rps138_slide_obat-obat_dalam_masa_kehamilan(2)

8/6/2019 rps138_slide_obat-obat_dalam_masa_kehamilan(2)

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Tri Widyawati - Datten Bangun

Departemen Farmakologi & Terapeutik

2007


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-

oleh ibu hamil dapat melewati plasenta danda at masuk ke tubuh anin

Efek farmakologi

e era ogen


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PharmacokineticsCritical factors affecting placental drug transfer anddrug effects on fetus :

1. Physicochemical properties of the drug

.

3. The amount of drug reaching the fetus

.

5. Distribution characteristic in different fetal

6. The stage of placental and fetal development at

7. The effects of drugs used in combination


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.1. Li ho hilic dru s :

- tends to diffuse readily across the placenta- enter the fetal circulation

Thiopental (used during caesarean section) :

cross the placenta immediately can produce sedation or apnea in the new


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..

- cross the placenta slowly achieve lowconcentration in the fetus

Succinylcholine or tubocurarine


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.

. , - -

concentration gradient cross the placenta

Salicylate


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B. Molecular SizeDrugs with mol. weight :

- -

- 500-1000 : more difficulty- > 1000 : poorly

Heparin :- very arge an po ar una e to cross t e p acenta

- safe to the fetus

- Warfarin : - smaller than heparin

-

- should be avoided


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.

-.

back to the maternal circulation

- cancer drugs (vinblastin, doxorubicin)- digoxin


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.

,

barbiturates, phenytoin, local anaesthetics

plasma than in fetal plasma because of


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.

- semipermeable barrier

- s te o meta o sm

2. Drugs enter the fetal circulation


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PharmacodynamicsA. Maternal Drug Actions

- e e ec s o rugs on repro uc ve ssuesof the pregnant woman sometimes are alteredby endocrine environment appropriate for thestage o t e pregnancy.

- Drug effects on other system tissue (heart,significantly, though sometimes cardiac outputor renal blood flow maybe altered

.insulin for pregnancy induced diabetic


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PharmacodynamicsB. Therapeutic Drug Actions in The Fetus

- Drugs are given to the mother with thefetus as the target of the drug

Examples:

maturation when preterm birth is expected.

jaundice


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.

- chronic used of opioid by mothers drug

- ACE-I used by the mothers renalamage n e e us

- diethylstilbesterol adenocarcinoma


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Pharmacod namicsD. Teratogenicity

Teratos = monster

malformed baby

Teratogen :* result in a characteristic set of malformation

* exerts its effect at a particular stage of fetal

eve opment organogenes s* show a dose-dependence incidence


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Teratogenic Action of Drugs influenced by :

Dose

requency

Length of exposure Stage of pregnancy upon exposure


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Schematic Diagram of Critical Periods of Human

Development

Prenatal death Major morphologic abnormalitiesPhysiologic defect and minor

morphologic abnormalities


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Poorl understood

Probably multifactorial :- maternal tissue

- differentiation process in the fetal tissue

* vit. A (retinol)- deficiency of critical substance

* folic acid deff. spina bifida

- chronic consumption of high dose of ethanol fetal alcohol syndrome


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Pregnancy Safety Index (US FDA)ategory :

- controlled studies in women (+)- fail to demonstrate a risk to the fetus in 1st semesterand later

Category B:- -* no foetal risk, but no controlled studies in pregnant

womens own an a verse e ec , u no con rme n con ro e

studies in women in 1st semester or later

Category C:

- studies in animal revealed adverse effect (teratogenic orembryogenic or other)- no controlled studies in women

Drugs should be given only if the potential benefit justifies

the potential risk to the fetus


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Pr n n f In x FDA

- there is positive evidence of human foetal risk, but thebenefits for the pregnant women may be acceptable (if the

Cate or X:- studies in animal and human being foetal abnormalities- evidence of foetal risk based on human experience

-outweights any possible benefit The drug is contraindicated in women who are or may


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Dru s to avoid in Pre nancPregnancy risk Description of Drugs to avoid

Unsafe

Acitretin, clomiphene,cocaine, ergots, ethanol,

XAbsolutely

contraindicated

HMG-CoA reductaseinhibitors, isotretinoin,

misoprostol, nicotin,premarin, quinine,

raloxifen, thalidomide

DEvidence of risk, but incertain circumtances,

ACE-I, angiotensinantagonist (2nd and 3rd

semesters),

use maybe justifiable am nog ycos es


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st

Teratogen


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Drug Effect Prenatal diagnosis

um ar ac e ec s

(Ebstein complex)

eas e

Warfarin Chondrodysplasia punctata Unlikely

Facial anomalies

Severe anomalies of CNS

Unlikely

Unlikely

Phenytoin Craniofacial Feasible

Limb

Growth deficiency

Feasible

Feasible

Sodium valproate CNS Feasible

Carbamazepine Craniofacial

Fingernail

Feasible

Feasible

Sex hormone Cardiac defectsMultiple anomalies

FeasibleFeasible

Retinoic acids Craniofacial Feasible

Cardiac

CNS

Feasible

Feasible


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Drugs Given After The 1st Trimester

,

moves from structural to physiologice ec s

Sometimes adverse effects occur in

the mother


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1. He arin : threatens mother rather than the fetus

- unfractionated heparin given to pregnantwomen 20.000 unit/day for 3 months

os eoporos s rac ure ver e rae

- risk is less with low-molecular-weight

2. Warfarin : damage the fetus, by causing bleeding into the

fetal brain, eventhough the mothers anticoagulant

control is good


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Antibiotic and Pregnancy

Considered safe Maybe safe, can be used in certain

circumstances

Should be avoided

Pnc G Trimethoprim/fetal abnormalities at 1st

Tm folate antagonist

Chloramphenicol

Pnc V Tetracycline

Ampicillin Aminoglycoside

Amoxycilline SulfonamideErythromycin Erythromycin estolate (cholestasis) Metronidazole

Floxacillin Ciprofloxacin

ep a ospor n a om eIsoniazid Rifampicinhemorrhagic disease :

give vit. K

Ethambutol


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Antibiotic and Pregnancy

Chloramphenicol Not teratogenic but gray baby

Tetracycline Tooth discoloration, enamelhypoplasia, bone hypoplasia and

Aminoglycoside Fetal citotoxicity

u onam e ven c ose to e very ern-icterus and hemolytic anaemia

Ciprofloxacin Fetal cartilage damage

Thalidomide For leprosy phocomelia


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Use paracetamol

Indomethacin could close the ductus

arteriosus rematurel


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Cancer Chemotherapy During Pregnancy

1. 1st trimester :-

teratogens- the risk for malformation 10% for singleagen an or com na on

2. Second and trimester :

-teratogenesis, but could have non teratogeniceffects

x. : owBrain development disturbances


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rps138_slide_obat-obat_dalam_masa_kehamilan(2)

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