Post on 07-May-2015
임신과 관련된 위장관 질환
내 과 정 성 훈
Clinicians treating a pregnant woman
Differentiate symptoms that are normal during pregnancy vs. serious disorders
Disorder and Pregnancy Safe evaluation tools Risk of disease against risk of treatment Safely treat without causing adverse effects
on mother or fetus
United States FDA Pharmaceutical Pregnancy Categories
Category A 인체를 대상으로 한 연구에서 임신 초기 태아에 대해 위험을 증명할 수 없는 경우 ( 임신 말기에도 위험의 증거가 없는 경우 ) 로서 태아에 해를 주는 것과 거리가 먼 경우
Category B 동물실험에서 태아에 대한 위험이 나타나지 않았거나 , 인체를 대상으로 확실하게 증명되지 않은 경우 . 동물실험에서 유해한 영향을 나타냈으나 , 임신 초기의 여성에서 증명이 안된 경우 ( 임신 말기 위험의 증거는 없음 )
Category C 동물실험에서 태아에 대한 유해한 영향 ( 기형 , 태아사망 등 ) 을 나타냈으나 인체에 대한 실험결과가 없는 약물 , 또는 인체나 동물에 있어서의 연구가 아직 없는 약물 ( 태아에 대한 위험성보다 엄마 몸에 대한 유익성이 클 경우에만 사용 )
Category D 태아에 대한 위험이 증명되었으나 산모에 사용함으로써 얻는 이익이 태아에 대한 위험보다 큰 경우 ( 임부의 생명이 위급한 경우나 다른 약물로 효과가 없는 경우에만 부득이하게 사용 )
Category X 인체와 동물 모두에서 태아의 기형이 증명된 약물 ( 임산부 , 가임 여성에게 금기 )
Contents
Diagnostic tools GI motility disorders
Nausea and vomiting Hyperemesis gravidarum Constipation Diarrhea GERD
Peptic ulcer disease Inflammatory bowel disease
Diagnostic Testing in Preg-nancy Radiologic and related studies
• Cell death• Teratogenic effects• Carcinogenesis• Genetic effects
• Missed diagnosis• Unnecessary elective abortion
Fetal risk of anomalies, growth re-striction, or abortion is not increased with radiation exposure of less than 5 Rad(50mGy).
Estimated Conceptus Dose
US / MRI better alternatives
Radioactive iodine contraindicated during pregnancy
MRI should be avoided in the 1st trimester
X-Ray/CT US/MRI
Gastrointestinal Endoscopy
Risk of Endoscopy to the Fetus
Risk Precipitating factor
Hypoxia Oversedation
Hypoperfusion Maternal positioning, arrhythmia, epinephrine use, maternal status
Teratogenensis Medication, radiation exposure
Uterine trauma Endoscopic trauma, abdominal compression techniques
Premature labor Uterine trauma, uterine compression
Risk of Endoscopy to the Mother
Risk Precipitating factor
Aspiration Abdominal distension
Hypotension IVC compression, anemia
Delayed diagnosis and treatment
Reluctance to employ tests and proce-dures, concern regarding administra-tion of medications, difficulty examin-ing abdomen, atypical presentation
Bowel and uterine trauma Distorted anatomy resulting from gravid uterus
Indications for Upper Endoscopy in Pregnancy
Indication
Significant or unremitting gastointestinal bleeding
Dysphagia or odynophagia
Severe or refractory abdominal pain
Severe or refractory nausea and vomiting
Feeding tube placement
Contraindication to Endoscopic Procedures
Obstetric condition
Imminent delivery
Abruptio placenta
Eclampsia
Summary of Recommendations for the Performance of Endoscopy in Breast-feeding Patients
Recommendation Grade
Breast Feeding may be continued after maternal fentanyl administration
B
Breast Feeding should be withheld for 4 h after midazo-lam administration
B
Continued breast feeding after propofol administration is not recommended, although it is unknown for how long it should be withheld
C
Penicillins, cephalosporins, and erythromycin are compat-ible with breast feeding; avoid quinolones and sulfon-amides
C
Grade B, observational studies; Grade C, expert opinion
Drugs used during En-doscopy
Medication FDA Category
Meperidine B
Fentanyl C
Diazepam D
Midazolam D
Propofol B
Scopolamine(Anticholinergic) C
Lidocaine B
Naloxone B
Flumazenil C
Medications for Endoscopy: Recommendations
Use smallest effective dosages
Involve patients in decisions about potentially fetotoxic drugs
When alternative drugs available, use safest one
Avoid category D drugs
Do not use category X drugs
Avoid optional drugs
Contact pharmacologist or review literature about drug teratogenicity
Consider involvement of anesthesiologist for sedatives
General Endoscopy: Recommendations
Gasatrointestinal Motility Disoders
Nausea and vomiting
