Student No. : 9760111
Ajman University for Sciences and Technology
Abu Dhabi Branch
UAE
Research for this project was carried out by me during the period of Hospital Pharmacy
Training-1 no.700315(academic year 2000-2001)
Signed Date Jan 10 th
2000

ACKNOWLEDGMENTS
Sincere gratitude were extended to Dr. Rafeeq Abu Shaaban from the pharmaceutical department, to the support, encouragement and fruitful accompaniment through out the training and presentation of this project.
Special project supervisor Dr Asim Ahmed, for the continuous follow up , constructive criticism , and valuable comments. The author is indebted to
The author wishes to express special gratitude and thanks to those contributing in this revolutionary, distinctive and advanced Hospital Pharmacy training 1; namely
Dr.Danna Sallam and the staff of the New Medical Center Hospital.
Finally, the author wishes to express heart felt thanks to D. Abuel Mula . R. Abduel
Karem. In charge of the central training committee for furnishing the entire clinical pharmacy services.
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INDEX
Description
Section l Introduction
1.0 Breast feeding (lactation)
1.1 Prolactin
1.2 Human milk composition
1.3 Practices interfering with successful lactation
Page no
5
5
5
6
12
Section 11 Drugs
2.0 Passage of the drugs into breast milk
2.1 Suppression of lactation
2.1.0Drugs producing gynaeecomastia
13
13
14
15
2.1.1 Mammotrophic drugs 16
2.2 Drugs that are contraindication during breast-feeding 16
2.3
Certain drugs used in breast feeding 19
2.3.0 Antibiotics
2.3.1 Gastrointestinal drugs.
2.3.2 Analgesic and anti-inflammatory drugs
2.3.3Opioids
2.3.3 Cardiovascular drugs
2.3.4 Anticovulsants
2.3.5 Antidepressants
2.3.6 Antipsychotic drugs
2.3.6 Anxiolytics, Sedatives. And Hypnotics
2.3.7 Parkinsonism drugs
2.3.8 Hematologic drugs
2.3.9 Antidiabetic drugs
2.3.10 Antithyroid drugs
2.3.11Renal and electrolytes
2.3.12 Antiashmatics
2.3.13 Contraceptives
Section lll conclusion
32
33
33
34
34
35
19
23
27
29
31
35
35
36
37
37
39
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Section l: Introduction
BREASTFEEDING: (lactation)
Nourishing anew born infant with milk secreted by the mammary gland. Although not essential to the infants well-being or the other infant relationship, breastfeeding afters many nuritional, immunologic, & psychosocial advantages to both mother
&baby.deciding whether or not to breastfeed is a woman choice, based on her feeding, beliefs,&life circumstances most woman who choose to breastfeed find the experience pleasurable &even erotic.those who consider brestfeeding distateful ,unclean or embarrassing stand little chance for success in this manner of nourishing their infant.commercial prepared formulas can meet an infants nutritional needs, &bottle feeding can still be a time of emotional closeness between mother&baby.
*Lactation is the production of milk by the breast, lactation is regulated by prolactin oxytocin .
*PROLACTIN: is mainly a female hormone in humans it is an anterior pituitary hormone as mysterious as STH in its range of activities &a tissue controller of development & functioning of mammary glands in the female breast development
&maternal behavior .it has growth hormone activity. Deficiencies include galactorrhea
& failure of lactation .its chief important is in the functions of lactation.
* prolactin is a water soluble protein with a very short half-life in blood .an excess of prolactin causes precocious lactation &longer maintenance of the corpus lutem in the ovary. No toxicity has been reported. Its chief synergists are STH, LH, estrogen
&progesterone, its antagonists are the same, but at different conc. from the synergistic ones, usually higher.
* Prolactin is formed in the anterior pituitary stored there. prolactin is unique among the pituitary hormones in being normally controlled by an inhibitor ( PIF) rather than by a releasing hormones from the hypothalamus as are the other pituitary hormones.
Releasing factors include: tranquilizers, oxytocin, external stimuli, TRH, estrogrn, T4,
4

serotonin, exercise, tryptophan. Releasing inhibiting factors are PIF, L-Dopa, and progesterone. prolactin apparently acts on the cell membranes .
Physiological function:
1.initiation of lactation
2.developent of mammary glands in females
3.nidation of zygote
4.protein anabolism
HUMAN MILK COPOSITION:
Introduction
Human milk was designed for human infants, &its composition is unique to the needs of our species .in addition to containing the necessary macronutrients, it also is endowed with the full spectrum of vitamins & minerals. Attention has been given to the array of nonutrient growth factors, hormones, &protective factors, such as immunoglobulins, there may be other important substances in human milk that have yet to be identified.
-Unfortunately, compounds enter human milk that may adversely affect the nursing infants, however, their numbers are few and their conc. Generally low .the value of human milk for the health & growth of the baby is undisputed, rarely dose breast feeding need to be discouraged.
**Each type of milk is unique & consists of a highly complex mixture of organic & inorganic compounds. It is likely that the characteristics of mammalian milks relate directly to variable mother-child relationship that takes place in infancy.
-Human milk is dilute &consists of a solution of protein, sugar, &salts in which a variety of fatty compounds are suspended. The composition varies of from one human to another, from one period of lactation to the next. & Even hourly during day .the composition of a given milk sample is related not only to the amount secreted 7 the stage of lactation but also to the timing of its withdrawal & to individual variation among lactating mother
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colostrum
In the first few days after birth of the baby the mammary glands secrete a small amount of thick fluid called (colostrum) which is yellow, a feature associated with its relatively high carotene content, it is also transparent & contains more protein, less sugar, & much less fat than milk produced there after .a benefit believed to be associated with colostrum is reported ability to facilitate the establishment of (bifidus…flora)in the digestive tract , also it facilitate the passage of meconium , the dark – green , mucilaginous material in the intestine of the newborn .
Protein
The human milk contains the least protein, the major proteins found in breast milk are casein and α –lactalbumin ,lactoferrin and secretory IgA ,rumalbumin , β – lactoglobuline , glycoprotiens . Mature milk contains about 0.7 to 0.9 g of proteins per
100 ml of whole milk. Human milk has been found to contain more than 25% of its nitrogen in non- – protein compounds, the lower protein conc. is now accepted as true amount.
