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PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

PHYSIOLOGIC BACKGROUND OF PREGNANT Maternal Physiological Changes in Pregnancy the normal adaptations that a woman undergoes during pregnancy to better accommodate the embryo or fetus o A. Systemic Changes o B. Local Changes A. Systemic Changes 1. Cardiovascular System a. blood volume by 30 to 50 percent This results in decrease concentration of red blood cells and hemoglobin. This explains why the need for iron is so important during pregnancy. Anemia o Maybe physiologic or pathologic anemia o The difference between physiological and pathological anemia is the hemoglobin level. As long as it is still above the normal threshold, than it is still considered as physiological. WHO said that the threshold for a physiological anemia in pregnant woman is 11.0 gram/dL or 6.8 mmol/L. Iron Sources o Liver o Swamp cabbage (kangkong) o Spinach o Bitter Melon (ampalaya) o Horse raddish (malunggay) o Malabar nightshade (alugbati) b. cardiac output for about 30 percent c. Normal blood pressure Pre-eclampsia develops after 20 weeks of gestation o Cause: not known, although some researchers suspect poor nutrition, high body fat or insufficient blood flow to the uterus as possible causes. o Sensitivity to Angiotensin II Respiratory rate rises Shortness of breath due to gravid uterus Gastrointestinal Morning Sickness Constipation Flatulence Hemorrhoids Heartburn Body Temperature "hot flashes" Urinary System Urinary Frequency Musculoskeletal Lordosis Waddling Gait Leg Cramps

3.

4. 5. 6.

B. Local Changes 1. Vagina - Chadwick Cervix - Goodells sign Uterus-Hegars sign 2. Abdominal changes Striae Gravidarum Linea nigra Protruding umbilicus 3. Skin Changes Chloasma 4. Breast changes r/t hormonal change Colostrum 5. Sign and Symptoms of Pregnancy

