teratogenic drugs
DESCRIPTION
no plagiarism, okay? just sharing and for learning purpose..TRANSCRIPT
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TERATOGENIC DRUG
1. NURUL MIZA SHASHEIHA BINTI ABDUL MUTALIB2. NURUL HUSNA BINTI MURYADI 3. WAN FATHIAH NASUHA BT WAN NUSDRI4. NURFATIN AFIQAH BT MOHD BADRONDIN5. ZATEEL FAHADA BT RUSLI6. NURUL FIRDAUS BT HANAFEE7. NURUL SAHIIRAH BT AHMAD ROFI8. WAN FARAH NASUHA BT WAN MUHAMMAD HUSNI
by:
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INTRODUCTION
• WHAT IS TERATOGEN ?
• TERATOGENIC DRUG
• FDA PREGNANCY CATEGORIES
• GENERAL MECHANISMS OF ACTION OF TERATOGENIC DRUGS
• TERATOGENIC MECHANISMS OF MEDICAL DRUGS
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TERATOGEN
• Is an agent that can disturb the development of the embryo or fetus
• Teratogens halt the pregnancy or produce a congenital malformation
• Include radiation, maternal infections, chemicals, and drugs.
• directly or indirectly, causes a structural or functional change in the fetus or child if it is administrated to pregnant mother
• If mother is taking this drug, It can be either stopped, switched or reduced to the lowest dose possible
• typically during sensitive periods of fetal development
• depending on the particular teratogenic process and target organ
TERATOGENIC DRUG
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FDA PREGNANCY CATEGORIES
CATEGORY A• failed to
demonstrate a risk to the fetus in the first trimester of pregnancy
• no evidence of risk in later trimesters
CATEGORY C• shown an
adverse effect on the fetus
• no adequate and well-controlled studies in humans
• potential benefits may warrant the use of drug despite potential risks.
CATEGORY D• positive
evidence of human fetal risk based on adverse reaction data
• potential benefits may warrant use of the drug in pregnant women despite potential risks
CATEGORY B• failed to
demonstrate a risk to the fetus
• no adequate and well-controlled studies in pregnant women.
CATEGORY X• demonstrate
s fetal abnormalities
• positive evidence of human fetal risk based on adverse reaction data
• the risks involved in use of the drug in pregnant women
CATEGORY N• FDA has
not classified the drug.
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POSSIBLE SITES OF ACTION OF TERATOGEN
DIRECT TOXIC
ACTION
• FETUS: -Direct toxicity.-Metabolites toxic.-Indirectly toxic, e.g. anti-metabolites, anti-vitamin.-Pharmacodynamic actions, e.g. on cardiovascular system. -Endocrine balance altered
• FAETOPLACENTAL UNIT:-Umbilical cord, e.g. spasm.-Amniotic fluid volume change. -Faetal or maternal placental blood flow.-Placental transfer of nutrients, e.g. decreased active transport
• MOTHER:-Nutritional changes, e.g. vitamin or mineral deficiencies.-Biochemical changes with secondary effects on the foetus, e.g. hyperglycaemia.-Endocrine balance
• FATHER:-Sperm changes
INDIRECT TOXIC
ACTION
• Cause malformation-interfering with faetal metabolism
• Drugs: -folic acid antagonists-antiepileptic drugs
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TERATOGENIC MECHANISMS OFMEDICAL DRUGS
• Folate antagonism• Neural crest cell disruption• Endocrine disruption • Oxidative stress• Vascular disruption and specific
receptor• Enzyme-mediated
teratogenesis
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Teratogenic Drugs
•Analgesic•Anticonvulsant•Anticoagulant
•Antidepressant•Antithyroid•Vitamin A
IN FIRST TRIMESTER OF PREGNANCY
•Metal toxic•Sedative/ hypnotics•Aminoglycosides
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Analgesic (aspirin)
• Gastroschisis• Decrease prostaglandin decrease uterine
contraction delayed onset of labor & prolonged period of pregnancy
• During delivery severe bleeding because aspirin decrease platelet aggregation
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Anticonvulsant
• Fetal hydantoin syndrome : cranio facial malformation:
-Cleft lip and palate
-Broad nasal bridge
-Ocular hypertelorism
-Abnormal ears congenital heart disease limb malformation mental and growth retardation
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Anticoagulant ( warfarin & Coumadin )
• Fetal wafarin syndrome: -Nasal hypoplasia-Bone stippling-Bilateral optic atrophy-Mental retardation
• Respiratory distress syndrome• Fetal and maternal hemorrhage
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Antidepressant (imipramine)
• Cleft palate• Defect in abdomen• Adrenal hypoplasia• Cardiovascular defect
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Antithyroid ( propylthiouracil & methimazole )
• Fetal goiter
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Vitamin A ( retinoic acid )
• Cranio-facial dysmorphism
• Cleft palate• Thymic aplasia• Neural tube defect ( spina bifida cystic )
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Metal toxic (lithium)
• Hypotonia• Cyanosis• Lethargy• Poor respiratory
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Sedative / hypnotics (diazepam )
• Cleft lip and palate• Inguinal hernia• Congenital heart disease• Pyloric stenosis• Breathing difficulties