Non protein nitrogen
The total amount of non protein nitrogen (NPN) in human milk is at least 25%of all nitrogen .NPN consists of organic &trace amount of inorganic compounds shed into the milk supply. Among these compounds are peptides & free amino acids, the latter of which may provide a nutritional advantage to the infant .NPN also includes urea, creatinine &sugar amine.
Lipids
The total lipid content of milk varies considerably from one woman to another. & Even affected by parity & season of the year. Nearly 90% of the lipids in human milk is present in the form of phospholipids, cholesterol diglycerides, free fatty acids,monoglyceride , glycolipid and sterol esters . Human milk contains cholesterol, which has benefits:
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1• it is needed by rapidly growing central nervous system for myelin synthesis.
2• it stimulates in early life for the development of enzymes necessary later for cholesterol degradation.
-Triglycerides content was found to increase (mainly during the first postpartum week) cholesterol conc. declined & phospholipid content remained the same. After an ordinary period of milk release a bout 20%of the milk remains in the gland & this milk contains 50% of fat.
*This phenomenon may result from the adsorption of the fat globules to the surface of the alveolar cell. It has been suggested that this changing fat composition of human milk during a feed may be one of the mechanisms of aiding appetite control of infants.
The higher fat composition of the hind milk in comparison with the fore-milk may serve to signal satiety in infants and gradually motivate them withdraw from the breast and cease feeding. This intriguing idea has not been supported, however, by several idea has been supported.
*In one study assessing milk intake and six parameters of sucking. There was no indication that high - fat milk acted as a cue to babies .to slower stop feeding .on contrary, babies appeared to feed more activity on the high-fat milk in that they sucked in longer bursts for it and spent a smaller proportion of the test period resting.
*Fat content of breast milk may be reduced to a low as 1g/100ml.
Fatty acids
Fatty acid can be changed by modifying energy intake and fatty acid composition of dietary fat Lactating women feed a diet rich in polyunsaturated fats, such as corn and cottonseed oil, produce milk with an increase content of polyunsaturated fats .
Cholesterol
The cholesterol content of human milk ranges from 10 - 20 mg/dl with an approximately daily consumption by the infant of 100 mg. the mount of cholesterol drops as lactation progress. Even through the fat content may rise. The cholesterol
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content of milk is not altered by diet, however, a fall in plasma cholesterol in linoleic acid conc. Of the milk. There is no evidence that consumption of breast milk as an infant provides for more efficient metabolism of cholesterol as an adult or that endogenous synthesis is indequate for the infant requirements .
Lipase
Human milk contains several fat- digesting enzymes or lipases .one is a serum – stimulated lipase that may appear in the milk as a result of leakage from the mammary tissues. Another lipolytic milk enzyme is similar to the activity of pancreatic lipase, breaking down triglycerides to free fatty acids & glycerol. This enzyme is present in the fat fraction &appears to be inhibited by bile salts .it is responsible for lipolysis of milk refrigerated or frozen for later use. Additional lipases in the skim milk fraction are in active until they encounter bile. These lipases are believed to be present only in the milk or primates &are though to complement the digestive activity of pancreatic lipase.
Since the bile salt stimulated lipases. Have been clearly shown to be stable &active in the intestine of infants. They can contribute signification to hydrolysis of milk triglycerides &partly account for the grater eases in fat digestion that is commonly demonstrated by breast-fed-babies. carnitine
It plays an important role in the oxidation of long-chin fatty acids by facilitating their transport across the mitochondrial membranes .it also helps regulate thermogenesis is brown adipose tissue & together with malonyl- coenzyme A in the initiation of ketogenesis .the body supply of carnitiine in part by ingestion of dietary carnitine & in part by endogenous synthesis from the essential amino acids lysine & methionine.
Newborns are especially in need of carnitine since providing fat a major source of energy.
Carbohydrates
Lactose is the main carbohydrate in human milk &for long time it was considered to be the only one present. Chromatographic processing of human milk samples, however
8

has revealed trace amount of glucose, galactose, glucosamines,& other nitrogencontaining oligosaccharides. Normal infants are able to digest lactose, it develops more slowly in some infants than previously suspected, undigested lactose moves into the lower bowel, when bacterial fermentation of the available sugars take place with liberation of measurable hydrogen gas. &Not associated with diarrhea or impaired growth.
Minerals
They are potassium, calcium, phosphorus, chloride, sodium, iron, copper, &manganese are found in only trace amounts. Since these elements are required for normal red cell synthesis infants fed too long an milk alone may become anemic. Minute amount of zinc, magnesium ,aluminium , iodine ,chromium ,selenium, and fluorine are also found in breast milk .Infants who are provided with fluoridated water in addition to breast milk may benefit from a daily oral fluoride supplement or regulated dosage predetermined by the physician & pharmacists.
Vitamins
The amount of biologically active vitamin D in human milk has been found to be low
(40-50 IV/L). 25-hydroxyvitamin D3 account for about 75% with vitamin D2& D3.
Milk is good source of vit. A and it is present as retinol, retinyl esters and beta carotene
. Also human milk contain vit. E,vit K which produced by intestinal flora .in addition it contain vit.C water soluble vitamins.
Resistance factors:
Human milk contains resistance factors to be described in human milk was the bifidus factor, which may be a nitrogen containing polysaccharide that favors the growth, of
(lactobacillus bifidus). It uniquenes to human milk has recently been confirmed.
L.bifidus confer a protective affect against invasive enteropathogenic organisms. This results from the accumulation of bacterial metabolites, among them short chain fatty acid, which create an intestinal milieu antagonistic to invasive enteric bacteria and protozoa. The striking resistance of breast fed infants to colonization by coliforms,
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enteropathogenic (Esherichia coli), (shigella species) &protozoa, even in environment in which the risk infection is high has been conclusively demonstrated in rural settings.
*Various immunloglobulines are present in human milk in human milk, including IgM,
IgA, IgG, and IgE. Although IgG appears to migrate from maternal serum into milk, evidance suggests that IgA, IgD and IgE be produced locally in mammary tissue. A variety of studies support the idea of migration of lymphoblasts from maternal gut associated lymphoid tissue to the mammary glands followed by local production of immunoglobuilnes at this site and secretion of them into the milk. This mechanism allows for maternal lymphoblasts to obtaine antigenic exposure from distant sites and carry this experience to the mammary tissu , where synthsis of appropriate antibodies can occur for protection of the sucking infant .
