3mg 6hrs apart ( no more than 2 pessaries in 24hrs and max. 3 doses) Side effect: Nausea ,vomiting, diarrhoea, fever, Uterine hyperstimulation , HTN, bronchospasm Advantages : - Mobile patient -Reduce need for syntocinon

Carboprost ( Hemabate) Sustained myometrial contraction & vasoconstriction Syntometrine IM: 5U syntocinon(rhythmic contraction in 2min) + 500µg ergometrine(sustained contraction in 7 min) Side effects – Nausea, vomiting, abdominal pain, chest pain, palpitation, severe HTN , Stroke & MI Contraindication- HTN, Cardiac disease Clinical use: - Management of 3rd stage - Management of PPH - 2nd dose give. Alternatively IV ergometrine can be given (works with in 40 sec)

Atosiban(Tractocile) Oxytocin receptor antagonist Inhibition of uncomplicated preterm labour between 24-33 weeks ( Tocolytic) Contraindication: severe PET, eclampsia, IUGR, IUD, placenta previa, placental abruption, abnormal CTG, SROM after 30/40 Side effects: Nausea,vomiting,headache, hot flushes, tachycardia, hypotension & hyperglycemia Dose- Stat IVI then continue infusion until no contraction for 6 hrs.

Other tocolytics Salbutamol inhaler- 100 mcg x 2 puffs stat Terbutaline- 250 mcg subcutaneous Clinical use: both drugs are used for short term. (i) relaxing uterus at C/S (ii) ECV procedure Side effects: Headache, palpitation, tachycardia, MI ,arrhythmias, hypotension & collapse

Nifedipine Calcium Channel blocker Clinical use: Mild to moderate- 5-20 mg TDS/PO Severe HTN- 10 mg Retard/PO Tocolytic- Incremental doses every 20 min until contraction stop, then 20 mg TDS/PO Side effects: Headache,dizziness,palpitation, tachycardia, hypotension,sweating & syncope

Mild /Moderate HTN/PET Methyldopa: -Dose: 250mg BD/TDS , PO max dose 3g /day -Side effects: Headache,dizziness,dry mouth , postural hypotension,nightmares, mild psychosis, depression,hepatitis & jaundice - Important to stop drug in postnatal period Labetolol 100-200mg BD/TDS PO max 2.4g/24hr ACE inhibitors are contraindicated in pregnancy

Severe Pre eclampsia / HTN IV Labetolol (ß blocker): - Side effects: headache, nausea, vomiting, postural hypotension & liver damage - Contraindication: Asthma, marked bradycardia IV hydralazine (vasodilator) : - Side effects: headache,nausea, vomitting, dizziness, flushing, tachycardia, palpitation & hypotension - Because of hypotension preload with gelofusin adv. - Contraindication- SLE, severe tachycardia & MI

Magnesium Sulphate Clinical use: Prevention & treatment of seizure in eclampsia / severe pre eclampsia Dose: 4g IV stat then 1g/hr to be continued 24hr after last seizure Side effects: nausea,vomiting,flushing, drowsiness,confusion,loss of tendon reflexes, hypotension, decrease U/O, respiratory depression, arrhythmias,cardiac arrest Because of toxicity, Mg levels monitored

Drugs in early pregnancy Mifepristone- 200mg PO Mechanism: Antiprogestogenic steroid Sensitizes myometrium to prostaglandin-induced contractions & ripens the cervix Clinical use: Medical termination of pregnancy Medical management of miscarriage/IUD Side effects: Gastro intestinal cramps, rash, urticaria, headache,dizziness, Contraindication: severe asthma

Misoprostol Synthetic prostaglandin PO/PV route Clinical use: - Medical TOP - Medical management of miscarriage/ IUD ( For 1st trimester single dose of 400mcg From 12- 34 weeks 400mcg 3hrly ,max 5 doses) - Postpartum hemorrhage- 800mcg PR/PV Side effects: nausea,vomiting, diarrhoea, abdominal pain

