DRUGS IN PREGNANCY

www.doctor.sdwww.doctor.sd

INTRODUCTION:INTRODUCTION: ONE SHOULD USE A SMALL ARMAMENTARIUM OF ONE SHOULD USE A SMALL ARMAMENTARIUM OF

DRUGS THAT HAVE A PROVEN VALUE WITH KNOWN DRUGS THAT HAVE A PROVEN VALUE WITH KNOWN AND RECORDED MINIMAL SIDE EFFECTS.AND RECORDED MINIMAL SIDE EFFECTS.

CONSIDER THAT ALL DRUGS MAY AFFECT THE CONSIDER 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 FIRST COUNTER' MEDICINES DURING THE FIRST TRIMESTER WITH POTENTIAL RISKS.TRIMESTER WITH POTENTIAL RISKS.

CONSIDER THAT ALL PATIENTS ARE AT RISK OF CONSIDER THAT ALL PATIENTS ARE AT RISK OF PREGNANCY DURING THEIR REPRODUCTIVE YEARS.PREGNANCY DURING THEIR REPRODUCTIVE YEARS.

ALWAYS CONSIDER THE RISK OF THERAPY AGAINST ALWAYS CONSIDER THE RISK OF THERAPY AGAINST THE POTENTIAL FOR NOT TREATING THE DISEASE.THE POTENTIAL FOR NOT TREATING THE DISEASE.

[1]


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 SLOW GASTROINTESTINAL 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 BODY PLASMA 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 ELIMINATED UNCHANGED,LIPID-SOLUBLE ARE METABOLIZED BY OXIDATION,OR CONJUGATED IN THE METABOLIZED BY OXIDATION,OR CONJUGATED IN THE LIVER.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]


B) FETAL;B) FETAL; DRUG DISTRIBUTION,METABOLISM AND DRUG DISTRIBUTION,METABOLISM AND

EXCRETIONS OCCUR IN THE FETUS AND EXCRETIONS OCCUR IN THE FETUS AND PLACENTA,PLACENTA,

FETAL LIVER AND ADRENAL GLAND METABOLIZES FETAL LIVER AND ADRENAL GLAND METABOLIZES DRUGS BY OXIDATION,OXIDATIVE DEALKYLATION, DRUGS BY OXIDATION,OXIDATIVE DEALKYLATION, REDUCTION HYDROXYLATION,HYDROLYSIS AND REDUCTION HYDROXYLATION,HYDROLYSIS AND CONJUGATION.CONJUGATION.

LOW-MOLECULAR-WEIGHT DRUGS DIFFUSE LOW-MOLECULAR-WEIGHT DRUGS DIFFUSE EASILY ACROSS THE PLACENTA,AMINO ACIDS EASILY ACROSS THE PLACENTA,AMINO ACIDS TRANSPORT BY ACTIVE TRANSFER,TRANSPORT BY ACTIVE TRANSFER,

LIPID SOLUBILITY AND PLASMA PROTEIN BINDING LIPID SOLUBILITY AND PLASMA PROTEIN BINDING ARE CONTRIBUTORY FACTORS.ARE CONTRIBUTORY FACTORS.

[3]


BASIC RULES OF PRESCRIBING IN BASIC RULES OF PRESCRIBING IN PREGNANCYPREGNANCY

A) REMEMBER THE A) REMEMBER THE OBSTETRIC RULES:OBSTETRIC RULES:

1. FIRST DO NO HARM1. FIRST DO NO HARM 2. NEVER BE THE 2. NEVER BE THE

FIRST TO USE THE FIRST TO USE THE NEW,NOR THE LAST NEW,NOR THE LAST TO USE THE OLDTO USE THE OLD

3. REMEMBER THAT 3. REMEMBER THAT ALL WOMEN ARE ALL WOMEN ARE PREGNANT UNTILL PREGNANT UNTILL PROVED OTHERWISE.PROVED OTHERWISE.