Hormones:
The presence of hormones in human milk was described many years ago but only lately have methodologic advance allowed for through research in this area . some have been found to be absorbed from the GIT, but their true physiological significance for the infant is largely unknown . However, a variety of growth factors have been identified in human milk; they are believed to be of significance in, among other things, inducing maturation of the gut. Much more remains to be learned about these non-nutritional components of human milk and their impact on health and development of the infant.
* hypothalamo-hypophseal hormones : prolactin , somatostatine, melatonin , oxytocin
, growth hormone releasing factor , gonadotropine –releasing factor , thyrotropin – releasing factor , thyroid – stimulating hormone .
*Thyroid gland hormones: T3 , T4, and calcitonin.
*Adrenal gland hormones.
* Sexual gland hormones: estrogen
*Pancreatic hormones: insulin.
*Epidermal growth factor.
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*Other hormones and homone like substances: erythropoietin , bombesin , neurotensin , vasoactive intestinal piptide , pG ,nucleotiddes .
Contaminants:
The lactating women are often exposed to a variety of nonnutritional substances that may be transferred to her milk. Such substances include drugs, environmental pollutant, caffeine, and alcohol and food allergens.
*Although moderate amounts of many these agents are believed to pose no risk to nursing infants, some substances provoke concern because of known or suspected adverse reaction.
Practices interfering with successful lactation
Delay first breast feed Inadequate stimulation of Putting infant to the breast let – down reflex immediately after birth
Excess material anesthesia Weak , unco-ordinated Avoidance of excessive resulting in sedated feeds suckling sedation of the mother
Supplying prelacted glucose Weakening of the stimulus avoidance feeds
The rigid 4 hrs routine of Confused mother resulting Frequent on demand feeding with no night feeds in anxiety , and a hungry fretful baby feeding during the day as well as the night
Separation of the infant Suppression of lactation from the mother rooming in
***
Uniformed , unsupported Interference with the let – Preparation of the mother mother down reflex for lactation during pregnancy and counseling from lactation (advisers) with emotional support in
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puerperium
Excessive use of instrument Suppression of lactation of delivery ( pain and anesthesia) avoidance
Unsympathetic , in Anxiety and frustration in Adequately trained staff experienced staff the mother skilled in the management of breast – feeding
Section 11 DRUGS
**Much research has focused on the release of drugs into the milk of lactating women.
Whether the mother drinks it, eats it, sniffs it, inserts it as an anal or vaginal suppository, or injects it , some level of the active agents in the drug enters the maternal tissue and blood a, finally migrates to the breast milk . The difference in the method of administration determines the amount of drug that finally enters the blood and the speed with which it research the capillaries of the breast. In general the amount of drug excreted in milk is not more than 1% to 2% of the maternal dose.
Mechanism of passage drugs into breast milk:
Drugs pass into milk by simple diffusion, carrier – mediated diffusion, or active transport. A summary of the steps in the passage of drugs into breast milk was developed as follows:
1* mammary alveolar epithelium represents lipid barrier with water – filled pores and is most permeable for drugs during the colostral phase of milk secretion (first week postpartum).
2* drugs excretion into milk depends on the drugs degree of ionization, molecular weight, solubility in fat and water, and relation of PH plasma (7.4) to PH of milk (7,0).
3* drugs preferably enter mammary cells basely in the un – ionized, non – protein bound from by diffusion or active transport.
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4* water – soluble drugs of molecular weight below 200 pass through water – filled membrane pores.
5* drugs leave mammary alveolar cells apically by diffusion, active transport, a porcine secretion.
6* drugs may enter milk via spaces between mammary alveolar cells.
7* most ingested drugs appear in milk. Drugs levels in milk usually not exceed 1 % of ingested dosage and are independent of milk volume.
8* drugs metabolizing capacity mammary epithelium is not understood.
**Although concern exists about the amount of a given drug in the breast milk, of grater concern is the amount that actually reaches the infant’s blood stream.
Unfortunately, there is no accurate way to measure this because other factors also affect the level in the in the infant blood stream. The tolerance of the chemical to the PH of the stomach and the enzymatic activity of the intestinal tract is significance. The volume of milk consumed by the infant is a factor as well.
**Many pharmacological agents transferred into human breast milk and their possible effects on the infant or on lactation. The impact of a number of drug on infant well – being is unknown; physicians who encounter adverse effects in breast fed infants due to exposure to drugs are urged to document the American academy of pediatrics (statement about transfer of drugs in breast milk).
Suppression of lactation:
▪ Engorgement of the breasts and galactorrhea (excessive or in appropriate milk secretion can be inhibited by oestrogens , which act by suppressing prolactin release , however , when used to suppress lactation in mothers who do not breast – feed their babies . the use of oestrogens stimulates the already hypertrophied puerperal endometrium . and if the oestrogen treatment is terminated too rapidly there may be massive withdrawal bleeding
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* Recently the drug bromocriptine has been introduced for the suppression of galactorrhea: it has a dopaminomimetic action in the hypothalamus. Therapy suppressing prolactin release. levodopa has a similar effect which is mediated by the dopaimne produced from it in central dopaminergic neurons .
Drugs producing gynaecomastia :
* gynaecomastia is the excessive development of the rudimentary mammary glands of the male . This effect can be produced by oestrogens and occurs transiently in the newborn, being induced by placental oestrogens. gynaecomastia tends to occur in eunuchs . suggisting that androgens suppress mammary development , and also occurs in men treated with the anti – androgen. In disorders of the testes involving the interstitial cells, such as tumors, or hyperplasia induced by chronic gonadotrophin , oestrogens , may be produced and induce gynaecomastia ; exogenous oestrogen have the same effect
; they may be taken for example in the treatment of acne . Carcinoma or to lower the blood cholesterol.
* gynaecomastia may occur in chronic liver disease , the effect being attributed to altered metabolism of steroid hormones and may also occur during recovery from a period of malnutrition .
* Drugs that have been reported to cause gynaecomastia , but which do not affect the female breast except occasionally in postmenopausal women include digitalis leaf and cardiac glycosides , spironolactone , ethionamide and griseofulvin .