Methotrexate Cinical use: Medical management of ectopic pregnancy Dose 50mg per kg/m2 Criteria- adenexal mass, non viable pregnancy hCG< 3000U, haemoperitonuem < 150ml Side effects: Disadvantage : repeated hCG levels, emergency surgery Advantage: Avoid surgery, tube preserved

Menorrhagia / dysmenorrhea Mefenamic acid: - NSAID, reduces bleeding by 25% - Dose: 250-500mgx TDS D1-3 of cycle or PRN - Side effects: Gastro-intestinal discomfort nausea, diarrhoea, bleeding/ulceration Tranexamic acid: - Antifibrinolytic,reduces bleeding by 50% - Dose: 1g TDS/QDS D1-4 of cycle - Contraindication: thromboembolic disease - Side effects: nausea,vomiting,diarrhoea, thrombo embolic event

Progestogens Progesterone is a hormone that naturally occurs in the human body. Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. ART Women with previous preterm labours -cyclogest pessary 200mg PV/PR daily till 36 weeks Following IVF/ICSI- Gestone inj + cyclogest pessary

periods of pregnancy, when the fetus is most susceptible to the damaging effects of drugs: 1Up to 11 days from the moment of conception. 2. On the 11th day prior to the third week, when the fetus begins the period of organogenesis. 3. Between 4 and 9 weeks of when the danger of fetal growth retardation, but teratogenic practically does not occur. 4. The fetal period (9th week before birth). In this period, the growth of structural defects usually do not occur, but may be in breach of postnatal functions and various behavioral abnormalities.

Efficient, effective and safe use of drugs during pregnancy involves the following conditions: • prescribe only established the security of their applications, with well-known pathways of metabolism in order to avoid possible side effects; due to the impossibility of determining the period of final completion of embryogenesis (in the absence of urgent and uncontested evidence) it is appropriate to postpone the use of drugs to 22-24 weeks of pregnancy; in the course of treatment requires careful monitoring of the mother and the fetus.

Drugs, the use of which is contraindicated in any period of pregnancy Antibacterials: tetracycline antibiotics - violate the bone formation in the fetus and have hepatotoxicity; chloramphenicol (chloramphenicol) - because of the risk of suppression of bone marrow function and the possibility of life-threatening so-called "gray baby syndrome"; fluoroquinolones - have a damaging effect on the cartilage between interarticular growth of the fetus and newborn; co-trimoxazole (biseptol and its analogues) - significantly increase the risk of congenital anomalies of the fetus; rifampicin, lincomycin, ethionamide, chloroquine (delagil), griseofulvin, levorin

Drugs, the use of which is contraindicated in any period of pregnancy Other drugs: All statins (lovastatin, simvastatin, Mevacor, Zocor); indirect anticoagulants (fenilin, pelentan);• Many antihistamines (diphenhydramine, pipolfen, suprastin); oral hypoglycemic agents; antigonadotropnym drugs (danazol, Clomid); androgens; Many antidepressants, barbiturates, antipsychotics (haloperidol, teralen, tizertsin); benzodiazepines; antiparkinsonian agents (parkopan, cyclodol, NAC); Non-steroidal anti-inflammatory drugs (meloxicam, phenylbutazone).

Based on the above, the physician of any specialty, choosing drug therapy of women of reproductive age, must first make sure there is no pregnancy, the patient!!!

Medical ethics and deontology Ethics - a philosophical discipline that studies the moral, morality. Medical ethics - the study of moral principles in the work of medical staff. The subject of her research is the psycho-emotional aspect of the doctor, nurse, technician, junior staff. In addition, the range of issues of medical ethics and the problems are, the successful solution of which the life and health of not only the living, but also future generations. Feature in the development of medical ethics is the fact that it, unlike the right to form and exist as a set of unwritten rules.

Medical ethics and deontology Medical deontology together should consider the ethical norms and regulations for health care providers in a professional activity in the hospital and beyond.Deontology (from Greek deon - duty and logos-Teaching) examines moral content of the actions and behavior of medical personnel in a particular situation.Deontology is closely related to medical ethics, as well as issues of health law, professional rules. Medical ethics is the theoretical basis of ethics. The latter is the practical application of medical ethics in the daily practice of medical staff.

