DRUGS IN PREGNANCY

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DRUGS IN PREGNANCY

  1. 1. www.doctor.sdwww.doctor.sd
  2. 2.  INTRODUCTION:INTRODUCTION:  ONE SHOULD USE A SMALL ARMAMENTARIUM OFONE SHOULD USE A SMALL ARMAMENTARIUM OF DRUGS THAT HAVE A PROVEN VALUE WITH KNOWNDRUGS THAT HAVE A PROVEN VALUE WITH KNOWN AND RECORDED MINIMAL SIDE EFFECTS.AND RECORDED MINIMAL SIDE EFFECTS.  CONSIDER THAT ALL DRUGS MAY AFFECT THECONSIDER THAT ALL DRUGS MAY AFFECT THE FETUS "EXCEPT HEPARIN & INSULIN".FETUS "EXCEPT HEPARIN & INSULIN".  MANY PATIENTS ARE EXPOSED TO ' OVER-THE-MANY PATIENTS ARE EXPOSED TO ' OVER-THE- COUNTER' MEDICINES DURING THE FIRSTCOUNTER' MEDICINES DURING THE FIRST TRIMESTER WITH POTENTIAL RISKS.TRIMESTER WITH POTENTIAL RISKS.  CONSIDER THAT ALL PATIENTS ARE AT RISK OFCONSIDER THAT ALL PATIENTS ARE AT RISK OF PREGNANCY DURING THEIR REPRODUCTIVE YEARS.PREGNANCY DURING THEIR REPRODUCTIVE YEARS.  ALWAYS CONSIDER THE RISK OF THERAPY AGAINSTALWAYS CONSIDER THE RISK OF THERAPY AGAINST THE POTENTIAL FOR NOT TREATING THE DISEASE.THE POTENTIAL FOR NOT TREATING THE DISEASE. [1] www.doctor.sdwww.doctor.sd
  3. 3.  PHARMACOKINETICS:PHARMACOKINETICS:  A) MATERNAL;A) MATERNAL;  1]1] DRUG ABSORPTION-DRUG ABSORPTION- - IS AFFECTED BY PHYSIOLOGICAL- IS AFFECTED BY PHYSIOLOGICAL CHANGES IN PREGNANCY,CHANGES IN PREGNANCY,  ALMOST ALL DRUGS CAN CROSS THE PLACENTA,ALMOST ALL DRUGS CAN CROSS THE PLACENTA,  GASTROINTESTINAL TRANSIT IS PROLONGED DUE TO SLOWGASTROINTESTINAL TRANSIT IS PROLONGED DUE TO SLOW STOMACH EMPTYING.STOMACH EMPTYING.  2]2] DRUG DISTRIBUTION-DRUG DISTRIBUTION-- LIPID SOLUBILITY & PROTEIN- LIPID SOLUBILITY & PROTEIN BINDING AFFECT THE DISTRIBUTION,BINDING AFFECT THE DISTRIBUTION,  PLASMA ALBUMINS FALL DUE TO INCREASED TOTAL BODYPLASMA ALBUMINS FALL DUE TO INCREASED TOTAL BODY WATER & PLASMA VOLUMES.WATER & PLASMA VOLUMES.  3]3] DRUG METABOLISM-DRUG METABOLISM-- WATER-SOLUBLE DRUGS ARE- WATER-SOLUBLE DRUGS ARE ELIMINATED UNCHANGED,LIPID-SOLUBLE ARE METABOLIZEDELIMINATED UNCHANGED,LIPID-SOLUBLE ARE METABOLIZED BY OXIDATION,OR CONJUGATED IN THE LIVER.BY OXIDATION,OR CONJUGATED IN THE LIVER.  4]4] DRUG EXCRETION-DRUG EXCRETION-- IS INCREASED DUE TO THE- IS INCREASED DUE TO THE INCREASED RPF,GFR AND CREATININE CLEARANCEINCREASED RPF,GFR AND CREATININE CLEARANCE [2] www.doctor.sdwww.doctor.sd