* The cardiac glycosides and spirnolactone resemble the sex hormones in having a steroid nucleus and a similar chemical relationship .can also be made out for griseofulvin
. it is postulated therefore that these drugs may mimic the action of oestrogens in stimulating mammary development . Alternatively, they may block a suppressant action of androgens. ehinoamide may act in a more indirect way by interfering with steriodogenesis or hepatic metabolism of steroid . mammotrophic drugs :
* A number of drugs produce gynaecomastia and also produce breast enlargment and galactorrhoea in women. These drugs include reserpine , metheyl dopa and α – methyl tyrosine and neuroleptic phenthiazines .
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* The effect of these drugs is attributed to distribution of a dopaminrgic mechanism in the hypothalamus through which prolactin release is normally inhibited, the mammotrophic side – effect is therefore mediated by prolactin . clomiphene may produce galactorrhea in women and presumably acts by blocking the inhibitory effect of oesteroidal on milk secretion .
DRUGS THAT ARE C.I DURING BREAST FEEDING OR THAT
WARRANT TEMPORARY CESSATION OF BREAST FEEDING: drug action bromociptine cocaine cyclophosphamide
Cyclosporine doxorubin ergotamine lithium methotrexate phenindion
Suppress lactation
Cocaine intoxication
Possible immunosupression; unknown effect on growth or associated with carcinogenesis; neutropenia.
Similar to cyclophsphamide.
Similar to cyclophosphamide
Vomiting , diarrhea , convulsion , (doses used in migraine medication)
1/3 to ½ therapeutic blood concentration in infants
Similar to cyclophosphamide
Anticoagulant; increased prothrombin and partial thromboplastine
Time in one infant.
Phencyclindine
(pcp)
Potent hallucinogen
Drugs of abuse that are contra indication during breast feeding: drug action
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amphetamine cocaine
Irritability , poor sleep pattern
Cocaine intoxication heroin marijuana phencyclidine
Nicotine (smoking)
****
Only one report in literature ; no effect mentioned
Potent hallucinogen
Shock, vomiting, diarrhea rapid H.R., restlessness, decreased milk production.
Some drugs appear in human milk in sufficient quantities to be harmful to the infant.
Sedatives used to relieve tension may produce drowsiness in the baby as well as in the mother.
Several anticoagulants may cause bleeding problems in nursing infants. The use of large doses of aspirin by the mother can also have such an effect. These risks are greater if there is inadequate intake of vitamin K.
Valium residual in mother’s milk induces lethargy in breast-fed babies.
Lithium carbonate, a drug prescribed for relief of manic depression, may induce lowered body temperature, loss of muscle tone and bluish skin in the nursing infant. cyclophosphamine and methotrexate cause bone marrow depression when ingested by infants . A variety of disorders follow intake by infants of breast milk contaminated with antimicrobial agents of one kind or another.
Penicillin in breast milk may produce an allergic reaction in sensitive infants; other antibiotics may produce similar reactions, as well as sleepiness, vomiting, and refusal to eat.
Nalidixic acid and sulphonamides in breast milk have been reported to produce hemolytic anemia in infants.
Radio active thyroid medications, may damage the thyroid gland. Bowel problems in infants.
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Some laxatives lead to bowel problems in infants may results from maternal consumption of some laxatives (e.g anthraquinone, aloes, cascara, emodine and rheum; safe laxatives include magnesia, castor oil, mineral oil, bisacody;, senna phenolphathalein, or nonprescription EX-lax , fecal softeners .
Heroine or painkiller dextroprophene (Darvon) can lead to infant addiction.
Alcohol inhibits the milk ejection reflex in a- dose dependant fashion , with singal dose over 2 g/kg completely blocking sucking-induced oxytocin release .
*** If a mother needs a specific medication and the hazards to the infant are believed to be small, the following important adjustments can be made to decrease
the effects :
1* do not use the long – acting form of the drug because then the mother does in excreting these agents, which usually require detoxification in the liver. Accumulation in the infant is then a genuine concern.
2* schedual the doses so the least amount gets into the milk. Given the usual absorption rates and peak blood level of the most drugs, having the mother take the medication immediately after breastfeeding is the safest time for the infant.
3* watch the infant for any unusual signs or symptoms such as change in feeding pattern or sleeping habits, fussiness, or rash.
4* when possible, choose the drug that produces the lowest level of the drug in the milk.
:
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**
Tetracycline is a broad – spectrum antibiotics. It is frequently used in treatment of respiratory tract infection, acne and other infection.
* The drug is usually administered orally in a dose of 1000- 2000 mg/d.
* Risk related to breast-feeding:
* Tetracycline is excreted into breast milk in low concentration based on data from six lactating women, the amount of tetracycline that a nursing infant would be expected to ingest is approximately 1% of the lowest therputice dose on weight –adjusted basis.
* Tooth staining caused by a tetracycline in breast milk has not been reported. Milk calcium apparently inhibits absorption of the small amounts of tetracycline in the milk.
Infant absorption and plasma concentration has not been reported with other tetracycline. But infants would only receive a few milligrams per day of demeclocylline
, doxycyclline , or more minocycline with with usual maternal dosages . doxycyclline concentration in milk progressively increase of duration of therapy in one study – although other drugs are preferred for most infections , tetracycline can be used for short time (7 – 14) days; avoid prolonged or repeat courses during nursing. minocycline has caused black milk .
* Tetracycline is contra indication in breast-feeding.
Usual adult dosage range : 250 to 500 milligram every 6 hrs, or 500 to 1000 mg every 12 hrs. The total daily dose should not exceed 4000 mg.
Possible side effects : (natural expected, and unavoidable drug action) super infection , often due to yeast organisms .these can occur in month , intestinal tract , rectum , resulting in vaginal and rectal itching .
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Penicillin appear in trace amounts in milk that can occasionally lead to allergic sensitization, allergic reaction in previously sensitized infants, or disruption of the GI flora, especially with the broader – spectrum agents. Unless the infant is allergic to penicillin, breast-feeding is generally safe with penicillin. Observe infants for diarrhea, rashes, and thrush.
sulfisoxazole is effective anti microbial against susceptible bacteria and protozoa . By interfering with their formation of folic acid , an essential nutrient .
* Some sulfonamide may cause the risk of kermicternus in neonatal haemolysis especially in G6PD deficient infant.
* sulfamethoxazole , with or without trimethoprim , and sulfisoxazole can be used mothers of healthy , full term infants over two months of age
Usual adult dose: initially 2 to 4 grams; then 750 to 1500 mg every 4 hrs, the total daily dose should not exceed 12 grams.