Hyperemesis gravidarum
Constipation
Diarrhea
GERD
Nausea and vomiting
Frequent (70~90%)
particularly in 1st trimester
Mild to moderate; physiologically statistically normal
m/c complaints during the 1st 5 months of pregnancy
Symptoms begin by 4~6 weeks, peak in 8~12 weeks and
resolve by 3~4 months
“morning sickness”
Excellent prognosis
Risk factors Younger, obese, women from western cultures
Fewer than 12 years of former education
Women who experience nausea and vomiting while taking oral contraceptives
Corpus luteum in the right ovary
Heaviness of placenta
Nonsmoker
History of nausea in previous pregnancy
History of nausea and vomiting in pt’s mother
Hyperemesis gravidarum
Severe, debilitating condition characterized by vomit-ing severe enough to result in weight loss(>5% of body weight), dehydration, hypokalemia, or acidosis
Up to 2% Exclusion diagnosis
Gastroenteritis
Cholecystitis
Pyelonephritis
Primary hyperparathyroidism
Liver dysfunction
Pathogenesis Estrogen and hCG increase during 1st
trimester Increased progesterone and reduced
motilin levels Gastric dysrhythmia in EGG H. pylori infection
Treatment Supportive therapy Ingestion of multiple small-portion meals
high in carbohydrate and low in fats Antiemetics; backbone Vitamin B6; good alternative psychotherapy
NVP
Nonphamaco-logic
Phamacologic
Dietary change - small, frequent meal - Avoid fatty, spicy, odorous foodsLifestyle modifica-tion - frequent naps - shorten work day
Complemen-tary & alter-native
Drugs
Ginger p.o.Acupres-sure
Pyridoxine –doxylamine
Add antihistamine (Diphenhydramine or meclizine
Add dopamine antag-onist (metoclo-pramide)
IV fluid with vitamin B12On-dansetron
Methylpred-nisolone
MildModerate to severeHG
persistent
Persistent with dehy-dration
persistentpersistent
Persistent without dehy-dration
+
+
Gastroesophageal Reflux Disease
“ 위 내용물의 비정상적인 식도로의 역류로 인한 증상 혹은 점막손상”
30~50% of pregnant women (up to 80%)
Symptoms worse during 3rd trimester and abate soon after delivery
Montreal Classification of GERD
Am J Gastroenterol 2006
Pathogenesis
This high incidence may relate to a hypo-tonic LES and GI dysmotility, attributed to gestational hormones(progesterone) gastric compression by the gravid uterus
Treatment
H2 antagonists gener-ally safe, including 1st trimester
Ironically, majority of studies of PPI safety involve omeprazole
Constipation I
Prevalence 11~38%
Symptoms tend to be worse in the 1st and 3rd
trimester Progesterone affects small intestine and colon
motility and may inhibit motilin release
Motilin(stimulatory GI hormone) decrease
Enlarging uterus physically affect the small
bowel motility
Constipation II
Initial treatment Patient education Reassurance Increased physical activity Increased fluid intake Dietary supplementary of fiber (bran or
wheat fiber)
Diarrhea
When a pregnant woman presents with new-onset diarrhea, a standard evaluation is indicated.
If the diarrhea appears to be mild and nonspecific but sufficiently bothersome to warrant treatment, non-systemically ab-sorbed medications should be tried first.
Peptic Ulcer Dis-ease
True incidence of PUD during pregnancy is unknown, but very low Only 6 cases in 23000 deliveries (Lancet 1969)
Beneficial effect on PUD 혈장의 히스타민 분해효소 증가로 위점막의 히스타민 농도 감소하고 위산 분비
감소 에스트로겐 증가로 위산 분비 억제 프로제스테론 증가로 위점막의 점액 분비 증가 면역학적 내성으로 H. pylori 에 대한 면역학적 공격이나 점막손상 감소 EGF 증가로 위십이지장 점막 성장 촉진 임신중 술 , 담배 , NSAIDS, 스트레스등의 궤양 원인을 피하고 충분한 영양과
휴식 취함
Treatment I
Antacids are generally safe for the fetus, magnesium should be avoided near delivery (retard labor and pos-
sibly cause neurologic depression in the newborn) sodium bicarbonate should be avoided throughout pregnancy(fluid
overload or metabolic alkalosis) Antacids must be administered frequently because of low potency,
and frequent administration can cause diarrhea or constipation and electrolyte or mineral abnormalities.