  4. 4.  B) FETAL;B) FETAL;  DRUG DISTRIBUTION,METABOLISM ANDDRUG DISTRIBUTION,METABOLISM AND EXCRETIONS OCCUR IN THE FETUS ANDEXCRETIONS OCCUR IN THE FETUS AND PLACENTA,PLACENTA,  FETAL LIVER AND ADRENAL GLAND METABOLIZESFETAL LIVER AND ADRENAL GLAND METABOLIZES DRUGS BY OXIDATION,OXIDATIVE DEALKYLATION,DRUGS BY OXIDATION,OXIDATIVE DEALKYLATION, REDUCTION HYDROXYLATION,HYDROLYSIS ANDREDUCTION HYDROXYLATION,HYDROLYSIS AND CONJUGATION.CONJUGATION.  LOW-MOLECULAR-WEIGHT DRUGS DIFFUSELOW-MOLECULAR-WEIGHT DRUGS DIFFUSE EASILY ACROSS THE PLACENTA,AMINO ACIDSEASILY ACROSS THE PLACENTA,AMINO ACIDS TRANSPORT BY ACTIVE TRANSFER,TRANSPORT BY ACTIVE TRANSFER,  LIPID SOLUBILITY AND PLASMA PROTEIN BINDINGLIPID SOLUBILITY AND PLASMA PROTEIN BINDING ARE CONTRIBUTORY FACTORS.ARE CONTRIBUTORY FACTORS. [3] www.doctor.sdwww.doctor.sd
  5. 5. BASIC RULES OF PRESCRIBING INBASIC RULES OF PRESCRIBING IN PREGNANCYPREGNANCY  A) REMEMBER THEA) REMEMBER THE OBSTETRIC RULES:OBSTETRIC RULES:  1. FIRST DO NO HARM1. FIRST DO NO HARM  2. NEVER BE THE2. NEVER BE THE FIRST TO USE THEFIRST TO USE THE NEW,NOR THE LASTNEW,NOR THE LAST TO USE THE OLDTO USE THE OLD  3. REMEMBER THAT3. REMEMBER THAT ALL WOMEN AREALL WOMEN ARE PREGNANT UNTILLPREGNANT UNTILL PROVED OTHERWISE.PROVED OTHERWISE.  B) PRESCRIBING INB) PRESCRIBING IN PREGNANCY:PREGNANCY:  1.1. PRECONCEPTIONALLY;PRECONCEPTIONALLY; THE PATEINT MAY BETHE PATEINT MAY BE TAKING DRUGSTAKING DRUGS  2. THE PATIENT MAY BE2. THE PATIENT MAY BE TAKING DRUGS ANDTAKING DRUGS AND FIND SHE IS PREGNANTFIND SHE IS PREGNANT  3. THE PATIENT WHO IS3. THE PATIENT WHO IS PREGNANT MAYPREGNANT MAY REQUIRE DRUGREQUIRE DRUG TREATMENT.TREATMENT. [4] www.doctor.sdwww.doctor.sd
  6. 6. Fetal therapy Teratogenesis 1/3 trimester 2/3 trimester 3/3 trimester labour puerperium Pre-pregnant Medical disorders of pregnancy Prelabour Induction of labour Analgesics Oxytocics Depression Contraception Breast-feeding Drugs of abuse Antibiotics POTENTIAL RISKS AT DIFFERENT MONTHS OF PREGNANCY [5] www.doctor.sdwww.doctor.sd
  7. 7.  DIETARY ADVICE:DIETARY ADVICE:  DEFICIENCIES IN PROTEINS,VITAMINS,MINERALS OR TRACEDEFICIENCIES IN PROTEINS,VITAMINS,MINERALS OR TRACE ELEMENTS CAN AFFECT FETAL GROWTH& DEVELOPMENT.ELEMENTS CAN AFFECT FETAL GROWTH& DEVELOPMENT.  THE OPTIMAL WEIGHT GAIN IN PREGNANCY ;FOR THINTHE OPTIMAL WEIGHT GAIN IN PREGNANCY ;FOR THIN WOMEN=12.5 Kg, AND FOR OBESE=5-10 Kg.WOMEN=12.5 Kg, AND FOR OBESE=5-10 Kg.  DIETARY SUPPLEMENTATION:DIETARY SUPPLEMENTATION:  IS AIMED,AMONGST OTHER FACTORS,TO REDUCEIS AIMED,AMONGST OTHER FACTORS,TO REDUCE CONGENITAL MALFORMATIONS;CONGENITAL MALFORMATIONS;  1) VITAMINS:1) VITAMINS: DAILY DOSE OF 400 U VIT. D=LOWER THE RISKDAILY DOSE OF 400 U VIT. D=LOWER THE RISK OF NEONATAL RICKETS,DENTAL ENAMEL DISPLACEMENT.OF NEONATAL RICKETS,DENTAL ENAMEL DISPLACEMENT.  VIT. A = EXCESSIVE DOSE >40 OOO IU,CAN BE HAZARDOUS.VIT. A = EXCESSIVE DOSE >40 OOO IU,CAN BE HAZARDOUS.  