Possible side effect : brownish coloration of the urine, super infection, bacterial or fungal.
chloramphenicol is very effective treatment of infection due to susceptible micro organisms by interfering with their formation of essential proteins .
* Breast-feeding is contra indication during maternal chloramphenicol treatment. Milk concentration are not sufficient to induce ((gray baby)) syndrome, but theoretically may be enough to cause the rare; idiosyncratic a plastic anemia. Adverse reaction in infant, including refusal of the breast falling a sleep during feeding, and vomiting after feeding, has occurred.
* Use another antibiotics, may cause bone – marrow toxicity in infant, concentration in milk usually insufficient to cause ((gray baby)).
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clindamycin is effective treatment for serious infections of the lower respiratory tract , abdominal cavity , gental tract in women , blood stream (septicema ) , skin and related tissues .caused by susceptible organisms combination treatment of pneumocystis carini pneumonia effective for the local treatment of acne .
* clindamycin is excreted variably in small amounts into milk . It is not certain what effects these amounts may have on infants, GI flora (e.g pseudomembranous colitis), but a singal case of bloody stools in an infant with normal stool flora was reported during maternal clindamycin use. clindamycin is best avoided if possible , but a few days of therapy with close monitoring of the infant is acceptable . Vaginal clindamycin presents less infant risk than oral or I.V use.
* clindamycin , amount probably two small to be harmful but bloody diarrhea reported in one infant .
metronidazole is effective treatment for trichomones infection , amebic dysentery and giardasis , and some anaerobic bacterial interacting with DNA ,this drug destroy essential components (nucleus) that are needed for life and growth of infecting organism .
* Both metronidazole and its hydroxy metabolite are found in the plasma of nursing infants concentration that are 10-20 % of maternal plasma concentaration anecodotal cases of diarrhea and isolation of candida species from breast – fed infants have been reported, but most infants do not have immediate reactions. Because of the carcinogenicity in animals, possible mutagenicity , and the relatively high infant plasma concentration achieved , metronidazole should probably be avoied in nursing mothers . when essential to treat trichomoniasis , metronidazoe may be given as a single 2 g dose
,and alternative feeding , nursing can resume 12 – 24 hr after the final dose .
* furazolidone , which is poorly absorbed orally , can be used to treat maternal giardiasis if the infant is over 1 month of age .
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cephalosporins appear in trace amounts in milk and can lead to distruption of the GI flora , or rarely allergic sensitization .
* Breast feeding is safe with first and second generation cephalosporins . The risk may be greater with the third generation cephalosporins (e.g: aztreonam and moxalactam ) that are more active against GI flora . Observe infants for diarrhea, thrush, and rash .
erthromycin
Antimicrobial vancomycin ciprofloxacin
Clofazimine
Sulfones
Antimicrobial antimicrobial
Antimyobacteria
Antimyobacterial
Excreted into milk in amounts much smaller than a typical infant dosage and is safe
Orally , it is not absorbed so excreted in small amount in milk so safer during nursing
Appears to have caused pseudomembranous colitis in a breast – fed infant via breast milk
It causes coloring the milk (bright pink ) breast fed infant can develop the typical skin discoloration and the skin discoloration returned normal 5 months after the end of maternal therapy in one infant
Amantadine antiviral
New borns and G6PD deficient infants are particularly susceptible to dapsone hemolysis . older infants may tolerate the amounts of sulfones excreted into milk
It is DA agonist that decreases serum prolactin .
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Aluminum, calcium, and magnesium antacids are partially absorbed; they are unlikely to appreciably increase concentration of the milk and are safe to use.
cimitidine is used to treat duodenal and other conditions in which stomach produces excess hydrochloric acids. It acts by blocking histamine release., and by doing this the ability of the stomach to make acid is decreased , the body is able to heal itself . ulcers which are resistant to healing have now been shown to have an infectious component ( helicobacter pylori ) , and antibiotics combined with a histamine H2 blocking drug can work .
* Benign gastric and duodenal ulceration, stomach ulcer, reflux oesphagitis , zollenger–
Ellison syndrome , other condition where gastric acid reduction is beneficial.
* Cimitidine is concentrated in milk because of ion tapping and possibly active secretion.
It is taken as single dose at bedtime with avoidance of night feeding.
Usual adult dosage: 300 mg by mouth 4 times daily or 400 mg at bedtime is useful in some patients.
ranitidine
Nazatidine
Famotidine
Similar to cimitidine but lesser extent
Similar to famotidine
Are lesser concentrated in milk and are preferred during nursing
150 mg by mouth twice daily, or 300 at bed time.
300 mg by mouth at bed time.
40 mg by mouth for 4 or up to 8 hrs weeks. Maintenance doses of 20 mg at bedtime have been used.
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omeprazole is very effective treatment of conditions associated with excessive production of gastric acid .
* It works by inhibiting a specific enzyme system (proton pump H/K ATPase ) in the stomach lining , stopping production of stomach acid and therapy (1) eliminates a principle cause of the condition and (2) creates an environment conductive to healing .
Usual adult dose : reflux esophagitis : 20 mg once daily for 4 to 8 weeks .
Excessive stomach acid conditions: 60 mg once daily for as long as necessary.
Gastric and duodenal ulcer: 20 mg once daily for 4 to 8 weeks.
In extreme conditions, doses of 120 mg three times a day have been used.
Possible side effects : acid in the stomach actually works to protect from some bacterial infections. Since omeprazole is so effective in decreasing acid, it may increase the like-lihood of infection by campylobacter . This organism causes gastroenteritis.
Symptoms may include mucousy, loose stools and fever.
* In one mother milk levels were low and her newborn breastfeed without harm.
Because sucralfate is virtually non -absorbable, it may be preferred to H2 receptor antagonists.
Usual adult dosage range: 1 gram 4 times / day
Possible side effects: constipation.
Non absorbable products such as kaolin – pectine are preferred in nursing mothers .
It is an effective relief of intestinal cramping and diarrhea. it acts directly on the nerve supply of the gastrointestinal tract , decreases secretions and helps relieve cramping and diarrhea .
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Usual adult dosage range : for acute diarrhea 4 mg initially, then 2 mg after each unformed stool until diarrhea is collected for chronic diarrhea 4 to 8 mg / day in divided dose .
Possible side effects: drowsiness, constipation.