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Aminoglycosides (streptomycin & canamycin )
• Congenital deafness• Ototoxicity
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TERATOGENIC DRUGS IN SECOND TRIMESTER OF
PREGNANCY
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ACE INHIBITORS
DIAZEPAM
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1) ACE INHIBITOR
MECHANISM OF ACTIONS
Produce vasodilatation by
1-inhibitting formation of angiotensin 11
2- breakdown bradykinin
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PHARMACOLOGICAL ACTION
Mixed vasodilator
In cases of heart failure, cardiac output is maintained / even increase
Increase renal blood flow BUT decrease glomerular filtration rate decrease glomerular hypertension
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THERAPEUTIC USES
USED IN Hypertension Heart failure Myocardial infarction
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SIDE EFFECTS
IF USED IN 2ND – 3RD TRIMESTER OF PREGNANCY
1- fetal hypotension
2- renal failure
3- oligohydromnios
4- death
3rd tri
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2) DIAZEPAM
Centrally acting spasmolytic drug
It facilitates action of GABA in CNS
It acts as GABA synapse and produce sedation at doses required to reduce muscles tone
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PHARMACOKINETICS
ABSORPTION:
- Delayed and decreased when administered with a moderate fat meal
DISTRIBUTION
- Highly bound to plasma protein
- Cross blood brain barrier
- Cross placental barrier
- Found in milk
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METABOLISM
N-demythylated Diazepam N-desmethyldiazepam
further metabolised hydroxylated temazepam oxazepam
Temazepam and oxazepam are largely eliminated by glucoronidation
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ELIMINATION
The initial distribution phase is followed by prolonged elimination phase
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SIDE EFFECTS
RISKS OF…
1) cleft palate
2) cardiac and circulatory defects
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TERATOGENIC DRUGS IN THIRD TRIMESTER OF PREGNANCY
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TETRACYCLINEACE INHIBITORS
CHLORAMPHENICOLAMINOGLYCOSIDES
SULFAMETHOXAZOLETRIMETHOPRIM
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1) TETRACYCLINEProtein synthesis inhibitorInhibit the binding of aminoacyl-tRNA to the
mRNA- ribosomes complex
Aminoacyl-tRNA mRNA-ribosomes complex
by binding to the 30S ribosomal subunit in mRNA translation complex
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SIDE EFFECTSIN PREGNANCY…..
dental discolouration in chilren maternal hepatotoxicity with large
parenteral doses
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2) ACE INHIBITORSAS IN SECOND TRIMESTER
Ace inhibitors in 2nd trimester
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3) CHLORAMPHENICOLBacteriostatic drug that stop bacterial growth
by inhibiting protein synthesisPrevent protein chain elongation by
inhibiting peptidyl transferase activity of bacterial chromosome
Intravenous chloramphenicol use has been associated with Gray Baby syndromeThis occur in newborn infants because they
liver enzymes not yet fully developedchloramphenicol remains
unmetabolised in body
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ADVERSE EFFECTSHypotensionCyanosis
The condition can be prevented by using the drug at recommended doses & monitoring blood levels
Gray Baby Syndrome
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4) AMINOGLYCOSIDESEG: GENTAMICIN, STREPTOMYCINHave several potential antibiotic mechanismsThey interfere with the proofreading process increased rate of error in
synthesis with premature termination
Inhibition of ribosomal translocation peptidyl tRNA moves from A-
site to P- siteDisrupt the integrity of the bacterial cell
membrane
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Aminoglycosides are in pregnancy category DThey may cause auditory or vestibular nerve
damage
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5) SULFAMETHOXAZOLE, TRIMETHOPRIMSulfonamide bacteriostatic antibioticStructural analogs and competitive
antagonist of PABAInhibit normal bacterial utilisation of PABA
for the synthesis of folic acidUsed as a bacteriostatic antibiotic in
prophylaxis and treatment of urinary tract infections
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Trimethoprim binds to dihydrofolate redustase and inhibit reduction of DHF to THF
Sulfamethoxazole inhibit dihydrofolate synthetase
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TERATOGENIC EFFECTS1) NEONATAL HAEMOLYSIS2)METHAEMOGLOBINAEMIA
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CONCLUSION• BE CAREFUL IN TAKING DRUGS DURING
PREGNANCY•ALL CLINICIANS INCLUDING PHARMACISTS
ARE RESPONSIBLE TO COUNSEL PATIENTS WITH COMPLETE , ACCURATE AND CURRENT INFORMATION ON THE RISKS AND BENEFITS
OF USING MEDICATIONS DURING PREGNANCY
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THANK YOU