FOLIC ACIDFOLIC ACID= DAILY DOSE OF 0.4 mg, WILL REDUCE THE= DAILY DOSE OF 0.4 mg, WILL REDUCE THE INCIDENCE OF NTD.INCIDENCE OF NTD.  2) HAEMATINICS:2) HAEMATINICS: ORALLY= FERROUS SALTS: SULPHATE ,ORALLY= FERROUS SALTS: SULPHATE , GLUCONATE AND FUMARATE,GLUCONATE AND FUMARATE, PARENTERALLY= I.M.,IV. OR AS TOTAL IRON INFUSIONSPARENTERALLY= I.M.,IV. OR AS TOTAL IRON INFUSIONS [6] www.doctor.sdwww.doctor.sd
  8. 8.  PAST OBSTETRIC HISTORY:PAST OBSTETRIC HISTORY:  1) OVULATION-INDUCING DRUGS;1) OVULATION-INDUCING DRUGS;  CLOMIPHENE CITRATECLOMIPHENE CITRATE -- 2 TO 3X RISK OF STD AND OVARIAN-- 2 TO 3X RISK OF STD AND OVARIAN MALIGNANCY,FOLLOWING EXCESSIVE USE >12/12.MALIGNANCY,FOLLOWING EXCESSIVE USE >12/12.  2) HORMONES;2) HORMONES;  -DES-DES = PRENATAL EXPOSURE,FOR THREATENED ABORTION,= PRENATAL EXPOSURE,FOR THREATENED ABORTION, MAY CAUSE ADENOCA OF VAGINA.MAY CAUSE ADENOCA OF VAGINA.  -PROGESTOGENS-PROGESTOGENS = USED IN RECURRENT MISCARRIAGES AND= USED IN RECURRENT MISCARRIAGES AND POOR LUTEAL PHASE. NO NEED TO USE THEM NOW.POOR LUTEAL PHASE. NO NEED TO USE THEM NOW.  -ORAL CONTRACEPTIVES-ORAL CONTRACEPTIVES = SUPPRESS FOLATE AND= SUPPRESS FOLATE AND PYRIDOXINE LEVELS, NO OTHER HARMS.PYRIDOXINE LEVELS, NO OTHER HARMS.  -ANTICOAGULANTS-ANTICOAGULANTS = ASPIRIN(75 Mg)& HEPARIN – ARE USED IN= ASPIRIN(75 Mg)& HEPARIN – ARE USED IN CASES OF RECURRENT ABORTIONS DUE TO SLE OR RAISEDCASES OF RECURRENT ABORTIONS DUE TO SLE OR RAISED APA.APA.  -OTHERS-OTHERS = ASPIRIN & NITRIC OXIDE ARE ALSO USED TO= ASPIRIN & NITRIC OXIDE ARE ALSO USED TO IMPROVE UTERINE PERFUSION IN RECURRENT MISCARRIAGES.IMPROVE UTERINE PERFUSION IN RECURRENT MISCARRIAGES. [7] www.doctor.sdwww.doctor.sd
  9. 9.  C) STD;C) STD; THE COMMONEST COMMUNICABLETHE COMMONEST COMMUNICABLE DISEASES GLOBALLY. SCREENING FORDISEASES GLOBALLY. SCREENING FOR SYPHILIS & AIDS IS IMPORTANT.ABOUT 30%SYPHILIS & AIDS IS IMPORTANT.ABOUT 30% OF THEIR BABIES WILL BE HIV +VE.OF THEIR BABIES WILL BE HIV +VE.  D) VACCINATION & TRAVELD) VACCINATION & TRAVEL ; FOR YELLOW; FOR YELLOW FEVER,CHOLERA,POLIOMYEILITIS ANDFEVER,CHOLERA,POLIOMYEILITIS AND INFLUENZA CAN BE GIVEN ANTENATALLY.INFLUENZA CAN BE GIVEN ANTENATALLY. RUBELLA VACC. IS ALLOWED ONLY PRE-RUBELLA VACC. IS ALLOWED ONLY PRE- CONCEPTUALLY OR POSTPARTUM.CONCEPTUALLY OR POSTPARTUM. [8] www.doctor.sdwww.doctor.sd