* prodrug lopramide oxide results in only small amounts of loperamide in breast milk. diphenoxylate .
It is effective treatment for of nocturnal heartburn little central nervous side effects
.it acts by increasing the movement of the esophagus (by activating a specific muscarnic receptor).
Possible side effects : sleepiness and fatigue.
Usual adult dosage range: 10 mg four times daily, given 15 minutes before meals and at bed time.
* Milk cisapride concentrations are low, but its effects on maternal prolactin or infants are not known.
It is an effective stomach stimulant for correcting delayed emptying. This drug inhibits relaxation of the stomach and enhances the stimulation of the parasympathetic nervous system that is responsible for stomach muscle contractions.
This action accelerates emptying of the stomach into the intestine.
Usual adult dosage : 10 mg taken 30 minutes before breakfast, lunch and dinner and at bedtime .the total daily dose should not exceed 0.5 mg per kg of body weight.
Possible side effects; drowsiness and lethargy breast tenderness and swelling milk production.
*Metoclopramide elevates serum prolactin via central dopaminergic antagonism and results in increased milk production and amore rapid transition from clostrum to mature milk. It may be used theraputically in mothers who are producing insufficient quantities of milk, such as the mothers of premature or sick infant, or adoptive
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mothers. hoever , metlocropamide may induce or worsen depression , so caution is warranted . Although infant dosages of metlocropamide from milk are low, the infant’s serum prolactin concentrations may sometimes be elevated. Limiting the duration of metoclpramide therapy to 14 days is essential.
Some anthraquinone derivatives, such as aloe, cascara, and other stimulant cathartics ( e.g phenolphathalein ) , shoul be avoided during nursing because of laxatives effect in breast fed infants . Laxatives that are not non absorbable or poorly absorbed, such as bulk – forming (e.g psyllium ) , osmotic ( e.g magnesium or phosphate salts ) or sttol softing ( e.g docusate ) types , are preferred during lactation , senna in moderate dosages is acceptable if other measures fail . bisacodyl is virtually unabsorbed from the GIT and should be safe .
It is an effective suppression of inflammatory bowel disease , symptomatic relief in treatment of regional enteritis and ulcerative colitis .it suppresses the formation of prostaglandin’s ( and related compounds ) , tissue substances that induces inflammation , tissue destruction and diarrhea .
Usual adult dose: 1 to 2 grams every 6 hrs to 8 hrs until symptoms are adequately controlled. For maintenance, 500 mg / 6 hrs.
Possible side effects : brownish coloration of the urine, of no significance, super infection, bacterial or fungal.
* It has been found in milk and infants plasma after oral use. Larger amounts of its metabolite are found in milk. Diarrhea has occurred in infants of mothers using mesalamine derivatives, which may be used cautiously during nursing with close infant observation.
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It was undetectable in the milk of one lactating mother, and her nursing infant developed normally during therapy.
Ergotamine used to prevent and relief of vascular headaches: migraine , migraine like and antihistamine headaches .
* It acts by constricting the walls of blood vessels in the head, this drug prevents or relives the excessive expansion (dilation) that causes the pain of migraine like headaches.
Usual adult dose : inhalation: 1 spray (0.36) at the onset of head. Ache; repeat 1 spray after 30 minutes for relief, up to maximum of 6 sprays / 24. Sublingual tablet: dissolve 2 mg under tongue at the onset of headache.
Possible side effects: cold hands and feet, with mild numbness and tingling .
* When given daily 6 days postpartum ergotamine did not affect lactation or infant weight in one study; however, the excretion of ergotamine in milk during lactation has not been studied. Avoid its use during lactation, because older ergot preparations have produced toxicity in infants.
It is rapid and effective relief or prevention of migraine, generally well tolerated.
Relieves photophobia (light sensitivity), relives phonophobia (sound sensitivity) and relives nausea and vomiting.
The drug binds to receptor arteries such as the basilar artery and in vasculature
(blood vessels) associated with the dura mater (part of the lining brain).
Usual adult dose : orally 25 mg taken as soon as headache pain starts subcutaneous
6 mg.
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Possible side effects: excessive thirst and frequent urination. Transient rises in blood pressure.
▪ Minimally excreted in milk, sumatriptan has oral absorption by the infant. It poses little risk during breastfeeding.
The amount of acetaaminophen excreted into milk is small . it is good analgesic choice during nursing .
•
Non steroidal anti-inflammatory drugs:
Amounts of most NSAIDs in milk are low because they are weak acids that are extensively plasma protein bound. However, short – acting agents are preferred, particualry in the case of breast – fed neonates. Some agents have active metabolites ( eg sulindac ) or glucuronide metabolites (e.g salicylate , fenoprofen , and ketoprofen ) that can add to infant intake . Because of the increased likeliood of accumulation, avoid long acting agents such as diflunisal , naproxen , piroxicam , and sulindac in mothers of neonates , although amounts of piroxicam in milk are low . The more toxic NSAIDs such as mefanemic acid and indomethacin should also be avoided, although recent studies on indomethacin indicate that it may be contraindication. ketorolac is contraindication during nursing . diclofenac was not detected in milk after signal dose 50 mg IM for one week , and the amount of tolmetin in one women milk was low . Ibuprofen and flubiprofen have the best documentation of safety during breast feeding; the dose of ibuprofen that an infant receive in milk is less than 0.001%of the mothers dosage, and flubiprofen levels are low up undetectable after dosages up to 50 mg td.
It is an effective relief of mild to moderate pain and inflammation, reduction of fever, prevention of blood clots, prevention of heart attack prevention of colon cancer and may act to limit the size and severity of a heart attack once it has started.
* It acts by reducing PG, chemical involved in the production of inflammation and pain.
Usual adult dose: for pain or fever 325 to 650 mg / 4 hrs as needed.
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Possible side effects : mild drowsiness in sensitive individuals.
* salicylates enters milk in low concentration relative to that in plasma , although its glucuronide metabolite increases the overall infant dosages . Dose over 1 g yields markedly higher salycilates concentrations in milk and may result in high infant plasma concentration. The risk of Reye syndrome caused by salicilates in milk is unknown. NSAIDs such as ibuprofen is preferred over aspirin in analgesics doses prabably poses a minimal risk of the infant except for the potential antiplatlet effect. Avoidance of breast-feeding for 1-2 hr after a dose should minimize this effect.