Sucralfate has minimal systemic absorption, but its aluminum con-tent is of concern to the fetus in mothers with renal insufficiency.
H2 receptor antagonists are useful in treating GERD and PUD when symptoms are more severe or occur later in pregnancy.
Ranitidine and famotidine are preferable because nizatidine is possibly toxic to the fetus, and cimetidine has antiandro-genic effects.
Treatment II
PPI were initially reserved for refractory, severe, or compli-cated GERD and PUD during pregnancy.
Lansoprazole, rabeprazole, and pantoprazole (FDA B) ap-pear to be safer than omeprazole (FDA C), and are there-fore recommended during pregnancy.
Metoclopramide is probably not teratogenic, but frequently causes maternal side effects.
Helicobacter pylori eradication should be deferred until af-ter parturition and lactation because of concern about the fetal safety of administered antibiotics such as clar-ithromycin and metronidazole.
Inflammatory Bowel Disease
The majority of cases of IBD first present in women younger than age 30 years, the years of peak fertility.
IBD may be more common in women than in men; some authors report approximately 30% greater risk
Effects on fertility; controversy Pregnancy rates may be spuriously low because of sexual avoid-
ance and voluntary childlessness. Female fertility itself, however, does not appear to be impaired
by uncomplicated IBD. UC patients treated with total colectomy and IPAA; three-fold in-
crease in the risk of infertility (pelvic adhesions and fallopian tube scarring)
Male fertility is impaired by sulfasalazine treatment, which causes decreased sperm counts that usually return to normal within 6 months of discontinuing the drug.
Effect of IBD on pregnancy
Inactive IBD; minimal effects on the course and outcome of pregnancy
Risk appear to be related to the disease activity rather than to the medication Active, nonfulminant UC combined abortion/stillbirth rate
18~40%, Fulminant UC necessitating surgery ~60% Severe CD necessitating surgery maternal fetal mortality
rates ~60%
There is every reason to strive for remission before concep-tion and to aggressively treat flares medically in order to prevent complications
Effect of pregnancy on IBD
ZS Heetun et al., Aliment Pharmacol Ther 2007;26:513
• Pregnancy does not appear to increase the severity of, or mor-bidity due to, preexisting IBD
• Disease activity prior to conception seems to be the most im-portant factor determining the cause of the illness during ges-tation.
IBD and Breast-Feeding
Oral 5-ASA products or corticosteroids is gener-ally safe (poorly secreted in milk)
Topical mesalamine is probably safe during
breast-feeding
No data about AZT/6-MP, ciprofloxacin, metron-
idazole
MTX and cyclosporine; contraindicated
Treatment
Most experts agree that during gestation affected patients should continue optimized prepregnancy therapy to avoid possible flares resulting from medication withdrawal.
Treatment of fulminant colitis is the same as in nonpreg-nant individuals, namely high-dose glucocorticoids, intra-venous antibiotics, cyclosporine, and salvage biological therapies.
IBD patients are at risk for poor pregnancy outcomes, even if they have mild or inactive disease. Major complications include premature birth, low-birth-weight and small-for-ges-tational-age infants, and increased cesarean section rates.
The risk of fetal malformations in this setting is unclear.
Summary I
The differential diagnosis of gastrointestinal symptoms and signs is particularly extensive during pregnancy. The differ-ential diagnosis includes obstetric, gynecologic, and gas-trointestinal disorders related to pregnancy
Pregnancy can affect the clinical presentation, frequency, or severity of gastrointestinal diseases. For example, GERD markedly increases in frequency, whereas PUD markedly de-creases in frequency (or becomes inactive) during preg-nancy.
Abdominal ultrasound is the most useful imaging modality to evaluate gastrointestinal conditions during pregnancy.
Summary II
EGD and flexible sigmoidoscopy can be performed when strongly indicated during pregnancy, for example, for sig-nificant acute upper and lower gastrointestinal bleeding, respectively.
Most gastrointestinal drugs appear to be relatively safe to the fetus and can be used with caution when strongly indi-cated during pregnancy, especially during the second and third trimesters after organogenesis has occurred (FDA category B and C).
Gastrointestinal drugs to be avoided during pregnancy in-clude misoprostol, which is an abortifacient (category X), methotrexate (category X), 6-mercaptopurine (category D), azathioprine (category D), most chemotherapeutic agents, and certain antibiotics.
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