1 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

5.1 Presumptive signs and symptoms felt and observe by the mother but does not confirm positive diagnosis of pregnancy 5.2 Probable- signs observe by the members of health team but do not confirm a positive diagnosis of pregnancy 5.3 Positive-undeniable signs confirmed by the use of instrument Three Periods of Pregnancy First trimester Period of Organogenesis The first 12 weeks of pregnancy are considered to make up the first trimester. The first two weeks from the first trimester are calculated as the first two weeks of pregnancy even though the pregnancy does not actually exist. These two weeks are the two weeks before conception and include the woman's last period. The third week is the week in which fertilization occurs and the 4th week is the period when implantation takes place. In the 4th week, the fecundated egg reaches the uterus and burrows into its wall which provides it with the nutrients it needs. At this point, the zygote becomes a blastocyst and the placenta starts to form. Moreover, most of the pregnancy tests may detect a pregnancy beginning with this week. The 5th week marks the start of the embryonic period. This is when the embryo's brain, spinal cord, heart and other organs begin to form. At this point the embryo is made up of three layers, of which the top one (called the ectoderm) will give rise to the embryo's outermost layer of skin, central and peripheral nervous systems, eyes, inner ear, and many connective tissues.[33] The heart and the beginning of the circulatory system as well as the bones, muscles and kidneys are made up from the mesoderm (the middle layer). The inner layer of the embryo will serve as the starting point for the development of the lungs, intestine and bladder. This layer is referred to as the endoderm. An embryo at 5 weeks is normally between 116and 18 inch (1.6 and 3.2 mm) in length. In the 6th week, the embryo will be developing basic facial features and its arms and legs start to grow. At this point, the embryo is usually no longer than 16 to 14 inch (4.2 to 6.3 mm). In the following week, the brain, face and arms and legs quickly develop. In the 8th week, the embryo starts moving and in the next 3 weeks, the embryo's toes, neck and genitals develop as well. Second trimester Period of Continuous Growth and Development Weeks 13 to 28 of the pregnancy are called the second trimester. Most women feel more energized in this period, and begin to put on weight as the symptoms of morning sickness subside and eventually fade away. The uterus, the muscular organ that holds the developing fetus, can expand up to 20 times its normal size during pregnancy. Although the fetus begins to move and takes a recognizable human shape during the first trimester, it is not until the second trimester that movement of the fetus, often referred to as "quickening", can be felt. This typically happens in the fourth month, more specifically in the 20th to 21st week, or by the 19th week if the woman has been pregnant before. However, it is not uncommon for some women not to feel the fetus move until much later. The placenta fully functions at this time and the fetus makes insulin and urinates. The reproductive organs distinguish the fetus as male or female. Third trimester Period of Most Rapid Growth and Development Final weight gain takes place, which is the most weight gain throughout the pregnancy. The fetus will be growing the most rapidly during this stage, gaining up to 28 g per day. The woman's belly will transform in shape as the belly drops due to the fetus turning in a downward position ready for birth. During the second trimester, the woman's belly would have been very upright, whereas in the third trimester it will drop down quite low, and the woman will be able to lift her belly up and down. The fetus begins to move regularly, and is felt by the woman. Fetal movement can become quite strong and be disruptive to the woman. The woman's navel will sometimes become convex, "popping" out, due to her expanding abdomen. This period of her pregnancy can be uncomfortable, causing symptoms like weak bladder control and backache. Movement of the fetus becomes stronger and more frequent and via improved brain, eye, and muscle function the fetus is prepared for ex utero viability. The woman can feel the fetus "rolling" and it may cause pain or discomfort when it is near the woman's ribs and spine. There is head engagement in the third trimester, that is, the fetal head descends into the pelvic cavity so that only a small part (or none) of it can be felt abdominally. The perenium and cervix are further flattened and the head may be felt vaginally. Head engagement is known colloquially as the baby drop, and in natural medicine as the lightening because of the release of pressure on the upper abdomen and renewed ease in breathing. However, it severely reduces bladder capacity, increases pressure on the pelvic floor and the rectum, and the mother may experience the perpetual sensation that the fetus will "fall out" at any moment.

2 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

It is during this time that a baby born prematurely may survive. The use of modern medical intensive care technology has greatly increased the probability of premature babies surviving, and has pushed back the boundary of viability to much earlier dates than would be possible without assistance. In spite of these developments, premature birth remains a major threat to the fetus, and may result in ill health in later life, even if the baby survives. PHARMACODYNAMICS IN PREGNANT WOMEN Is it Safe to Use Medicine while Pregnant? There is no clear-cut answer to this question How should a pregnant woman decide whether to use a medicine? Choice vs. Need How does a medicine affect the developing baby? First Trimester- period of greatest risk for the baby. This is because during this stage the baby's organs are developing. Medicines taken during this time have the potential to affect this development, which could result in malformations or birth defects. If a defect is very severe this could cause a miscarriage. Second Trimester-medicines can interfere with the development of the baby's nervous system, or with the growth of the baby During the second trimester medicines can interfere with the development of the baby's nervous system, or with the growth of the baby, resulting in a low birth weight. However, generally, experts believe that the second trimester is the safest period to take medicines. Third Trimester-Medicines taken in the final three months of pregnancy can cause complications such as breathing difficulties for the baby after birth This is because the medicine remains in the baby's body after birth, and the newborn baby may not be able to cope with the medicine in its bloodstream the way the mother can. How do prescription and over-the-counter (OTC) medicine labels help the doctor to choose the right medicine for pregnant women? Drug Classification System Category A- Controlled human studies show no fetal risks; these drugs are the safest. Category B- Animal studies show no risk to the fetus and no controlled human studies have been conducted, or animal studies show a risk to the fetus but well-controlled human studies do not. Category C- No adequate animal or human studies have been conducted, or adverse fetal effects have been shown in animals but no human data are available. Category D- Evidence of human fetal risk exists, but benefits may outweigh risks in certain situations (eg, life-threatening disorders, serious disorders for which safer drugs cannot be used or are ineffective). Category X- Proven fetal risks outweigh any possible benefit. MEDICATIONS DURING PREGNANCY A. Supplements and Vitamins 1. Folic Acid Essential for: Formation of red blood cells and prevention of anemia DNA synthesis and cell formation reduces the chance of a baby having a neural tube defect, like spina bifida, where the spine or brain does not form the right way Dosage: 400 800 micrograms OD 5 grams if the mother or partner has spina bifida or has a history of delivering a baby with neural tube defects Onset: Unknown Peak: 30-60 min Duration: Unknown 2. Iron Essential for: Expansion of blood volume and red blood cell formation Establishment of fetal iron stores for first few months of life