* Neonates are particularly susceptible to narcotics in breast milk. Postpartum maternal opioids (oral codeine or propoxyphene with or without prior IM meperidine ) may be a causative factor in episodes of apnea, Brady cardia, and cyanosis during the first week of life. Avoid maternal narcotics when the breast – fed neonate has experienced such as an episode Although single analgesics doses of most narcotics are excreted into milk in small amount. Infant drowsiness caused by repeated administration of postpartum oral narcotics in milk is more prevalent than commonly though – about 20 % in one study drowsiness is a dose related and can be serve with the maximum dosage. Analgesic can be supplemented with additional acetaminophen or ibuprofen.
Used for effective relief of moderate to sever pain.
* It acts primly as depressant of certain brain functions; these drugs suppressed the perception of pain and calm the emotional response to pain.
Usual adult dose : 50 to 150 mg every 3 to 4 hrs as needed.
Possible side effects: drowsiness, light-headedness, weakness, and euphoria dry mouth, urinary retention and constipation.
* meperidine is particularly likely to interfere with infant nursing behavior when given during labor . Further more, repeated postpartum meperidine doses, including patient – controlled analgesia, cause diminished alterness and orientation in breast – fed neonates compared with equivalent doses of morphine. meperidine is best
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avoided during labor and nursing , although a single small dose for anesthesia or conscious sedation may not cause problems in older breast feeding infants .
Used for effective treatment of moderate to sever pain.
* Usual adult dose: injection 5 to 20 mg every 4 hrs, by mouth 10 to 30 mg every 4
* Morphine 10 to 15 mg in a single parental doses produces only low concentration in milk, but are repeated doses may result in drug accumulation in infant plasma to near therapeutic concentrations. Morphine glucuronides in milk contribute an additional 50 to 100 % to the infant dose via deconjugation in the infants gut to the active drug epidural administration and patient – controlled analgesia cause fewer infant effects than IV administration and are preferred.
Fentanyl and sufentanil buprenophine
Produce low milk level and they have poor oral biavalibility so, good during nursing
It is narcotic partial agonists and it causes decreases in milk production and infant weight.
It indicates that infants may receive relatively large amounts of the drug and its active metabolite, with plasma concentrations near the therapeutic range.
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* Disopyramide may be used cautiously during lactation when other alternatives are unacceptable. Observe the infant for anticholinergic symptoms, and monitor infant plasma concentration if there is a concern.
Lidocaine concentrations in milk during continuo IV infusion and as a local anaesthetic are low and poorly absorbed by the infant, so it poses no hazard to infant.
Drugs tocainide
N-acetyl procinamde digoxin
Comments
It concentrated in milk so used with caution
Concentrated in small amount
Infant receive trivial doses of digoxin via breast milk
Milk concentrations of clonidine are much higher than maternal plasma concentrations and breast – fed infants have plasma concentrations approaching those of mother. And it decreases the prolactin secretion.
reserpine must be avoided , because it causes nasal stuffiness and increased tracheobroncial secretions in infant .
Drug comment
ACEI(captopril) Found in small amount and no adverse effect
Hydralazine and methyl dopa Safe
The most water-soluble drugs reach the infant in the greatest amounts because of low plasma protein binding. Additionally they have the longest half- life, are renal eliminated, and are therefore more likely to accumulate in infant.
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They have intermediate excretion, and they should be avoided during the early neonate period.
They have adverse effects (bradycardia, hypotension, tachycardia, and cyanosis) in breast – fed infant.
They are excreted in low enough quantities to allow nursing even in the neonatal period.
All calcium channel blockers are excreted in small amount into milk, like verapamil, nifedipine,diltiazem .verapamil and norverapamil appears to be safe during nursing .
* Breast – fed may achieve plasma anticonvulsant concentrations that produce pharmacological effect; mild drowsiness, irritability , and feeding difficulties are common in the infants of mothers taking anticonvulsants , especially during the early neonatal period. Breast-feeding can mitigate withdrawal symptoms in infants whose mothers took anticonvulsants during pregnancy, and withdrawal symptoms have been observed after adrupt weaning. Plasma concentration monitoring in breast – fed infants may be indicated, particularly in infants who are excessively drowsy, feed poorly or gain weight inadequately . Long – term effects of exposure are not well studied.
Infants of mothers taking anticonvulsants may have more difficulty nursing and may breast – feed for a short duration.
* It is used to relief pain in trigeminal neuralgia. And for effective control of certain types of epilpetic seizuers .
Usual adult dose : 200mg /12hours
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*Both carbamazepine and its major active metabolite are excreted into milk and can be detected in nursing infants, plasma concentrations are usually low, but near the therapeutic range in some infants. Two cases of hepatic dysfunction in breast – fed neonates have been reported. carbamazepine can be used during lactation , but close observation of the infant for jaundice and other signs of possible adverse idiosyncratic effects is advisable . Measurement of infant plasma concentration may be indicated if symptoms occur.
Only small amounts of phenytoin are excreted into milk. Infant may experience idiosyncratic reactions such as cyanosis and methemoglobinemia, but infants generally tolerate phenytion in milk well.
Tricyclic antidepressant is acceptable. Follow up for 1-3yr in small group of breast – fed infants indicates no adverse effects on growth and development. Respiratory depression was reported in one breast – fed infant whose mother was taking doxepine
250mg tide.
In combination with chlorpramazine lead to detoriation of mental and psychomotor development scores over the first 12-18 month of life.
Lead to sedation in one and granulocytosis in another, which resolved upon discontinuation. Nursing is not recommended during clozapine.
These drugs may stimulate metabolism of endogenous compounds in the infant when small amounts pass into milk. Short acting agents are preferable to long acting agents,
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because smaller amounts are excreted into milk. Large single dose may have more potential for causing infant drowsiness than multiple small doses.
Long acting can accumulate and cause adverse effect in infant, because of their immature excretory mechanism. A single dose of diazepam for short dental, surgical, or diagnostic procedure is not likely to cause sedation in infants past the neonatal period. Milk apralozam levels are low, but infant drowsiness and withdrawal symptoms have been reported with alprazolam use during nursing. When oral therapy is essential.