B) PRESCRIBING IN B) PRESCRIBING IN PREGNANCY:PREGNANCY:

1. PRECONCEPTIONALLY; 1. PRECONCEPTIONALLY; THE PATEINT MAY BE THE PATEINT MAY BE TAKING DRUGSTAKING DRUGS

2. THE PATIENT MAY BE 2. THE PATIENT MAY BE TAKING DRUGS AND FIND TAKING DRUGS AND FIND SHE IS PREGNANTSHE IS PREGNANT

3. THE PATIENT WHO IS 3. THE PATIENT WHO IS PREGNANT MAY REQUIRE PREGNANT MAY REQUIRE DRUG TREATMENT.DRUG TREATMENT.

[4]


Fetal therapy

Teratogenesis

1/3trimester

2/3

trimester

3/3

trim

este

r

labour

puerperiu

m

Pre-

preg

nant Medical disorders

of pregnancy

PrelabourInduction of labour

AnalgesicsOxytocics

DepressionContraceptionBreast-feeding

Drugs of abuseAntibiotics

POTENTIAL RISKS AT DIFFERENT MONTHS OF PREGNANCY

[5]


DIETARY ADVICE: DIETARY ADVICE: DEFICIENCIES IN PROTEINS,VITAMINS,MINERALS OR TRACE DEFICIENCIES 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 THIN THE 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 REDUCE IS AIMED,AMONGST OTHER FACTORS,TO REDUCE

CONGENITAL MALFORMATIONS;CONGENITAL MALFORMATIONS; 1) VITAMINS:1) VITAMINS: DAILY DOSE OF 400 U VIT. D=LOWER THE DAILY DOSE OF 400 U VIT. D=LOWER THE

RISK OF NEONATAL RICKETS,DENTAL ENAMEL RISK OF NEONATAL RICKETS,DENTAL ENAMEL DISPLACEMENT.DISPLACEMENT.

VIT. A = EXCESSIVE DOSE >40 OOO IU,CAN BE VIT. A = EXCESSIVE DOSE >40 OOO IU,CAN BE HAZARDOUS.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]


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 = ASPIRIN(75 Mg)& HEPARIN – ARE USED

IN CASES OF RECURRENT ABORTIONS DUE TO SLE OR RAISED IN CASES 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]


C) STD;C) STD; THE COMMONEST COMMUNICABLE THE COMMONEST COMMUNICABLE DISEASES GLOBALLY. SCREENING FOR DISEASES GLOBALLY. SCREENING FOR SYPHILIS & AIDS IS IMPORTANT.ABOUT SYPHILIS & AIDS IS IMPORTANT.ABOUT 30% OF THEIR BABIES WILL BE HIV +VE.30% OF THEIR BABIES WILL BE HIV +VE.

D) VACCINATION & TRAVELD) VACCINATION & TRAVEL ; FOR YELLOW ; FOR YELLOW FEVER,CHOLERA,POLIOMYEILITIS AND FEVER,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]


GENERAL MEDICAL DISORDERSGENERAL MEDICAL DISORDERS ; ; A) EPILEPSYA) EPILEPSY = A RISK OF FETAL MALFORMATIONS WHICH = A RISK OF FETAL MALFORMATIONS WHICH IS INCREASED ON TAKING ANTIEPILEPTICS – THESE ARE : IS 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 & —SPINA BIFIDA & CRANIAL + FACIAL ANOMALIES.( CRANIAL + FACIAL ANOMALIES.( b) CARBAMAZEPINEb) CARBAMAZEPINE – SPINA – SPINA BIFIDA. (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 FOLIC ACID(4-5MG) BEFORE CONCEPTION AND UP TO 12/52 PREGNANCY12/52 PREGNANCY.(3).(3) ADVISE SINGLE DRUG AND ADVISE SINGLE DRUG AND LOWEST DOSE. LOWEST DOSE. CARBAMAZEPINECARBAMAZEPINE IS THE DRUG OF CHOICE IS THE DRUG OF CHOICE.(4).(4) VITAMIN K TO BE GIVEN AT BIRTH TO PROTECT THE INFANT.VITAMIN K TO BE GIVEN AT BIRTH TO PROTECT THE INFANT.