BIOETHICS Are there limits to medical care, and what they have in sustaining life terminally ill person? Whether euthanasia is acceptable?  At what point should count of death? When does the fetus can be considered a living person? Permissible at abortion? представляет собой важную точку философского знания. Формирование и развитие биоэтики связано с процессом трансформации традиционной этики вообще, медицинской и биологической этики в частности. Оно обусловлено, прежде всего, резко усиливающимся вниманием к правам человека (в медицине -это права пациента, испытуемого и т.д.) и созданием новых медицинских технологий, порождающих множество проблем, требующих решения, как с точки зрения права, так и морали.

«Многих воителей стоит один врачеватель искусный» Гомер «Многих воителей стоит один врачеватель искусный» Гомер "When the embryo is considered a person?“for performing the abortion destruction of "spare" embryos without violating the commandment “Do not kill."

«Medicine is truly the most prudent of all the arts». Hippocrates The extent to which pregnancy occurred in infertile women, contributeincrease the genetic load in the population due to the birth of children with congenital disorders? What is the influence of drugs, long used to treat infertility (especially hormones) on the fetus? 3. What is the genetic risk of using donor sperm for artificial insemination?

Ethical issues of artificial insemination Artificial insemination is an unmarried woman Artificial insemination is a married woman without her husband Artificial insemination with the husband's consent and with the use of donor genetic material Homogenous conception (fertilization with sperm of her husband). Method of artificial fertilization in vitro with the destruction of the "extra" embryos Modification fertilization using a single egg or with all the resulting embryo in the womb. “ Egg Donation and fertilized embryos8. All varieties of surrogacy.

Problems of surrogate motherhood 1. Children transformed into a commodity, and motherhood - in contract work, paid secured childless couples. Health security of the child and the surrogate mother are secondary to the material gain. 2. Surrogate mother mentally traumatized need to "give" her unborn child. 3 A child may inherit genetic defects of a surrogate mother, some of which can not be detected by modern methods. 1. и т.д. 4. Instills fear psychological adaptation of the child when he learns of his birth, in communication with the surrogate mother

The desire to have grandchildren prompted 42-year-old Miss Evans to seek permission for preservation of sperm of her dead son. Nikolas Colton Evans was killed while trying to stop a fight in a bar. Despite the fact that the mission has another son - 22-year-old Ryan, who could easily make happy mother of his grandchildren, a woman seeking a surrogate mother for gestation of her first-born son.

Euthanasia. The term "euthanasia" comes from the Greek words "evos" - «good" and thanatos-«Death", literally meaning "good" death. the act or practice of killing or permitting the death of hopelessly sick or injured individuals (as persons or domestic animals) in a relatively painless way for reasons of mercy

Classification of euthanasia. Medical decision concerning end of life (MDEL), (Phisician assisted sucide - PAS), when the doctor prepares a deadly drug that enters the patient himself. Actually euthanasia - cases of active participation of a physician in the patient's death. in fact, produced the doctor killing the patient with the informed consent of the latter; Cases where the physician's role is reduced to a consistent rejection of the patient appointments, allowing to extend the life of the patient, or to the implementation of the actions and / or increase the dose to relieve the suffering medications (such as pain medication or sleeping pills), resulting in the patient's life is reduced. Basically - is welcome opioid analgesicsв. Also, in this group should include a conscious awareness hopelessly sick lethal dose of the drug they received.

52-year-old Sebir living in Côte d'Or in central France for eight years has suffered from an incurable tumor nasal cavity, which is strongly deformed her face and caused unbearable suffering, and requested euthanasia. Chantal Sebir did not wait euthanasia. French woman was found dead at his home. Story of a woman caused a great resonance in France, resumed debate on the resolution of euthanasia.

The principle of informed consent. Key elements of this process: the provision of information  obtaining consent Doctor s are obliged to inform the patient: the nature and purpose of the proposed treatment of him; of the associated significant risk; on possible alternatives to this kind of treatment .

Resolve conflicts . . . as close to the bedside as possible.

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