3 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

Inadequate iron intake results in: Maternal effects: anemia, decreased energy and appetite, cardiac stress during labor and birth Fetal effects: availability of oxygen thereby affecting fetal growth Dosage: 15-30 mg/day since diet alone is unable to meet pregnancy requirement 60 to 120 mg/day for women who have low hemoglobin values prior to pregnancy or who have iron deficiency anemia Onset: 4 days Peak: 7-10 days Duration: 2-4 months B. OTC Medicines 1. For Cough and Colds a. Antihistamine Essential for: Allergic Rhinitis Dosage: 5-10 mg OD Onset: 20-60 min Peak: 30-90 min Duration: 24 hours b. Guafenesin Action: increase production of respiratory tract fluids to help liquefy and reduce the viscosity of tenacious secretions. Essential to: help loosen a chesty cough can be used Dosage: 200-400 mg PO q 4hours Onset: Unknown Peak: Unknown Duration: Unknown c. Dextromethorphan hydrobromide Action: Antitussive that suppresses the cough reflex by direct action on the cough center in the medulla Essential for: non-productive cough Dosage: 10-20 mg PO q 4hours or 30mg q6 to 8 hours Onset: < 30 min Peak:Unknown Duration: 3-6 hours 2. For Constipation Bisacodyl (Dulcolax) Action: Stimulant laxative that increase peristalsis, probably by direct effect on smooth muscle of the intestine Dosage: 10 to 20 mg PO in the evening Onset: 6-12 hr Peak: Variable Duration: Variable 3. For Minor Headache or Body Ache a. Acetaminophen Action: Unknown. Thought to produce analgesia by blocking pain impulses Essential for: mild pain Dosage: 325-650 mg PO q 4 to 6 hours Onset: Unknown Peak: to 2 hr Duration: 3-4 hours b. Aspirin

4 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

Do not take aspirin during pregnancy Aspirin may interfere with blood clotting and cause problems during labor and delivery It can cause serious blood flow problems in the baby Trimesters of risk - First, second, and third Associated defects and complications - Unclear; may be associated with an increased risk of gastroschisis c. Ibuprofen Do not take ibuprofen (such as Advil) Action: Unknown, produce anti-inflammatory effects Dosage: 400 mg PO q 4-6 hours prn Onset: Variable Peak: 1-2 hour Duration: 4-6 hour 4. For Nausea and Vomiting (antiemetics) Metoclopramide HCl Action: Stimulates motility of upper GI tract Dosage: 5-10 mg PO TID Onset: 30-60 min Peak: 1-2 hour Duration: 1-2 hour 5. For Heartburn (antacid) Calcium carbonate (Maalox) Action: Reduces total acid load in the GI tract Dosage: 350 mg to 1.5 g PO or two pieces of chewing gum 1 hour after meals and HS prn Onset: 20 min Peak : Unknown Duration: 20-180 minutes C. TERATOGENIC DRUGS Drug use is an uncommon cause of birth defects, yet approximately 200,000 children (3-5% of live births) are born with birth defects each year Gestational Age When Organ Systems are Most Sensitive to Birth Defects Developmental stage Embryonic Stage Fetal Stage Gestational Age (Months) Gestational Age(Weeks) CNS* Heart Ear Eyes Limbs Lip Palate Teeth External genitals The red bars in the table show the gestational age when different organ systems are most sensitive to major birth defects in that organ system. The gray bars show the gestational age when different organ systems are sensitive to functional defects and minor malformations. A. Antihypertensive Medications 1 2 1 2 3 4 5 6 7 8 9 3 10 11 12 13