Lithium in milk can adversely affect the infant when its elimination is impaired, as in dehydration or in neonates or premature infants. Neonates may also have transplacentally acquired plasma lithium levels. The long-term effects of lithium on infants are not known; many authors consider lithium therapy a contraindication to breastfeeding but other does not. Lithium may be used cautiously in mothers who are carefully selected for their ability to monitor their full –term infants. Discontinue breastfeeding immediately if the infant appears restless or looks ill. Measurement of plasma lithium concentrations in the infant can also help rule out lithium toxicity.
Some ergot alkaloids have dopaminergic activity can suppress prolactine release and lactation. bromocriptine was used therapeutically for this purpose .
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Prednisone and prednisolone methlprednisolone
Beclomethasone
Excretion in milk is low even in large dose safe
Depot injections no risk because of low maternal plasma concentration
Diabetic mother using insulin may nurse their infants. However, it has been empirically found that mother may need to reduce her insulin dosage to about 75% of the pregnancy dosage.
Tolbutamide is excreted in milk in small amounts that should cause no harm.
Inorganic iodide is contraindicated during breast-feeding, because of possible thyroid suppression and rash. Topical and vaginal povidone-iodine in nursing mother’s results in elevated milk iodine concentrations and occasional thyroid suppression in nursing infant. So avoided during nursing.
is a drug of choice during lactation.
It passes into milk in greater quantities and has longer half-life than propylthiouracil; thus they are less desirable alternatives. A potential for idiosyncratic reaction and hypothyrodism exists and measurement of the infant serum thyrotoxine and TSH concentrations at 2-4 week intervals is prudent during maternal antithyroid drug
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Normal lactation requires thyroid hormones. Levothrotoxine (T4) pass into milk poorly, although liothyronine (T3) may pass in more physiologically relevant amount. Milk concentration of thyroid hormones have not been measured after exogenous administration, but a physiologic replacement doses of levothyrotoxine to a breast feeding mother is not expected to result in excessive thyroid administration to the infant. Replacement therapy with liothironine maternal levothyroxine dosage may transfer larger amounts of liothyronine to the infant.
It is thyrotropin – releasing hormones (TRH) causes an increasing in prolactin secretion and may enhance milk yield.
Ergonovine Lower postpartum serum prolactin concentrations
Not found in milk Methylergonovine
Low dose regimens of these agents immediately postpartum pose no hazard to the infant, but methylergonovine is preferred.
Calcitriol requirements in hypoparathyroid women decrease during lactation. Failure to substantially decrease the calctriol dosage results in maternal hypercalcemia .
Furosemide and hydrochlorothiazide can suppress lactation and may also accumulate in infant’s plasma.
Magnesium sulfate when given IV, it increases magnesium concentration in milk.
Difficulty in establishing milk supply by the mother and difficulty in nursing by the
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infant are sometimes observed after mothers have received magnesium sulfate infusions for the treatment of pre-eclampsia or eclampsia.
It may cause irritability and fretful sleep in infants. Newborn infants are mostly likely to be affected because of their slow elimination and low plasma protein binding of thiophylline. No need to avoid thiophylline but keeping maternal plasma concentration in the lower part of therapeutic range and measure infant plasma concentration.
Nursing infant readily metabolizes them. Rare case reports of breast enlargement in infants and proliferation of the vaginal epithelium in female infants have been attributed to combination oral contraceptives. These effects occur primly with products containing >50 mg of estrogen. These high estrogen contraceptives also markedly suppress lactation, especially when administered immediately postpartum. When currently available low dose estrogen – progestine combination contraceptives are begun 6 or more weeks postpartum. Long term negative effects on milk yield lead to early feeding supplementation and discontinuation of breastfeeding. Also may lead to decrease infant growth. An 8 year follow up of breast – fed infants of mothers taking contraceptives containing ethinyl estradiol 50 mg found no adverse effect on the infant development.
Progestin contraceptives like levenorgesrel implants, depot medroxyprogesterone acetate, or oral norethindrone have no effect on, or enhance, milk supply and may
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extend the duration of lactation. Although infant growth may undergo a slight, transit depression after insertion of levonogestral implants. Early initiation of these agents is controversial. Because physiologic postpartum progesterone withdrawal is primly stimulus for lactation, it appears best to wait for 3 days postpartum before starting aprogestin – only contraceptives.
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There is no doubt that breastfeeding is best for both mothers and baby. To encourage more mothers to breast-feed their infants, we must be prepared to support mothers with education and practical information. These require those health care professionals and understand the process of lactation, as well as the cultural differences that affect a woman’s decision to breast-feed. The mother’s nutritional requirements must be adapted to the foods easily available and culturally acceptable to her. Free and low cost promotional materials need to be identified and used. Hospital and clinic staff also needs to be thought to promote breastfeeding and support families who make this choice.
* Mothers who breast-feed have a special and unique relationship with their baby, and may say how much pleasure being able to nourish food and comfort their offspring brings. Breast milk is the natural food for babies. Breast-feeding is also convenient and cheap and protects a baby against some illness. It isn’t without problems, but virtually all of these can be prevented or over come. The problem most often experienced with breast-feeding is insufficient milk, which is a shame because it is preventable problem.
* Breast feeding works as demand and supply babies the more time the baby spends at the breast, the more milk is made.
General Health Care:
Looking after a child is perhaps the most important in the world. In most instances our own experience, intuition, imagination and sensitivity equip as perfectly well to carry out this care and it helps if we have confidence to listen and learn from ourselves and our children. But we also need the wisdom to learn from others and to know how and when to ask for help in the form of encouragement, emotional support , advice , or practical assistance is desirable or even downright necessary .
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Caring For Growing Child :
Once your baby is born its important to take advantages of the routine tests and development assessments after by your family, doctor, and health visitor or clinic doctor. These away of screening thousands of normal, healthy children in order to pick up problems in a few. The early detection of many problems can save both your child and you from unnecessary suffering or worry in the future. One such test is the guthrie test, used soon after birth to detect the rare genetic disorder, phenylketonuria . It involves making a tiny pinprick on your baby’s heel and taking a few drops of blood for testing.
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References:
*Nutrition in pregnancy and lactation.
*The effects of drugs on the fetus and nursing infant.
*Pregnancy and children (nicky wesson).
*The complete guide to child health ((DR. penny stanway)).
*Basic and clinical endocinology ((fracis S. greenpan and peter H. forsham)).
*Text book of pharmacology ((wc bowman / MJ Rand )).
*Nutrition in mother and child health
*The essential guide to prescription drugs ((James J rybacki, Pharm. D. and James w. long, M.D.))
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