  10. 10.  GENERAL MEDICAL DISORDERSGENERAL MEDICAL DISORDERS ;; A) EPILEPSYA) EPILEPSY = A RISK OF FETAL MALFORMATIONS WHICH IS= A RISK OF FETAL MALFORMATIONS WHICH IS INCREASED ON TAKING ANTIEPILEPTICS – THESE ARE :INCREASED ON TAKING ANTIEPILEPTICS – THESE ARE : 1) MINOR1) MINOR STRUCTURAL WITH NO THREAT TO HEALTH.STRUCTURAL WITH NO THREAT TO HEALTH. 2) MAJOR2) MAJOR = CLEFT LIP,SPINA BIFIDA AND CHD.= CLEFT LIP,SPINA BIFIDA AND CHD. ANTIEPILEPTICSANTIEPILEPTICS : (: (a)VALPORATEa)VALPORATE—SPINA BIFIDA & CRANIAL +—SPINA BIFIDA & CRANIAL + FACIAL ANOMALIES.(FACIAL ANOMALIES.( b) CARBAMAZEPINEb) CARBAMAZEPINE – SPINA BIFIDA.– SPINA BIFIDA. ((c) PHENOBARBITONEc) PHENOBARBITONE – CHD & CLEFT PALATE.(– CHD & CLEFT PALATE.(d) PHENYTOINd) PHENYTOIN –– HYDANTOIN SYNDROME.HYDANTOIN SYNDROME.  MANAGEMENT:(1)MANAGEMENT:(1) ADVICE HIGHER DOSES OF COCS.ADVICE HIGHER DOSES OF COCS. (2)(2) FOLIC ACID(4-5MG) BEFORE CONCEPTION AND UP TO 12/52FOLIC ACID(4-5MG) BEFORE CONCEPTION AND UP TO 12/52 PREGNANCYPREGNANCY.(3).(3) ADVISE SINGLE DRUG AND LOWEST DOSE.ADVISE SINGLE DRUG AND LOWEST DOSE. CARBAMAZEPINECARBAMAZEPINE IS THE DRUG OF CHOICEIS THE DRUG OF CHOICE.(4).(4) VITAMIN K TO BEVITAMIN K TO BE GIVEN AT BIRTH TO PROTECT THE INFANT.GIVEN AT BIRTH TO PROTECT THE INFANT.  B) PSYCHIATRIC ILLNESSB) PSYCHIATRIC ILLNESS = like depression= like depression (a)(a) Meprobamate orMeprobamate or benzodiazepines --- serious neonatal symptoms.Not teratogenic.benzodiazepines --- serious neonatal symptoms.Not teratogenic. bb) (Monoamine-oxidase inhibitors– c/i in pregnancy due to) (Monoamine-oxidase inhibitors– c/i in pregnancy due to anaesthesiaanaesthesia.(c).(c) Tricyclic antidepressants--- babies refusal to feed.Tricyclic antidepressants--- babies refusal to feed. (d)(d) Lithium salts ;lithium clearance in pregnancy increases.It mayLithium salts ;lithium clearance in pregnancy increases.It may affect the fetus causing cyanosis,lethargy,hypotonia,poor suckling andaffect the fetus causing cyanosis,lethargy,hypotonia,poor suckling and CHDCHD.(e).(e) Phenothiazines can cause Parkinsonism .Phenothiazines can cause Parkinsonism . [10] www.doctor.sdwww.doctor.sd
  11. 11.  C)TRANSPLANTATIONC)TRANSPLANTATION :: INCLUDING RENAL,LUNG,LIVER,BONE MARROW ANDINCLUDING RENAL,LUNG,LIVER,BONE MARROW AND HEART.SURVIVAL RATE = 70-80%.DRUGS USED;HEART.SURVIVAL RATE = 70-80%.DRUGS USED; 1)ADRENAL STEROIDS1)ADRENAL STEROIDS – PEPTIC– PEPTIC ULCERATION,ULCERATION, OSTEOPOROSIS,HYPERTENSION,MATERNALOSTEOPOROSIS,HYPERTENSION,MATERNAL INFECTION AND POOR TISSUE HEALING.INFECTION AND POOR TISSUE HEALING. 2)AZATHIOPRINE2)AZATHIOPRINE – HEPATIC TOXICITY,BONE– HEPATIC TOXICITY,BONE MARROW DEPRESSION,INFECTION AND NEOPLASIA.MARROW DEPRESSION,INFECTION AND NEOPLASIA. 