Developing Organ(s)

5 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

The major therapeutic goal of treating hypertension in pregnancy is to protect the mother from the development of acute complications and to deliver a healthy infant Antihypertensive drugs are widely used to treat chronic hypertension, gestational hypertension, or preeclampsia. 1. Atenolol o It decreases cardiac output and cardiac oxygen consumption and depresses renin secretion o Trimesters of risk - First, second, and third o Associated defects and complications IUGR, hypotension, oliguria o Studies: Animal and human studies have shown growth retardation in humans and animals, as well as growth and structural abnormalities in animals. Reduced fetal size is a function of the length of exposure to the medication. The earlier the treatment starts, the greater the incidence of defects. B. Pulmonary Drugs Bronchial asthma occurs in 48% of pregnancies. Severe and uncontrolled asthma during pregnancy may cause serious maternal and fetal complications such as gestational hypertension and eclampsia and an increased risk of perinatal death. There are no pharmacokinetic or pharmacodynamic studies during pregnancy on oral or inhaled steroids. 1. Beclomethasone has been proposed as the inhalational steroid of choice for the treatment of asthma in pregnancy o Action: unknown o Onset: 1-4 wk o Peak: unknown o Duration: unknown C. Psychopharmacologic Drugs Trimester of risk - Unknown Associated defects and complications - Variable; possible cardiac effects D. Anticonvulsant Drugs 1. Phenobarbital Action: Unknown; Probably depresses CNS and increases seizure threshold Trimester of risk - Late in pregnancy Associated defects and complications - Phenobarbital slightly increases the risk of cleft palate or lip and congenital heart disease. These drugs can cause fetal addiction and newborn withdrawal symptoms or newborn hemorrhage E. Antineoplastic Drugs Trimesters of risk - First, second, and third Associated defects and complications: Observed problems included IUGR, cleft palate, digital malformations, cardiac anomalies, and cloudy corneas. D. DRUGS GIVEN DURING LABOR AND DELIVERY 1. Systemic Analgesics Essential for: o managing discomforts of labor and birth Types 1. Meperidine (Demerol) 2. Fentanyl (Sublimaze) 3. Nalbuphine (Nubain) Maternal Effects o Slowing of uterine contractions o CNS depression BP and Respiration decrease o Maternal relaxation can enhance labor and facilitate fetal descent Fetal-newborn Effects o Direct effect of analgesic drug crosses placenta and is metabolized slowly CNS depression of fetus and of newborn if given within two hours of expected birth 2. Nerve Block Anesthesia a. Local Infiltration anesthesia Maternal Effects