B) PSYCHIATRIC ILLNESSB) PSYCHIATRIC ILLNESS = like depression = like depression (a)(a) Meprobamate Meprobamate or benzodiazepines --- serious neonatal symptoms.Not or benzodiazepines --- serious neonatal symptoms.Not teratogenic. teratogenic. bb) (Monoamine-oxidase inhibitors– c/i in ) (Monoamine-oxidase inhibitors– c/i in pregnancy due to anaesthesiapregnancy due to anaesthesia.(c).(c) Tricyclic antidepressants--- Tricyclic antidepressants--- babies refusal to feed. babies refusal to feed. (d)(d) Lithium salts ;lithium clearance in Lithium salts ;lithium clearance in pregnancy increases.It may affect the fetus causing pregnancy increases.It may affect the fetus causing cyanosis,lethargy,hypotonia,poor suckling and CHDcyanosis,lethargy,hypotonia,poor suckling and CHD.(e).(e) Phenothiazines can cause Parkinsonism . Phenothiazines can cause Parkinsonism .

[10]


C)TRANSPLANTATION C)TRANSPLANTATION : : INCLUDING RENAL,LUNG,LIVER,BONE MARROW AND INCLUDING 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,MATERNAL OSTEOPOROSIS,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 VIRAL SERUM 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 ARE CONVERTING ENZYME INHIBITORS ARE CONTRAINDICATED. CONTRAINDICATED. E)DIABETES E)DIABETES MELLITUSMELLITUS: ORAL HYPOGLYCAEMICS ARE : ORAL HYPOGLYCAEMICS ARE CONTRAINDICATED.CONTRAINDICATED.

[11]


INDUSTRIAL HISTORYINDUSTRIAL HISTORY A)OPERATING THEATRESA)OPERATING THEATRES: VOLATILE GASES : VOLATILE GASES

MAY CAUSE SPON. ABORTIONS AND MAY CAUSE SPON. ABORTIONS AND CONGENITAL ANOMALIES. SCAVENGER CONGENITAL ANOMALIES. SCAVENGER SYSTEMS SHOULD BE INSTALLED. SYSTEMS SHOULD BE INSTALLED. B) LAUNDRIESB) LAUNDRIES: ORGANIC : ORGANIC SOLVENTS CAN CAUSE ANENCEPHALY OR SOLVENTS 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 AN 80% MAGNESIUM ARE REPORTED TO GIVE AN 80% CHANCE OF A MALE FETUS.CHANCE OF A MALE FETUS.

[12]


TERATOGENESISTERATOGENESIS A TERATOGEN: IS AN AGENT THAT CAUSES PHYSICAL A TERATOGEN: IS AN AGENT THAT CAUSES PHYSICAL

AND/OR DEVELOPMENTAL ABNORMALITIES IN THE EMBRYO AND/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 ]PRE-EMBRYONIC PHASE = 1–17 DAY POSTCONCEPTION [POSTCONCEPTION [22] EMBRYONIC = 18-] EMBRYONIC = 18-55 DAY. 55 DAY. [[33]ORGANOGENESIS.]ORGANOGENESIS.

TERATOGENIC MECHANISMSTERATOGENIC MECHANISMS: : (a)(a) DIRECT EMBRYO TOXICITY. DIRECT EMBRYO TOXICITY. (b) INDIRECT TOXICITY– BY ALTERATION (b) INDIRECT TOXICITY– BY ALTERATION OF METABOLIC FACTORS. OF METABOLIC FACTORS. (c)(c) GENETIC FACTORS– DETERMINING THE GENETIC FACTORS– DETERMINING THE SUSCEPTIBILITY TO TERATOGENESIS (WARFARIN !).SUSCEPTIBILITY TO TERATOGENESIS (WARFARIN !).

CLASSIFICATION:CLASSIFICATION: {1}{1} MAJOR TERATOGENS = WITH PROVEN RISKS MAJOR TERATOGENS = WITH PROVEN RISKS [THALIDOMIDE,CYTOTOXICS AND RADIOCHEMICALS]. [THALIDOMIDE,CYTOTOXICS AND RADIOCHEMICALS]. {2}{2} DRUGS WITH SMALL RISKS BUT OCCASIONALLY DRUGS WITH SMALL RISKS BUT OCCASIONALLY NEEDED FOR THE HEALTH OF THE WOMAN.NEEDED FOR THE HEALTH OF THE WOMAN.

[13]


DRUGS IN PREGNANCY

Health & Medicine

Transcript of DRUGS IN PREGNANCY