3)CYCLOSPORIN3)CYCLOSPORIN – NEPHROTOXICITY,ELEVATED– NEPHROTOXICITY,ELEVATED SERUM URIC ACID,LYMPHOMAS AND VIRALSERUM URIC ACID,LYMPHOMAS AND VIRAL INFECTION.INFECTION. D) HYPERTENSIOND) HYPERTENSION: MOST DRUGS: MOST DRUGS HAVE A FAVOURABLE BENEFIT. ANGIOTENSIN-HAVE A FAVOURABLE BENEFIT. ANGIOTENSIN- CONVERTING ENZYME INHIBITORS ARECONVERTING ENZYME INHIBITORS ARE CONTRAINDICATED.CONTRAINDICATED. E)DIABETESE)DIABETES MELLITUSMELLITUS: ORAL HYPOGLYCAEMICS ARE: ORAL HYPOGLYCAEMICS ARE CONTRAINDICATED.CONTRAINDICATED. [11] www.doctor.sdwww.doctor.sd
  12. 12.  INDUSTRIAL HISTORYINDUSTRIAL HISTORY  A)OPERATING THEATRESA)OPERATING THEATRES: VOLATILE GASES: VOLATILE GASES MAY CAUSE SPON. ABORTIONS ANDMAY CAUSE SPON. ABORTIONS AND CONGENITAL ANOMALIES. SCAVENGERCONGENITAL ANOMALIES. SCAVENGER SYSTEMS SHOULD BE INSTALLED.SYSTEMS SHOULD BE INSTALLED. B) LAUNDRIESB) LAUNDRIES: ORGANIC: ORGANIC SOLVENTS CAN CAUSE ANENCEPHALY ORSOLVENTS CAN CAUSE ANENCEPHALY OR FETAL DYSMORPHOLOGY.FETAL DYSMORPHOLOGY. C) COMPUTERSC) COMPUTERS:: NO RISK.NO RISK. D) SAUNASD) SAUNAS: NO: NO HARM .HARM .  FAMILY HISTORYFAMILY HISTORY GENDER CHOICEGENDER CHOICE: DIETS HIGH IN SODIUM &: DIETS HIGH IN SODIUM & POTASSIUM AND LOW IN CALCIUM &POTASSIUM AND LOW IN CALCIUM & MAGNESIUM ARE REPORTED TO GIVE ANMAGNESIUM ARE REPORTED TO GIVE AN 80% CHANCE OF A MALE FETUS.80% CHANCE OF A MALE FETUS. [12] www.doctor.sdwww.doctor.sd
  13. 13.  TERATOGENESISTERATOGENESIS  A TERATOGEN: IS AN AGENT THAT CAUSES PHYSICALA TERATOGEN: IS AN AGENT THAT CAUSES PHYSICAL AND/OR DEVELOPMENTAL ABNORMALITIES IN THE EMBRYOAND/OR DEVELOPMENTAL ABNORMALITIES IN THE EMBRYO OR THE FETUS.OR THE FETUS.  TIMING OF FETAL LIFE:TIMING OF FETAL LIFE: [[11]PRE-EMBRYONIC PHASE = 1–17 DAY POSTCONCEPTION]PRE-EMBRYONIC PHASE = 1–17 DAY POSTCONCEPTION [[22] EMBRYONIC = 18-55 DAY.] EMBRYONIC = 18-55 DAY. [[33]ORGANOGENESIS.]ORGANOGENESIS.  TERATOGENIC MECHANISMSTERATOGENIC MECHANISMS:: (a)(a) DIRECT EMBRYO TOXICITY.DIRECT EMBRYO TOXICITY. (b) INDIRECT TOXICITY– BY ALTERATION OF(b) INDIRECT TOXICITY– BY ALTERATION OF METABOLIC FACTORS.METABOLIC FACTORS. (c)(c) GENETIC FACTORS– DETERMINING THEGENETIC FACTORS– DETERMINING THE SUSCEPTIBILITY TO TERATOGENESIS (WARFARIN !).SUSCEPTIBILITY TO TERATOGENESIS (WARFARIN !).  CLASSIFICATION:CLASSIFICATION: {1}{1} MAJOR TERATOGENS = WITH PROVEN RISKSMAJOR TERATOGENS = WITH PROVEN RISKS [THALIDOMIDE,CYTOTOXICS AND RADIOCHEMICALS].[THALIDOMIDE,CYTOTOXICS AND RADIOCHEMICALS]. {2}{2} DRUGS WITH SMALL RISKS BUT OCCASIONALLY NEEDEDDRUGS WITH SMALL RISKS BUT OCCASIONALLY NEEDED FOR THE HEALTH OF THE WOMAN.FOR THE HEALTH OF THE WOMAN. [13] www.doctor.sdwww.doctor.sd

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