6 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

Interrupts conduction of pain impulses from the perineum prior to performance of an episiotomy Fetal/Newborn Effects: None b. Epidural Block Onset occurs within 10 to 20 minutes Duration of action ranges from 30 minutes to 4 hours depending on the agent used Maternal Effects o Hypotension o Respiratory depression may occur o Relaxation of muscles including perineum Fetal/Newborn Effects o Primarily an indirect effect related to fetal response to maternal respiratory depression and hypotension, and to a prolonged labor requiring invasive medical procedures o 3. General Anesthesia Intravenous or inhalation induction resulting in loss of body sensation and consciousness Used primarily for emergency caesarean birth or vaginal birth requiring emergency intervention Maternal Effects o Vomiting with aspiration r/t decreased gastric emptying and loss of gag reflex o Loss of consciousness o Uterine relaxation increases Fetal/Newborn Effects o CNS depression, hypoxia, postnatal respiratory depression, decreased newborn responsiveness limiting interaction, sucking Beta-adrenergic stimulants Ritodrine labor suppression Effects: Maternal fetal tachycardia and palpitations CNS irritability tremors, nervousness, agitation, restlessness Nausea and vomiting DRUGS GIVEN TO INDUCE LABOR Oxytocin- hormone that causes potent and selective stimulation of uterine and mammary gland smooth muscle Dosage: Initially 10 units in 1000 ml of D5W injection, lactated ringers or normal saline solution IV infused at 1-2 milliunits/min. Increase by 1-2 at 15-20 intervals until normal contraction is established Max dose; 20 mu.min Onset: Immediate Peak: Unknown Duration: 1 hour OBSTETRICS AND PERINATAL PHARMACOKINETICS Introduction: One of the most neglected areas in drug development and clinical pharmacology. (Kearns, 2007) Only a handful of drugs have been approved for use in pregnancy, or contain obstetric dosing information in the product or package insert with the possible exception of adverse fetal effects. (Zajicek & Giacoia, 2007) Pregnancy poses a unique situation because drugs are generally given to treat the mother, however, the fetus is always a recipient and may be the target. (Kleinman, 2004). Most of the available information on the Pharmacokinetics of the drugs during pregnancy has been obtained from animal experiments and cannot applied directly and in vivo to humans. (Kulkarni, 2007) Pharmacokinetics: The Mother 1. Absorption - Certain Factors affect how medicines are absorbed by the body of pregnant women. - Factors such normal physiology of pregnancy that leads to signs of pregnancy such as Nausea and Vomiting may affect absorption during pregnancy. - Increased levels of progesterone that decreases gastric motility and therefore increasing intestinal transit time also affects drug absorption by increased drug metabolism in the GI tract. - Medicines taken by pregnant women such as Iron, Antacids and Vitamins may affect absorption of other drugs in the pregnant body. - Parenteral absorption may be used during this period if a quick drug response is the goal, however, Parenteral absorption may be affected at term since most of the blood flow is focuse on the uterus.

7 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

Absorption: Late stages to end Stages of Pregnancy Baden, Rice, Sierra (1983) studied this phenomenon by testing the efficacy of Meperidine IM to compare its Absorption to pregnant and non pregnant women. Indeed, the absorption rate of meperidine after intramuscular administration has been found to be slower in women during labor than in nonpregnant controls. Absorption: Late stages to end Stages of Pregnancy On the other hand, circulatory changes are on occasion pharmacologically advantageous. Studies have shown that pregnant women at term require 4050% less drugs for peridural block because at term the capacity of the peridural space is reduced by the physiologic engorgement of the internal vertebral plexus. 2. Distribution - Due to an increase in the total body water, total body plasma also increases creating an imbalance ratio between albumin and the plasma. This causes Dilutional Hypoalbuminemia decreasing the protein binding capacity and thus increasing the free drug in the pregnant system. - When two highly protein bound drugs are given concurrently, they compete for protein binding sites, thus causing more free drug to be released in the Circulation. - A low protein level decreases the number of protein binding sites.

However, some physiology of pregnancy may also protect the women from possible toxicity.

3. Metabolism (Biotransformation) - Increased progesterone levels resulted to increase liver enzyme activity resulting to increased drug metabolism and degradation. 4. Excretion - Due to mark increase from 70% to 100% in the glomerular filtration rate of the kidneys there is an increased elimination of the free drug in the pregnant system. - Metabolism and Excretion that are highlighted during pregnant state can be a form of protection from free drugs for it shortens the half lives of most medicines in the system. - Therefore, an important parameter to ensure safety in pharmacologic therapy for a pregnant patient is to ensure that the kidneys and liver are working properly. PHARMACOKINETICS: THE FETUS Placental Transfer of Drugs The primary function of the placenta in all species is to promote selective transport of nutrients and waste products between mother and fetus. The placenta has the unique characteristic of being perfused by 2 independent circulations: the umbilical circulation and the uterine circulation. Furthermore, most of the blood flow in the umbilical vein goes directly into perfusion of the fetal liver. The primary function of the placenta in all species is to promote selective transport of nutrients and waste products between mother and fetus. The placenta has the unique characteristic of being perfused by 2 independent circulations: the umbilical circulation and the uterine circulation. Furthermore, most of the blood flow in the umbilical vein goes directly into perfusion of the fetal liver.

8 | P a g e Obstetric and Perinatal Pharmacology Reported by: Maricris G. Espiritu, R.N. & Ryan-Michael DR. Pambuan, R.N.

PAMANTASAN NG LUNGSOD NG MAYNILA SCIENCES

GRADUATE SCHOOL OF HEALTH

PHARMACODYNAMICS AND PATHOPHYSIOLOGICAL PRINCIPLES IN NURSINC CARE

Modes of Transfer 1. Simple Diffusion 2. Pinocytosis 3. Passage through the membrane 4. Active Transport/ Facilitated Diffusion Placental Transporters - The role of such transporters is to facilitate the transport of molecules across the placenta. - This is also the transport mechanism of most drugs across the placenta. The following are some Placental transporters used by Drugs to be transported across the placenta. 1. 2. 3. 4. 5. 6. Monoamine Transporters Serotonin Transporters (SERT) Norepinephrine Transporters (NET) Located in the brush border membranes Capable of transporting Amphetamines and its derivatives. Binds with drugs such as Cocaine and tricyclic antidepressants but do not transport it across placenta. Carnitine Transporters Expressed in the brush border membrane Mediates the transport of several pharmacologic agents. quinidine, verapamil, pyrilamine, and the beta-lactam antibiotic cephaloridine. Indirect evidence from competition studies exists for the transport of several other drugs by this transporter. This includes a wide spectrum of b-lactam antibiotics containing quaternary nitrogen. Equilibrative Nucleoside Transporters Both the transporters are targets for the coronary vasodilators dilazep and dipyridamole, which bind to these transporters and block their transport function. Organic Cation/Proton Antiporters facilitate the efflux of cationic drugs from the placenta. substrates include cimetidine,clonidine, amiloride, imipramine, and benzamil. Sodium/Multivitamin Transporter The brush-border location of SMVT in the placenta indicates that SMVT mediates the entry of these vitamins into the placenta from the maternal blood. P-glycoprotein for the removal of xenobiotics from the cell, thus protecting the cell from the potential toxic effects of xenobiotics

Placental Metabolism One unique characteristic of the placenta compared to other body membrane is its capability to metabolize drugs. This is of little relevance to the mother but can protect the fetus from the entry of many drugs. Fetal-Neonatal Pharmacokinetics The fetal liver and the kidneys are capable of metabolizing many substrates by oxidation. However, due their immaturity, there is a very limited metabolizing capacity. Drugs such as aminoglycosides, digoxin, chloropromide, penicillin, salicylic acid, indomethacin, paracetamol and several sulfonamides are cleared very slowly by the neonate. Repeated administration of these drugs can cause neonatal toxicity. NURSING REMINDERS IN RELATION TO PHARMACOKINETICS OF PREGNANCY. 1. Treat minor ailments without drugs. 2. Counter check the drug prescribed. It should be one, which is known to be safe during pregnancy. 3. Prefer a drug, which has been in use for long periods of time to a newly introduced drug. 4. Check the drug dose and make sure that it is adjusted to the pregnant state. 5. Discourage the patient from self-administering over-the counter drugs. 6. Advise the patient that absolute safety of the fetus cannot be guaranteed even by not prescribing any drug to women. 7. Five-plus-five Rights of Drug Administration

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